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

Management of newborn infant born to mother suffering from tuberculosis: current recommendations & gaps in knowledge.

PubMed

Mittal, Hema; Das, Saurabhi; Faridi, M M A

2014-07-01

Tuberculosis (TB) is a global disease with increase in concern with growing morbidity and mortality after drug resistance and co-infection with HIV. Mother to neonatal transmission of disease is well known. Current recommendations regarding management of newborns of mothers with tuberculosis are variable in different countries and have large gaps in the knowledge and practices. We compare and summarize here current recommendations on management of infants born to mothers with tuberculosis. Congenital tuberculosis is diagnosed by Cantwell criteria and treatment includes three or four anti-tubercular drug regimen. Prophylaxis with isoniazid (3-6 months) is recommended in neonates born to mother with TB who are infectious. Breastfeeding should be continued in these neonates and isolation is recommended only till mother is infectious, has multidrug resistant tuberculosis or non adherent to treatment. BCG vaccine is recommended at birth or after completion of prophylaxis (3-6 months) in all neonates.

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

Treatment of extensively drug-resistant tuberculosis and role of the pharmacist.

PubMed

Mitrzyk, Beatriz Manzor

2008-10-01

Abstract Outbreaks of extensively drug-resistant tuberculosis (XDR-TB) in developing countries and recent headlines of an American traveling with a resistant variant of tuberculosis have brought XDR-TB into the spotlight. The World Health Organization and the United States Centers for Disease Control and Prevention have identified XDR-TB as a serious public health threat and are mandating increased efforts at control of tuberculosis. Although XDR-TB is believed to be no more infectious than other variants of tuberculosis, infection with and spread of XDR-TB are concerning because of the ineffectiveness, toxicity, and cost of the available tuberculosis treatment options. Pharmacists may not be aware of the recent trends in tuberculosis resistance or of the impact that they can have on educating the public about this disease. To gain a better understanding of this disease and the potential roles for pharmacists in public health awareness of tuberculosis and in the care of patients with and at risk for this disease, we undertook an extensive search of the Internet, including Web sites of tuberculosis advocacy groups, and of MEDLINE from January 1968-March 2008. Currently, XDR-TB infection is uncommon in the United States, but if history is any indication, there is a high potential for an outbreak or epidemic. The XDR-TB variant has emerged from mismanaging multidrug-resistant tuberculosis, treating tuberculosis with too few drugs, using less effective second-line drugs, and not educating patients about the dangers of nonadherence. With only limited hopes of a novel effective drug combination regimen, use of available antimycobacterial drugs needs to be optimized. Pharmacists can be key players in the prevention and treatment of tuberculosis by promoting adherence, assessing patients for risk factors for resistant disease, providing information about disease control and prevention, and monitoring for effectiveness, adverse effects, and drug interactions.

Host-Directed Therapeutics as a Novel Approach for Tuberculosis Treatment.

PubMed

Kim, Ye-Ram; Yang, Chul-Su

2017-09-28

Despite significant efforts to improve the treatment of tuberculosis (TB), it remains a prevalent infectious disease worldwide owing to the limitations of current TB therapeutic regimens. Recent work on novel TB treatment strategies has suggested that directly targeting host factors may be beneficial for TB treatment. Such strategies, termed host-directed therapeutics (HDTs), focus on host-pathogen interactions. HDTs may be more effective than the currently approved TB drugs, which are limited by the long durations of treatment needed and the emergence of drug-resistant strains. Targets of HDTs include host factors such as cytokines, immune checkpoints, immune cell functions, and essential enzyme activities. This review article discusses examples of potentially promising HDTs and introduces novel approaches for their development.

[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.

Advances in Mycobacterium tuberculosis therapeutics discovery utlizing structural biology

PubMed Central

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

2013-01-01

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

Anti-tubercular peptides: A quest of future therapeutic weapon to combat tuberculosis.

PubMed

Khusro, Ameer; Aarti, Chirom; Agastian, Paul

2016-11-01

Tuberculosis (TB) is a symbolic menace to mankind, infecting almost one third of the world's populace and causing over a million mortalities annually. Mycobacterium tuberculosis (Mtb) is the key pathogen of TB that invades and replicates inside the host's macrophage. With the emerging dilemma of multi-drug resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB), the exigency for developing new TB drugs is an obligation now for worldwide researchers. Among the propitious antimycobacterial agents examined in last few decades, anti-tubercular peptides have been substantiated to be persuasive with multiple advantages such as low immunogenicity, selective affinity to bacterial negatively charged cell envelopes and most importantly divergent mechanisms of action. In this review, we epitomized the current advances in the anti-tubercular peptides, focusing the sources and highlighting the mycobactericidal mechanisms of promising peptides. The review investigates the current anti-tubercular peptides exploited not only from human immune cells, human non-immune cells, bacteria and fungi but also from venoms, cyanobacteria, bacteriophages and several other unplumbed sources. The anti-tubercular peptides of those origins are also known to have unique second non-membrane targets within Mtb. The present context also describes the several cases that manifested the severe side effects of extant anti-TB drugs. The downfall, failure to reach clinical trial phases, inept to MDR- or XDR-TB and severe complications of the currently available anti-tubercular drugs accentuate the imperative necessity to develop efficacious drugs from adequate anti-tubercular peptides. Keeping in view of the emerging trends of drug resistant Mtb globally and unexampled mycobactericidal characteristics of peptides, the anti-tubercular peptides of varied origins can be used as a potential weapon to eradicate TB in future by developing new therapeutic drugs. Copyright © 2016 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Use of whole genome sequencing in surveillance of drug resistant tuberculosis.

PubMed

McNerney, Ruth; Zignol, Matteo; Clark, Taane G

2018-05-01

The threat of resistance to anti-tuberculosis drugs is of global concern. Current efforts to monitor resistance rely on phenotypic testing where cultured bacteria are exposed to critical concentrations of the drugs. Capacity for such testing is low in TB endemic countries. Drug resistance is caused by mutations in the Mycobacterium tuberculosis genome and whole genome sequencing to detect these mutations offers an alternative means of assessing resistance. Areas covered: The challenges of assessing TB drug resistance are discussed. Progress in elucidating the M. tuberculosis resistome and evidence of the accuracy of next generation sequencing for detecting resistance is reviewed. Expert Commentary: There are considerable advantages to using next generation sequencing for TB drug resistance surveillance. Accuracy is high for detecting resistance to the major first-line drugs but is currently lower for the second-line drugs due to our incomplete knowledge regarding resistance causing mutations. With the advances in sequencing technology and the opportunity to replace phenotypic drug susceptibility testing with safer and more cost effective methods it would appear that the question is when to implement. Current bottlenecks are sample extraction to allow whole genome sequencing directly from sputum and the lack of bioinformatics expertise in some TB endemic countries.

Clinical research in the treatment of tuberculosis: current status and future prospects.

PubMed

Chang, K-C; Yew, W-W; Sotgiu, G

2015-12-01

To supplement previous state-of-art reviews on anti-tuberculosis treatment and to pave the way forward with reference to the current status, we systematically reviewed published literature on clinical research on tuberculosis (TB) over the past decade in the treatment of drug-susceptible and multidrug-resistant TB (MDR-TB), with a focus on drugs, dosing factors and regimens. Our review was restricted to Phase II/III clinical trials, cohort and case-control studies, and systematic reviews of clinical studies. TB programmatic and patient behavioural factors, non-TB drugs, adjunctive surgery, new vaccines, immunotherapy, antiretroviral therapy and management of latent tuberculous infection are outside the scope of this review. An algorithm was used to systematically search PubMed for relevant articles published in English from 1 January 2005 to 31 December 2014. Articles without evaluated factors (drugs, dosing factors and regimens) or comparative analysis of specified anti-tuberculosis treatment outcomes were excluded. Of the 399 articles initially identified, 294 were excluded. The main findings of the remaining 105 articles are described under two categories: presumed drug-susceptible TB and MDR-TB. Fifty-nine articles included under drug-susceptible TB were divided into 12 subcategories: isoniazid, rifampicin, pyrazinamide, fluoroquinolones, fixed-dose combination drugs, dosing frequency, treatment phases, treatment duration, experimental regimens for pulmonary (surrogate markers vs. clinical outcomes) and extra-pulmonary TB. Forty-nine articles included under MDR-TB were divided into seven subcategories: fluoroquinolones, pyrazinamide, second-line injectable drugs, World Health Organization Group 4 and Group 5 drugs, MDR-TB regimens and novel drugs. Clinical research in the last decade and ongoing trials might furnish new paradigms for improving the treatment of this recalcitrant ancient disease.

The development, evaluation and performance of molecular diagnostics for detection of Mycobacterium tuberculosis.

PubMed

Bates, Matthew; Zumla, Alimuddin

2016-01-01

The unique pathogenesis of tuberculosis (TB) poses several barriers to the development of accurate diagnostics: a) the establishment of life-long latency by Mycobacterium tuberculosis (M.tb) after primary infection confounds the development of classical antibody or antigen based assays; b) our poor understanding of the molecular pathways that influence progression from latent to active disease; c) the intracellular nature of M.tb infection in tissues means that M.tb and/or its components, are not readily detectable in peripheral specimens; and d) the variable presence of M.tb bacilli in specimens from patients with extrapulmonary TB or children. The literature on the current portfolio of molecular diagnostics tests for TB is reviewed here and the developmental pipeline is summarized. Also reviewed are data from recently published operational research on the GeneXpert MTB/RIF assay and discussed are the lessons that can be taken forward for the design of studies to evaluate the impact of TB diagnostics.

The Tuberculosis Drug Discovery and Development Pipeline and Emerging Drug Targets

PubMed Central

Mdluli, Khisimuzi; Kaneko, Takushi; Upton, Anna

2015-01-01

The recent accelerated approval for use in extensively drug-resistant and multidrug-resistant-tuberculosis (MDR-TB) of two first-in-class TB drugs, bedaquiline and delamanid, has reinvigorated the TB drug discovery and development field. However, although several promising clinical development programs are ongoing to evaluate new TB drugs and regimens, the number of novel series represented is few. The global early-development pipeline is also woefully thin. To have a chance of achieving the goal of better, shorter, safer TB drug regimens with utility against drug-sensitive and drug-resistant disease, a robust and diverse global TB drug discovery pipeline is key, including innovative approaches that make use of recently acquired knowledge on the biology of TB. Fortunately, drug discovery for TB has resurged in recent years, generating compounds with varying potential for progression into developable leads. In parallel, advances have been made in understanding TB pathogenesis. It is now possible to apply the lessons learned from recent TB hit generation efforts and newly validated TB drug targets to generate the next wave of TB drug leads. Use of currently underexploited sources of chemical matter and lead-optimization strategies may also improve the efficiency of future TB drug discovery. Novel TB drug regimens with shorter treatment durations must target all subpopulations of Mycobacterium tuberculosis existing in an infection, including those responsible for the protracted TB treatment duration. This review summarizes the current TB drug development pipeline and proposes strategies for generating improved hits and leads in the discovery phase that could help achieve this goal. PMID:25635061

Cerebrospinal fluid protein and glucose examinations and tuberculosis:
Will laboratory safety regulations force a change of practice?

PubMed

Tormey, William P; O'Hagan, Christopher

2015-01-01

Cerebrospinal fluid (CSF) protein and glucose examinations are usually performed in chemical pathology departments on autoanalysers. Tuberculosis (TB) is a group 3 biological agent under Directive 2000/54/EC of the European Parliament but in the biochemistry laboratory, no extra precautions are taken in its analysis in possible TB cases. The issue of laboratory practice and safety in the biochemical analyses of CSF specimens, when tuberculosis infection is in question is addressed in the context of ambiguity in the implementation of current national and international health and safety regulations. Additional protective measures for laboratory staff during the analysis of CSF TB samples should force a change in current laboratory practice and become a regulatory issue under ISO 15189. Annual Mantoux skin test or an interferon-γ release assay for TB should be mandatory for relevant staff. This manuscript addresses the issue of biochemistry laboratory practice and safety in the biochemical analyses of CSF specimens when tuberculosis infection is in question in the context of the ambiguity of statutory health and safety regulations.

Human tuberculosis due to Mycobacterium bovis in the United States, 1995-2005.

PubMed

Hlavsa, Michele C; Moonan, Patrick K; Cowan, Lauren S; Navin, Thomas R; Kammerer, J Steve; Morlock, Glenn P; Crawford, Jack T; Lobue, Philip A

2008-07-15

Understanding the epidemiology of human Mycobacterium bovis tuberculosis (TB) in the United States is imperative; this disease can be foodborne or airborne, and current US control strategies are focused on TB due to Mycobacterium tuberculosis and airborne transmission. The National TB Genotyping Service's work has allowed systematic identification of M. tuberculosis-complex isolates and enabled the first US-wide study of M. bovis TB. Results of spacer oligonucleotide and mycobacterial interspersed repetitive units typing were linked to corresponding national surveillance data for TB cases reported for the period 2004-2005 and select cases for the period 1995-2003. We also used National TB Genotyping Service data to evaluate the traditional antituberculous drug resistance-based case definition of M. bovis TB. Isolates from 165 (1.4%) of 11,860 linked cases were identified as M. bovis. Patients who were not born in the United States, Hispanic patients, patients <15 years of age, patients reported to be HIV infected, and patients with extrapulmonary disease each had increased adjusted odds of having M. bovis versus M. tuberculosis TB. Most US-born, Hispanic patients with TB due to M. bovis (29 [90.6%] of 32) had extrapulmonary disease, and their overall median age was 9.5 years. The National TB Genotyping Service's data indicated that the pyrazinamide-based case definition's sensitivity was 82.5% (95% confidence interval; 75.3%-87.9%) and that data identified 14 errors in pyrazinamide-susceptibility testing or reporting. The prevalence of extrapulmonary disease in the young, US-born Hispanic population suggests recent transmission of M. bovis, possibly related to foodborne exposure. Because of its significantly different epidemiologic profile, compared with that of M. tuberculosis TB, we recommend routine surveillance of M. bovis TB. Routine surveillance and an improved understanding of M. bovis TB transmission dynamics would help direct the development of additional control measures.

Implications of the 2015 World Health Organization isoniazid preventive therapy recommendations on tuberculosis prevention efforts in Namibia.

PubMed

Oloo, Stella Anne

2016-07-01

The World Health Organization recently released guidelines recommending 36-month use of isoniazid preventive therapy in adults and adolescents living with HIV in resource-limited settings. Namibia continues to grapple with one of the highest incidences of tuberculosis (TB) worldwide. Implementation of these guidelines requires considerations of TB epidemiology, health infrastructure, programmatic priorities and patient adherence. This article explores the challenges Namibia currently faces in its fight against TB and the implications of the new guidelines on Namibian TB prevention efforts.

Latent tuberculosis infection among sailors and civilians aboard U.S.S. Ronald Reagan--United States, January-July 2006.

PubMed

2007-01-05

Crews aboard ships live and work in crowded, enclosed spaces. Historically, large tuberculosis (TB) outbreaks and extensive transmission of Mycobacterium tuberculosis have occurred on U.S. Navy ships. On July 13, 2006, smear- and culture-positive, cavitary, pulmonary TB was diagnosed in a sailor aboard the aircraft carrier U.S.S. Ronald Reagan; the patient, aged 32 years, had a negative human immunodeficiency virus test. The M. tuberculosis strain cultured was susceptible to all first-line TB medications. The sailor was born in the Philippines, had latent tuberculosis infection (LTBI) diagnosed in 1995 shortly after enlisting in the U.S. Navy, and completed the 6-month daily isoniazid course that was standard treatment at that time (current treatment standard is 9 months). This report describes the contact investigation conducted by the U.S. Navy and CDC and demonstrates the importance of timely diagnosis of TB, identification and treatment of new LTBI, and cooperation among local, state, and federal agencies during large contact investigations.

Influence of diabetes mellitus on immunity to human tuberculosis.

PubMed

Kumar Nathella, Pavan; Babu, Subash

2017-09-01

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

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.

Tuberculosis Relief Belt Supporting Project (Tuberculosis Patient Management Project for Poverty Group).

PubMed

Kim, Jae Kyoung; Jeong, Ina; Lee, Ji Yeon; Kim, Jung Hyun; Han, Ah Yeon; Kim, So Yeon; Joh, Joon Sung

2018-03-07

The "Tuberculosis Relief Belt Supporting Project (Tuberculosis Patient Management Project for Poverty Groups)" is a national program for socioeconomically vulnerable tuberculosis (TB) patients. We sought to evaluate the clinical and socioeconomic characteristics of poverty-stricken TB patients, and determined the need for relief. We examined in-patients with TB, who were supported by this project at the National Medical Center from 2014 to 2015. We retrospectively investigated the patients' socioeconomic status, clinical characteristics, and project expenditures. Fifty-eight patients were enrolled. Among 55 patients with known income status, 24 (43.6%) had no income. Most patients (80%) lived alone. A total of 48 patients (82.8%) had more than one underlying disease. More than half of the enrolled patients (30 patients, 51.7%) had smear-positive TB. Cavitary disease was found in 38 patients (65.5%). Among the 38 patients with known resistance status, 19 (50%) had drug-resistant TB. In terms of disease severity, 96.6% of the cases had moderate-to-severe disease. A total of 14 patients (26.4%) died during treatment. Nursing expenses were supported for 12 patients (20.7%), with patient transportation costs reimbursed for 35 patients (60%). In terms of treatment expenses for 31 people (53.4%), 93.5% of them were supported by uninsured benefits. Underlying disease, infectivity, drug resistance, severity, and death occurred frequently in socioeconomically vulnerable patients with TB. Many uninsured treatment costs were not supported by the current government TB programs, and the "Tuberculosis Relief Belt Supporting Project" compensated for these limitations. Copyright©2018. The Korean Academy of Tuberculosis and Respiratory Diseases.

Toward Novel Vaccines Against Tuberculosis: Current Hopes and Obstacles

PubMed Central

Thaiss, Christoph A.; Kaufmann, Stefan H.E.

2010-01-01

Approximately 2 million people die of tuberculosis (TB) each year. The current vaccine, Bacille Calmette-Guérin (BCG), albeit widely employed, does not protect against adult pulmonary disease, and new vaccines are urgently needed to reduce the incidence of TB worldwide. New insights into the cellular and molecular mechanisms that underlie the interactions between Mycobacterium tuberculosis and its host have been exploited to develop novel vaccine candidates that recently have entered clinical trials. This review provides a brief overview of different approaches toward a new vaccination strategy and summarizes major challenges for the next decade. PMID:21165340

Metformin: Candidate host-directed therapy for tuberculosis in diabetes and non-diabetes patients.

PubMed

Restrepo, Blanca I

2016-12-01

Despite major advances in tuberculosis (TB) control, TB continues to be a leading cause of death worldwide. The discovery of new anti-TB treatment drugs and regimens that target drug-sensitive and drug-resistant TB are being complemented with a search for adjunct host-directed therapies that synergize for Mycobacterium tuberculosis (Mtb) elimination. The goal of host-directed therapies is to boost immune mechanisms that diminish excess inflammation to reduce lung tissue damage and limit Mtb growth. Metformin is the most commonly-used medication for type 2 diabetes, and a candidate for host-directed therapy for TB. Preliminary data suggests metformin may be beneficial for TB control by reducing the deleterious inflammation associated with immune pathology and enhancing the anti-mycobacterial activity of immune cells. In this review I summarize current findings, knowledge gaps and the potential benefits as well as points of caution for using metformin as adjunct therapy for TB in patients with and without type 2 diabetes. Copyright © 2016 Elsevier Ltd. All rights reserved.

Current status of new tuberculosis vaccine in children

PubMed Central

Pang, Yu; Zhao, Aihua; Cohen, Chad; Kang, Wanli; Lu, Jie; Wang, Guozhi; Zhao, Yanlin; Zheng, Suhua

2016-01-01

ABSTRACT Pediatric tuberculosis contributes significantly to the burden of TB disease worldwide. In order to achieve the goal of eliminating TB by 2050, an effective TB vaccine is urgently needed to prevent TB transmission in children. BCG vaccination can protect children from the severe types of TB such as TB meningitis and miliary TB, while its efficacy against pediatric pulmonary TB ranged from no protection to very high protection. In recent decades, multiple new vaccine candidates have been developed, and shown encouraging safety and immunogenicity in the preclinical experiments. However, the limited data on protective efficacy in infants evaluated by clinical trials has been disappointing, an example being MVA85A. To date, no vaccine has been shown to be clinically safer and more effective than the presently licensed BCG vaccine. Hence, before a new vaccine is developed with more promising efficacy, we must reconsider how to better use the current BCG vaccine to maximize its effectiveness in children. PMID:27002369

Tuberculosis vaccine development at a divide.

PubMed

Kaufmann, Stefan H E

2014-05-01

Tuberculosis (TB) remains a major health threat that will only be defeated by a combination of better drugs, diagnostics and vaccines. The only licensed TB vaccine, bacille Calmette-Guérin (BCG), protects against extrapulmonary TB in infants. Novel vaccine candidates that could protect against pulmonary TB either in TB naïve or in latent TB-infected healthy individuals have been developed and are currently being assessed in clinical trials. Subunit booster vaccines are either based on viral vectors expressing TB-specific antigens or on TB-protein antigens in adjuvants. Subunit vaccines are administered on top of BCG. Replacement vaccines for BCG are recombinant viable BCG or Mycobacterium tuberculosis. Several candidates are undergoing, or will soon start, phase IIb assessment for efficacy. The first vaccine candidate, MVA85A, to complete a phase IIb trial, unfortunately failed to show protection against TB in infants. Therapeutic vaccines composed of killed mycobacterial preparations target patients with complicated TB in adjunct to drug treatment. With increasing numbers of TB vaccine candidates in clinical trials, financial, regulatory and infrastructural issues arise, which would be best tackled by a global strategy. In addition, selection of the most promising vaccine candidates for further clinical development gains increasing importance.

Advances in the development of new tuberculosis drugs and treatment regimens.

PubMed

Zumla, Alimuddin; Nahid, Payam; Cole, Stewart T

2013-05-01

Despite the introduction 40 years ago of the inexpensive and effective four-drug (isoniazid, rifampicin, pyrazinamide and ethambutol) treatment regimen, tuberculosis (TB) continues to cause considerable morbidity and mortality worldwide. For the first time since the 1960s, new and novel drugs and regimens for all forms of TB are emerging. Such regimens are likely to utilize both repurposed drugs and new chemical entities, and several of these regimens are now progressing through clinical trials. This article covers current concepts and recent advances in TB drug discovery and development, including an update of ongoing TB treatment trials, newer clinical trial designs, TB biomarkers and adjunct host-directed therapies.

Social leverage of intellectual property: road to the development of better therapy for tuberculosis.

PubMed

Thangaraj, Harry; Reljic, Rajko

2009-06-01

Current TB drug development is beset with many problems. There is a perceived lack of commercial return on investment, as the vast majority of TB patients come from impoverished areas of the world. Clinical trials for new TB drugs are complex, protracted and very expensive. Therefore, the development of new anti-tuberculosis drugs requires simultaneous forward planning of the design of the trials that will be required for licensing purposes. In this article we briefly review the current state of new TB drug development and discuss issues related to intellectual property (IP), with a special emphasis on how IP can facilitate rather than hinder the development of better TB drugs. We also list and discuss the major patent applications that underpin TB drugs that have entered prominent clinical trials and additional applications that were filed over the last five years for drugs resulting from basic upstream research.

Current Development and Future Prospects in Chemotherapy of Tuberculosis

PubMed Central

Nuermberger, Eric L.; Spigelman, Melvin K.; Yew, Wing Wai

2015-01-01

Although treatment of drug-susceptible tuberculosis (TB) under ideal conditions may be successful in ≥95% of cases, cure rates in the field are often significantly lower due to the logistical challenges of administering and properly supervising the intake of combination chemotherapy for 6–9 months. Success rates are far worse for multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases. There is general agreement that new anti-TB drugs are needed to shorten or otherwise simplify treatment for drug-susceptible and MDR/XDR-TB, including TB associated with HIV infection. For the first time in over 40 years, a nascent pipeline of new anti-TB drug candidates has been assembled. Eleven candidates from 7 classes are currently being evaluated in clinical trials. They include novel chemical entities belonging to entirely new classes of antibacterials, agents approved for use against infections other than TB, and an agent already approved for limited use against TB. In this article, we review the current state of TB treatment and its limitations and provide updates on the status of new drugs in clinical trials. In the conclusion, we briefly highlight ongoing efforts to discover new compounds and recent advances in alternative drug delivery systems. PMID:20546189

Tuberculosis: General Information

MedlinePlus

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

Is Knowledge Regarding Tuberculosis Associated with Stigmatising and Discriminating Attitudes of General Population towards Tuberculosis Patients? Findings from a Community Based Survey in 30 Districts of India.

PubMed

Sagili, Karuna D; Satyanarayana, Srinath; Chadha, Sarabjit S

2016-01-01

Stigmatising and discriminating attitudes may discourage tuberculosis (TB) patients from actively seeking medical care, hide their disease status, and discontinue treatment. It is expected that appropriate knowledge regarding TB should remove stigmatising and discriminating attitudes. In this study we assessed the prevalence of stigmatising and discriminating attitudes towards TB patients among general population and their association with knowledge regarding TB. A cross-sectional knowledge, attitude and practice survey was conducted in 30 districts of India in January-March 2011. A total of 4562 respondents from general population were interviewed using semi-structured questionnaires which contained items to measure stigma, discrimination and knowledge on TB. Of the 4562 interviewed, 3823 were eligible for the current analysis. Of these, 73% (95% CI 71.4-74.2) had stigmatising and 98% (95% CI 97.4-98.3) had discriminating attitude towards TB patients. Only 17% (95% CI 15.6-18.0) of the respondents had appropriate knowledge regarding TB with even lower levels observed amongst females, rural areas and respondents from low income groups. Surprisingly stigmatising (adjusted OR 1.31 (0.78-2.18) and discriminating (adjusted OR 0.79 (0.43-1.44) attitudes were independent of knowledge regarding TB. Stigmatising and discriminating attitudes towards TB patients remain high among the general population in India. Since these attitudes were independent of the knowledge regarding TB, it is possible that the current disseminated knowledge regarding TB which is mainly from a medical perspective may not be adequately addressing the factors that lead to stigma and discrimination towards TB patients. Therefore, there is an urgent need to review the messages and strategies currently used for disseminating knowledge regarding TB among general population and revise them appropriately. The disseminated knowledge should include medical, psycho-social and economic aspects of TB that not only informs people about medical aspects of TB disease, but also removes stigma and discrimination.

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

PubMed

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

2014-01-01

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

Tuberculosis Reports - UDOH-EPI

Science.gov Websites

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

Tuberculosis-a World Health Organization Perspective.

PubMed

Sotgiu, Giovanni; Sulis, Giorgia; Matteelli, Alberto

2017-01-01

Tuberculosis (TB) is an important cause of morbidity and mortality worldwide. The World Health Organization (WHO) has implemented and scaled-up three important global public health strategies (i.e., DOTS, Stop TB, and End TB) to improve the international scenario. Their epidemiological impact was relevant, as they decreased the number of potential new cases of disease and death. However, the emergence and spread of TB/HIV coinfection and multidrug-resistant TB have hindered the progress towards the elimination of TB by 2050. More efforts are required to increase the global annual decline of the TB incidence rate. Political commitment is necessary, with global and national strategies oriented to the adoption and adaptation of the international, evidence-based recommendations on diagnosis, treatment, and prevention. Research and development activities should be planned to improve the current tools adopted to fight the disease. New rapid diagnostics, an updated and effective therapeutic armamentarium, and an effective preventive vaccine could represent the solution to address the current epidemiological threats.

Multidrug-resistant tuberculosis.

PubMed

Zager, Ellen M; McNerney, Ruth

2008-01-25

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

Immune Responses to Bacillus Calmette–Guérin Vaccination: Why Do They Fail to Protect against Mycobacterium tuberculosis?

PubMed Central

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

2017-01-01

Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB), is the current leading cause of death due to a single infectious organism. Although curable, the broad emergence of multi-, extensive-, extreme-, and total-drug resistant strains of M.tb has hindered eradication efforts of this pathogen. Furthermore, computational models predict a quarter of the world’s population is infected with M.tb in a latent state, effectively serving as the largest reservoir for any human pathogen with the ability to cause significant morbidity and mortality. The World Health Organization has prioritized new strategies for improved vaccination programs; however, the lack of understanding of mycobacterial immunity has made it difficult to develop new successful vaccines. Currently, Mycobacterium bovis bacillus Calmette–Guérin (BCG) is the only vaccine approved for use to prevent TB. BCG is highly efficacious at preventing meningeal and miliary TB, but is at best 60% effective against the development of pulmonary TB in adults and wanes as we age. In this review, we provide a detailed summary on the innate immune response of macrophages, dendritic cells, and neutrophils in response to BCG vaccination. Additionally, we discuss adaptive immune responses generated by BCG vaccination, emphasizing their specific contributions to mycobacterial immunity. The success of future vaccines against TB will directly depend on our understanding of mycobacterial immunity. PMID:28424703

On the spread and control of MDR-TB epidemics: an examination of trends in anti-tuberculosis drug resistance surveillance data

PubMed Central

Cohen, Ted; Jenkins, Helen E.; Lu, Chunling; McLaughlin, Megan; Floyd, Katherine; Zignol, Matteo

2015-01-01

SUMMARY Background Multidrug resistant tuberculosis (MDR-TB) poses serious challenges for tuberculosis control in many settings, but trends of MDR-TB have been difficult to measure. Methods We analyzed surveillance and population-representative survey data collected worldwide by the World Health Organization between 1993 and 2012. We examined setting-specific patterns associated with linear trends in the estimated per capita rate of MDR-TB among new notified TB cases to generate hypotheses about factors associated with trends in the transmission of highly drug resistant tuberculosis. Results 59 countries and 39 sub-national settings had at least three years of data, but less than 10% of the population in the WHO-designated 27-high MDR-TB burden settings were in areas with sufficient data to track trends. Among settings in which the majority of MDR-TB was autochthonous, we found 10 settings with statistically significant linear trends in per capita rates of MDR-TB among new notified TB cases. Five of these settings had declining trends (Estonia, Latvia, Macao, Hong Kong, and Portugal) ranging from decreases of 3-14% annually, while five had increasing trends (four individual oblasts of the Russian Federation and Botswana) ranging from 14-20% annually. In unadjusted analysis, better surveillance indicators and higher GDP per capita were associated with declining MDR-TB, while a higher existing absolute burden of MDR-TB was associated with an increasing trend. Conclusions Only a small fraction of countries in which the burden of MDR-TB is concentrated currently have sufficient surveillance data to estimate trends in drug-resistant TB. Where trend analysis was possible, smaller absolute burdens of MDR-TB and more robust surveillance systems were associated with declining per capita rates of MDR-TB among new notified cases. PMID:25458783

[Women's knowledge, perceptions, beliefs, and behaviors related to tuberculosis: results from a survey with participants of seminars held by the National Federation of Community Women's Organizations for Tuberculosis Control].

PubMed

Akishinonomiya, Kiko

2012-10-01

With an aim of advancing knowledge: that supports strategies for tuberculosis (TB) prevention, the current study was designed (1) to examine knowledge, perceptions, beliefs, and behaviors towards general health and diseases, including TB, and (2) to explore relationships among knowledge, perceptions, beliefs of TB, and TB prevention behaviors. Questionnaire surveys were conducted for 827 study participants who were attendees of seminars held by the National Federation of Community Women's Organizations for TB Control and the Japan Anti-Tuberculosis Association, between February 2010 and February 2011. More than 70% of the participants understood correctly such general facts on TB as the necessity of TB examinations for those who had contact with TB patients and individuals whose coughing persists for more than two weeks, and differences between TB infection and active TB disease. Only 30% to 40% of the participants answered correctly questions about epidemiological facts on TB, such as "TB infection tends to progress to active TB disease within one year," or "The proportion of individuals who develop active disease after TB infection is less than one fifth." The study participants perceived their susceptibility to TB to be significantly lower than that of the average peer, suggesting that so-called "optimistic bias," a cognitive bias, should exist on this matter. Those study participants who do not have personal history of TB nor contact with TB patients tend to perceive their susceptibility to be significantly lower than those who have. There were statistically significant gaps between intentions to prevent TB and actual behaviors taken to prevent it. The results from the current survey revealed several aspects of TB that are not fully understood yet. It is suggested that it should still remain important for healthcare providers in Japan to disseminate accurate and detailed knowledge on TB to the public in more easy-to-understand formats. Findings on optimistic bias and gaps between intentions and behaviors imply the needs for closer considerations to diverse psychological facets in the process of designing of disease prevention programs. Future investigations on psychological aspects of disease prevention behaviors are recommended in order to promote effective preventions of TB.

Pulmonary tuberculosis

MedlinePlus

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

[Riddles in human tuberculous infection].

PubMed

Tsuyuguchi, I

2000-10-01

Tuberculosis is indeed an infectious disease caused by Mycobacterium tuberculosis. However, only a small percentage of individuals infected develops overt disease, tuberculosis whereas the infected bacilli persist alive years long within the vast majority of persons infected but remained healthy. There are several riddles or enigmas in the natural history of M. tuberculosis infection in humans. Some of them are as follows: 1. What is the virulence of M. tuberculosis? 2. How does M. tuberculosis persist dormant within the host? 3. What determines the development of disease from remaining healthy after infection with M. tuberculosis? 4. What is the mechanism of "endogenous reactivation" of dormant M. tuberculosis within the host? 5. Can we expect more potent anti-TB vaccine than BCG in near future? Most of these issues cited above remain unsolved. What is urgently needed today to answer correctly to these questions is the production of appropriate animal model of tuberculosis infection which mimics human tuberculosis. Murine TB does not reflect human TB at all. What characterizes the mycobacterial organism is its armour-plated unique cell wall structure which is rich in lipid and carbohydrate. Cord factor or trehalose dimycolate (TDM), the main component of cell wall, has once been regarded as the virulence factor of mycobacteria. Cord factor is responsible for the pathogenesis of TB and cachexia or even death of the patients infected. However, cord factor in itself is not toxic but exerts its detrimental effect to the host through the excessive stimulation of the host's immune system to produce abundant varied cytokines including TNF-alpha. How to evade this embarrassing effect of mycobacterial cell wall component on the host immune system seems very important for the future development of better TB vaccine than the currently used BCG.

HIV and tuberculosis: a deadly human syndemic.

PubMed

Kwan, Candice K; Ernst, Joel D

2011-04-01

A syndemic is defined as the convergence of two or more diseases that act synergistically to magnify the burden of disease. The intersection and syndemic interaction between the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have had deadly consequences around the world. Without adequate control of the TB-HIV syndemic, the long-term TB elimination target set for 2050 will not be reached. There is an urgent need for additional resources and novel approaches for the diagnosis, treatment, and prevention of both HIV and TB. Moreover, multidisciplinary approaches that consider HIV and TB together, rather than as separate problems and diseases, will be necessary to prevent further worsening of the HIV-TB syndemic. This review examines current knowledge of the state and impact of the HIV-TB syndemic and reviews the epidemiological, clinical, cellular, and molecular interactions between HIV and TB.

Tuberculosis genotyping information management system: enhancing tuberculosis surveillance in the United States.

PubMed

Ghosh, Smita; Moonan, Patrick K; Cowan, Lauren; Grant, Juliana; Kammerer, Steve; Navin, Thomas R

2012-06-01

Molecular characterization of Mycobacterium tuberculosis complex isolates (genotyping) can be used by public health programs to more readily identify tuberculosis (TB) transmission. The Centers for Disease Control and Prevention's National Tuberculosis Genotyping Service has offered M. tuberculosis genotyping for every culture-confirmed case in the United States since 2004. The TB Genotyping Information Management System (TB GIMS), launched in March 2010, is a secure online database containing genotype results linked with case characteristics from the national TB registry for state and local TB programs to access, manage and analyze these data. As of September 2011, TB GIMS contains genotype results for 89% of all culture-positive TB cases for 2010. Over 400 users can generate local and national reports and maps using TB GIMS. Automated alerts on geospatially concentrated cases with matching genotypes that may represent outbreaks are also generated by TB GIMS. TB genotyping results are available to enhance national TB surveillance and apply genotyping results to conduct TB control activities in the United States. Published by Elsevier B.V.

Multidrug and extensively drug-resistant tuberculosis.

PubMed

Maitre, T; Aubry, A; Jarlier, V; Robert, J; Veziris, N

2017-02-01

The emergence of drug-resistant tuberculosis (TB) compromises global tuberculosis control. The incidence of multidrug-resistant strains (MDR) defined as resistant to the two main antituberculosis drugs, rifampicin and isoniazid, was raised in the 1990s. Ten percent of these strains have developed additional resistance to the main second-line antituberculosis drugs: fluoroquinolones and aminoglycosides. These strains are defined as extensively drug-resistant (XDR). The prognosis of MDR-TB and XDR-TB is poor due to limited therapeutic resources. However, many new innovations may lead to a radical change in this field. Genotypic testing is now able to detect drug resistance within a few hours. Genotypic diagnosis of rifampicin resistance is now recommended in France for each new case of TB. The currently recommended treatment for MDR-TB is long (18-24 months) and toxic. It is, however, on the verge of being replaced by a 9-month treatment. New antituberculosis drugs such as bedaquiline and delamanid should also improve the prognosis of MDR-TB and XDR-TB. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Tuberculosis

MedlinePlus

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

Striking the right immunological balance prevents progression of tuberculosis.

PubMed

Vyas, Shachi Pranjal; Goswami, Ritobrata

2017-12-01

Tuberculosis (TB) caused by infection with Mycobacterium tuberculosis (Mtb) is a major burden for human health worldwide. Current standard treatments for TB require prolonged administration of antimycobacterial drugs leading to exaggerated inflammation and tissue damage. This can result in the reactivation of latent TB culminating in TB progression. Thus, there is an unmet need to develop therapies that would shorten the duration of anti-TB treatment and to induce optimal protective immune responses to control the spread of mycobacterial infection with minimal lung pathology. Granulomata is the hallmark structure formed by the organized accumulation of immune cells including macrophages, natural killer cells, dendritic cells, neutrophils, T cells, and B cells to the site of Mtb infection. It safeguards the host by containing Mtb in latent form. However, granulomata can undergo caseation and contribute to the reactivation of latent TB, if the immune responses developed to fight mycobacterial infection are not properly controlled. Thus, an optimal balance between innate and adaptive immune cells might play a vital role in containing mycobacteria in latent form for prolonged periods and prevent the spread of Mtb infection from one individual to another. Optimal and well-regulated immune responses against Mycobacterium tuberculosis may help to prevent the reactivation of latent TB. Moreover, therapies targeting balanced immune responses could help to improve treatment outcomes among latently infected TB patients and thereby limit the dissemination of mycobacterial infection.

Current status of pharmacokinetic and safety studies of multidrug-resistant tuberculosis treatment in children.

PubMed

Garcia-Prats, A J; Svensson, E M; Weld, E D; Schaaf, H S; Hesseling, A C

2018-05-01

After decades of neglect, data are finally becoming available on the appropriate, safe dosing of key second-line anti-tuberculosis drugs used for treating multidrug-resistant tuberculosis (MDR-TB) in children, including levofloxacin (LVX), moxifloxacin (MFX), linezolid (LZD) and delamanid (DLM). Much needed data on some novel and repurposed drugs are still lacking, including for bedaquiline (BDQ), pretomanid (PTM) and clofazimine (CFZ). We review the status of pharmacokinetic (PK) and safety studies of key anti-tuberculosis medications in children with MDR-TB, identify priority knowledge gaps and note ongoing work to address those gaps, in the context of planning for an efficacy trial in children with MDR-TB. There is international consensus that an efficacy trial of a novel, all-oral, shortened MDR-TB treatment trial in children is both needed and feasible. Key novel and repurposed second-line anti-tuberculosis drugs include BDQ, DLM, PTM, MFX, LVX, CFZ and LZD. The rapidly emerging PK and safety data on these medications in children with MDR-TB from studies that are underway, completed or planned, will be critical in supporting such an efficacy trial. Commitment to addressing the remaining knowledge gaps, developing child-friendly formulations of key medications, improving the design of paediatric PK and safety studies, and development of international trial capacity in children with MDR-TB are important priorities.

Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations

PubMed Central

Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

2014-01-01

Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed. PMID:26344627

Novel GMO-Based Vaccines against Tuberculosis: State of the Art and Biosafety Considerations.

PubMed

Leunda, Amaya; Baldo, Aline; Goossens, Martine; Huygen, Kris; Herman, Philippe; Romano, Marta

2014-06-16

Novel efficient vaccines are needed to control tuberculosis (TB), a major cause of morbidity and mortality worldwide. Several TB vaccine candidates are currently in clinical and preclinical development. They fall into two categories, the one of candidates designed as a replacement of the Bacille Calmette Guérin (BCG) to be administered to infants and the one of sub-unit vaccines designed as booster vaccines. The latter are designed as vaccines that will be administered to individuals already vaccinated with BCG (or in the future with a BCG replacement vaccine). In this review we provide up to date information on novel tuberculosis (TB) vaccines in development focusing on the risk assessment of candidates composed of genetically modified organisms (GMO) which are currently evaluated in clinical trials. Indeed, these vaccines administered to volunteers raise biosafety concerns with respect to human health and the environment that need to be assessed and managed.

[Health examination in future at the era of low tuberculosis incidence--from contacts examination toward active epidemiological studies].

PubMed

Maeda, Hideo; Shirai, Chika

2013-03-01

Japan is still "intermediate burden" country as medium-incidence of tuberculosis (TB). But the incidence of TB varies by public health units. The priority for TB control would be lowering in the areas where the incidence of TB is relatively low. In addition, younger age groups get low prevalence of TB infection than elderly persons. As a result, fewer experiences for TB diagnosis and treatment in the hospital and the medical facility would cause the delay in the detection of TB patients which eventually cause outbreaks. Although there are differences in population density and population mobility between urban and rural areas, the socially economic vulnerable patients and foreign patients are the common risks. Any public health units' policies of TB should correspond to the individual situation. At the era of low tuberculosis incidence, the infection risk is to be "From ubiquitous to the uneven distribution". This makes TB detection much more difficult. At this symposium, each speaker presented the case for actually experienced with QFT test and/or VNTR analysis. They mainly focused on the paradigm shift in TB control which is indispensable for resolving the gaps in regional differences and the differences in diagnostic capability. Although the cases in this symposium were not for the low incidence situation, the pioneering approaches presented here would boost the future application of QFT and VNTR analysis nationwide. The discussions also partially covered the technical infrastructure for molecular epidemiology which covers the whole country. By making full use of QFT test and VNTR analysis as a contact screening tool, we can appropriately understand the risk of TB infection in the region from a buildup of bacteria and patient information. Now is the time to prepare for. Active surveillance of TB by this way would clarify the risk of the disease and lead to the advocacy essential for the resolution. 1. Current situation and challenge of contact survey by using QFT test in Tokyo: Hideo MAEDA (Bureau of Social Welfare and Public Health, Tokyo Metropolitan Government). 2. Contact investigation of a tuberculosis outbreak: Kenichi MIYAMOTO (Takaido Community Health Center). We have experienced a TB outbreak in integrated junior and senior high school in Tokyo. Index patient was a student with persistent respiratory symptoms for six months before diagnosis of sputum smear-positive TB. Public health center started contact investigation immediately. QFT-positive rates were high in close contacts, especially in classmates. Additionally, a student outside of contact investigation was diagnosed as TB and considered to be infected from the first patient by VNTR analysis. Therefore, public health center expanded QFT-tests to all students and teachers in this school. Finally, 9 students and 2 teachers in this school were diagnosed as sputum smear-negative TB by contact investigation. 3. Utilization of molecular epidemiological procedure in contact investigation in Kyoto City: Masahiro ITO (Public Health Center of Kyoto City) Molecular epidemiological procedure using VNTR analysis has been used for contact investigation of tuberculosis since January 2011 in Kyoto City. One hundred forty four strains of Mycobacterium tuberculosis from patients with tuberculosis were investigated and 130 strains were fully analyzed. Fourteen clusters were found and the number of strains included in the cluster was ranged from two to 11. Epidemiological relationship between patients in one cluster was found, however, significant relationship in another clusters was not demonstrated. It was suggested that VNTR analysis is useful for molecular epidemiological analysis of tuberculosis. 4. The population based molecular epidemiological studies and QFT test in a contact examination: Riyo FUJIYAMA, Keisuke MATSUBAYASHI, Setsuko MIZUSHIRI, Junko HIGUCHIL Chika SHIRAI, Yuko KATAGAMI, Mieko CHIHARA, Akihiro IJICHI (Kobe City Public Health Center), Kentaro ARIKAWA, Noriko NAKANISHI, Tomotada IWAMOTO (Kobe Institute of Health). The population based molecular epidemiological studies should be made good use of contacts examination. In future, we expect the tuberculosis molecular epdimiological study improve search for the process of tuberculosis infection. The QFT positive rates correlated well with closeness of contact. QFT test is considered useful for diagnosing tuberculosis infection. However, in the judgment of tuberculosis infection, we should consider the total result of contact investigation not only QFT test but also the contact situation. 5. Insights into the TB epidemiology through population based molecular epidemiological studies: Tomotada IWAMOTO (Kobe Institute of Health) The population based molecular epidemiological studies unveiled the transmission dynamics of tuberculosis at bacterial clone level. This provides scientific evidences for achieving better TB control programs. In the advanced stage of the tuberculosis molecular epidemiological study, we expect to change the current geno-typing based molecular epidemiology to whole genome-typing based molecular epidemiology on the basis of the rapid innovation of next-generation sequencing technology.

Impact of the national full herd depopulation policy on the recurrence of bovine tuberculosis in Irish herds, 2003 to 2005.

PubMed

Good, M; Clegg, T A; Duignan, A; More, S J

2011-11-26

This study evaluated the impact of the Irish herd bovine tuberculosis (bTB) depopulation policy (depopulation, disinfection, contiguous testing and local badger removal where implicated) on the recurrence of bTB infection, by comparing the future risk in restocked herds following depopulation for either bTB or bovine spongiform encephalopathy (BSE) during 2003 to 2005. Each herd was assigned a 'previous bTB risk', based on bTB history during the five years before depopulation. Future bTB risk was estimated, using a multivariable Cox proportional hazard model for time-to-breakdown for each study herd, to identify risk factors associated with bTB. Future bTB risk varied significantly by reason for depopulation and previous bTB risk. Herds depopulated for bTB (by definition, at high bTB risk) were not significantly different from BSE herds with no or a low previous bTB risk. BSE herds with a high previous bTB risk were found to be at significantly greater future bTB risk. Herd bTB depopulation measures, as currently applied in Ireland, are shown to be effective in enabling herds to attain and retain bTB freedom following restocking. Based on the data presented, and consistent with current knowledge of the bTB epidemiology, local badger removal contributes to efforts to limit recurrence of bTB in Ireland.

Tuberculosis in Newborns: The Lessons of the “Lübeck Disaster” (1929–1933)

PubMed Central

Fox, Gregory J.; Orlova, Marianna; Schurr, Erwin

2016-01-01

In an accident later known as the Lübeck disaster, 251 neonates were orally given three doses of the new Bacille Calmette–Guérin (BCG) antituberculosis (TB) vaccine contaminated with Mycobacterium tuberculosis. A total of 173 infants developed clinical or radiological signs of TB but survived the infection, while 72 died from TB. While some blamed the accident on BCG itself by postulating reversion to full virulence, such a possibility was conclusively disproven. Rather, by combining clinical, microbiological, and epidemiological data, the chief public health investigator Dr. A. Moegling concluded that the BCG vaccine had been contaminated with variable amounts of fully virulent M. tuberculosis. Here, we summarize the conclusions drawn by Moegling and point out three lessons that can be learned. First, while mortality was high (approximately 29%), the majority of neonates inoculated with M. tuberculosis eventually overcame TB disease. This shows the high constitutional resistance of humans to the bacillus. Second, four semiquantitative levels of contamination were deduced by Moegling from the available data. While at low levels of M. tuberculosis there was a large spread of clinical phenotypes reflecting a good degree of innate resistance to TB, at the highest dose, the majority of neonates were highly susceptible to TB. This shows the dominating role of dose for innate resistance to TB. Third, two infants inoculated with the lowest dose nevertheless died of TB, and their median time from inoculation to death was substantially shorter than for those who died after inoculation with higher doses. This suggests that infants who developed disease after low dose inoculation are those who are most susceptible to the disease. We discuss some implications of these lessons for current study of genetic susceptibility to TB. PMID:26794678

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.

Management of multidrug-resistant tuberculosis in human immunodeficiency virus patients

NASA Astrophysics Data System (ADS)

Jamil, K. F.

2018-03-01

Tuberculosis (TB) is a chronic infectious disease mainly caused by Mycobacterium tuberculosis(MTB). 10.4 million new TB cases will appear in 2015 worldwide. There were an estimated 1.4 million TB deaths in 2015, and an additional 0.4 million deaths resulting from TB disease among people living with human immunodeficiency virus (HIV). Multidrug- resistant and extensively drug-resistant tuberculosis (MDR and XDR-TB) are major public health concerns worldwide. 480.000 new cases of MDR-TB will appear in 2015 and an additional 100,000 people with rifampicin-resistant TB (RR-TB) who were also newly eligible for MDR-TB treatment. Their association with HIV infection has contributed to the slowing down of TB incidence decline over the last two decades, therefore representing one important barrier to reach TB elimination. Patients infected with MDR-TB require more expensive treatment regimens than drug-susceptible TB, with poor treatment.Patients with multidrug- resistant tuberculosis do not receive rifampin; drug interactions risk is markedly reduced. However, overlapping toxicities may limit options for co-treatment of HIV and multidrug- resistant tuberculosis.

Tuberculosis Treatment and Pregnancy

MedlinePlus

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

Management of patients with multidrug-resistant/extensively drug-resistant tuberculosis in Europe: a TBNET consensus statement

PubMed Central

Lange, Christoph; Abubakar, Ibrahim; Alffenaar, Jan-Willem C.; Bothamley, Graham; Caminero, Jose A.; Carvalho, Anna Cristina C.; Chang, Kwok-Chiu; Codecasa, Luigi; Correia, Ana; Crudu, Valeriu; Davies, Peter; Dedicoat, Martin; Drobniewski, Francis; Duarte, Raquel; Ehlers, Cordula; Erkens, Connie; Goletti, Delia; Günther, Gunar; Ibraim, Elmira; Kampmann, Beate; Kuksa, Liga; de Lange, Wiel; van Leth, Frank; van Lunzen, Jan; Matteelli, Alberto; Menzies, Dick; Monedero, Ignacio; Richter, Elvira; Rüsch-Gerdes, Sabine; Sandgren, Andreas; Scardigli, Anna; Skrahina, Alena; Tortoli, Enrico; Volchenkov, Grigory; Wagner, Dirk; van der Werf, Marieke J.; Williams, Bhanu; Yew, Wing-Wai; Zellweger, Jean-Pierre; Cirillo, Daniela Maria

2014-01-01

The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) substantially challenges TB control, especially in the European Region of the World Health Organization, where the highest prevalence of MDR/XDR cases is reported. The current management of patients with MDR/XDR-TB is extremely complex for medical, social and public health systems. The treatment with currently available anti-TB therapies to achieve relapse-free cure is long and undermined by a high frequency of adverse drug events, suboptimal treatment adherence, high costs and low treatment success rates. Availability of optimal management for patients with MDR/XDR-TB is limited even in the European Region. In the absence of a preventive vaccine, more effective diagnostic tools and novel therapeutic interventions the control of MDR/XDR-TB will be extremely difficult. Despite recent scientific advances in MDR/XDR-TB care, decisions for the management of patients with MDR/XDR-TB and their contacts often rely on expert opinions, rather than on clinical evidence. This document summarises the current knowledge on the prevention, diagnosis and treatment of adults and children with MDR/XDR-TB and their contacts, and provides expert consensus recommendations on questions where scientific evidence is still lacking. PMID:24659544

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

Tuberculosis in children with sickle cell anaemia: a retrospective study in French tertiary care centres.

PubMed

Droz, Nina; De Lauzanne, Agathe; Holvoet, Laurent; Missud, Florence; Benkerrou, Malika; Brousse, Valentine; Odièvre, Marie-Hélène; Faye, Albert; Koehl, Berengere

2017-06-01

Tuberculosis (TB) and sickle cell anaemia (SCA) may affect the same population of patients, particularly in Africa but also in high-TB incidence areas in developed countries. However, few data are available from children with SCA who develop TB. The aim of this study was to describe the clinical features and outcome of TB diagnosed in children with SCA. We conducted a retrospective, descriptive study in three referral centre of Sickle Cell Disease in Paris, France. We included 11 patients with SCA who develop TB. The median age at TB diagnosis was 11 years [7.5-14.5]. Two patients were asymptomatic and nine patients were symptomatic. Six patients had pulmonary TB (pulmonary, pleural and mediastinal lesions). Five patients had extrapulmonary TB (osteoarticular TB, hepatic TB, cervical and mediastinal TB). Mycobacterium tuberculosis was isolated in four of the 11 cases. All patients recovered after a median of 6 months of anti-TB treatment. The localisation of TB and outcome after treatment in our SCA patients were similar to the one observed in an age-and sex-matched control group of non-SCA patient with TB. despite the low number of patients included in our study, SCA does not seem to be a risk factor for severe TB. What is Known: • Tuberculosis (TB) remains a global health problem particularly in developing countries, and Sickle cell anaemia (SCA) is currently one of the most common genetic diseases in the world that mainly affects African populations. • Very few data are available on TB in SCA patients. What is New: • The features of TB in children with SCA seem to be comparable to those expected in general population, with favourable outcomes in response to standard treatment. • Monitoring the dosage of anti-TB treatments could be of interest because of the possible impact of SCA on drug metabolism.

Trend in case detection rate for all tuberculosis cases notified in Ebonyi, Southeastern Nigeria during 1999-2009.

PubMed

Ukwaja, Kingsley Nnanna; Alobu, Isaac; Ifebunandu, Ngozi Appolonia; Osakwe, Chijioke; Igwenyi, Chika

2013-01-01

Unlike previous annual WHO tuberculosis reports that reported case detection rate for only smear-positive tuberculosis cases, the 2010 report presented case detection rate for all tuberculosis cases notified in line with the current Stop TB strategy. To help us understand how tuberculosis control programmes performed in terms of detecting tuberculosis, there is need to document the trend in case detection rate for all tuberculosis cases notified in high burden countries. This evidence is currently lacking from Nigeria. Therefore, this study aimed to assess the trend in case detection rate for all tuberculosis cases notified from Ebonyi state compared to Nigeria national figures. Reports of tuberculosis cases notified between 1999 and 2009 were reviewed from the Ebonyi State Ministry of Health tuberculosis quarterly reports. Tuberculosis case detection rates were computed according to WHO guidelines. 22, 508 patients with all forms of tuberculosis were notified during the study. Case detection rate for all tuberculosis rose from 27% in 1999 to gradually reach a peak of 40% during 2007 to 2008 before a slight decline in 2009 to 38%. However, the national case detection rate for all tuberculosis cases in Nigeria rose from 7% in 1999 and progressively increased to reach a peak of 19% during 2008 and 2009. Since the introduction of DOTS in Ebonyi, the programme has achieved 40% case detection rate for all tuberculosis cases - about 20% better than national figures. However, with the current low case detection rates, alternative mechanisms are needed to achieve the current global stop- TB targets in Nigeria.

Antitubercular Nanocarrier Combination Therapy: Formulation Strategies and in Vitro Efficacy for Rifampicin and SQ641

PubMed Central

2015-01-01

Tuberculosis (TB) remains a major global health concern, and new therapies are needed to overcome the problems associated with dosing frequency, patient compliance, and drug resistance. To reduce side effects associated with systemic drug distribution and improve drug concentration at the target site, stable therapeutic nanocarriers (NCs) were prepared and evaluated for efficacy in vitro in Mycobacterium tuberculosis-infected macrophages. Rifampicin (RIF), a current, broad-spectrum antibiotic used in TB therapy, was conjugated by degradable ester bonds to form hydrophobic prodrugs. NCs encapsulating various ratios of nonconjugated RIF and the prodrugs showed the potential ability to rapidly deliver and knockdown intracellular M. tuberculosis by nonconjugated RIF and to obtain sustained release of RIF by hydrolysis of the RIF prodrug. NCs of the novel antibiotic SQ641 and a combination NC with cyclosporine A were formed by flash nanoprecipitation. Delivery of SQ641 in NC form resulted in significantly improved activity compared to that of the free drug against intracellular M. tuberculosis. A NC formulation with a three-compound combination of SQ641, cyclosporine A, and vitamin E inhibited intracellular replication of M. tuberculosis significantly better than SQ641 alone or isoniazid, a current first-line anti-TB drug. PMID:25811733

Ambulatory tuberculosis treatment in post-Semashko health care systems needs supportive financing mechanisms.

PubMed

Kohler, S; Asadov, D A; Bründer, A; Healy, S; Khamraev, A K; Sergeeva, N; Tinnemann, P

2014-12-01

The tuberculosis (TB) control strategy in the Republic of Karakalpakstan, Uzbekistan, is being changed to decentralised out-patient care for most TB patients by the Government of Uzbekistan, in collaboration with the international medical humanitarian organisation Médecins Sans Frontières. Ambulatory treatment of both drug-susceptible and drug-resistant TB from the first day of treatment has been recommended since 2011. Out-patient treatment of TB from the beginning of treatment was previously prohibited. However, the current Uzbek health financing system, which evolved from the Soviet Semashko model, offers incentives that work against the adoption of ambulatory TB treatment. Based on the 'Comprehensive TB Care for All' programme implemented in Karakalpakstan, we describe how existing policies for the allocation of health funds complicate the scale-up of ambulatory-based management of TB.

Treatment of Latent Tuberculosis Infection.

PubMed

Tang, Patrick; Johnston, James

2017-01-01

The treatment of latent tuberculosis infection (LTBI) is an essential component of tuberculosis (TB) elimination in regions that have a low incidence of TB. However, the decision to treat individuals with LTBI must consider the limitations of current diagnostic tests for LTBI, the risk of developing active TB disease, the potential adverse effects from chemoprophylactic therapy, and the importance of treatment adherence. When an individual has been diagnosed with LTBI and active TB has been ruled out, this is followed by an evaluation of the risks and benefits of LTBI treatment within the context of the regional epidemiology of TB and public health priorities. Once the decision to treat LTBI has been reached, and the infection is not suspected to be due to drug-resistant TB, the recommended regimens include isoniazid and/or rifamycin-derivatives, and the choice of regimen will depend upon the clinical considerations for that individual, such as patient preference, concomitant medications, hepatic disease, pregnancy, or immunodeficiency. As the duration of treatment of LTBI therapy is many months, therapy must be offered within a plan that monitors for adverse drug reactions and emphasizes adherence. For latent multidrug-resistant TB (MDR-TB) or extensively drug-resistant TB (XDR-TB) infection, the management is more complicated as there are few options for chemoprophylactic therapy and little evidence regarding the efficacy or risks of these regimens.

Low tuberculosis knowledge among HIV-infected patients in a high HIV prevalence region within southeast India.

PubMed

Arora, Nick; Vadrevu, Ravi; Chandrasekhar, Aditya; Gupta, Amita

2013-01-01

A private multispecialty hospital in Kakinada, Andhra Pradesh, India. A survey of knowledge, attitudes, and perceptions adapted from a pretested questionnaire was administered to 128 HIV-infected adults, from July to August 2008. A total of 31% had not heard of tuberculosis (TB), with 15 (38%) currently receiving anti-TB therapy or had received it in the past. Of those familiar with TB, 70% could not list a method by which it was spread. Low education attainment, female sex, and less frequent television exposure were associated with low TB literacy. HIV-infected patients in southeast India have poor knowledge of TB and the methods by which it is spread. Scale-up of patient-directed educational programs is necessary to help control TB in India.

HIV and Tuberculosis: a Deadly Human Syndemic

PubMed Central

Kwan, Candice K.; Ernst, Joel D.

2011-01-01

Summary: A syndemic is defined as the convergence of two or more diseases that act synergistically to magnify the burden of disease. The intersection and syndemic interaction between the human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have had deadly consequences around the world. Without adequate control of the TB-HIV syndemic, the long-term TB elimination target set for 2050 will not be reached. There is an urgent need for additional resources and novel approaches for the diagnosis, treatment, and prevention of both HIV and TB. Moreover, multidisciplinary approaches that consider HIV and TB together, rather than as separate problems and diseases, will be necessary to prevent further worsening of the HIV-TB syndemic. This review examines current knowledge of the state and impact of the HIV-TB syndemic and reviews the epidemiological, clinical, cellular, and molecular interactions between HIV and TB. PMID:21482729

Mycobacterium tuberculosis: approach to development of improved strategies for disease control through vaccination and immunodiagnosis.

PubMed

Mirlekar, B; Pathak, S; Pathade, G

2013-01-01

Tuberculosis is a major health problem throughout the world causing large number of deaths, more than that from any other single infectious disease. Estimates till date ascertain the fact that Tuberculosis (TB) is continuing to be the leading cause of death worldwide. The infection from single infectious agent Mycobacterium tuberculosis is killing about 3 million individuals every year and accounts for around 18.5% of all deaths in adults between the age group of 15 and 65. An average of 1.79 billion people, which constitutes roughly one-third of the world's population, is infected with the causative agent M. tuberculosis and is at risk of developing the disease. This situation highlights the relative shortcomings of the current treatment and diagnosis strategies for TB and the limited effectiveness of public health systems, particularly in resource-poor countries where the main TB burden lies. The timely identification of persons infected with Mycobacterium tuberculosis and rapid laboratory confirmation of tuberculosis are two key factors for the treatment and prevention of the disease. Novel molecular assays for diagnosis and drug susceptibility testing offer several potential advantages over the above methods including faster turnaround times, very sensitive and specific detection of nucleic acids, and minimal, or possibly no, prior culture. The need for new technologies for rapid diagnosis of tuberculosis is clear. Most studies of mycobacterial immunity attributes focus on proliferation of T cells, production of cytokines and cytolytic activity. A proper vaccine for tuberculosis can be developed by using a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. Development of new vaccines against TB should include some important aspects learned from BCG use such as mucosal routes of immunization; revaccination of BCG immunized subjects, booster immunization and prime-boost strategy with wild-type BCG, and other vaccine candidates. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future.

Anti-bacterial Treatments Using Peptide-Based Inhibitors of the STAT3-IL10 Pathway | NCI Technology Transfer Center | TTC

Cancer.gov

Tuberculosis (TB) is an infectious disease that typically affects the lungs. Current therapies include a panel of antibiotics given over a range of 6-9 months. As a result of the expense of treatment, the extended timeframe needed for effective treatment, and the scarcity of medicines in some developing countries, patient compliance with TB treatment is very low and results in multi-drug resistant TB (MDR-TB). There remains a need for a faster, more effective treatment for TB. NCI researchers seek licensing and/or co-development of peptide inhibitors of STAT3 and IL-10 developed to treat bacterial infections such as tuberculosis. See aslo: NIH inventions E-164-2007 and E-167-2010

Recently disclosed chemical entities as potential candidates for management of tuberculosis.

PubMed

Stec, Jozef; Abourashed, Ehab A

2015-01-01

Tuberculosis (TB) is one of the deadliest infectious diseases worldwide. The drug discovery process of novel, safe and effective agents to combat TB involves identification of new molecular targets and novel chemical scaffolds. The current anti-TB drug pipeline includes several small molecules with more to follow as new candidates are disclosed. This review highlights the most significant findings described in 78 international, European and US patents for chemically diverse compounds as prospective anti-TB medications. Main points of emphasis include chemical classification, in vitro and in vivo activity, ADME/Tox profile and mycobacterial target as described in each patent. The collective mass of compounds disclosed in the reviewed patents introduces new candidates as potential therapeutic agents for TB infections.

Opportunities for Improved Serodiagnosis of Human Tuberculosis, Bovine Tuberculosis, and Paratuberculosis

PubMed Central

Wadhwa, Ashutosh; Hickling, Graham J.; Eda, Shigetoshi

2012-01-01

Mycobacterial infections—tuberculosis (TB), bovine tuberculosis (bTB), and Johne's disease (JD)—are major infectious diseases of both human and animals. Methods presently in use for diagnosis of mycobacterial infections include bacterial culture, nucleic acid amplification, tuberculin skin test, interferon-γ assay, and serology. Serological tests have several advantages over other methods, including short turn-around time, relatively simple procedures, and low cost. However, current serodiagnostic methods for TB, bTB and JD exhibit low sensitivity and/or specificity. Recent studies that have aimed to develop improved serodiagnostic tests have mostly focused on identifying useful species-specific protein antigens. A review of recent attempts to improve diagnostic test performance indicates that the use of multiple antigens can improve the accuracy of serodiagnosis of these mycobacterial diseases. Mycobacteria also produce a variety of species-specific nonprotein molecules; however, only a few such molecules (e.g., cord factor and lipoarabinomannan) have so far been evaluated for their effectiveness as diagnostic antigens. For TB and bTB, there has been recent progress in developing laboratory-free diagnostic methods. New technologies such as microfluidics and “Lab-on-Chip” are examples of promising new technologies that can underpin development of laboratory-free diagnostic devices for these mycobacterial infections. PMID:22720192

Application Values of T-SPOT.TB in Clinical Rapid Diagnosis of Tuberculosis.

PubMed

Zhu, Feng; Ou, Qinfang; Zheng, Jian

2018-01-01

This paper aims to explore the application value of tuberculosis-specific enzyme-linked immunospot assay (T-SPOT.TB) in the diagnosis of tuberculosis. Fifty one patients with tuberculosis (TB) admitted to Wuxi No.5 People's Hospital, Wuxi, China from June 2015 to June 2017 were selected as the TB group, and 40 patients without tuberculosis admitted in the same period were randomly selected as the non-TB group. Patients in the two groups received T-SPOT.TB, TB antibody (TB-Ab) test and mycobacterium TB deoxyribonucleic acid (TB-DNA) test, and the results were compared. Comparisons of the sensitivity of the three methods showed that the sensitivity of T-SPOT.TB was the highest, followed by TB-DNA from sputum samples, and that of TB-Ab was the lowest. The specificity of TB-Ab was the highest, followed by T-SPOT.TB, and that of TB-DNA from sputum samples was the lowest. In the receiver operating characteristic (ROC) curve analysis, the area under curve (AUC) of T-SPOT.TB (0.896) was the highest, followed by TB-DNA from sputum samples (0.772), and that of sputum smears (0.698) was the lowest. T-SPOT.TB can quickly and accurately determine the presence of tuberculosis infection, and it is a non-invasive examination, which can further assist in the diagnosis and guide the treatment.

Recent advances in tuberculosis diagnostics in resource-limited settings.

PubMed

Seki, Mitsuko; Kim, Chang-Ki; Hayakawa, Satoshi; Mitarai, Satoshi

2018-04-19

Smear-negative and drug-resistant cases of tuberculosis (TB) disease necessitate the development of new diagnostic methods, especially in resource-limited settings. To improve the current TB situations, sensitive and specific TB point-of-care tests (POCTs) should be developed. This review addresses the current status of TB, novel diagnostic methodologies for TB, and the impact of those new diagnostics on TB control in such situations. Moreover, the perspective of TB management based on laboratory examinations is described. Smear microscopy with sputum samples is the only laboratory examination available in many resource-limited settings and is still used globally. Several nucleic acid amplification tests (NATs) have been developed. The World Health Organization (WHO) endorsed novel diagnostics based on NATs and updated their definition of a bacteriologically confirmed case requiring the biological specimen to be positive by smear microscopy, culture, or the WHO-recommended rapid diagnostic protocols. The use of new diagnostics increased the number of bacteriologically confirmed TB cases. Novel diagnostics are now available, but their sensitivity is still lower than that of conventional liquid culture method. To address the increasing incidence of TB, more resources including novel diagnostics as POCTs with higher sensitivity must be allocated to healthcare systems.

PrimaTB STAT-PAK Assay, a Novel, Rapid Lateral-Flow Test for Tuberculosis in Nonhuman Primates▿

PubMed Central

Lyashchenko, Konstantin P.; Greenwald, Rena; Esfandiari, Javan; Greenwald, David; Nacy, Carol A.; Gibson, Susan; Didier, Peter J.; Washington, Marc; Szczerba, Peter; Motzel, Sherri; Handt, Larry; Pollock, John M.; McNair, James; Andersen, Peter; Langermans, Jan A. M.; Verreck, Frank; Ervin, Sean; Ervin, Frank; McCombs, Candace

2007-01-01

Tuberculosis (TB) is the most important zoonotic bacterial disease in nonhuman primates (NHP). The current diagnostic method, the intradermal palpebral tuberculin test, has serious shortcomings. We characterized antibody responses in NHP against Mycobacterium tuberculosis to identify immunodominant antigens and develop a rapid serodiagnostic test for TB. A total of 422 NHP were evaluated, including 243 rhesus (Macaca mulatta), 46 cynomolgus (Macaca fascicularis), and 133 African green (Cercopithecus aethiops sabaeus) monkeys at five collaborative centers. Of those, 50 monkeys of the three species were experimentally inoculated with M. tuberculosis. Antibody responses were monitored every 2 to 4 weeks for up to 8 months postinfection by MultiAntigen Print ImmunoAssay with a panel of 12 recombinant antigens. All of the infected monkeys produced antibodies at various levels and with different antigen recognition patterns. ESAT-6 and MPB83 were the most frequently recognized proteins during infection. A combination of selected antigens which detected antibodies in all of the infected monkeys was designed to develop the PrimaTB STAT-PAK assay by lateral-flow technology. Serological evaluation demonstrated high diagnostic sensitivity (90%) and specificity (99%). The highest rate of TB detection was achieved when the skin test was combined with the PrimaTB STAT-PAK kit. This novel immunoassay provides a simple, rapid, and accurate test for TB in NHP. PMID:17652522

Molecular epidemiology of tuberculosis: achievements and challenges to current knowledge.

PubMed Central

Murray, Megan; Nardell, Edward

2002-01-01

Over the past 10 years, molecular methods have become available with which to strain-type Mycobacterium tuberculosis. They have allowed researchers to study certain important but previously unresolved issues in the epidemiology of tuberculosis (TB). For example, some unsuspected microepidemics have been revealed and it has been shown that the relative contribution of recently acquired disease to the TB burden in many settings is far greater than had been thought. These findings have led to the strengthening of TB control. Other research has demonstrated the existence and described the frequency of exogenous reinfection in areas of high incidence. Much recent work has focused on the phenotypic variation among strains and has evaluated the relative transmissibility, virulence, and immunogenicity of different lineages of the organism. We summarize the recent achievements in TB epidemiology associated with the introduction of DNA fingerprinting techniques, and consider the implications of this technology for the design and analysis of epidemiological studies. PMID:12132006

Evaluation of hsp65 Nested PCR-Restriction Analysis (PRA) for Diagnosing Tuberculosis in a High Burden Country

PubMed Central

Macente, Sara; Fujimura Leite, Clarice Queico; Santos, Adolfo Carlos Barreto; Siqueira, Vera Lúcia Dias; Machado, Luzia Neri Cosmo; Marcondes, Nadir Rodrigues; Hirata, Mario Hiroyuki; Hirata, Rosário Dominguez Crespo

2013-01-01

Current study evaluated the hsp65 Nested PCR Restriction Fragment Length Polymorphism Analysis (hsp65 Nested PCR-PRA) to detect and identify Mycobacterium tuberculosis complex directly in clinical samples for a rapid and specific diagnosis of tuberculosis (TB). hsp65 Nested PCR-PRA was applied directly to 218 clinical samples obtained from 127 patients suspected of TB or another mycobacterial infection from July 2009 to July 2010. The hsp65 Nested PCR-PRA showed 100% sensitivity and 95.0 and 93.1% specificity in comparison with culture and microscopy (acid fast bacillus smear), respectively. hsp65 Nested PCR-PRA was shown to be a fast and reliable assay for diagnosing TB, which may contribute towards a fast diagnosis that could help the selection of appropriate chemotherapeutic and early epidemiological management of the cases which are of paramount importance in a high TB burden country. PMID:24260739

Mucosal Vaccination against Tuberculosis Using Inert Bioparticles

PubMed Central

Reljic, Rajko; Sibley, Laura; Huang, Jen-Min; Pepponi, Ilaria; Hoppe, Andreas; Hong, Huynh A.

2013-01-01

Needle-free, mucosal immunization is a highly desirable strategy for vaccination against many pathogens, especially those entering through the respiratory mucosa, such as Mycobacterium tuberculosis. Unfortunately, mucosal vaccination against tuberculosis (TB) is impeded by a lack of suitable adjuvants and/or delivery platforms that could induce a protective immune response in humans. Here, we report on a novel biotechnological approach for mucosal vaccination against TB that overcomes some of the current limitations. This is achieved by coating protective TB antigens onto the surface of inert bacterial spores, which are then delivered to the respiratory tract. Our data showed that mice immunized nasally with coated spores developed humoral and cellular immune responses and multifunctional T cells and, most importantly, presented significantly reduced bacterial loads in their lungs and spleens following pathogenic challenge. We conclude that this new vaccine delivery platform merits further development as a mucosal vaccine for TB and possibly also other respiratory pathogens. PMID:23959722

Is Knowledge Regarding Tuberculosis Associated with Stigmatising and Discriminating Attitudes of General Population towards Tuberculosis Patients? Findings from a Community Based Survey in 30 Districts of India

PubMed Central

Sagili, Karuna D.; Satyanarayana, Srinath; Chadha, Sarabjit S.

2016-01-01

Background Stigmatising and discriminating attitudes may discourage tuberculosis (TB) patients from actively seeking medical care, hide their disease status, and discontinue treatment. It is expected that appropriate knowledge regarding TB should remove stigmatising and discriminating attitudes. In this study we assessed the prevalence of stigmatising and discriminating attitudes towards TB patients among general population and their association with knowledge regarding TB. Method A cross-sectional knowledge, attitude and practice survey was conducted in 30 districts of India in January-March 2011. A total of 4562 respondents from general population were interviewed using semi-structured questionnaires which contained items to measure stigma, discrimination and knowledge on TB. Result Of the 4562 interviewed, 3823 were eligible for the current analysis. Of these, 73% (95% CI 71.4–74.2) had stigmatising and 98% (95% CI 97.4–98.3) had discriminating attitude towards TB patients. Only 17% (95% CI 15.6–18.0) of the respondents had appropriate knowledge regarding TB with even lower levels observed amongst females, rural areas and respondents from low income groups. Surprisingly stigmatising (adjusted OR 1.31 (0.78–2.18) and discriminating (adjusted OR 0.79 (0.43–1.44) attitudes were independent of knowledge regarding TB. Conclusion Stigmatising and discriminating attitudes towards TB patients remain high among the general population in India. Since these attitudes were independent of the knowledge regarding TB, it is possible that the current disseminated knowledge regarding TB which is mainly from a medical perspective may not be adequately addressing the factors that lead to stigma and discrimination towards TB patients. Therefore, there is an urgent need to review the messages and strategies currently used for disseminating knowledge regarding TB among general population and revise them appropriately. The disseminated knowledge should include medical, psycho-social and economic aspects of TB that not only informs people about medical aspects of TB disease, but also removes stigma and discrimination. PMID:26829713

Tuberculosis vaccines: time to think about the next generation.

PubMed

Kaufmann, Stefan H E

2013-04-01

Efforts over the last 2 decades have led to a rich research and development pipeline of tuberculosis (TB) vaccines. Although none of the candidates has successfully completed the clinical trial pipeline, many are under advanced clinical assessment. These vaccines aim at prevention of active TB, with most of them being considered for preexposure with recent additions for postexposure or multistage administration. A few therapeutic vaccines are under clinical assessment, as well. Preexposure vaccination with the licensed TB vaccine BCG prevents severe forms of TB in children but not in adolescents and adults. The current vaccine pipeline does not include strategies which prevent or eliminate infection with the causative agent Mycobacterium tuberculosis (Mtb). Rather in a best-case scenario, they are quantitatively superior to BCG in preventing active TB over prolonged periods of time, ideally lifelong in the face of latent Mtb infection. Qualitatively superior vaccines should be capable of preventing or eliminating Mtb infection, in this way eliminating the risk of TB reactivation. The time is now ripe to exploit radically new strategies to achieve this goal. Copyright © 2013. Published by Elsevier Ltd.

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.

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

Evaluating the tuberculosis hazard posed to cattle from wildlife across Europe.

PubMed

Hardstaff, Joanne L; Marion, Glenn; Hutchings, Michael R; White, Piran C L

2014-10-01

Tuberculosis (TB) caused by infection with Mycobacterium bovis (M. bovis) and other closely related members of the M. tuberculosis complex (MTC) infects many domestic and wildlife species across Europe. Transmission from wildlife species to cattle complicates the control of disease in cattle. By determining the level of TB hazard for which a given wildlife species is responsible, the potential for transmission to the cattle population can be evaluated. We undertook a quantitative review of TB hazard across Europe on a country-by-country basis for cattle and five widely-distributed wildlife species. Cattle posed the greatest current and potential TB hazard other cattle for the majority of countries in Europe. Wild boar posed the greatest hazard of all the wildlife species, indicating that wild boar have the greatest ability to transmit the disease to cattle. The most common host systems for TB hazards in Europe are the cattle-deer-wild boar ones. The cattle-roe deer-wild boar system is found in 10 countries, and the cattle-red deer-wild boar system is found in five countries. The dominance of cattle with respect to the hazards in many regions confirms that intensive surveillance of cattle for TB should play an important role in any TB control programme. The significant contribution that wildlife can make to the TB hazard to cattle is also of concern, given current population and distribution increases of some susceptible wildlife species, especially wild boar and deer, and the paucity of wildlife TB surveillance programmes. Copyright © 2013 Elsevier Ltd. All rights reserved.

A Prospective Study of Tuberculosis Drug Susceptibility in Sabah, Malaysia, and an Algorithm for Management of Isoniazid Resistance

PubMed Central

Rashid Ali, Muhammad Redzwan S.; Parameswaran, Uma; William, Timothy; Bird, Elspeth; Wilkes, Christopher S.; Lee, Wai Khew; Yeo, Tsin Wen; Anstey, Nicholas M.; Ralph, Anna P.

2015-01-01

Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results. Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB) in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study. Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9%) and nontuberculous Mycobacterium (NTM) in three (1.7%). Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB). Seven people (4.5%) had isoniazid resistance (INH-R); all were switched to an appropriate second-line regimen for varying durations (4.5–9 months). Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant), 2 had INH-R, and 4 had NTM. Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB. PMID:25838829

A prospective study of tuberculosis drug susceptibility in sabah, malaysia, and an algorithm for management of isoniazid resistance.

PubMed

Rashid Ali, Muhammad Redzwan S; Parameswaran, Uma; William, Timothy; Bird, Elspeth; Wilkes, Christopher S; Lee, Wai Khew; Yeo, Tsin Wen; Anstey, Nicholas M; Ralph, Anna P

2015-01-01

Introduction. The burden of tuberculosis is high in eastern Malaysia, and rates of Mycobacterium tuberculosis drug resistance are poorly defined. Our objectives were to determine M. tuberculosis susceptibility and document management after receipt of susceptibility results. Methods. Prospective study of adult outpatients with smear-positive pulmonary tuberculosis (PTB) in Sabah, Malaysia. Additionally, hospital clinicians accessed the reference laboratory for clinical purposes during the study. Results. 176 outpatients were enrolled; 173 provided sputum samples. Mycobacterial culture yielded M. tuberculosis in 159 (91.9%) and nontuberculous Mycobacterium (NTM) in three (1.7%). Among outpatients there were no instances of multidrug resistant M. tuberculosis (MDR-TB). Seven people (4.5%) had isoniazid resistance (INH-R); all were switched to an appropriate second-line regimen for varying durations (4.5-9 months). Median delay to commencement of the second-line regimen was 13 weeks. Among 15 inpatients with suspected TB, 2 had multidrug resistant TB (one extensively drug resistant), 2 had INH-R, and 4 had NTM. Conclusions. Current community rates of MDR-TB in Sabah are low. However, INH-resistance poses challenges, and NTM is an important differential diagnosis in this setting, where smear microscopy is the usual diagnostic modality. To address INH-R management issues in our setting, we propose an algorithm for the treatment of isoniazid-resistant PTB.

Epigenetics and Proteomics Join Transcriptomics in the Quest for Tuberculosis Biomarkers

PubMed Central

Esterhuyse, Maria M.; Weiner, January; Caron, Etienne; Loxton, Andre G.; Iannaccone, Marco; Wagman, Chandre; Saikali, Philippe; Stanley, Kim; Wolski, Witold E.; Mollenkopf, Hans-Joachim; Schick, Matthias; Aebersold, Ruedi; Linhart, Heinz; Walzl, Gerhard

2015-01-01

ABSTRACT An estimated one-third of the world’s population is currently latently infected with Mycobacterium tuberculosis. Latent M. tuberculosis infection (LTBI) progresses into active tuberculosis (TB) disease in ~5 to 10% of infected individuals. Diagnostic and prognostic biomarkers to monitor disease progression are urgently needed to ensure better care for TB patients and to decrease the spread of TB. Biomarker development is primarily based on transcriptomics. Our understanding of biology combined with evolving technical advances in high-throughput techniques led us to investigate the possibility of additional platforms (epigenetics and proteomics) in the quest to (i) understand the biology of the TB host response and (ii) search for multiplatform biosignatures in TB. We engaged in a pilot study to interrogate the DNA methylome, transcriptome, and proteome in selected monocytes and granulocytes from TB patients and healthy LTBI participants. Our study provides first insights into the levels and sources of diversity in the epigenome and proteome among TB patients and LTBI controls, despite limitations due to small sample size. Functionally the differences between the infection phenotypes (LTBI versus active TB) observed in the different platforms were congruent, thereby suggesting regulation of function not only at the transcriptional level but also by DNA methylation and microRNA. Thus, our data argue for the development of a large-scale study of the DNA methylome, with particular attention to study design in accounting for variation based on gender, age, and cell type. PMID:26374119

The Human Microbiome in the Fight Against Tuberculosis

PubMed Central

Wood, Madeleine R.; Yu, Elaine A.; Mehta, Saurabh

2017-01-01

The human microbiome is an intriguing potentially modifiable risk factor in our arsenal against Mycobacterium tuberculosis, the leading infectious disease killer globally. Previous studies have shown associations between the human microbiome and pulmonary disease states; however, etiological links between the microbiome and tuberculosis (TB) infection or disease remain unclear. Immunomodulatory roles of the microbiome may prove to be a critical asset in the host response against TB, including in preventing TB infection, reducing progression from latency, mitigating disease severity, and lowering the incidence of drug resistance and coinfections. This review examined the associations between TB and the gut and lung microbiome. Eight studies were identified through a PubMed database search, including one animal study (N = 1), case report (N = 1), and case–control studies (N = 6). TB infection and disease were associated with reduced gastrointestinal microbial diversity in a murine model and human case report. Sputum microbial diversity differed by TB status in case–control studies, although some reported heterogeneous findings. Current evidence suggests that the gut and lung microbiome are associated with TB infection and disease. However, as studies are limited, etiological and longitudinal research is needed to determine clinical relevance. PMID:28719264

The multidrug-resistant tuberculosis challenge to public health efforts to control tuberculosis.

PubMed Central

Villarino, M E; Geiter, L J; Simone, P M

1992-01-01

After years of steady decline, there has been an unprecedented resurgence of tuberculosis (TB) in the United States and outbreaks of multidrug-resistant tuberculosis (MDR-TB). The authors assess the nature, epidemiology, and implications of MDR-TB; provide suggestions for preventing drug resistance among patients with drug-susceptible TB; and offer recommendations for managing patients with MDR-TB. They outline the National Action Plan to Combat MDR-TB. Close collaboration among medical practitioners and staff members of TB control programs is needed to ensure the most effective management of patients with TB and their contacts. This collaboration is one of the most important steps for successful control of MDR-TB. PMID:1454973

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.

Phenotypic and genotypic analysis of anti-tuberculosis drug resistance in Mycobacterium tuberculosis isolates in Myanmar.

PubMed

Aung, Wah Wah; Ei, Phyu Win; Nyunt, Wint Wint; Swe, Thyn Lei; Lwin, Thandar; Htwe, Mi Mi; Kim, Kyung Jun; Lee, Jong Seok; Kim, Chang Ki; Cho, Sang Nae; Song, Sun Dae; Chang, Chulhun L

2015-09-01

Tuberculosis (TB) is one of the most serious health problems in Myanmar. Because TB drug resistance is associated with genetic mutation(s) relevant to responses to each drug, genotypic methods for detecting these mutations have been proposed to overcome the limitations of classic phenotypic drug susceptibility testing (DST). We explored the current estimates of drug-resistant TB and evaluated the usefulness of genotypic DST in Myanmar. We determined the drug susceptibility of Mycobacterium tuberculosis isolated from sputum smear-positive patients with newly diagnosed pulmonary TB at two main TB centers in Myanmar during 2013 by using conventional phenotypic DST and the GenoType MTBDRplus assay (Hain Lifescience, Germany). Discrepant results were confirmed by sequencing the genes relevant to each type of resistance (rpoB for rifampicin; katG and inhA for isoniazid). Of 191 isolates, phenotypic DST showed that 27.7% (n=53) were resistant to at least one first-line drug and 20.9% (n=40) were resistant to two or more, including 18.3% (n=35) multidrug-resistant TB (MDR-TB) strains. Monoresistant strains accounted for 6.8% (n=13) of the samples. Genotypic assay of 189 isolates showed 17.5% (n=33) MDR-TB and 5.3% (n=10) isoniazid-monoresistant strains. Genotypic susceptibility results were 99.5% (n=188) concordant and agreed almost perfectly with phenotypic DST (kappa=0.99; 95% confidence interval 0.96-1.01). The results highlight the burden of TB drug resistance and prove the usefulness of the genotypic DST in Myanmar.

Doxycycline and HIV Infection Suppress Tuberculosis-induced Matrix Metalloproteinases

PubMed Central

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

2012-01-01

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

Tuberculosis (TB): Treatment

MedlinePlus

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

In silico design of Mycobacterium tuberculosis epitope ensemble vaccines.

PubMed

Shah, Preksha; Mistry, Jaymisha; Reche, Pedro A; Gatherer, Derek; Flower, Darren R

2018-05-01

Effective control of Mycobacterium tuberculosis is a global necessity. In 2015, tuberculosis (TB) caused more deaths than HIV. Considering the increasing prevalence of multi-drug resistant forms of M. tuberculosis, the need for effective TB vaccines becomes imperative. Currently, the only licensed TB vaccine is Bacillus Calmette-Guérin (BCG). Yet, BCG has many drawbacks limiting its efficacy and applicability. We applied advanced computational procedures to derive a universal TB vaccine and one targeting East Africa. Our approach selects an optimal set of highly conserved, experimentally validated epitopes, with high projected population coverage (PPC). Through rigorous data analysis, five different potential vaccine combinations were selected each with PPC above 80% for East Africa and above 90% for the World. Two potential vaccines only contained CD8+ epitopes, while the others included both CD4+ and CD8+ epitopes. Our prime vaccine candidate was a putative seven-epitope ensemble comprising: SRGWSLIKSVRLGNA, KPRIITLTMNPALDI, AAHKGLMNIALAISA, FPAGGSTGSL, MLLAVTVSL, QSSFYSDW and KMRCGAPRY, with a 97.4% global PPC and a 92.7% East African PPC. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

Identification and characterization of potential druggable targets among hypothetical proteins of extensively drug resistant Mycobacterium tuberculosis (XDR KZN 605) through subtractive genomics approach.

PubMed

Uddin, Reaz; Siddiqui, Quratulain Nehal; Azam, Syed Sikander; Saima, Bibi; Wadood, Abdul

2018-03-01

Among the resistant isolates of tuberculosis (TB), the multidrug resistance tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) are the areas of growing concern for which the front-line antibiotics are no more effective. As a result, the search of new therapeutic targets against TB is an imperative need of time. On the other hand, the target identification is an a priori step in drug discovery based research. Furthermore, the availability of the complete proteomic data of extensively drug resistant Mycobacterium tuberculosis (XDR-MTB) made it possible to carry out in silico analysis for the discovery of new drug targets. In the current study, we aimed to prioritize the potential drug targets among the hypothetical proteins of XDR-TB via subtractive genomics approach. In the subtractive genomics, we stepwise reduced the complete proteome of XDR-MTB to only two hypothetical proteins and evidently proposed them as new therapeutic targets. The 3D structure of one of the two target proteins was predicted via homology modeling and later on, validated by various analysis tools. Our study suggested that the domains identified and the motif hits found in the sequences of the shortlisted drug targets are crucial for the survival of the XDR-MTB. To the best of our knowledge, the current study is the first attempt in which the complete proteomic data of XDR-MTB was subjected to the computational subtractive genomics approach and therefore, would provide an opportunity to identify the unique therapeutic targets against deadly XDR-MTB. Copyright © 2017 Elsevier B.V. All rights reserved.

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

Uncovering the hidden: complexity and strategies for diagnosing latent tuberculosis.

PubMed

Flores-Valdez, Mario Alberto

2017-10-24

Tuberculosis produces two clinical manifestations: active and latent (non-apparent) disease. The latter is estimated to affect one-third of the world population and constitutes a source of continued transmission should the disease emerge from its hidden state (reactivation). Methods to diagnose latent TB have been evolving and aim to detect the disease in people who are truly infected with M. tuberculosis , versus those where other mycobacteria, or even other pathologies not related to TB, are present. The current use of proteomic and transcriptomic approaches may lead to improved detection methods in the coming years.

Exposure to human alveolar lining fluid enhances Mycobacterium bovis BCG vaccine efficacy against Mycobacterium tuberculosis infection in a CD8+ T-cell-dependent manner.

PubMed

Moliva, J I; Hossfeld, A P; Canan, C H; Dwivedi, V; Wewers, M D; Beamer, G; Turner, J; Torrelles, J B

2018-05-01

Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.tb) cell wall, revealing alternate antigenic epitopes on the bacterium surface that alter its pathogenicity. We hypothesized that ALF-induced modification of BCG would induce better protection against aerosol infection with M.tb. Here we vaccinated mice with ALF-exposed BCG, mimicking the mycobacterial cell surface properties that would be present in the lung during M.tb infection. ALF-exposed BCG-vaccinated mice were more effective at reducing M.tb bacterial burden in the lung and spleen, and had reduced lung inflammation at late stages of M.tb infection. Improved BCG efficacy was associated with increased numbers of memory CD8 + T cells, and CD8 + T cells with the potential to produce interferon-γ in the lung in response to M.tb challenge. Depletion studies confirmed an essential role for CD8 + T cells in controlling M.tb bacterial burden. We conclude that ALF modifications to the M.tb cell wall in vivo are relevant in the context of vaccine design.

Breaking Transmission with Vaccines: The Case of Tuberculosis.

PubMed

Gonzalo-Asensio, Jesus; Aguilo, Nacho; Marinova, Dessislava; Martin, Carlos

2017-07-01

Members of the Mycobacterium tuberculosis complex (MTBC) have evolved causing tuberculosis (TB) in different mammalian hosts. MTBC ecotypes have adapted to diverse animal species, with M. bovis being the most common cause of TB in livestock. Cattle-to-human transmission of M. bovis through ingestion of raw milk was common before introduction of the pasteurization process. TB in humans is mainly caused by M. tuberculosis . This bacterium is considered a genetically clonal pathogen that has coevolved with humans due to its ability to manipulate and subvert the immune response. TB is a major public health problem due to airborne person-to-person transmission of M. tuberculosis . The essential yet unanswered question on the natural history of TB is when M. tuberculosis decides to establish latent infection in the host (resambling the lysogenic cycle of lambda phage) or to cause pulmonary disease (comparable to the lytic cycle of lambda phage). In this latter case, M. tuberculosis kills the host with the aim of achieving transmission to new hosts. Combating the TB epidemic requires stopping transmission. M. bovis BCG, the present vaccine against TB, is derived from M. bovis and only protects against disseminated forms of TB. Thus, a priority in TB research is development of new effective vaccines to prevent pulmonary disease. Attenuated vaccines based on M. tuberculosis as MTBVAC are potential candidates that could contribute to break the TB transmission cycle.

Drug resistance characteristics of Mycobacterium tuberculosis isolates to four first-line antituberculous drugs from tuberculosis patients with AIDS in Beijing, China.

PubMed

Gao, Gui-ju; Lian, Lulu; Sun, Yue; Wei, Jianhao; Xiao, Jiang; Wang, Xiaoying; Zhang, Ling; Zhao, Xiuqin; Yang, Di; Zhao, Hong-xin; Zhao, Hui; Wang, Hui-zhu; Wan, Kang-lin; Li, Xing-wang

2015-02-01

The objective of this study was to investigate the drug resistance characteristics of Mycobacterium tuberculosis isolates to four first-line antituberculous drugs (ATDs) from tuberculosis (TB) patients with AIDS in Beijing, China. All M. tuberculosis strains were isolated from specimens from TB patients with AIDS hospitalised between April 2010 and October 2012. Isolates were cultured by mycobacterial culture methods and were identified by multilocus PCR. Drug sensitivity testing was performed by the proportion method with the following first-line ATDs: isoniazid; rifampicin; streptomycin; and ethambutol. Results were compared with the drug resistance status of M. tuberculosis strains isolated from TB patients without HIV infection in Beijing. Among 41 M. tuberculosis isolates from TB patients with AIDS, the rates of total drug resistance (58.5%), initial drug resistance (46.7%) and acquired drug resistance (90.9%) were significantly higher than in TB patients without HIV infection (34.1%, 24.5% and 48.5%, respectively; P<0.05). In TB patients with AIDS, the rates of acquired drug resistance (90.9%) and acquired multidrug-resistant TB (MDR-TB) (54.5%) were significantly higher than the rates of initial drug resistance (46.7%) and initial MDR-TB (10.0%) (P<0.05). In patients with TB without HIV infection, the rate of acquired drug resistance (48.5%) was significantly higher than the rate of initial drug resistance (24.5%) (P<0.05). M. tuberculosis drug resistance in TB patients with AIDS is significantly more serious than in TB patients without HIV infection. These results showed that more attention should be paid to M. tuberculosis drug resistance in AIDS patients. Copyright © 2014 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Proteomic analysis of drug-resistant Mycobacterium tuberculosis by one-dimensional gel electrophoresis and charge chromatography.

PubMed

Yari, Shamsi; Hadizadeh Tasbiti, Alireza; Ghanei, Mostafa; Shokrgozar, Mohammad Ali; Fateh, Abolfazl; Mahdian, Reza; Yari, Fatemeh; Bahrmand, Ahmadreza

2017-01-01

Multidrug-resistant tuberculosis (MDR-TB) is a form of TB caused by Mycobacterium tuberculosis (M. tuberculosis) that do not respond to, at least, isoniazid and rifampicin, the two most powerful, first-line (or standard) anti-TB drugs. Novel intervention strategies for eliminating this disease were based on finding proteins that can be used for designing new drugs or new and reliable kits for diagnosis. The aim of this study was to compare the protein profiles of MDR-TB with sensitive isolates. Proteomic analysis of M. tuberculosis MDR-TB and sensitive isolates was obtained with ion exchange chromatography coupled with MALDI-TOF-TOF (matrix-assisted laser desorption/ionization) in order to identify individual proteins that have different expression in MDR-TB to be used as a drug target or diagnostic marker for designing valuable TB vaccines or TB rapid tests. We identified eight proteins in MDR-TB isolates, and analyses showed that these proteins are absent in M. tuberculosis-sensitive isolates: (Rv2140c, Rv0009, Rv1932, Rv0251c, Rv2558, Rv1284, Rv3699 and MMP major membrane proteins). These data will provide valuable clues in further investigation for suitable TB rapid tests or drug targets against drug-resistant and sensitive M. tuberculosis isolates.

Treatment: Latent TB Infection (LTBI) and TB Disease

MedlinePlus

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

PubMed

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

2016-11-01

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

TB Terms

MedlinePlus

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

PubMed

Graham, Stephen M

2017-01-01

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

Molecular Epidemiology of Pulmonary Tuberculosis in Belgrade, Central Serbia

PubMed Central

Vuković, Dragana; Rüsch-Gerdes, Sabine; Savić, Branislava; Niemann, Stefan

2003-01-01

In order to gain precise data on the actual epidemiology of tuberculosis (TB) in Belgrade, central Serbia, we conducted the molecular epidemiological investigation described herein. IS6110 restriction fragment length polymorphism (RFLP) typing of 176 Mycobacterium tuberculosis isolates was performed. These strains were obtained from 48.4% of all patients diagnosed with culture-proven pulmonary TB from April through September 1998 and from May through October 1999. Clusters containing strains with identical RFLP IS6110 patterns were assumed to have arisen from recent transmission. Of the 176 cases, 55 (31.2%) were grouped into 23 clusters ranging in size from two to six patients. Nearly 80% of clustered patients were directly interviewed, and transmission between family-unrelated contacts was found to be predominant in the study population. Classical contact investigation identified only 2 (3.6%) of the 55 clustered patients. The clustering of TB patients was not associated with any demographic or clinical characteristic other than infection with multidrug-resistant (MDR) M. tuberculosis strains. Nearly 70% of MDR strains were clustered, which indicates active transmission of MDR TB in Belgrade. However, this was not observed by conventional epidemiologic surveillance. In conclusion, the first molecular epidemiologic analysis of TB in the region revealed frequent recent transmission of TB and pointed out significant shortcomings of the current concept for conventional contact tracing. The results presented also demonstrate that transmission of MDR TB in Belgrade is not optimally controlled, and they provide support for the development of improved control strategies, including application of molecular methods. PMID:12958271

Immunogenicity and protective efficacy of DMT liposome-adjuvanted tuberculosis subunit CTT3H vaccine

PubMed Central

Teng, Xindong; Tian, Maopeng; Li, Jianrong; Tan, Songwei; Yuan, Xuefeng; Yu, Qi; Jing, Yukai; Zhang, Zhiping; Yue, Tingting; Zhou, Lei; Fan, Xionglin

2015-01-01

Different strategies have been proposed for the development of protein subunit vaccine candidates for tuberculosis (TB), which shows better safety than other types of candidates and the currently used Bacillus Calmette-Guérin (BCG) vaccine. In order to develop more effective protein subunits depending on the mechanism of cell-mediated immunity against TB, a polyprotein CTT3H, based on 5 immunodominant antigens (CFP10, TB10.4, TB8.4, Rv3615c, and HBHA) with CD8+ epitopes of Mycobacterium tuberculosis, was constructed in this study. We vaccinated C57BL/6 mice with a TB subunit CTT3H protein in an adjuvant of dimethyldioctadecylammonium/monophosphoryl lipid A/trehalose 6,6′-dibehenate (DDA/MPL/TDB, DMT) liposome to investigate the immunogenicity and protective efficacy of this novel vaccine. Our results demonstrated that DMT liposome-adjuvanted CTT3H vaccine not only induced an antigen-specific CD4+ Th1 response, but also raised the number of PPD- and CTT3H-specific IFN-γ+ CD8+ T cells and elicited strong CTL responses against TB10.4, which provided more effective protection against a 60 CFU M. tuberculosis aerosol challenge than PBS control and DMT adjuvant alone. Our findings indicate that DMT-liposome is an effective adjuvant to stimulate CD8+ T cell responses and the DMT-adjuvanted subunit CTT3H vaccine is a promising candidate for the next generation of TB vaccine. PMID:25905680

Immunogenicity and protective efficacy of DMT liposome-adjuvanted tuberculosis subunit CTT3H vaccine.

PubMed

Teng, Xindong; Tian, Maopeng; Li, Jianrong; Tan, Songwei; Yuan, Xuefeng; Yu, Qi; Jing, Yukai; Zhang, Zhiping; Yue, Tingting; Zhou, Lei; Fan, Xionglin

2015-01-01

Different strategies have been proposed for the development of protein subunit vaccine candidates for tuberculosis (TB), which shows better safety than other types of candidates and the currently used Bacillus Calmette-Guérin (BCG) vaccine. In order to develop more effective protein subunits depending on the mechanism of cell-mediated immunity against TB, a polyprotein CTT3H, based on 5 immunodominant antigens (CFP10, TB10.4, TB8.4, Rv3615c, and HBHA) with CD8(+) epitopes of Mycobacterium tuberculosis, was constructed in this study. We vaccinated C57BL/6 mice with a TB subunit CTT3H protein in an adjuvant of dimethyldioctadecylammonium/monophosphoryl lipid A/trehalose 6,6'-dibehenate (DDA/MPL/TDB, DMT) liposome to investigate the immunogenicity and protective efficacy of this novel vaccine. Our results demonstrated that DMT liposome-adjuvanted CTT3H vaccine not only induced an antigen-specific CD4(+) Th1 response, but also raised the number of PPD- and CTT3H-specific IFN-γ(+) CD8(+) T cells and elicited strong CTL responses against TB10.4, which provided more effective protection against a 60 CFU M. tuberculosis aerosol challenge than PBS control and DMT adjuvant alone. Our findings indicate that DMT-liposome is an effective adjuvant to stimulate CD8(+) T cell responses and the DMT-adjuvanted subunit CTT3H vaccine is a promising candidate for the next generation of TB vaccine.

Testing for TB Infection

MedlinePlus

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Substantially Higher and Earlier Occurrence of Anti-Tuberculosis Drug-Related Adverse Reactions in HIV Coinfected Tuberculosis Patients: A Matched-Cohort Study.

PubMed

Matono, Takashi; Nishijima, Takeshi; Teruya, Katsuji; Morino, Eriko; Takasaki, Jin; Gatanaga, Hiroyuki; Kikuchi, Yoshimi; Kaku, Mitsuo; Oka, Shinichi

2017-11-01

Little information exists on the frequency, severity, and timing of first-line anti-tuberculosis drug-related adverse events (TB-AEs) in HIV-tuberculosis coinfected (HIV-TB) patients in the antiretroviral therapy (ART) era. This matched-cohort study included HIV-TB patients as cases and HIV-uninfected tuberculosis (non-HIV-TB) patients as controls. Tuberculosis was culture-confirmed in both groups. Cases were matched to controls in a 1:4 ratio on age, sex, and year of diagnosis. TB-AEs were defined as Grade 2 or higher requiring drug discontinuation/regimen change. From 2003 to 2015, 94 cases and 376 controls were analyzed (95% men, 98% Asians). Standard four-drug combination therapy was initiated in 91% of cases and 89% of controls (p = 0.45). Cases had a higher frequency of TB-AE [51% (48/94) vs. 10% (39/376), p < 0.001]. Their major TB-AEs were fever (19%), rash (11%), and neutropenia (11%). TB-AEs were more severe in cases [Grade 3 or higher: cases (71%, 34/48) vs. controls (49%, 19/39), p < 0.001]. The time from treatment initiation to TB-AE was shorter in cases [median 18 (interquartile range 12-28) vs. 27 (15-57) days, p = 0.027], and 73% of TB-AEs in cases occurred within 4 weeks of starting anti-tuberculosis treatment. HIV infection was an independent risk factor for TB-AEs in the multivariate Cox analysis [adjusted HR (aHR): 6.96; 95% confidence interval: 3.93-12.3]. TB-AEs occurred more frequently in HIV-TB than in non-HIV-TB patients, and were more severe. The majority of TB-AEs occurred within 4 weeks of initiating anti-tuberculosis treatment. Because TB-AEs may delay ART initiation, careful monitoring during this period is warranted in coinfected patients.

Tuberculosis and Diabetes

MedlinePlus

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

[Tuberculosis patient disease knowledge, attitudes and behavioral intentions: the impact of individualized counseling].

PubMed

Wu, Shiau-Jiun; Lu, Po-Liang; Chen, Yen-Hsu; Pan, Hui-Juan; Feng, Ming-Chu

2011-12-01

The Taiwan government currently promotes a case management approach to tuberculosis (TB) treatment to address the growing number of TB and multiple drug-resistant TB cases in Taiwan. The approach aims to improve medical follow-up and monitor quality of care. The efficacy of this case management approach has yet to be evaluated. The current study was designed to evaluate the effect of individualized case manager counseling on TB patient disease knowledge, attitudes, and behavioral intention. This study employed a one-group pretest-posttest quasi-experimental design. Participants first answered an initial questionnaire survey including three structured scales that addressed, respectively, the facets of disease knowledge, attitudes, and behavioral intention. TB case managers then delivered two- stage counseling to participants based on assessed individual needs and outstanding issues identified in questionnaire answers. A second questionnaire survey was administered 30~42 days after the intervention. Data on a total of 96 TB patients were collected. Key study findings were (1) individualized counseling significantly improved TB patient disease knowledge (p < .001) and (2) TB patient attitudes correlated significantly and positively with behavior intention (p < .001). Individualized counseling provided during the early stages of TB helps elevate patient awareness of the importance of treatment, enhances compliance and increases the cure rate.

Tuberculosis control in prisons: current situation and research gaps.

PubMed

Dara, Masoud; Acosta, Colleen D; Melchers, Natalie V S Vinkeles; Al-Darraji, Haider A A; Chorgoliani, Dato; Reyes, Hernan; Centis, Rosella; Sotgiu, Giovanni; D'Ambrosio, Lia; Chadha, Sarabjit S; Migliori, Giovanni Battista

2015-03-01

Tuberculosis (TB) in penitentiary services (prisons) is a major challenge to TB control. This review article describes the challenges that prison systems encounter in TB control and provides solutions for the more efficient use of limited resources based on the three pillars of the post-2015 End TB Strategy. This paper also proposes research priorities for TB control in prisons based on current challenges. Articles (published up to 2011) included in a recent systematic review on TB control in prisons were further reviewed. In addition, relevant articles in English (published 1990 to May 2014) were identified by searching keywords in PubMed and Google Scholar. Article bibliographies and conference abstracts were also hand-searched. Despite being a serious cause of morbidity and mortality among incarcerated populations, many prison systems encounter a variety of challenges that hinder TB control. These include, but are not limited to, insufficient laboratory capacity and diagnostic tools, interrupted supply of medicines, weak integration between civilian and prison TB services, inadequate infection control measures, and low policy priority for prison healthcare. Governmental commitment, partnerships, and sustained financing are needed in order to facilitate improvements in TB control in prisons, which will translate to the wider community. Copyright © 2015 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

Serum vitamin d level and susceptibility to multidrug-resistant tuberculosis among household contacts

NASA Astrophysics Data System (ADS)

Herlina, N.; Sinaga, B. Y. M.; Siagian, P.; Mutiara, E.

2018-03-01

Low levels of vitamin D is a predisposing factor for Multidrug-resistant tuberculosis. Family members in contact with the patient are also at risk of infection. Currently, there is no study that compares vitamin D levels between MDR-TB patients and household contact. This study aims to identify the association between level vitamin D within MDR-TB occurrence. This was a case-control study, with the number of samples in each group (MDR-TB) patients and household contactswere40 people. Each member of each group was checked for vitamin D levels using enzyme-linked immunosorbent assay (ELISA) technique. Statistical analysis was by using Chi-Square analysis using SPSS. Mean levels of vitamin D in MDR-TB patients were 32.21, household contact 31.7. There was anosignificant association between vitamin D levels and MDR-TB occurrence (p=1.0).No significant associationbetween vitamin D level with theMDR-TB occurrence.

Latent tuberculosis infections in hard-to-reach drug using population-detection, prevention and control.

PubMed

Hwang, Lu-Yu; Grimes, Carolyn Z; Beasley, R Palmer; Graviss, Edward A

2009-12-01

Interferon-gamma release assays (IGRAs) need be evaluated for effectiveness as screening tests for tuberculosis (TB) infection in drug users. These tests have demonstrated improved sensitivity and specificity, but have not been studied in drug users. These one step blood tests are intended to replace the tuberculin skin test (TST), which is difficult to use and requires 48 hour follow-up, so they are expected to be particularly suitable for risk groups, like drug users, in whom follow-up is problematic. Drug users have traditionally been identified as being at increased risk for acquiring TB disease. The results of our pilot study using the TST and simpler and more sensitive interferon-gamma release assays showed that about 45% of current drug users in Houston tested have at least one test positive for latent tuberculosis infection (LTBI). These preliminary data suggest that there is an important reservoir of LTBI in drug using populations, and the risk of progression to active TB disease with other infections is great. However, LTBI in drug using populations has not been studied in depth and deserves further investigation. We need to evaluate the validity of IGRAs for detection of latent TB infection, the factors associated with LTBI, the incidence and risk for developing active TB disease in drug users and the effectiveness of early treatment of LTBI. We believe that using better tuberculosis screening tools will allow us to more accurately measure the prevalence of latent TB infection and incidence of active TB disease in drug using populations and develop more effective TB prevention and treatment interventions in the community.

Highly Accurate Antibody Assays for Early and Rapid Detection of Tuberculosis in African and Asian Elephants

USDA-ARS?s Scientific Manuscript database

Tuberculosis (TB) in elephants is a re-emerging zoonotic disease caused primarily by Mycobacterium tuberculosis. Current methods for screening and diagnosis rely on trunk wash culture, which has serious limitations due to low test sensitivity, slow turn-around time, and variable sample quality. Inn...

Questions and Answers about TB

MedlinePlus

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Safety and Immunogenicity of Adenovirus 35 Tuberculosis Vaccine Candidate in Adults with Active or Previous Tuberculosis. A Randomized Trial.

PubMed

van Zyl-Smit, Richard N; Esmail, Aliasgar; Bateman, Mary E; Dawson, Rodney; Goldin, Jonathan; van Rikxoort, Eva; Douoguih, Macaya; Pau, Maria Grazia; Sadoff, Jerald C; McClain, J Bruce; Snowden, Margaret Ann; Benko, Jacqueline; Hokey, David A; Rutkowski, Kathryn Tucker; Graves, Andrew; Shepherd, Barbara; Ishmukhamedov, Sadritdin; Kagina, Benjamin M N; Abel, Brian; Hanekom, Willem A; Scriba, Thomas J; Bateman, Eric D

2017-05-01

Administration of tuberculosis (TB) vaccines in participants with previous or current pulmonary TB may have the potential for causing harmful postvaccination immunologic (Koch-type) reactions. To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored TB candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary TB. We performed a phase II randomized, placebo-controlled, double-blinded dose-escalation study in an HIV-negative adult South African cohort (n = 72) with active pulmonary TB (on treatment for 1-4 mo) or pulmonary TB treated at least 12 months before study entry and considered cured. Safety endpoints included clinical assessment, flow volume curves, diffusing capacity of the lung for carbon monoxide, pulse oximetry, chest radiograph, and high-resolution thoracic computerized tomography scans. Cytokine expression by CD4 and CD8 T cells, after stimulation with Ag85A, Ag85B, and TB10.4 peptide pools, was examined by intracellular cytokine staining. No apparent temporal or dose-related changes in clinical status (specifically acute, Koch phenomenon-like reactions), lung function, or radiology attributable to vaccine were observed. Injection site reactions were mild or moderate. Hematuria (by dipstick only) occurred in 25 (41%) of 61 AERAS-402 recipients and 3 (27%) of 11 placebo recipients, although no gross hematuria was reported. AERAS-402 induced robust CD8 + and moderate CD4 + T-cell responses, mainly to Ag85B in both vaccine groups. Administration of the AERAS-402 candidate TB vaccine to participants with current or previous pulmonary TB induced a robust immune response and is not associated with clinically significant pulmonary complications. Clinical trial registered with www.clinicaltrials.gov (NCT 02414828) and in the South African National Clinical Trials Register ( www.sanctr.gov.za DOH 27-0808-2060).

Multidrug-resistant tuberculosis patients' views of interventions to reduce treatment loss to follow-up.

PubMed

Tupasi, T; Garfin, A M C G; Mangan, J M; Orillaza-Chi, R; Naval, L C; Balane, G I; Basilio, R; Golubkov, A; Joson, E S; Lew, W-J; Lofranco, V; Mantala, M; Pancho, S; Sarol, J N; Blumberg, A; Burt, D; Kurbatova, E V

2017-01-01

Patients who initiated treatment for multidrug-resistant tuberculosis (MDR-TB) at 15 Programmatic Management of Drug-resistant Tuberculosis (PMDT) health facilities in the Philippines between July and December 2012. To describe patients' views of current interventions, and suggest changes likely to reduce MDR-TB loss to follow-up. In-depth interviews were conducted between April and July 2014 with MDR-TB patients who were undergoing treatment, had finished treatment at the time of the interview (controls), or had been lost to follow-up (LTFU). Responses were thematically analyzed. Interviews were conducted with 182 patients who were undergoing or had completed treatment and 91 LTFU patients. Views and suggestions could be thematically categorized as approaches to facilitate adherence or address barriers to adherence. The top themes were the need for transportation assistance or improvements to the current transportation assistance program, food assistance, and difficulties patients encountered related to their medications. These themes were addressed by respectively 63%, 60%, and 32% of the participants. A more patient-centered approach is needed to improve MDR-TB treatment adherence. Programs should strive to provide assistance that considers patient preferences, is adequate to cover actual costs or needs, and is delivered in a timely, uninterrupted manner.

Efficacy of Adjunctive Tofacitinib Therapy in Mouse Models of Tuberculosis

PubMed Central

Maiga, Mamoudou; Ahidjo, Bintou Ahmadou; Maiga, Mariama C.; Cheung, Laurene; Pelly, Shaaretha; Lun, Shichun; Bougoudogo, Flabou; Bishai, William R.

2015-01-01

The global tuberculosis (TB) epidemic and the spread of multi- and extensively-drug resistant strains of Mycobacterium tuberculosis (M.tb) have been fueled by low adherence to following lengthy treatment protocols, and the rapid spread of HIV (Human Immunodeficiency Virus). Persistence of the infection in immunocompetent individuals follows from the ability of M.tb to subvert host immune responses in favor of survival within macrophages. Alternative host-directed strategies are therefore being currently sought to improve treatment efficacy and duration. In this study, we evaluated tofacitinib, a new oral Janus kinase (JAK) blocker with anti-inflammatory properties, in shortening tuberculosis treatment. BALB/c mice, which are immunocompetent, showed acceleration of M.tb clearance achieving apparent sterilization after 16 weeks of adjunctive tofacitinib therapy at average exposures higher than recommended in humans, while mice receiving standard treatment alone did not achieve clearance until 24 weeks. True sterilization with tofacitinib was not achieved until five months. C3HeB/FeJ mice, which show reduced pro-inflammatory cytokines during M.tb infection, did not show improved clearance with adjunctive tofacitinib therapy, indicating that the nature of granulomatous lesions and host immunity may influence responsiveness to tofacitinib. Our findings suggest that the JAK pathway could be explored further for host-directed therapy in immunocompetent individuals. PMID:26425693

Comparison of the socio-demographic and clinical features of pulmonary TB patients infected with sub-lineages within the W-Beijing and non-Beijing Mycobacterium tuberculosis.

PubMed

Hu, Yi; Mathema, Barun; Zhao, Qi; Zheng, Xubin; Li, Dange; Jiang, Weili; Wang, Weibing; Xu, Biao

2016-03-01

Highly lethal outbreaks of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis are increasing. Mycobacterium tuberculosis variant Beijing family and its members is regarded as a successful clone of M. tuberculosis that is associated with drug resistance in China. Understanding the genetic characteristics and molecular mechanism of drug resistant tuberculosis within Beijing family may help to clarify its origin and evolutionary history and the driving forces behind its emergence and current dissemination. Totally of 1222 Mycobacterium tuberculosis isolates were recovered from patients in six counties of two provinces in eastern China within 2010/2012. Strain lineage and its major subgroups were studied respectively by using Spoligotyping and MIRU-VNTR. The 1st-line drug susceptibility was analyzed by proportional method and 2nd-line drug susceptibility was determined by the HAINs MTBDRsl test. The genetic characterization of drug resistance was analyzed by sequencing the previously reported genes and loci associated with drug resistance together with the multiple genotyping including MIRU-VNTR, Spoligotyping and LSP genotyping. Of the 1222 Mtb isolates, 298 (24.4%) were resistant to 1st-line drug and 73 (5.9%) were simultaneously resistant to INH and RIF namely MDR-TB. Respectively 23.8% of 1st-line drug resistant TB and 12.0% of the drug susceptible TB contained the mutation associated with 2nd-line drugs by HAINs test. The Spoligotyping of 1222 Mtb isolates revealed the 967 (79.1%) of the isolates belonged to the W-Beijing family. Within W-Beijing family, 78.8% MDR-TB were observed in the isolates with simultaneous deletion of RD105 and RD207, with sub-lineage 181 accounting for 75% of MDR-TB. Analysis of 24 MIRU-VNTR loci revealed that 88.2% (15/17) of MDR and extensively drug resistant (XDR) clustered isolates were sub-lineage 181. Sublineage 181 might have the capacity to spread throughout the general community in rural China. This is the first report on the extensive association of sub-lineage 181 with MDR TB and possibly pre-XDR TB and XDR TB. It is important to monitor sublineage 181 to verify its heightened transmission and understand its importance in the global MDR-TB and XDR-TB epidemics. Copyright © 2015 Elsevier Ltd. All rights reserved.

TB in Children in the United States

MedlinePlus

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Dietary Vitamin D3 Suppresses Pulmonary Immunopathology Associated with Late-Stage Tuberculosis in C3HeB/FeJ Mice.

PubMed

Reeme, Allison E; Robinson, Richard T

2016-02-01

Tuberculosis (TB) is a significant human disease caused by inhalation of Mycobacterium tuberculosis. Left untreated, TB mortality is associated with a failure to resolve pulmonary immunopathology. There is currently widespread interest in using vitamin D3 (VitD3) as an adjunct therapy for TB because numerous in vitro studies have shown that VitD3 has direct and indirect mycobactericidal activities. However, to date, there have been no in vivo studies addressing whether VitD3 affects experimental TB outcome. In this study, we used C3HeB/FeJ mice to determine whether dietary VitD3 influences the outcome of experimental TB. We observed that although M. tuberculosis burdens did not differ between mice on a VitD3-replete diet (VitD(HI) mice) and mice on a VitD3-deficient diet (VitD(LO) mice), the inflammatory response in VitD(HI) mice was significantly attenuated relative to VitD(LO) controls. Specifically, the expression of multiple inflammatory pathways was reduced in the lungs at later disease stages as were splenocyte IL12/23p40 and IFN-γ levels following ex vivo restimulation. Dietary VitD3 also suppressed the accumulation of T cells in the mediastinal lymph nodes and lung granulomatous regions while concomitantly accelerating the accumulation of F4/80(+) and Ly6C/Ly6G(+) lineages. The altered inflammatory profile of VitD(HI) mice also associated with reductions in pulmonary immunopathology. VitD receptor-deficient (vdr(-/-)) radiation bone marrow chimeras demonstrate that reductions in pulmonary TB immunopathology are dependent on hematopoietic VitD responsiveness. Collectively, our data support a model wherein the in vivo role of VitD3 during TB is not to promote M. tuberculosis killing but rather to function through hematopoietic cells to reduce M. tuberculosis-elicited immunopathology. Copyright © 2016 by The American Association of Immunologists, Inc.

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

PubMed

Thakur, Harshad P

2013-01-01

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

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

PubMed

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

2014-03-01

Observational data from Eastern Europe on the management and outcome of multi-drug-resistant tuberculosis (MDR TB) in HIV positive populations remain sparse in the English-language literature. We compared clinical characteristics and outcomes of 55 patients who were diagnosed with HIV and MDR TB in Eastern Europe between 2004 and 2006 to 89 patients whose Mycobacterium tuberculosis isolates were susceptible to isoniazid and rifampicin. Patients with HIV and MDR TB were young and predominantly male with high rates of intravenous drug use, imprisonment and hepatitis C co-infection. Eighty-four per cent of patients with MDR TB had no history of previous TB drug exposure suggesting that the majority of MDR TB resulted from transmission of drug-resistant M. tuberculosis. The use of non-standardized tuberculosis treatment was common, and the use of antiretroviral therapy infrequent. Compared to those with susceptible tuberculosis, patients with MDR TB were less likely to achieve cure or complete tuberculosis treatment (21.8% vs. 62.9%, p < 0.0001), and they were more likely to die (65.5% vs. 27.0%, p < 0.0001). Our study documents suboptimal management and poor outcomes in HIV positive patients with MDR TB. Implementation of WHO guidelines, rapid TB diagnostics and TB drug susceptibility testing for all patients remain a priority in this region. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Tuberculosis in Poland in 2012.

PubMed

Korzeniewska-Koseła, Maria

2014-01-01

To evaluate the main features of TB epidemiology in 2012 in Poland and to compare with the corresponding EU data. Analysis of case- based clinical and demographic data on TB patients from Central TB Register, of data submitted by laboratories on anti-TB drug susceptibility testing results in cases notified in 2012, data from National Institute of Public Health - National Institute of Hygiene on cases of tuberculosis as AIDS-defining disease, from Central Statistical Office on deaths from tuberculosis based on death certificates, data from ECDC report "Tuberculosis Surveillance in Europe, 2014 (situation in 2012). 7 542 TB cases were reported in Poland in 2012. The incidence rate was 19.6 cases per 100 000, with large variability between voivodships from 10.6 to 30.2. The mean annual decrease of TB incidence in 2008-2012 was 2.4%. 6 665 cases had no history of previous treatment; 17.3 per 100 000. The number of all notified pulmonary tuberculosis cases was 7 018; 18.2 per 100 000. The proportion of extrapulmonary tuberculosis among all registered cases was 6.9% (524 cases). In 2012, 36 patients had fibrous-cavernous pulmonary tuberculosis (0.5% of all cases of pulmonary tuberculosis). TB was diagnosed in 95 children (1.3% of all cases, incidence 1.6). The incidence of tuberculosis increased progressively with age to 34.8 among patients 65 years old and older. The mean age of new TB cases was 53.1 years. The incidence among men (27.4) was more than two times higher than among women (12.2). The incidence rate in rural population was lower than in urban; 20.2 vs. 18.6. Bacteriologically confirmed pulmonary cases (4870) constituted 69,4% of all pulmonary TB cases. The number of smear positive pulmonary TB cases was 2 778 (39.6% of all pulmonary cases). In 2012 in the all group of TB patients in Poland there were 276 (3.7%) of homeless and 1 905 (25.3%) of unemployed. There were 48 foreigners registered among all cases of tuberculosis in Poland (0.6%) and 243 cases registered among prisoners (rate 288.0). There were 31 patients with MDR-TB (0.7% of 4659 cases with known anti-TB DST results). TB was initial AIDS indicative disease in 26 cases. There were 640 deaths due to tuberculosis in 2011 (1.7 TB deaths per 100 000). Mortality among males - 2.7 - was four times higher than among females - 0.7. CONCLUSIONS. In Poland in 2012 the incidence of tuberculosis was higher than the average in EU countries. The highest incidence rates occurred in older age groups. The incidence in men was more than 2 times higher than in women. The incidence of tuberculosis in children and the percentage of patients with drug-resistant tuberculosis are lower than average in EU and that is favorable for epidemiological situation of tuberculosis in our country.

Your Child with Tuberculosis: A Guide for Parents and Guardians = Su Nino con Tuberculosis: Un Manual para Los Padres.

ERIC Educational Resources Information Center

Amaro, Rodolfo

Presented in both Spanish and English versions, this booklet is a guide for parents and guardians of children who have tuberculosis (TB). The booklet is organized around specific questions covering topics such as the causes and spread of TB, demographics of TB sufferers, detecting and curing TB, TB treatment and medications, research on the…

Tuberculosis: a balanced diet of lipids and carbohydrates.

PubMed

Bhowruth, Veemal; Alderwick, Luke J; Brown, Alistair K; Bhatt, Apoorva; Besra, Gurdyal S

2008-08-01

In spite of effective antibiotics to treat TB (tuberculosis) since the early 1960s, we enter the new millennium with TB currently the leading cause of death from a single infectious agent, killing more than 3 million people worldwide each year. Thus an understanding of drug-resistance mechanisms, the immunobiology of cell wall components to elucidate host-pathogen interactions and the discovery of new drug targets are now required for the treatment of TB. Above the plasma membrane is a classical chemotype IV peptidoglycan to which is attached the macromolecular structure, mycolyl-arabinogalactan via a unique diglycosylphosphoryl bridge. The present review discusses the assembly of the mAGP (mycolyl-arabinogalactan-peptidoglycan) complex and the site of action of EMB (ethambutol), bringing forward a new era in TB research and focus for new drugs to combat multidrug-resistant TB.

Tuberculosis care: Olympics 1948 vs 2012.

PubMed

Karim, Kelvin

Tuberculosis (TB) is a multi-faceted illness associated with a long and fascinating history. Although much has changed in the diagnosis, treatment and prevention of TB over the past six decades, many of the challenges remain remarkably similar. In developing solutions to these challenges, key stakeholders and politicians would do well to learn from some of the more effective strategies from the pre-chemotherapy era. Despite working with insufficient resources, nurses have historically contributed significantly to the work of the multidisciplinary teams in delivering care to patients and families, as well as in implementing national TB control and prevention programmes. The current resurgence of TB in the UK makes it imperative to achieve consistently and appropriately-funded TB services across the country. Whether NHS commissioners and politicians will engage with nurses and others in the reconfigured NHS to achieve this, however, remains to be seen.

Mycobacterium tuberculosis Lipolytic Enzymes as Potential Biomarkers for the Diagnosis of Active Tuberculosis

PubMed Central

Brust, Belinda; Lecoufle, Mélanie; Tuaillon, Edouard; Dedieu, Luc; Canaan, Stéphane; Valverde, Viviane; Kremer, Laurent

2011-01-01

Background New diagnosis tests are urgently needed to address the global tuberculosis (TB) burden and to improve control programs especially in resource-limited settings. An effective in vitro diagnostic of TB based on serological methods would be regarded as an attractive progress because immunoassays are simple, rapid, inexpensive, and may offer the possibility to detect cases missed by standard sputum smear microscopy. However, currently available serology tests for TB are highly variable in sensitivity and specificity. Lipolytic enzymes have recently emerged as key factors in lipid metabolization during dormancy and/or exit of the non-replicating growth phase, a prerequisite step of TB reactivation. The focus of this study was to analyze and compare the potential of four Mycobacterium tuberculosis lipolytic enzymes (LipY, Rv0183, Rv1984c and Rv3452) as new markers in the serodiagnosis of active TB. Methods Recombinant proteins were produced and used in optimized ELISA aimed to detect IgG and IgM serum antibodies against the four lipolytic enzymes. The capacity of the assays to identify infection was evaluated in patients with either active TB or latent TB and compared with two distinct control groups consisting of BCG-vaccinated blood donors and hospitalized non-TB individuals. Results A robust humoral response was detected in patients with active TB whereas antibodies against lipolytic enzymes were infrequently detected in either uninfected groups or in subjects with latent infection. High specifity levels, ranging from 93.9% to 97.5%, were obtained for all four antigens with sensitivity values ranging from 73.4% to 90.5%, with Rv3452 displaying the highest performances. Patients with active TB usually exhibited strong IgG responses but poor IgM responses. Conclusion These results clearly indicate that the lipolytic enzymes tested are strongly immunogenic allowing to distinguish active from latent TB infections. They appear as potent biomarkers providing high sensitivity and specificity levels for the immunodiagnosis of active TB. PMID:21966416

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

PubMed

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

2018-02-01

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

Managing and monitoring tuberculosis using web-based tools in combination with traditional approaches

PubMed Central

Chapman, Ann LN; Darton, Thomas C; Foster, Rachel A

2013-01-01

Tuberculosis (TB) remains a global health emergency. Ongoing challenges include the coordination of national and international control programs, high levels of drug resistance in many parts of the world, and availability of accurate and rapid diagnostic tests. The increasing availability and reliability of Internet access throughout both affluent and resource-limited countries brings new opportunities to improve TB management and control through the integration of web-based technologies with traditional approaches. In this review, we explore current and potential future use of web-based tools in the areas of TB diagnosis, treatment, epidemiology, service monitoring, and teaching and training. PMID:24294008

Screening and Rapid Molecular Diagnosis of Tuberculosis in Prisons in Russia and Eastern Europe: A Cost-Effectiveness Analysis

PubMed Central

Winetsky, Daniel E.; Negoescu, Diana M.; DeMarchis, Emilia H.; Almukhamedova, Olga; Dooronbekova, Aizhan; Pulatov, Dilshod; Vezhnina, Natalia; Owens, Douglas K.; Goldhaber-Fiebert, Jeremy D.

2012-01-01

Background Prisons of the former Soviet Union (FSU) have high rates of multidrug-resistant tuberculosis (MDR-TB) and are thought to drive general population tuberculosis (TB) epidemics. Effective prison case detection, though employing more expensive technologies, may reduce long-term treatment costs and slow MDR-TB transmission. Methods and Findings We developed a dynamic transmission model of TB and drug resistance matched to the epidemiology and costs in FSU prisons. We evaluated eight strategies for TB screening and diagnosis involving, alone or in combination, self-referral, symptom screening, mass miniature radiography (MMR), and sputum PCR with probes for rifampin resistance (Xpert MTB/RIF). Over a 10-y horizon, we projected costs, quality-adjusted life years (QALYs), and TB and MDR-TB prevalence. Using sputum PCR as an annual primary screening tool among the general prison population most effectively reduced overall TB prevalence (from 2.78% to 2.31%) and MDR-TB prevalence (from 0.74% to 0.63%), and cost US$543/QALY for additional QALYs gained compared to MMR screening with sputum PCR reserved for rapid detection of MDR-TB. Adding sputum PCR to the currently used strategy of annual MMR screening was cost-saving over 10 y compared to MMR screening alone, but produced only a modest reduction in MDR-TB prevalence (from 0.74% to 0.69%) and had minimal effect on overall TB prevalence (from 2.78% to 2.74%). Strategies based on symptom screening alone were less effective and more expensive than MMR-based strategies. Study limitations included scarce primary TB time-series data in FSU prisons and uncertainties regarding screening test characteristics. Conclusions In prisons of the FSU, annual screening of the general inmate population with sputum PCR most effectively reduces TB and MDR-TB prevalence, doing so cost-effectively. If this approach is not feasible, the current strategy of annual MMR is both more effective and less expensive than strategies using self-referral or symptom screening alone, and the addition of sputum PCR for rapid MDR-TB detection may be cost-saving over time. Please see later in the article for the Editors' Summary PMID:23209384

A Mycobacterium tuberculosis cytochrome bd oxidase mutant is hypersensitive to bedaquiline.

PubMed

Berney, Michael; Hartman, Travis E; Jacobs, William R

2014-07-15

The new medicinal compound bedaquiline (BDQ) kills Mycobacterium tuberculosis by inhibiting F1Fo-ATP synthase. BDQ is bacteriostatic for 4 to 7 days and kills relatively slowly compared to other frontline tuberculosis (TB) drugs. Here we show that killing with BDQ can be improved significantly by inhibiting cytochrome bd oxidase, a non-proton-pumping terminal oxidase. BDQ was instantly bactericidal against a cytochrome bd oxidase null mutant of M. tuberculosis, and the rate of killing was increased by more than 50%. We propose that this exclusively bacterial enzyme should be a high-priority target for new drug discovery. Importance: A major drawback of current TB chemotherapy is its long duration. New drug regimens with rapid killing kinetics are desperately needed. Our study demonstrates that inhibition of a nonessential bacterial enzyme greatly improves the efficacy of the latest TB drug bedaquiline and emphasizes that screening for compounds with synergistic killing mechanisms is a promising strategy. Copyright © 2014 Berney et al.

Current ante-mortem techniques for diagnosis of bovine tuberculosis.

PubMed

Bezos, Javier; Casal, Carmen; Romero, Beatriz; Schroeder, Bjoern; Hardegger, Roland; Raeber, Alex J; López, Lissette; Rueda, Paloma; Domínguez, Lucas

2014-10-01

Bovine tuberculosis (TB), mainly caused by Mycobacterium bovis, is a zoonotic disease with implications for Public Health and having an economic impact due to decreased production and limitations to the trade. Bovine TB is subjected to official eradication campaigns mainly based on a test and slaughter policy using diagnostic assays based on the cell-mediated immune response as the intradermal tuberculin test and the gamma-interferon (IFN-γ) assay. Moreover, several diagnostic assays based on the detection of specific antibodies (Abs) have been developed in the last few years with the aim of complementing the current diagnostic techniques in the near future. This review provides an overview of the current ante-mortem diagnostic tools for diagnosis of bovine TB regarding historical background, methodologies and sensitivity (Se) and specificity (Sp) obtained in previous studies under different epidemiological situations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Immune Response to Mycobacterial Infection: Lessons from Flow Cytometry

PubMed Central

Rovina, Nikoletta; Panagiotou, Marios; Koulouris, Nikolaos G.

2013-01-01

Detecting and treating active and latent tuberculosis are pivotal elements for effective infection control; yet, due to their significant inherent limitations, the diagnostic means for these two stages of tuberculosis (TB) to date remain suboptimal. This paper reviews the current diagnostic tools for mycobacterial infection and focuses on the application of flow cytometry as a promising method for rapid and reliable diagnosis of mycobacterial infection as well as discrimination between active and latent TB: it summarizes diagnostic biomarkers distinguishing the two states of infection and also features of the distinct immune response against Mycobacterium tuberculosis (Mtb) at certain stages of infection as revealed by flow cytometry to date. PMID:24376464

Immune response to mycobacterial infection: lessons from flow cytometry.

PubMed

Rovina, Nikoletta; Panagiotou, Marios; Pontikis, Konstantinos; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Koutsoukou, Antonia

2013-01-01

Detecting and treating active and latent tuberculosis are pivotal elements for effective infection control; yet, due to their significant inherent limitations, the diagnostic means for these two stages of tuberculosis (TB) to date remain suboptimal. This paper reviews the current diagnostic tools for mycobacterial infection and focuses on the application of flow cytometry as a promising method for rapid and reliable diagnosis of mycobacterial infection as well as discrimination between active and latent TB: it summarizes diagnostic biomarkers distinguishing the two states of infection and also features of the distinct immune response against Mycobacterium tuberculosis (Mtb) at certain stages of infection as revealed by flow cytometry to date.

Infection control, genetic assessment of drug resistance and drug susceptibility testing in the current management of multidrug/extensively-resistant tuberculosis (M/XDR-TB) in Europe: A tuberculosis network European Trialsgroup (TBNET) study.

PubMed

Bothamley, Graham H; Lange, Christoph

2017-11-01

Europe has the highest documented caseload and greatest increase in multidrug and extensively drug-resistant tuberculosis (M/XDR-TB) of all World Health Organization (WHO) regions. This survey examines how recommendations for M/XDR-TB management are being implemented. TBNET is a pan-European clinical research collaboration for tuberculosis. An email survey of TBNET members collected data in relation to infection control, access to molecular tests and basic microbiology with drug sensitivity testing. 68/105 responses gave valid information and were from countries within the WHO European Region. Inpatient beds matched demand, but single rooms with negative pressure were only available in low incidence countries; ultraviolet decontamination was used in 5 sites, all with >10 patients with M/XDR-TB per year. Molecular tests for mutations associated with rifampicin resistance were widely available (88%), even in lower income and especially in high incidence countries. Molecular tests for other first line and second line drugs were less accessible (76 and 52% respectively). A third of physicians considered that drug susceptibility results were delayed by > 2 months. Infection control for inpatients with M/XDR-TB remains a problem in high incidence countries. Rifampicin resistance is readily detected, but tests to plan regimens tailored to the drug susceptibilities of the strain of Mycobacterium tuberculosis are significantly delayed, allowing for further drug resistance to develop. Copyright © 2017 Elsevier Ltd. All rights reserved.

In vitro cytotoxicity of CD8+ T cells in multi-drug-resistant tuberculosis. A preliminary report.

PubMed

Sada-Ovalle, Isabel; Torre-Bouscoulet, Luis; Valdez-Vázquez, Rafael; Lascurain, Ricardo

2009-05-01

Specific CD8+ T-cell cytotoxicity has been recognized as being involved in the elimination of drug-susceptible tuberculosis (DS-TB). Given that there is currently no information on the cytotoxic effector functions of CD8+ T cells in multi-drug-resistant tuberculosis (MDR-TB), our objective was to analyse the cytotoxic activity, both basal and stimulated, of CD8+ T cells from MDR-TB patients and compare it with that of DS-TB patients, as well as purified protein derivative (PPD)+ and PPD- subjects. Cytotoxic activity of CD8+ T cells from MDR-TB patients, DS-TB patients, PPD+ and PPD- subjects was measured by a colorimetric assay, using H37Rv culture filtrate protein as the antigenic stimulus. Twenty-eight subjects were studied (7 MDR-TB patients, 7 DS-TB patients, 7 PPD+ subjects and 7 PPD- subjects). In the presence of the antigenic stimulus, the cytotoxic activity of CD8+ T cells from MDR-TB patients (% lysis) increased from 6.7% to 59.6% (P < 0.001). In DS-TB patients lysis increased from 3.2% to 22.5% (P < 0.001), whereas in PPD+ subjects it increased from 2.7% to 12.0% (P < 0.001) and in PPD- subjects from 1.3% to 3.2% (P < 0.001). Basal cytotoxic activity was significantly higher for MDR-TB patients than PPD+ and PPD- subjects (P = 0.003), but not compared with that for DS-TB patients (P = 0.05). Stimulated cytotoxic activity was highest for MDR-TB patients. CD8+ T cells from MDR-TB patients showed an exaggerated cytotoxic activity after antigenic stimulation. Further studies are required to elucidate the role of this response in the immunopathogenesis of MDR-TB.

Global Tuberculosis Report 2016

MedlinePlus

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

Estimating tuberculosis incidence from primary survey data: a mathematical modeling approach.

PubMed

Pandey, S; Chadha, V K; Laxminarayan, R; Arinaminpathy, N

2017-04-01

There is an urgent need for improved estimations of the burden of tuberculosis (TB). To develop a new quantitative method based on mathematical modelling, and to demonstrate its application to TB in India. We developed a simple model of TB transmission dynamics to estimate the annual incidence of TB disease from the annual risk of tuberculous infection and prevalence of smear-positive TB. We first compared model estimates for annual infections per smear-positive TB case using previous empirical estimates from China, Korea and the Philippines. We then applied the model to estimate TB incidence in India, stratified by urban and rural settings. Study model estimates show agreement with previous empirical estimates. Applied to India, the model suggests an annual incidence of smear-positive TB of 89.8 per 100 000 population (95%CI 56.8-156.3). Results show differences in urban and rural TB: while an urban TB case infects more individuals per year, a rural TB case remains infectious for appreciably longer, suggesting the need for interventions tailored to these different settings. Simple models of TB transmission, in conjunction with necessary data, can offer approaches to burden estimation that complement those currently being used.

The rural-to-urban migrant population in China: gloomy prospects for tuberculosis control.

PubMed

Tobe, Ruoyan Gai; Xu, Lingzhong; Song, Peipei; Huang, Yong

2011-12-01

The migrant population is a population with a high risk of tuberculosis (TB) infection and transmission. Globally, migration is likely to have a significant impact on TB epidemiology, particularly in countries that receive substantial numbers of migrants from countries with a high infection burden. China, a country with the world's second highest TB burden, faces a considerable increase in the number of rural-to-urban migrants. This population has a significant impact on urban TB epidemics and is specifically targeted by national guidelines for TB control. TB control among the migrant population has had relatively poor outcomes. Barriers to detection and treatment have both financial and non-financial aspects, such as the "migratory" nature of the migrant population, their marginalized working and living environment, poor financial status, little awareness of TB, inadequate referral to TB dispensaries, and potential social stigma in the workplace. Currently, the free TB treatment policy has limited ability to relieve the financial burden on most migrant TB patients as would allow optimal outcomes of TB detection and treatment. Universal health insurance coverage and fostering of personnel in community-based primary health care for the rural-to- urban migrant population represent two pillars of successful TB control.

Feasibility study of strengthening the public-private partnership for tuberculosis case detection in Bandung City, Indonesia.

PubMed

Lestari, Bony Wiem; Arisanti, Nita; Siregar, Adiatma Y M; Sihaloho, Estro Dariatno; Budiman, Gelar; Hill, Philip C; Alisjahbana, Bachti; McAllister, Susan

2017-08-14

Private practitioner's (PPs) collaboration for detection, diagnosis and treatment of tuberculosis (TB) is recommended by the World Health Organization and encouraged by the Indonesian National TB control programme. TB case management by PPs, however, are mostly not in line with current guidelines. Therefore, we developed an intervention package for PPs comprising of TB training, implementation of a mobile phone application for notification of TB cases and a 6-month regular follow-up with PPs. This study aimed to evaluate the feasibility of the intervention package to increase TB case detection and notification rates among PPs in five community health centre areas in Bandung City, Indonesia. A total of 87 PPs were registered within the study area of whom 17 attended the training and 12 had the mobile phone application successfully installed. The remaining five PPs had phones that did not support the application. During the follow-up period, five PPs registered patients with TB symptoms and cases into the application. A total of 36 patients with TB symptoms were identified and 17 were confirmed TB positive.

Sensitivity, completeness and agreement of the tuberculosis electronic system in Ho Chi Minh City, Viet Nam.

PubMed

Thai, L H; Nhat, L M; Shah, N; Lyss, S; Ackers, M

2017-12-21

Setting: Since 2011, tuberculosis (TB) clinics in Ho Chi Minh City (HCMC), Viet Nam, have been entering data from a paper-based TB treatment register into an electronic database known as VITIMES (Viet Nam TB Information Management Electronic System), which is currently used in parallel with the paper system. Objective: To evaluate the sensitivity, completeness and agreement of data in VITIMES with that of paper-based registers among TB patients co-infected with the human immunodeficiency virus (HIV) being treated for TB in HCMC. Design: This was a retrospective data review of all TB-HIV patients receiving anti-tuberculosis treatment in each of the 24 district TB clinics in HCMC in 2013. Data were abstracted from the paper-based TB treatment registers at district level and extracted electronically at the provincial level. Records were matched based on name, age and address. The sensitivity, completeness and agreement of the electronic data were compared with data from the paper system. Results: The findings showed that the electronic system had high sensitivity (99.2%), high completeness (87-99%) and high agreement (κ 0.78-0.97) for all variables. Conclusion: The results of this study suggest that data are being correctly entered into VITIMES and that patient data can be directly entered into VITIMES instead of having a parallel, paper-based system.

Sensitivity, completeness and agreement of the tuberculosis electronic system in Ho Chi Minh City, Viet Nam

PubMed Central

Nhat, L. M.; Shah, N.; Lyss, S.; Ackers, M.

2017-01-01

Setting: Since 2011, tuberculosis (TB) clinics in Ho Chi Minh City (HCMC), Viet Nam, have been entering data from a paper-based TB treatment register into an electronic database known as VITIMES (Viet Nam TB Information Management Electronic System), which is currently used in parallel with the paper system. Objective: To evaluate the sensitivity, completeness and agreement of data in VITIMES with that of paper-based registers among TB patients co-infected with the human immunodeficiency virus (HIV) being treated for TB in HCMC. Design: This was a retrospective data review of all TB-HIV patients receiving anti-tuberculosis treatment in each of the 24 district TB clinics in HCMC in 2013. Data were abstracted from the paper-based TB treatment registers at district level and extracted electronically at the provincial level. Records were matched based on name, age and address. The sensitivity, completeness and agreement of the electronic data were compared with data from the paper system. Results: The findings showed that the electronic system had high sensitivity (99.2%), high completeness (87–99%) and high agreement (κ 0.78–0.97) for all variables. Conclusion: The results of this study suggest that data are being correctly entered into VITIMES and that patient data can be directly entered into VITIMES instead of having a parallel, paper-based system. PMID:29584795

Increased Tuberculosis Patient Mortality Associated with Mycobacterium tuberculosis Mutations Conferring Resistance to Second-Line Antituberculous Drugs

PubMed Central

Seifert, Marva; Garfein, Richard S.; Rodwell, Timothy C.

2017-01-01

ABSTRACT Rapid molecular diagnostics have great potential to limit the spread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) (M/XDR-TB). These technologies detect mutations in the Mycobacterium tuberculosis genome that confer phenotypic drug resistance. However, there have been few data published regarding the relationships between the detected M. tuberculosis resistance mutations and M/XDR-TB treatment outcomes, limiting our current ability to exploit the full potential of molecular diagnostics. We analyzed clinical, microbiological, and sequencing data for 451 patients and their clinical isolates collected in a multinational, observational cohort study to determine if there was an association between M. tuberculosis resistance mutations and patient mortality. The presence of an rrs 1401G mutation was associated with significantly higher odds of patient mortality (adjusted odds ratio [OR] = 5.72; 95% confidence interval [CI], 1.65 to 19.84]) after adjusting for relevant patient clinical characteristics and all other resistance mutations. Further analysis of mutations, categorized by the associated resistance level, indicated that the detection of mutations associated with high-level fluoroquinolone (OR, 3.99 [95% CI, 1.10 to 14.40]) and kanamycin (OR, 5.47 [95% CI, 1.64 to 18.24]) resistance was also significantly associated with higher odds of patient mortality, even after accounting for clinical site, patient age, reported smoking history, body mass index (BMI), diabetes, HIV, and all other resistance mutations. Specific gyrA and rrs resistance mutations, associated with high-level resistance, were associated with patient mortality as identified in clinical M. tuberculosis isolates from a diverse M/XDR-TB patient population at three high-burden clinical sites. These results have important implications for the interpretation of molecular diagnostics, including identifying patients at increased risk for mortality during treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT02170441.) PMID:28404672

Increased Tuberculosis Patient Mortality Associated with Mycobacterium tuberculosis Mutations Conferring Resistance to Second-Line Antituberculous Drugs.

PubMed

Georghiou, Sophia B; Seifert, Marva; Catanzaro, Donald G; Garfein, Richard S; Rodwell, Timothy C

2017-06-01

Rapid molecular diagnostics have great potential to limit the spread of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) (M/XDR-TB). These technologies detect mutations in the Mycobacterium tuberculosis genome that confer phenotypic drug resistance. However, there have been few data published regarding the relationships between the detected M. tuberculosis resistance mutations and M/XDR-TB treatment outcomes, limiting our current ability to exploit the full potential of molecular diagnostics. We analyzed clinical, microbiological, and sequencing data for 451 patients and their clinical isolates collected in a multinational, observational cohort study to determine if there was an association between M. tuberculosis resistance mutations and patient mortality. The presence of an rrs 1401G mutation was associated with significantly higher odds of patient mortality (adjusted odds ratio [OR] = 5.72; 95% confidence interval [CI], 1.65 to 19.84]) after adjusting for relevant patient clinical characteristics and all other resistance mutations. Further analysis of mutations, categorized by the associated resistance level, indicated that the detection of mutations associated with high-level fluoroquinolone (OR, 3.99 [95% CI, 1.10 to 14.40]) and kanamycin (OR, 5.47 [95% CI, 1.64 to 18.24]) resistance was also significantly associated with higher odds of patient mortality, even after accounting for clinical site, patient age, reported smoking history, body mass index (BMI), diabetes, HIV, and all other resistance mutations. Specific gyrA and rrs resistance mutations, associated with high-level resistance, were associated with patient mortality as identified in clinical M. tuberculosis isolates from a diverse M/XDR-TB patient population at three high-burden clinical sites. These results have important implications for the interpretation of molecular diagnostics, including identifying patients at increased risk for mortality during treatment. (This study has been registered at ClinicalTrials.gov under registration no. NCT02170441.). Copyright © 2017 American Society for Microbiology.

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

PubMed

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

2011-12-01

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

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

PubMed Central

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

2006-01-01

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

Drug resistant Mycobacterium tuberculosis in Mexico.

PubMed

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

2009-04-30

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

Detection of anti-HspX antibodies and HspX protein in patient sera for the identification of recent latent infection by Mycobacterium tuberculosis

PubMed Central

García-Jacobo, Paola; Rivera-Morales, Lydia G.; Barber, James; Karls, Russell; Haas, Debra; Helms, Shelly; Gupta, Tuhina; Blumberg, Henry; Tapia, Jane; Luna-Cruz, Itza; Rendon, Adrián; Vargas-Villarreal, Javier; Vera-Cabrera, Lucio; Rodríguez-Padilla, Cristina

2017-01-01

Mycobacterium tuberculosis is a pathogen causing tuberculosis (TB) a spectrum of disease including acute and asymptomatic latent stages. Identifying and treating latently-infected patients constitutes one of the most important impediments to TB control efforts. Those individuals can remain undiagnosed for decades serving as potential reservoirs for disease reactivation. Tests for the accurate diagnosis of latent infection currently are unavailable. HspX protein (α-crystallin), encoded by Rv2031c gene, is produced in vitro by M. tuberculosis during stationary growth phase and hypoxic or acidic culture conditions. In this study, using standard, and Luminex xMAP® bead capture ELISA, respectively, we report on detection of anti-HspX IgG and IgM antibodies and HspX protein in sera from acute and latent TB patients. For the antibody screen, levels of IgG and IgM antibodies were similar between non-infected and active TB patients; however, individuals classified into the group with latent TB showed higher values of anti-HspX IgM (p = 0.003) compared to active TB patients. Using the bead capture antigen detection assay, HspX protein was detected in sera from 56.5% of putative latent cases (p< 0.050) compared to the background median with an average of 9,900 pg/ml and a range of 1,000 to 36,000 pg/ml. Thus, presence of anti-HspX IgM antibodies and HspX protein in sera may be markers of latent TB. PMID:28813434

Plants in our combating strategies against Mycobacterium tuberculosis: progress made and obstacles met.

PubMed

Gupta, Vivek Kumar; Kumar, M Madhan; Bisht, Deepa; Kaushik, Anupam

2017-12-01

Traditionally used plants for treating chest-related problems/tuberculosis (TB) have not been evaluated in detail and hence a thorough study is needed in this regard. This knowledge may find application in developing new anti-TB drugs. This article elaborates on studying the activity of medicinal plants against different forms of Mycobacterium tuberculosis (Mtb) using different model strains, in vitro and ex vivo assays for studying the tuberculocidal activity and discusses the results from different studies on the activity against different forms of Mtb and human immunodeficiency virus-tuberculosis (HIV-TB) co-infection. Scientific databases such as PubMed, Elsevier, Scopus, Google scholar, were used to retrieve the information from 86 research articles (published from 1994 to 2016) related to the topic of this review. Twenty-three plant species have been reported to possess active molecules against multi-drug resistant (MDR) isolates of Mtb. Seven plants were found to be active against intracellular Mtb and six against dormant bacilli. Seven plants were synergistically effective when combined with anti-TB drugs. Six studies suggest that the beneficial effects of plant extracts are due to their wide array of immuno-modulatory effects manifested by the higher expression of cytokines. Some studies have also shown the dual activity (anti-HIV and anti-TB) of plants. We emphasize on identifying plants based on traditional uses and testing their extracts/phytomolecules against MDR strains, intracellular Mtb as well as against dormant Mtb. This will help in future to shorten the current therapeutic regimens for TB and also for treating HIV-TB co-infection.

Mycobacterium tuberculosis infection in cattle from the Eastern Cape Province of South Africa.

PubMed

Hlokwe, Tiny Motlatso; Said, Halima; Gcebe, Nomakorinte

2017-10-10

Mycobacterium tuberculosis is the main causative agent of tuberculosis (TB) in human and Mycobacterium bovis commonly causes tuberculosis in animals. Transmission of tuberculosis caused by both pathogens can occur from human to animals and vice versa. In the current study, M. tuberculosis, as confirmed by polymerase chain reaction (PCR) using primers targeting 3 regions of difference (RD4, RD9 and RD12) on the genomes, was isolated from cattle originating from two epidemiologically unrelated farms in the Eastern Cape (E.C) Province of South Africa. Although the isolates were genotyped with variable number of tandem repeat (VNTR) typing, no detailed epidemiological investigation was carried out on the respective farms to unequivocally confirm or link humans as sources of TB transmission to cattle, a move that would have embraced the 'One Health' concept. In addition, strain comparison with human M. tuberculosis in the database from the E.C Province and other provinces in the country did not reveal any match. This is the first report of cases of M. tuberculosis infection in cattle in South Africa. The VNTR profiles of the M. tuberculosis strains identified in the current study will form the basis for creating M. tuberculosis VNTR database for animals including cattle for future epidemiological studies. Our findings however, call for urgent reinforcement of collaborative efforts between the veterinary and the public health services of the country.

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

PubMed

Yang, Chongguang; Gao, Qian

2018-02-01

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

Comparing an Interferon Gamma Release Assay with the Tuberculin Skin Test During Pregnancy: Implications for Tuberculosis Screening During Prenatal Care.

PubMed

Molina, Rose; Venkatesh, Kartik; Schantz-Dunn, Julianna; Meadows, Audra; Nour, Nawal; Diouf, Khady

2016-06-01

Background Currently there are no guidelines regarding optimal screening for latent tuberculosis infection during pregnancy. Objective This study measures completion rates and the concordance between the TSPOT.TB, a commercially available interferon gamma release assay (IGRA), and the traditional tuberculin skin test (TST) in a predominantly urban minority obstetrics practice. Design This is an observational cohort study of 141 pregnant women enrolled from an obstetrics practice with a large immigrant population. Women with a history of a positive TST result were excluded. Demographic and clinical risk factors for tuberculosis were assessed. Enrolled women underwent a T-SPOT.TB test and placement of TST, and returned in 48-72 h for TST interpretation. We calculated the completion rate and frequency of a positive result for each test, as well as the concordance between the T-SPOT.TB and TST. Results Among the 141 women enrolled, 75 % were either Latina or African-American, 44 % were born in a country with a high TB prevalence, and 52 % had received the Bacillus Calmette-Guerin vaccine. Seven women (5 %) had a positive screening test, a total of 3 positive T-SPOT.TB results and 6 positive TST results, and all were from countries with a high TB prevalence. The concordance of the two tests was 96.3 %. The completion rate for the T-SPOT.TB was 98 %, while the completion rate for the TST was 63 %. The IGRA test had a markedly higher completion rate in addition to maintaining high concordance with the two-step TST in this population of pregnant women with a high prevalence of prior TB exposure. Targeted screening of women from countries with a high prevalence of tuberculosis may be warranted during prenatal care.

The Global Fund in China: Multidrug-resistant tuberculosis nationwide programmatic scale-up and challenges to transition to full country ownership.

PubMed

Wang, Lixia; Li, Renzhong; Xu, Caihong; Zhang, Hui; Ruan, Yunzhou; Chen, Mingting; Wang, Dongmei; Dirlikov, Emilio; Du, Xin; Zhao, Jin; Zhao, Yanlin; Wang, ShengFen; Liu, Yuhong; Li, Liang; Falzon, Dennis; Sun, Yanni; Wang, Yu; Schwartländer, Bernhard; Scano, Fabio

2017-01-01

China has the world's second largest burden of multidrug-resistant tuberculosis (MDR-TB; resistance to at least isoniazid and rifampicin), with an estimated 57,000 cases (range, 48,000-67,000) among notified pulmonary TB patients in 2015. During October 1, 2006-June 30, 2014, China expanded MDR-TB care through a partnership with the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund). We analyzed data on site expansion, patient enrolment, treatment outcomes, cost per patient, and overall programme expenditure. China expanded MDR-TB diagnostic and treatment services from 2 prefectures in 2006 to 92 prefectures, covering 921 of the country's 3,000 counties by June 2014. A total of 130,910 patients were tested for MDR-TB, resulting in 13,744 laboratory-confirmed cases, and 9,183 patients started on MDR-TB treatment. Treatment success was 48.4% (2011 cohort). The partnership between China and the Global Fund resulted in enormous gains. However, changes to health system TB delivery and financing coincided with the completion of the Global Fund Programme, and could potentially impact TB and MDR-TB control. Transition to full country financial ownership is proving difficult, with a decline in enrollment and insufficient financial coverage. Given needed improvement to the current treatment success rates, these factors jeopardise investments made for MDR-TB control and care. China now has a chance to cement its status in TB control by strengthening future financing and ensuring ongoing commitment to quality service delivery.

The Global Fund in China: Multidrug-resistant tuberculosis nationwide programmatic scale-up and challenges to transition to full country ownership

PubMed Central

Wang, Dongmei; Dirlikov, Emilio; Du, Xin; Zhao, Jin; Wang, ShengFen; Falzon, Dennis; Sun, Yanni; Wang, Yu; Schwartländer, Bernhard; Scano, Fabio

2017-01-01

China has the world’s second largest burden of multidrug-resistant tuberculosis (MDR-TB; resistance to at least isoniazid and rifampicin), with an estimated 57,000 cases (range, 48,000–67,000) among notified pulmonary TB patients in 2015. During October 1, 2006–June 30, 2014, China expanded MDR-TB care through a partnership with the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund). We analyzed data on site expansion, patient enrolment, treatment outcomes, cost per patient, and overall programme expenditure. China expanded MDR-TB diagnostic and treatment services from 2 prefectures in 2006 to 92 prefectures, covering 921 of the country’s 3,000 counties by June 2014. A total of 130,910 patients were tested for MDR-TB, resulting in 13,744 laboratory-confirmed cases, and 9,183 patients started on MDR-TB treatment. Treatment success was 48.4% (2011 cohort). The partnership between China and the Global Fund resulted in enormous gains. However, changes to health system TB delivery and financing coincided with the completion of the Global Fund Programme, and could potentially impact TB and MDR-TB control. Transition to full country financial ownership is proving difficult, with a decline in enrollment and insufficient financial coverage. Given needed improvement to the current treatment success rates, these factors jeopardise investments made for MDR-TB control and care. China now has a chance to cement its status in TB control by strengthening future financing and ensuring ongoing commitment to quality service delivery. PMID:28628669

Evaluating the impact of health resource reconstruction on improving spatial accessibility of tuberculosis care.

PubMed

Izumi, K; Kawatsu, L; Ohkado, A; Uchimura, K; Kato, S

2016-11-01

In Japan, a decline in tuberculosis (TB) notification rates and shortening of duration of hospitalisation have led to a drastic decrease in the number of hospital beds for TB patients (TB beds), causing severe undersupply in certain regions. To assess the current status of spatial access to TB beds in Japan and evaluate the potential impact of health resource reconstruction in mitigating undersupply of TB beds. A cross-sectional study was conducted whereby a two-step floating catchment area (2SFCA) method was used to calculate an 'accessibility score' to evaluate spatial accessibility of TB beds in the regions classified by four levels of urbanisation. The impact of introducing 'potential TB beds' was assessed via the changes in the proportion of undersupplied regions and TB patients notified from undersupplied regions. Undersupplied regions were characterised by 'very low', 'low' and 'moderate' level of urbanisation. By introducing 'potential TB beds', the proportion of both undersupplied regions and TB patients could be significantly reduced, especially in less urbanised regions. Our results may be used to guide future decision-making over resource allocation of TB care in Japan. The 2SFCA method may be applied to other countries using appropriate demand and supply variables.

Pulmonary Tuberculosis Is Associated With Biomass Fuel Use Among Rural Women in Pakistan: An Age- and Residence-Matched Case-Control Study.

PubMed

Rabbani, Unaib; Sahito, Ambreen; Nafees, Asaad Ahmed; Kazi, Ambreen; Fatmi, Zafar

2017-04-01

Facility-based, age- and residential area-matched case-control study was conducted in Sindh, Pakistan to determine association between biomass fuel use for cooking and pulmonary tuberculosis (TB). Cases were women with pulmonary TB, and controls were those suffering from other diseases. Current users of biomass fuel were at higher risk of pulmonary TB (adjusted matched odds ratio [mOR] = 3.0; 95% CI = 1.1-4.9) compared with nonusers. In comparison with former biomass users (women not using biomass for >10 years), recent biomass users (women who switched from biomass to nonbiomass ≤10 years ago), and current (lifetime) users were at a higher risk in a dose-response manner (adjusted mOR = 2.8, 95% CI = 0.9-8.2 and adjusted mOR = 3.9, 95% CI = 1.4-10.7, respectively). Population attributable fraction for TB related to biomass fuel use was 40.6% (95% CI = 35.5%-45.7%). This study strengthens the evidence that biomass fuel use for cooking is associated with pulmonary TB and risk increases with duration of exposure.

Drug discovery in tuberculosis. New drug targets and antimycobacterial agents.

PubMed

Campaniço, André; Moreira, Rui; Lopes, Francisca

2018-04-25

Tuberculosis (TB) remains a major health problem worldwide. The infectious agent, Mycobacterium tuberculosis, has a unique ability to survive within the host, alternating between active and latent disease states, and escaping the immune system defences. The extended duration of anti-TB regimens and the increasing prevalence of multidrug- (MDR) and extensively drug-resistant (XDR) M. tuberculosis strains have created an urgent need for new antibiotics active against drug-resistant organisms and that can shorten standard therapy. However, despite success in identifying active compounds through phenotypic screens, the conversion of hits into novel chemical series and ultimately into clinical candidates is hampered by the poor efficacy in eliminating M. tuberculosis within different host compartments, including macrophages, as well as a lack of knowledge about the specific target(s) inhibited and/or upregulated. The current status of anti-TB lead generation has much improved over the last decade, as exemplified by the recent approval of bedaquiline and delamanid to treat MDR-TB and XDR-TB. This review provides a critical analysis on the strategies used to progress hit compounds into viable lead candidates, and how emerging targets may play a role in TB drug discovery in the near future. Four new relevant targets are addressed: the enoyl-acyl carrier protein reductase, InhA; the transmembrane transport protein large, MmpL3; the decaprenylphospho-beta-d-ribofuranose 2-oxidase, DprE1; and the ubiquinol-cytochrome C reductase, QcrB. Validated hit compounds for each target are presented and explored, and the medicinal chemistry strategies to expand SAR around novel chemotypes analyzed. In addition, very recent emerging targets are also discussed. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis

PubMed Central

Tran, Anh T.; Watson, Emma E.; Pujari, Venugopal; Conroy, Trent; Dowman, Luke J.; Giltrap, Andrew M.; Pang, Angel; Wong, Weng Ruh; Linington, Roger G.; Mahapatra, Sebabrata; Saunders, Jessica; Charman, Susan A.; West, Nicholas P.; Bugg, Timothy D. H.; Tod, Julie; Dowson, Christopher G.; Roper, David I.; Crick, Dean C.; Britton, Warwick J.; Payne, Richard J.

2017-01-01

Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues are nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis. PMID:28248311

Sansanmycin natural product analogues as potent and selective anti-mycobacterials that inhibit lipid I biosynthesis

NASA Astrophysics Data System (ADS)

Tran, Anh T.; Watson, Emma E.; Pujari, Venugopal; Conroy, Trent; Dowman, Luke J.; Giltrap, Andrew M.; Pang, Angel; Wong, Weng Ruh; Linington, Roger G.; Mahapatra, Sebabrata; Saunders, Jessica; Charman, Susan A.; West, Nicholas P.; Bugg, Timothy D. H.; Tod, Julie; Dowson, Christopher G.; Roper, David I.; Crick, Dean C.; Britton, Warwick J.; Payne, Richard J.

2017-03-01

Tuberculosis (TB) is responsible for enormous global morbidity and mortality, and current treatment regimens rely on the use of drugs that have been in use for more than 40 years. Owing to widespread resistance to these therapies, new drugs are desperately needed to control the TB disease burden. Herein, we describe the rapid synthesis of analogues of the sansanmycin uridylpeptide natural products that represent promising new TB drug leads. The compounds exhibit potent and selective inhibition of Mycobacterium tuberculosis, the etiological agent of TB, both in vitro and intracellularly. The natural product analogues are nanomolar inhibitors of Mtb phospho-MurNAc-pentapeptide translocase, the enzyme responsible for the synthesis of lipid I in mycobacteria. This work lays the foundation for the development of uridylpeptide natural product analogues as new TB drug candidates that operate through the inhibition of peptidoglycan biosynthesis.

Frequent Detection of Latent Tuberculosis Infection among Aged Underground Hard Coal Miners in the Absence of Recent Tuberculosis Exposure

PubMed Central

Ringshausen, Felix C.; Nienhaus, Albert; Schablon, Anja; Torres Costa, José; Knoop, Heiko; Hoffmeyer, Frank; Bünger, Jürgen; Merget, Rolf; Harth, Volker; Schultze-Werninghaus, Gerhard; Rohde, Gernot

2013-01-01

Background Miners are at particular risk for tuberculosis (TB) infection due to exposure to silica dust and silicosis. The objectives of the present observational cohort study were to determine the prevalence of latent TB infection (LTBI) among aged German underground hard coal miners with silicosis or chronic obstructive pulmonary disease (COPD) using two commercial interferon-gamma release assays (IGRAs) and to compare their performance with respect to predictors of test positivity. Methods Between October 2008 and June 2010, miners were consecutively recruited when routinely attending pneumoconiosis clinics for an expert opinion. Both IGRAs, the QuantiFERON®-TB Gold In-Tube (QFT) and the T-SPOT®.TB (T-SPOT), were performed at baseline. A standardized clinical interview was conducted at baseline and at follow-up. The cohort was prospectively followed regarding the development of active TB for at least two years after inclusion of the last study subject. Independent predictors of IGRA positivity were calculated using logistic regression. Results Among 118 subjects (mean age 75 years), none reported recent exposure to TB. Overall, the QFT and the T-SPOT yielded similarly high rates of positive results (QFT: 46.6%; 95% confidence interval 37.6–55.6%; T-SPOT: 61.0%; 95% confidence interval 52.2–69.8%). Positive results were independently predicted by age ≥80 years and foreign country of birth for both IGRAs. In addition, radiological evidence of prior healed TB increased the chance of a positive QFT result fivefold. While 28 subjects were lost to follow-up, no cases of active TB occurred among 90 subjects during an average follow-up of >2 years. Conclusions Considering the high prevalence of LTBI, the absence of recent TB exposure, and the currently low TB incidence in Germany, our study provides evidence for the persistence of specific interferon-gamma responses even decades after putative exposure. However, the clinical value of current IGRAs among our study population, although probably limited, remains uncertain. PMID:24312620

Potential and development of inhaled RNAi therapeutics for the treatment of pulmonary tuberculosis.

PubMed

Man, Dede K W; Chow, Michael Y T; Casettari, Luca; Gonzalez-Juarrero, Mercedes; Lam, Jenny K W

2016-07-01

Tuberculosis (TB), caused by the infection of Mycobacterium tuberculosis (Mtb), continues to pose a serious threat to public health, and the situation is worsening with the rapid emergence of multidrug resistant (MDR) TB. Current TB regimens require long duration of treatment, and their toxic side effects often lead to poor adherence and low success rates. There is an urgent need for shorter and more effective treatment for TB. In recent years, RNA interference (RNAi) has become a powerful tool for studying gene function by silencing the target genes. The survival of Mtb in host macrophages involves the attenuation of the antimicrobial responses mounted by the host cells. RNAi technology has helped to improve our understanding of how these bacilli interferes with the bactericidal effect and host immunity during TB infection. It has been suggested that the host-directed intervention by modulation of host pathways can be employed as a novel and effective therapy against TB. This therapeutic approach could be achieved by RNAi, which holds enormous potential beyond a laboratory to the clinic. RNAi therapy targeting TB is being investigated for enhancing host antibacterial capacity or improving drug efficacy on drug resistance strains while minimizing the associated adverse effects. One of the key challenges of RNAi therapeutics arises from the delivery of the RNAi molecules into the target cells, and inhalation could serve as a direct administration route for the treatment of pulmonary TB in a non-invasive manner. However, there are still major obstacles that need to be overcome. This review focuses on the RNAi candidates that are currently explored for the treatment of TB and discusses the major barriers of pulmonary RNAi delivery. From this, we hope to stimulate further studies of local RNAi therapeutics for pulmonary TB treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Tuberculosis in a South African prison – a transmission modelling analysis

PubMed Central

Johnstone-Robertson, Simon; Lawn, Stephen D; Welte, Alex; Bekker, Linda-Gail; Wood, Robin

2015-01-01

Background Prisons are recognised internationally as institutions with very high tuberculosis (TB) burdens where transmission is predominantly determined by contact between infectious and susceptible prisoners. A recent South African court case described the conditions under which prisoners awaiting trial were kept. With the use of these data, a mathematical model was developed to explore the interactions between incarceration conditions and TB control measures. Methods Cell dimensions, cell occupancy, lock-up time, TB incidence and treatment delays were derived from court evidence and judicial reports. Using the Wells-Riley equation and probability analyses of contact between prisoners, we estimated the current TB transmission probability within prison cells, and estimated transmission probabilities of improved levels of case finding in combination with implementation of national and international minimum standards for incarceration. Results Levels of overcrowding (230%) in communal cells and poor TB case finding result in annual TB transmission risks of 90% per annum. Implementing current national or international cell occupancy recommendations would reduce TB transmission probabilities by 30% and 50%, respectively. Improved passive case finding, modest ventilation increase or decreased lock-up time would minimally impact on transmission if introduced individually. However, active case finding together with implementation of minimum national and international standards of incarceration could reduce transmission by 50% and 94%, respectively. Conclusions Current conditions of detention for awaiting-trial prisoners are highly conducive for spread of drug-sensitive and drug-resistant TB. Combinations of simple well-established scientific control measures should be implemented urgently. PMID:22272961

Recent developments in the diagnosis and management of tuberculosis.

PubMed

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

2016-11-03

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

Molecular Characteristics and Drug Susceptibility of Mycobacterium tuberculosis Isolates from Patients Co-infected with Human Immunodeficiency Virus in Beijing, China.

PubMed

Liu, Jie; Wang, Hui Zhu; Lian, Lu Lu; Yu, Yan Hua; Zhao, Xiu Qin; Guo, Cai Ping; Liu, Hai Can; Liu, Shu Mei; Zhao, Hui; Zeng, Zhao Ying; Zhao, Xiu Ying; Wan, Kang Lin

2015-03-01

70 clinical Mycobacterium tuberculosis strains isolated from AIDS patients in two HIV/AIDS referral hospitals in Beijing were used in this study. M. tuberculosis and non-tuberculosis mycobacterium (NTM) were identified by using multi-locus PCR. M. tuberculosis was genotyped by using 15-locus MIRU-VNTR technique and spoligotyping afterwards. Meanwhile, the drug susceptibilities of the strains to the four first-line anti TB drugs (rifampin, isoniazid, streptomycin, and ethambutol) and the four second-line anti-TB drugs (capreomycin, kanamycin, ofloxacin, and ethionanide) were tested with proportional method. In this study, M. tuberculosis and NTM strains isolated from AIDS patients with TB-like symptoms were identified and genotyping analysis indicated that Beijing genotype was the predominant genotype. In addition, the prevalence of drug-resistant TB, especially the prevalence of XDR-TB, was higher than that in TB patients without HIV infection. Copyright © 2015 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Future vaccination strategies against tuberculosis: thinking outside the box.

PubMed

Kaufmann, Stefan H E

2010-10-29

With almost a dozen vaccine candidates in clinical trials, tuberculosis (TB) research and development is finally reaping the first fruits of its labors. Vaccine candidates in clinical trials may prevent TB disease reactivation by efficiently containing the pathogen Mycobacterium tuberculosis (Mtb). Future research should target vaccines that achieve sterile eradication of Mtb or even prevent stable infection. These are ambitious goals that can be reached only by highly cooperative engagement of basic immunologists, vaccinologists, and clinical researchers--or in other words, by translation from basic immunology to vaccine research and development, as well as reverse translation of insights from clinical trials back to hypothesis-driven research in the basic laboratory. Here, we review current and future strategies toward the rational design of novel vaccines against TB, as well as the progress made thus far, and the hurdles that need to be overcome in the near and distant future. Copyright © 2010 Elsevier Inc. All rights reserved.

Beyond multidrug-resistant tuberculosis in Europe: a TBNET study.

PubMed

Günther, G; van Leth, F; Altet, N; Dedicoat, M; Duarte, R; Gualano, G; Kunst, H; Muylle, I; Spinu, V; Tiberi, S; Viiklepp, P; Lange, C

2015-12-01

The emergence of drug-resistant tuberculosis (TB) is a challenge to TB control in Europe. We evaluated second-line drug susceptibility testing in Mycobacterium tuberculosis isolates from patients with multidrug-resistant, pre-extensively drug-resistant (pre-XDR-TB) and XDR-TB at 23 TBNET sites in 16 European countries. Over 30% of bacilli from patients with pre-XDR-TB showed resistance to any fluoroquinolone and almost 70% to any second-line injectable drug. Respectively >90% and >80% of the XDR-TB strains tested showed phenotypic resistance to pyrazinamide and ethambutol. Resistance to prothionamide/ethionamide was high in bacilli from pre-XDR-TB patients (43%) and XDR-TB patients (49%).

Tuberculosis in Greece: bacteriologically confirmed cases and anti-tuberculosis drug resistance, 1995-2009.

PubMed

Papaventsis, D; Nikolaou, S; Karabela, S; Ioannidis, P; Konstantinidou, E; Marinou, I; Sainti, A; Kanavaki, S

2010-07-15

The Greek National Reference Laboratory for Mycobacteria is a major source of tuberculosis (TB)-related data for Greece, where the TB burden and epidemiology still need to be better defined. We present data regarding newly diagnosed TB cases and resistance to anti-TB drugs during the last 15 years in Greece. Although the total number of newly detected TB cases has declined, cases among immigrants are increasing. Resistance to first-line anti-TB drugs is widely prevalent, although stable or declining. The implementation of an efficient and effective countrywide TB surveillance system in Greece is urgently needed.

The TB Portals: an Open-Access, Web-Based Platform for Global Drug-Resistant-Tuberculosis Data Sharing and Analysis.

PubMed

Rosenthal, Alex; Gabrielian, Andrei; Engle, Eric; Hurt, Darrell E; Alexandru, Sofia; Crudu, Valeriu; Sergueev, Eugene; Kirichenko, Valery; Lapitskii, Vladzimir; Snezhko, Eduard; Kovalev, Vassili; Astrovko, Andrei; Skrahina, Alena; Taaffe, Jessica; Harris, Michael; Long, Alyssa; Wollenberg, Kurt; Akhundova, Irada; Ismayilova, Sharafat; Skrahin, Aliaksandr; Mammadbayov, Elcan; Gadirova, Hagigat; Abuzarov, Rafik; Seyfaddinova, Mehriban; Avaliani, Zaza; Strambu, Irina; Zaharia, Dragos; Muntean, Alexandru; Ghita, Eugenia; Bogdan, Miron; Mindru, Roxana; Spinu, Victor; Sora, Alexandra; Ene, Catalina; Vashakidze, Sergo; Shubladze, Natalia; Nanava, Ucha; Tuzikov, Alexander; Tartakovsky, Michael

2017-11-01

The TB Portals program is an international consortium of physicians, radiologists, and microbiologists from countries with a heavy burden of drug-resistant tuberculosis working with data scientists and information technology professionals. Together, we have built the TB Portals, a repository of socioeconomic/geographic, clinical, laboratory, radiological, and genomic data from patient cases of drug-resistant tuberculosis backed by shareable, physical samples. Currently, there are 1,299 total cases from five country sites (Azerbaijan, Belarus, Moldova, Georgia, and Romania), 976 (75.1%) of which are multidrug or extensively drug resistant and 38.2%, 51.9%, and 36.3% of which contain X-ray, computed tomography (CT) scan, and genomic data, respectively. The top Mycobacterium tuberculosis lineages represented among collected samples are Beijing, T1, and H3, and single nucleotide polymorphisms (SNPs) that confer resistance to isoniazid, rifampin, ofloxacin, and moxifloxacin occur the most frequently. These data and samples have promoted drug discovery efforts and research into genomics and quantitative image analysis to improve diagnostics while also serving as a valuable resource for researchers and clinical providers. The TB Portals database and associated projects are continually growing, and we invite new partners and collaborations to our initiative. The TB Portals data and their associated analytical and statistical tools are freely available at https://tbportals.niaid.nih.gov/.

The TB Portals: an Open-Access, Web-Based Platform for Global Drug-Resistant-Tuberculosis Data Sharing and Analysis

PubMed Central

Gabrielian, Andrei; Engle, Eric; Hurt, Darrell E.; Alexandru, Sofia; Crudu, Valeriu; Sergueev, Eugene; Kirichenko, Valery; Lapitskii, Vladzimir; Snezhko, Eduard; Kovalev, Vassili; Astrovko, Andrei; Skrahina, Alena; Harris, Michael; Long, Alyssa; Wollenberg, Kurt; Akhundova, Irada; Ismayilova, Sharafat; Skrahin, Aliaksandr; Mammadbayov, Elcan; Gadirova, Hagigat; Abuzarov, Rafik; Seyfaddinova, Mehriban; Avaliani, Zaza; Strambu, Irina; Zaharia, Dragos; Muntean, Alexandru; Ghita, Eugenia; Bogdan, Miron; Mindru, Roxana; Spinu, Victor; Sora, Alexandra; Ene, Catalina; Vashakidze, Sergo; Shubladze, Natalia; Nanava, Ucha; Tuzikov, Alexander; Tartakovsky, Michael

2017-01-01

ABSTRACT The TB Portals program is an international consortium of physicians, radiologists, and microbiologists from countries with a heavy burden of drug-resistant tuberculosis working with data scientists and information technology professionals. Together, we have built the TB Portals, a repository of socioeconomic/geographic, clinical, laboratory, radiological, and genomic data from patient cases of drug-resistant tuberculosis backed by shareable, physical samples. Currently, there are 1,299 total cases from five country sites (Azerbaijan, Belarus, Moldova, Georgia, and Romania), 976 (75.1%) of which are multidrug or extensively drug resistant and 38.2%, 51.9%, and 36.3% of which contain X-ray, computed tomography (CT) scan, and genomic data, respectively. The top Mycobacterium tuberculosis lineages represented among collected samples are Beijing, T1, and H3, and single nucleotide polymorphisms (SNPs) that confer resistance to isoniazid, rifampin, ofloxacin, and moxifloxacin occur the most frequently. These data and samples have promoted drug discovery efforts and research into genomics and quantitative image analysis to improve diagnostics while also serving as a valuable resource for researchers and clinical providers. The TB Portals database and associated projects are continually growing, and we invite new partners and collaborations to our initiative. The TB Portals data and their associated analytical and statistical tools are freely available at https://tbportals.niaid.nih.gov/. PMID:28904183

Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis.

PubMed

Parlato, Stefania; Chiacchio, Teresa; Salerno, Debora; Petrone, Linda; Castiello, Luciano; Romagnoli, Giulia; Canini, Irene; Goletti, Delia; Gabriele, Lucia

2018-01-01

Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity.

Impaired IFN-α-mediated signal in dendritic cells differentiates active from latent tuberculosis

PubMed Central

Parlato, Stefania; Chiacchio, Teresa; Salerno, Debora; Petrone, Linda; Castiello, Luciano; Romagnoli, Giulia; Canini, Irene; Goletti, Delia; Gabriele, Lucia

2018-01-01

Individuals exposed to Mycobacterium tuberculosis (Mtb) may be infected and remain for the entire life in this condition defined as latent tuberculosis infection (LTBI) or develop active tuberculosis (TB). Among the multiple factors governing the outcome of the infection, dendritic cells (DCs) play a major role in dictating antibacterial immunity. However, current knowledge on the role of the diverse components of human DCs in shaping specific T-cell response during Mtb infection is limited. In this study, we performed a comparative evaluation of peripheral blood circulating DC subsets as well as of monocyte-derived Interferon-α DCs (IFN-DCs) from patients with active TB, subjects with LTBI and healthy donors (HD). The proportion of circulating myeloid BDCA3+ DCs (mDC2) and plasmacytoid CD123+ DCs (pDCs) declined significantly in active TB patients compared to HD, whereas the same subsets displayed a remarkable activation in LTBI subjects. Simultaneously, the differentiation of IFN-DCs from active TB patients resulted profoundly impaired compared to those from LTBI and HD individuals. Importantly, the altered developmental trait of IFN-DCs from active TB patients was associated with down-modulation of IFN-linked genes, marked changes in molecular signaling conveying antigen (Ag) presentation and full inability to induce Ag-specific T cell response. Thus, these data reveal an important role of IFN-α in determining the induction of Mtb-specific immunity. PMID:29320502

The Association Between Lung Carcinoma and Tuberculosis

PubMed Central

Cukic, Vesna

2017-01-01

Introduction: The association between lung tuberculosis and lung carcinoma is still controversial. Objective: to describe the characteristics of patients with associated lung tuberculosis (TB) and lung carcinoma (LC) in patients treated in Clinic for pulmonary diseases and TB “Podhrastovi”. Material and Methods: This is the retrospective study of patients with LC associated with TB treated in Clinic for pulmonary diseases and TB “Podhrastovi” in five-year period -from 2012 to 2016. We analyzed sex and age of patients, whether TB preceded LC or LC preceded TB, a time period between the developments of these two diseases, activity of TB, the histopathological type of LC, localization of LC in lungs (bronchial, peripheral, cavern) according to histopathological type. Results: In this period there were 2608 patients treated for LC. Among them there were 34 patients with diagnosed TB or 1.3%. All of them were smokers. No one had active TB. TB was the first diagnosis in all these patients. Each patient was previously treated for TB in hospital and had regular anti TB treatment. TB preceded LC in median time of 5 years (interquartile range 2 to 25 years). In 21 cases it was carcinoma of the drainage bronchus, in 11 cases it was peripheral lung carcinoma and 2 cases it was cavern carcinoma. Conlusion: patients with cured pulmonary tuberculosis represent a group at risk for developing lung carcinoma. Changes in the bronchial and alveolar mucosa which tuberculosis leaves behind in the lungs must be taken as a possible place of later malignant alteration. Patients with any form of pulmonary tuberculosis have to be controlled continuously. PMID:28974836

Advocacy, partnership and political commitment for TB vaccine research.

PubMed

Olesen, Ole F; Chan, Sharon; Chappell, Janice; Guo, Yan; Leite, Luciana C C

2016-08-01

The 4th Global Forum on TB Vaccines, convened in Shanghai, China, from 21 - 24 April 2015, brought together a wide and diverse community involved in tuberculosis vaccine research and development to discuss the current status of, and future directions for this critical effort. This paper summarizes the sessions on Advancing the Pipeline: A Vision for the Next Decade, Engaging the BRICS: Basic Research to Manufacturing, and Regulatory and Access Issues for New TB Vaccines. Summaries of all sessions from the 4th Global Forum are compiled in a special supplement of Tuberculosis. [August 2016, Vol 99, Supp S1, S1-S30]. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2017-01-01

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

Multidrug-resistant tuberculosis patients’ views of interventions to reduce treatment loss to follow-up

PubMed Central

Tupasi, T.; Garfin, A. M. C. G.; Mangan, J. M.; Orillaza-Chi, R.; Naval, L. C.; Balane, G. I.; Basilio, R.; Golubkov, A.; Joson, E. S.; Lew, W-J.; Lofranco, V.; Mantala, M.; Pancho, S.; Sarol, J. N.; Blumberg, A.; Burt, D.; Kurbatova, E. V.

2017-01-01

SUMMARY SETTING Patients who initiated treatment for multi-drug-resistant tuberculosis (MDR-TB) at 15 Programmatic Management of Drug-resistant Tuberculosis (PMDT) health facilities in the Philippines between July and December 2012. OBJECTIVES To describe patients’ views of current interventions, and suggest changes likely to reduce MDR-TB loss to follow-up. METHODS In-depth interviews were conducted between April and July 2014 with MDR-TB patients who were undergoing treatment, had finished treatment at the time of the interview (controls), or had been lost to follow-up (LTFU). Responses were thematically analyzed. RESULTS Interviews were conducted with 182 patients who were undergoing or had completed treatment and 91 LTFU patients. Views and suggestions could be thematically categorized as approaches to facilitate adherence or address barriers to adherence. The top themes were the need for transportation assistance or improvements to the current transportation assistance program, food assistance, and difficulties patients encountered related to their medications. These themes were addressed by respectively 63%, 60%, and 32% of the participants. CONCLUSIONS A more patient-centered approach is needed to improve MDR-TB treatment adherence. Programs should strive to provide assistance that considers patient preferences, is adequate to cover actual costs or needs, and is delivered in a timely, uninterrupted manner. PMID:28157461

Tuberculosis and infection control.

PubMed

Karim, Kelvin

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

Xpert®MTB/RIF for the Diagnosis of Tuberculosis in a Remote Arctic Setting: Impact on Cost and Time to Treatment Initiation.

PubMed

Oxlade, Olivia; Sugarman, Jordan; Alvarez, Gonzalo G; Pai, Madhukar; Schwartzman, Kevin

2016-01-01

Tuberculosis (TB) remains a significant health problem in the Canadian Arctic. Substantial health system delays in TB diagnosis can occur, in part due to the lack of capacity for onsite microbiologic testing. A study recently evaluated the yield and impact of a rapid automated PCR test (Xpert®MTB/RIF) for the diagnosis of TB in Iqaluit (Nunavut). We conducted an economic analysis to evaluate the expected cost relative to the expected reduction in time to treatment initiation, with the addition of Xpert®MTB/RIF to the current diagnostic and treatment algorithms used in this setting. A decision analysis model compared current microbiologic testing to a scenario where Xpert®MTB/RIF was added to the current diagnostic algorithm for active TB, and incorporated costs and clinical endpoints from the Iqaluit study. Several sensitivity analyses that considered alternative use were also considered. We estimated days to TB diagnosis and treatment initiation, health system costs, and the incremental cost per treatment day gained for each individual evaluated for possible TB. With the addition of Xpert®MTB/RIF, costs increased while days to TB treatment initiation were reduced. The incremental cost per treatment day gained (per individual investigated for TB) was $164 (95% uncertainty range $85, $452). In a sensitivity analysis that considered hospital discharge after a single negative Xpert®MTB/RIF, the Xpert®MTB/RIF scenario was cost saving. Adding Xpert®MTB/RIF to the current diagnostic algorithm for TB in Nunavut appears to reduce time to diagnosis and treatment at reasonable cost. It may be especially well suited to overcome some of the other logistical barriers that are unique to this and other remote communities.

Successes and failures in human tuberculosis vaccine development.

PubMed

Zenteno-Cuevas, Roberto

2017-12-01

Tuberculosis (TB) is an infectious disease caused mainly by Mycobacterium tuberculosis. In 2016, the WHO estimated 10.5 million new cases and 1.8 million deaths, making this disease the leading cause of death by an infectious agent. The current and projected TB situation necessitates the development of new vaccines with improved attributes compared to the traditional BCG method. Areas covered: In this review, the authors describe the most promising candidate vaccines against TB and discuss additional key elements in vaccine development, such as animal models, new adjuvants and immunization routes and new strategies for the identification of candidate vaccines. Expert opinion: At present, around 13 candidate vaccines for TB are in the clinical phase of evaluation; however, there is still no substitute for the BCG vaccine. One major impediment to developing an effective vaccine is our lack of understanding of several of the mechanisms associated with infection and the immune response against TB. However, the recent implementation of an entirely new set of technological advances will facilitate the proposal of new candidates. Finally, development of a new vaccine will require a major coordination of effort in order to achieve its effective administration to the people most in need of it.

Novel approaches in diagnosing tuberculosis

NASA Astrophysics Data System (ADS)

Kolk, Arend H. J.; Dang, Ngoc A.; Kuijper, Sjoukje; Gibson, Tim; Anthony, Richard; Claassens, Mareli M.; Kaal, Erwin; Janssen, Hans-Gerd

2011-06-01

The WHO declared tuberculosis (TB) a global emergency. An estimated 8-9 million new cases occur each year with 2-3 million deaths. Currently, TB is diagnosed mostly by chest-X ray and staining of the mycobacteria in sputum with a detection limit of 1x104 bacteria /ml. There is an urgent need for better diagnostic tools for TB especially for developing countries. We have validated the electronic nose from TD Technology for the detection of Mycobacterium tuberculosis by headspace analysis of 284 sputum samples from TB patients. We used linear discriminant function analysis resulting in a sensitivity of 75% a specificity of 67% and an accuracy of 69%. Further research is still required to improve the results by choosing more selective sensors and sampling techniques. We used a fast gas chromatography- mass spectrometry method (GC-MS). The automated procedure is based on the injection of sputum samples which are methylated inside the GC injector using thermally assisted hydrolysis and methylation (THM-GC-MS). Hexacosanoic acid in combination with tuberculostearic acid was found to be specific for the presence of M. tuberculosis. The detection limit was similar to microscopy. We found no false positives, all microscopy and culture positive samples were also found positive with the THM-GC-MS method. The detection of ribosomal RNA from the infecting organism offers great potential since rRNA molecules outnumber chromosomal DNA by a factor 1000. It thus may possible to detect the organism without amplification of the nucleic acids (NA). We used a capture and a tagged detector probe for the direct detection of M. tuberculosis in sputum. So far the detection limit is 1x106 bacteria / ml. Currently we are testing a Lab-On-A-Chip Interferometer detection system.

Knowledge and perceptions of national and provincial tuberculosis control programme managers in Pakistan about the WHO Stop TB strategy: a qualitative study.

PubMed

Khan, Wasiq Mehmood; Smith, Helen; Qadeer, Ejaz; Hassounah, Sondus

2016-01-01

To understand how national and provincial tuberculosis programme managers in Pakistan perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. National and provincial tuberculosis programme managers play an important role in effective implementation of the Stop TB strategy. A qualitative interview study was conducted with 10 national and provincial tuberculosis programme managers to understand how they perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). National and provincial tuberculosis programme managers in Pakistan. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). National and provincial tuberculosis programmes in Pakistan. 1. Knowledge and perceptions of national and provincial tuberculosis programme managers about the Stop TB strategy 2. Progress in implementing the strategy in Pakistan 3. Significant success factors 4. Significant implementation challenges 5. Lessons learnt to scale up successful implementation. The managers reported that most progress had been made in extending DOTS, health systems strengthening, public -private mixed interventions, MDR-TB care and TB/HIV care. The four factors that contributed significantly to progress were the availability of DOTS services, the public-private partnership approach, comprehensive guidance for TB control and government and donor commitment to TB control. This study identified three main challenges as perceived by national and provincial tuberculosis programme managers in terms of implementing the Stop TB strategy: 1. Inadequate political commitment, 2. Issue pertaining to prioritisation of certain components in the TB strategy over others due to external influences and 3. Limitations in the overall health system. To improve the tuberculosis control programme in the country political commitment needs to be enhanced and public -private partnerships increased. This can be done through government prioritisation of TB control at both national and provincial levels; donor-funded components should not receive undue attention; and partnerships with the private health sector, health institutions not yet covered by DOTS services, non-governmental organisations and patient coalitions should be increased.

Uses of tuberculosis mortality surveillance to identify programme errors and improve database reporting.

PubMed

Selig, L; Guedes, R; Kritski, A; Spector, N; Lapa E Silva, J R; Braga, J U; Trajman, A

2009-08-01

In 2006, 848 persons died from tuberculosis (TB) in Rio de Janeiro, Brazil, corresponding to a mortality rate of 5.4 per 100 000 population. No specific TB death surveillance actions are currently in place in Brazil. Two public general hospitals with large open emergency rooms in Rio de Janeiro City. To evaluate the contribution of TB death surveillance in detecting gaps in TB control. We conducted a survey of TB deaths from September 2005 to August 2006. Records of TB-related deaths and deaths due to undefined causes were investigated. Complementary data were gathered from the mortality and TB notification databases. Seventy-three TB-related deaths were investigated. Transmission hazards were identified among firefighters, health care workers and in-patients. Management errors included failure to isolate suspected cases, to confirm TB, to correct drug doses in underweight patients and to trace contacts. Following the survey, 36 cases that had not previously been notified were included in the national TB notification database and the outcome of 29 notified cases was corrected. TB mortality surveillance can contribute to TB monitoring and evaluation by detecting correctable and specific programme- and hospital-based care errors, and by improving the accuracy of TB database reporting. Specific local and programmatic interventions can be proposed as a result.

Impact and cost-effectiveness of current and future tuberculosis diagnostics: the contribution of modelling

PubMed Central

Houben, R.; Cohen, T.; Pai, M.; Cobelens, F.; Vassall, A.; Menzies, N. A.; Gomez, G. B.; Langley, I.; Squire, S. B.; White, R.

2014-01-01

SUMMARY The landscape of diagnostic testing for tuberculosis (TB) is changing rapidly, and stakeholders need urgent guidance on how to develop, deploy and optimize TB diagnostics in a way that maximizes impact and makes best use of available resources. When decisions must be made with only incomplete or preliminary data available, modelling is a useful tool for providing such guidance. Following a meeting of modelers and other key stakeholders organized by the TB Modelling and Analysis Consortium, we propose a conceptual framework for positioning models of TB diagnostics. We use that framework to describe modelling priorities in four key areas: Xpert® MTB/RIF scale-up, target product profiles for novel assays, drug susceptibility testing to support new drug regimens, and the improvement of future TB diagnostic models. If we are to maximize the impact and cost-effectiveness of TB diagnostics, these modelling priorities should figure prominently as targets for future research. PMID:25189546

Vaccination against tuberculosis in badgers and cattle: an overview of the challenges, developments and current research priorities in Great Britain.

PubMed

Chambers, M A; Carter, S P; Wilson, G J; Jones, G; Brown, E; Hewinson, R G; Vordermeier, M

2014-07-26

Bovine tuberculosis (TB) is a significant threat to the cattle industry in England and Wales. It is widely acknowledged that a combination of measures targeting both cattle and wildlife will be required to eradicate bovine TB or reduce its prevalence until European official freedom status is achieved. Vaccination of cattle and/or badgers could contribute to bovine TB control in Great Britain, although there are significant gaps in our knowledge regarding the impact that vaccination would actually have on bovine TB incidence. Laboratory studies have demonstrated that vaccination with BCG can reduce the progression and severity of TB in both badgers and cattle. This is encouraging in terms of the prospect of a sustained vaccination programme achieving reductions in disease prevalence; however, developing vaccines for tackling the problem of bovine TB is challenging, time-consuming and resource-intensive, as this review article sets out to explain. British Veterinary Association.

Field evaluation of a blood based test for active tuberculosis in endemic settings

PubMed Central

Hussainy, Syed Fahadulla; Krishnan, Viwanathan V.; Ambreen, Atiqa; Yusuf, Noshin Wasim; Irum, Shagufta; Rashid, Abdul; Jamil, Muhammad; Zaffar, Fareed; Chaudhry, Muhammad Nawaz; Gupta, Puneet K.; Akhtar, Muhammad Waheed; Khan, Imran H.

2017-01-01

Over 9 million new active tuberculosis (TB) cases emerge each year from an enormous pool of 2 billion individuals latently infected with Mycobacterium tuberculosis (M. tb.) worldwide. About 3 million new TB cases per year are unaccounted for, and 1.5 million die. TB, however, is generally curable if diagnosed correctly and in a timely manner. The current diagnostic methods for TB, including state-of-the-art molecular tests, have failed in delivering the capacity needed in endemic countries to curtail this ongoing pandemic. Efficient, cost effective and scalable diagnostic approaches are critically needed. We report a multiplex TB serology panel using microbead suspension array containing a combination of 11 M.tb. antigens that demonstrated overall sensitivity of 91% in serum/plasma samples from TB patients confirmed by culture. Group wise sensitivities for sputum smear positive and negative patients were 95%, and 88%, respectively. Specificity of the test was 96% in untreated COPD patients and 91% in general healthy population. The sensitivity of this test is superior to that of the frontline sputum smear test with a comparable specificity (30–70%, and 93–99%, respectively). The multiplex serology test can be performed with scalability from 1 to 360 patients per day, and is amenable to automation for higher (1000s per day) throughput, thus enabling a scalable clinical work flow model for TB endemic countries. Taken together, the above results suggest that well defined antibody profiles in blood, analyzed by an appropriate technology platform, offer a valuable approach to TB diagnostics in endemic countries. PMID:28380055

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

PubMed Central

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

2011-01-01

Background Given the considerable geographic overlap in the endemic regions for malaria and tuberculosis, it is probable that co-infections with Mycobacterium tuberculosis and Plasmodium species are prevalent. Thus, it is quite likely that both malaria and TB vaccines may be used in the same populations in endemic areas. While novel vaccines are currently being developed and tested individually against each of these pathogens, the efficacy of these vaccines has not been evaluated in co-infection models. To further assess the effectiveness of these new immunization strategies, we investigated whether co-infection with malaria would impact the anti-tuberculosis protection induced by four different types of TB vaccines in a mouse model of pulmonary tuberculosis. Principal Findings Here we show that the anti-tuberculosis protective immunity induced by four different tuberculosis vaccines was not impacted by a concurrent infection with Plasmodium yoelii NL, a nonlethal form of murine malaria. After an aerogenic challenge with virulent M. tuberculosis, the lung bacterial burdens of vaccinated animals were not statistically different in malaria infected and malaria naïve mice. Multi-parameter flow cytometric analysis showed that the frequency and the median fluorescence intensities (MFI) for specific multifunctional T (MFT) cells expressing IFN-γ, TNF-α, and/or IL-2 were suppressed by the presence of malaria parasites at 2 weeks following the malaria infection but was not affected after parasite clearance at 7 and 10 weeks post-challenge with P. yoelii NL. Conclusions Our data indicate that the effectiveness of novel TB vaccines in protecting against tuberculosis was unaffected by a primary malaria co-infection in a mouse model of pulmonary tuberculosis. While the activities of specific MFT cell subsets were reduced at elevated levels of malaria parasitemia, the T cell suppression was short-lived. Our findings have important relevance in developing strategies for the deployment of new TB vaccines in malaria endemic areas. PMID:22205939

High clustering rates of multidrug-resistant Mycobacterium tuberculosis genotypes in Panama

PubMed Central

2013-01-01

Background Tuberculosis continues to be one of the leading causes of death worldwide and in the American region. Although multidrug-resistant tuberculosis (MDR-TB) remains a threat to TB control in Panama, few studies have focused in typing MDR-TB strains. The aim of our study was to characterize MDR Mycobacterium tuberculosis clinical isolates using PCR-based genetic markers. Methods From 2002 to 2004, a total of 231 Mycobacterium tuberculosis isolates from TB cases country-wide were screened for antibiotic resistance, and MDR-TB isolates were further genotyped by double repetitive element PCR (DRE-PCR), (GTG)5-PCR and spoligotyping. Results A total of 37 isolates (0.85%) were resistant to both isoniazid (INH) and rifampicin (RIF). Among these 37 isolates, only two (5.4%) were resistant to all five drugs tested. Dual genotyping using DRE-PCR and (GTG)5-PCR of MDR Mycobacterium tuberculosis isolates revealed eight clusters comprising 82.9% of the MDR-TB strain collection, and six isolates (17.1%) showed unique fingerprints. The spoligotyping of MDR-TB clinical isolates identified 68% as members of the 42 (LAM9) family genotype. Conclusion Our findings suggest that MDR Mycobacterium tuberculosis is highly clustered in Panama’s metropolitan area corresponding to Panama City and Colon City, and our study reveals the genotype distribution across the country. PMID:24053690

[Retrospect of tuberculosis control in Brazil].

PubMed

Hijjar, Miguel Aiub; Gerhardt, Germano; Teixeira, Gilmário M; Procópio, Maria José

2007-09-01

The aim of the study was to look back on the course of action involving measures of tuberculosis control in Brazil since the end of the 19th century, covering the history of social struggles and pointing out institutions and people that have dedicated themselves to looking for solutions to these issues. The Brazilian response to tuberculosis started in society with the Ligas Contra a Tuberculose (Leagues Against Tuberculosis), promoting scientific advances, such as the BCG vaccination, which begun in 1927. From the public power, the Inspetoria de Profilaxia da TB (TB Prophylaxis Inspection Service - 1920), the Serviço Nacional de Tuberculose (National Service of Tuberculosis - 1940), and the Campanha Nacional Contra a Tuberculose (National Campaign Against Tuberculosis - 1946), coordinated national policies such as chemotherapy, beginning with the discovery of streptomycin in 1944. The emergence of bacterial resistance led to the development of several therapeutic schemes. The Scheme 1 (rifampycin, hydrazide and pyrazinamid), which was the main one in 1979 and is still used nowadays, had a great epidemiological effect. The WHO declared TB a public health emergency in 1993. In response, Brazil developed some strategies; the first one was the Plano Emergencial para Controle da Tuberculose (Emergency Plan for Tuberculosis Control - 1994), prioritizing 230 municipalities. The current prospects are an effective municipalization of actions and their greater integration with the Programas de Agentes Comunitários e Saúde da Família (Humanitarian Agents and Family Health Programs).

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.

Defining the research agenda to measure and reduce tuberculosis stigmas.

PubMed

Macintyre, K; Bakker, M I; Bergson, S; Bhavaraju, R; Bond, V; Chikovore, J; Colvin, C; Craig, G M; Cremers, A L; Daftary, A; Engel, N; France, N Ferris; Jaramillo, E; Kimerling, M; Kipp, A; Krishnaratne, S; Mergenthaler, C; Ngicho, M; Redwood, L; Rood, E J J; Sommerland, N; Stangl, A; van Rie, A; van Brakel, W; Wouters, E; Zwerling, A; Mitchell, E M H

2017-11-01

Crucial to finding and treating the 4 million tuberculosis (TB) patients currently missed by national TB programmes, TB stigma is receiving well-deserved and long-delayed attention at the global level. However, the ability to measure and evaluate the success of TB stigma-reduction efforts is limited by the need for additional tools. At a 2016 TB stigma-measurement meeting held in The Hague, The Netherlands, stigma experts discussed and proposed a research agenda around four themes: 1) drivers: what are the main drivers and domains of TB stigma(s)?; 2) consequences: how consequential are TB stigmas and how are negative impacts most felt?; 3) burden: what is the global prevalence and distribution of TB stigma(s) and what explains any variation? 4): intervention: what can be done to reduce the extent and impact of TB stigma(s)? Each theme was further subdivided into research topics to be addressed to move the agenda forward. These include greater clarity on what causes TB stigmas to emerge and thrive, the difficulty of measuring the complexity of stigma, and the improbability of a universal stigma 'cure'. Nevertheless, these challenges should not hinder investments in the measurement and reduction of TB stigma. We believe it is time to focus on how, and not whether, the global community should measure and reduce TB stigma.

Estimating tuberculosis incidence from primary survey data: a mathematical modeling approach

PubMed Central

Chadha, V. K.; Laxminarayan, R.; Arinaminpathy, N.

2017-01-01

SUMMARY BACKGROUND: There is an urgent need for improved estimations of the burden of tuberculosis (TB). OBJECTIVE: To develop a new quantitative method based on mathematical modelling, and to demonstrate its application to TB in India. DESIGN: We developed a simple model of TB transmission dynamics to estimate the annual incidence of TB disease from the annual risk of tuberculous infection and prevalence of smear-positive TB. We first compared model estimates for annual infections per smear-positive TB case using previous empirical estimates from China, Korea and the Philippines. We then applied the model to estimate TB incidence in India, stratified by urban and rural settings. RESULTS: Study model estimates show agreement with previous empirical estimates. Applied to India, the model suggests an annual incidence of smear-positive TB of 89.8 per 100 000 population (95%CI 56.8–156.3). Results show differences in urban and rural TB: while an urban TB case infects more individuals per year, a rural TB case remains infectious for appreciably longer, suggesting the need for interventions tailored to these different settings. CONCLUSIONS: Simple models of TB transmission, in conjunction with necessary data, can offer approaches to burden estimation that complement those currently being used. PMID:28284250

Matrix Degradation in Human Immunodeficiency Virus Type 1-Associated Tuberculosis and Tuberculosis Immune Reconstitution Inflammatory Syndrome: A Prospective Observational Study.

PubMed

Walker, Naomi F; Wilkinson, Katalin A; Meintjes, Graeme; Tezera, Liku B; Goliath, Rene; Peyper, Janique M; Tadokera, Rebecca; Opondo, Charles; Coussens, Anna K; Wilkinson, Robert J; Friedland, Jon S; Elkington, Paul T

2017-07-01

Extensive immunopathology occurs in human immunodeficiency virus (HIV)/tuberculosis (TB) coinfection, but the underlying molecular mechanisms are not well-defined. Excessive matrix metalloproteinase (MMP) activity is emerging as a key process but has not been systematically studied in HIV-associated TB. We performed a cross-sectional study of matrix turnover in HIV type 1 (HIV-1)-infected and -uninfected TB patients and controls, and a prospective cohort study of HIV-1-infected TB patients at risk of TB immune reconstitution inflammatory syndrome (TB-IRIS), in Cape Town, South Africa. Sputum and plasma MMP concentrations were quantified by Luminex, plasma procollagen III N-terminal propeptide (PIIINP) by enzyme-linked immunosorbent assay, and urinary lipoarabinomannan (LAM) by Alere Determine TB LAM assay. Peripheral blood mononuclear cells from healthy donors were cultured with Mycobacterium tuberculosis and extracellular matrix in a 3D model of TB granuloma formation. MMP activity differed between HIV-1-infected and -uninfected TB patients and corresponded with specific TB clinical phenotypes. HIV-1-infected TB patients had reduced pulmonary MMP concentrations, associated with reduced cavitation, but increased plasma PIIINP, compared to HIV-1-uninfected TB patients. Elevated extrapulmonary extracellular matrix turnover was associated with TB-IRIS, both before and during TB-IRIS onset. The predominant collagenase was MMP-8, which was likely neutrophil derived and M. tuberculosis-antigen driven. Mycobacterium tuberculosis-induced matrix degradation was suppressed by the MMP inhibitor doxycycline in vitro. MMP activity in TB differs by HIV-1 status and compartment, and releases matrix degradation products. Matrix turnover in HIV-1-infected patients is increased before and during TB-IRIS, informing novel diagnostic strategies. MMP inhibition is a potential host-directed therapy strategy for prevention and treatment of TB-IRIS. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Tuberculosis in Poland in 2014

PubMed

Korzeniewska-Koseła, Maria

To evaluate the main features of TB epidemiology in 2014 in Poland and to compare with the data on the same phenomena in EU/EEA countries. Analysis of case- based data on TB patients from National TB Register, data on anti-TB drugsusceptibility testing results in cases notified in 2014, data from National Institute of Public Health- NationalInstitute of Hygiene on cases of tuberculosis as AIDS-defining disease, data from Central Statistical Office ondeaths from tuberculosis based on death certificates, data from ECDC report „ European Centre for DiseasePrevention and Control/WHO Regional Office for Europe. Tuberculosis surveillance and monitoring in Europe 2016. Stockholm: European Centre for Disease Prevention and Control, 2016”. 6 698 TB cases were reported in Poland in 2014. The incidence rate was 17.4 cases per 100 000, withlarge variability between voivodeships from 9.3 to 26.5 per 100 000. The mean annual decrease of TB incidence in 2010- 2014 was 2.1%. 6 066 cases had no history of previous treatment i.e. 15.8 per 100 000. 632 cases i.e. 1.6 per 100 000 – 9.4% of all registered subjects were relapses. The number of all notified pulmonary tuberculosis cases in 2014 was 6311 i.e. 16.4 per 100 000. Pulmonary cases represented 94.2% of all TB cases. In the presented year 387 extrapulmonary TB cases were reported. Children with TB (70 cases) accounted for 1.0% of all cases notified in Poland. The incidence of tuberculosis increases with age from 1.2 per 100 000 among children to 30.4 per 100 000 among patients 65 years old and older. The incidence among men i.e. 24.6 per 100 000 was 2.3 times higher than among women i.e. 10.7 per 100 000. The biggest difference in the TB incidence between the two sex groups occurred in persons aged 45 to 49 years – 40.4 vs. 9.3. The TB incidence in rural population was lower than in urban, respectively 17.0 per 100 000 and 17.7 per 100 000. The number of all registered culture positive TB cases, including relapses, was 4 781. Culture-confirmed cases constituted 71.4% of all TB cases and 72.9% of all pulmonary TB cases. The number of smear-positive pulmonary TB cases reported in 2014 was 2800 i.e. 7.3 per 100 000 respectively what constituted 44.4% of all pulmonary TB cases. TB was initial AIDS indicative disease in 13 persons. In Poland in 2014 there were 35 cases with MDR-TB (including 7 patients of foreign origin) and 97 patients with resistance to isoniazid only, constituting respectively 0.8% and 2.2% of cases with known DST results (DSTs were done in 93.3% of all culture-confirmed TB cases). In 2014, there were 49 foreign-origin TB cases reported in Poland. There were 532 deaths due to tuberculosis reported in 2013 – 1.4 per 100 000; 518 and 14 from extrapulmonary tuberculosis. Mortality among males – 2.2 per 100.000 – was 3.6 X higher than among females – 0.6. 38,5% of all TB deaths were cases 65 years old and older – 3.7 per 100 000. There were no deaths from tuberculosis in children. TB was cause of death in one adolescent. TB mortality in 2013 constituted 0.14% of total mortality in Poland and 27.1% of mortality from infectious diseases. In Poland in 2014 the incidence of tuberculosis was higher than the average in EU/EEA countries. The highest incidence rates occurred in older age groups. The incidence in men was more than 2 times higher than in women. In Poland, unfavorable phenomena as tuberculosis in children, tuberculosis in persons infected with HIV and MDR-TB are less common than in EU/EEA countries.

Diabetes and Other Risk Factors for Multi-drug Resistant Tuberculosis in a Mexican Population with Pulmonary Tuberculosis: Case Control Study.

PubMed

Gómez-Gómez, Alejandro; Magaña-Aquino, Martin; López-Meza, Salvador; Aranda-Álvarez, Marcelo; Díaz-Ornelas, Dora E; Hernández-Segura, María Guadalupe; Salazar-Lezama, Miguel Ángel; Castellanos-Joya, Martín; Noyola, Daniel E

2015-02-01

Multidrug resistant tuberculosis (MDR-TB) poses problems in treatment, costs and treatment outcomes. It is not known if classically described risk factors for MDR-TB in other countries are the same in Mexico and the frequency of the association between diabetes mellitus (DM) and MDR-TB in our country is not clear. We undertook this study to analyze risk factors associated with the development of MDR-TB, with emphasis on DM. A case-control study in the state of San Luis Potosi (SLP), Mexico was carried out. All pulmonary MDR-TB patients diagnosed in the state of SLP between 1998 and 2013 (36 cases) evaluated at a state pharmacoresistant tuberculosis (TB) clinic and committee; 139 controls were randomly selected from all pulmonary non-multidrug-resistant tuberculosis (non-MDR-TB) cases identified between 2003 and 2008. Cases and controls were diagnosed and treated under programmatic conditions. Age, gender, malnutrition, being a health-care worker, HIV/AIDS status, and drug abuse were not significantly different between MDR-TB and non-MDR-TB patients. Significant differences between MDR-TB and non-MDR-TB patients were DM (47.2 vs. 28.1%; p = 0.028); previous anti-TB treatments (3 vs. 0, respectively; p <0.001), and duration of first anti-TB treatment (8 vs. 6 months, respectively; p <0.001). MDR-TB and DM are associated in 47.2% of MDR TB cases (17/36) in this study. Other recognized factors were not found to be significantly different in MDR-TB compared to non-MDR-TB in this study. Cost-feasible strategies must be implemented in the treatment of DM-TB in order to prevent the selection of MDR-TB. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Knowledge of Bovine Tuberculosis, Cattle Husbandry and Dairy Practices amongst Pastoralists and Small-Scale Dairy Farmers in Cameroon

PubMed Central

Kelly, Robert F.; Hamman, Saidou M.; Morgan, Kenton L.; Nkongho, Egbe F.; Ngwa, Victor Ngu; Tanya, Vincent; Andu, Walters N.; Sander, Melissa; Ndip, Lucy; Handel, Ian G.; Mazeri, Stella; Muwonge, Adrian; Bronsvoort, Barend M. de. C.

2016-01-01

Background Control of bovine tuberculosis (bTB) and zoonotic tuberculosis (zTB) has relied upon surveillance and slaughter of infected cattle, milk pasteurisation and public health education. In Cameroon, like many other sub-Saharan African countries, there is limited understanding of current cattle husbandry or milk processing practices or livestock keepers awareness of bTB. This paper describes husbandry and milk processing practices within different Cameroonian cattle keeping communities and bTB awareness in comparison to other infectious diseases. Study design A population based cross-sectional sample of herdsmen and a questionnaire were used to gather data from pastoralists and dairy farmers in the North West Region and Vina Division of Cameroon. Results Pastoralists were predominately male Fulanis who had kept cattle for over a decade. Dairy farmers were non-Fulani and nearly half were female. Pastoralists went on transhumance with their cattle and came into contact with other herds and potential wildlife reservoirs of bTB. Dairy farmers housed their cattle and had little contact with other herds or wildlife. Pastoralists were aware of bTB and other infectious diseases such as foot-and-mouth disease and fasciolosis. These pastoralists were also able to identify clinical signs of these diseases. A similar proportion of dairy farmers were aware of bTB but fewer were aware of foot-and-mouth and fasciolosis. In general, dairy farmers were unable to identify any clinical signs for any of these diseases. Importantly most pastoralists and dairy farmers were unaware that bTB could be transmitted to people by consuming milk. Conclusions Current cattle husbandry practices make the control of bTB in cattle challenging especially in mobile pastoralist herds. Routine test and slaughter control in dairy herds would be tractable but would have profound impact on dairy farmer livelihoods. Prevention of transmission in milk offers the best approach for human risk mitigation in Cameroon but requires strategies that improved risk awareness amongst producers and consumers. PMID:26745871

Knowledge of Bovine Tuberculosis, Cattle Husbandry and Dairy Practices amongst Pastoralists and Small-Scale Dairy Farmers in Cameroon.

PubMed

Kelly, Robert F; Hamman, Saidou M; Morgan, Kenton L; Nkongho, Egbe F; Ngwa, Victor Ngu; Tanya, Vincent; Andu, Walters N; Sander, Melissa; Ndip, Lucy; Handel, Ian G; Mazeri, Stella; Muwonge, Adrian; Bronsvoort, Barend M de C

2016-01-01

Control of bovine tuberculosis (bTB) and zoonotic tuberculosis (zTB) has relied upon surveillance and slaughter of infected cattle, milk pasteurisation and public health education. In Cameroon, like many other sub-Saharan African countries, there is limited understanding of current cattle husbandry or milk processing practices or livestock keepers awareness of bTB. This paper describes husbandry and milk processing practices within different Cameroonian cattle keeping communities and bTB awareness in comparison to other infectious diseases. A population based cross-sectional sample of herdsmen and a questionnaire were used to gather data from pastoralists and dairy farmers in the North West Region and Vina Division of Cameroon. Pastoralists were predominately male Fulanis who had kept cattle for over a decade. Dairy farmers were non-Fulani and nearly half were female. Pastoralists went on transhumance with their cattle and came into contact with other herds and potential wildlife reservoirs of bTB. Dairy farmers housed their cattle and had little contact with other herds or wildlife. Pastoralists were aware of bTB and other infectious diseases such as foot-and-mouth disease and fasciolosis. These pastoralists were also able to identify clinical signs of these diseases. A similar proportion of dairy farmers were aware of bTB but fewer were aware of foot-and-mouth and fasciolosis. In general, dairy farmers were unable to identify any clinical signs for any of these diseases. Importantly most pastoralists and dairy farmers were unaware that bTB could be transmitted to people by consuming milk. Current cattle husbandry practices make the control of bTB in cattle challenging especially in mobile pastoralist herds. Routine test and slaughter control in dairy herds would be tractable but would have profound impact on dairy farmer livelihoods. Prevention of transmission in milk offers the best approach for human risk mitigation in Cameroon but requires strategies that improved risk awareness amongst producers and consumers.

Use of Transrenal DNA for the Diagnosis of Extrapulmonary Tuberculosis in Children: a Case of Tubercular Otitis Media

PubMed Central

Petrucci, Roberta; Corsini, Ilaria; Visciotti, Francesca; Pirodda, Antonio; Cazzato, Salvatore; Landini, Maria Paola; Dal Monte, Paola

2014-01-01

The diagnosis of tuberculosis (TB) is difficult in children, especially for smear-negative pulmonary and extrapulmonary TB, which are common at this age. We report an 11-year-old girl with TB otitis media with negative smear microscopy and Xpert MTB/RIF but positive Mycobacterium tuberculosis-specific transrenal DNA (Tr-MTB-DNA) test results and culture for M. tuberculosis. PMID:25339389

Addressing poverty through disease control programmes: examples from Tuberculosis control in India.

PubMed

Kamineni, Vishnu Vardhan; Wilson, Nevin; Das, Anand; Satyanarayana, Srinath; Chadha, Sarabjit; Sachdeva, Kuldeep Singh; Chauhan, Lakbir Singh

2012-03-26

Tuberculosis remains a major public health problem in India with the country accounting for one-fifth or 21% of all tuberculosis cases reported globally. The purpose of the study was to obtain an understanding on pro-poor initiatives within the framework of tuberculosis control programme in India and to identify mechanisms to improve the uptake and access to TB services among the poor. A national level workshop was held with participation from all relevant stakeholder groups. This study conducted during the stakeholder workshop adopted participatory research methods. The data was elicited through consultative and collegiate processes. The research study also factored information from primary and secondary sources that included literature review examining poverty headcount ratios and below poverty line population in the country; and quasi-profiling assessments to identify poor, backward and tribal districts as defined by the TB programme in India. Results revealed that current pro-poor initiatives in TB control included collaboration with private providers and engaging community to improve access among the poor to TB diagnostic and treatment services. The participants identified gaps in existing pro-poor strategies that related to implementation of advocacy, communication and social mobilisation; decentralisation of DOT; and incentives for the poor through the available schemes for public-private partnerships and provided key recommendations for action. Synergies between TB control programme and centrally sponsored social welfare schemes and state specific social welfare programmes aimed at benefitting the poor were unclear. Further in-depth analysis and systems/policy/operations research exploring pro-poor initiatives, in particular examining service delivery synergies between existing poverty alleviation schemes and TB control programme is essential. The understanding, reflection and knowledge of the key stakeholders during this participatory workshop provides recommendations for action, further planning and research on pro-poor TB centric interventions in the country.

Characterization of extensively drug-resistant Mycobacterium tuberculosis in Nepal.

PubMed

Poudel, Ajay; Maharjan, Bhagwan; Nakajima, Chie; Fukushima, Yukari; Pandey, Basu D; Beneke, Antje; Suzuki, Yasuhiko

2013-01-01

The emergence of extensively drug-resistant tuberculosis (XDR-TB) has raised public health concern for global control of TB. Although molecular characterization of drug resistance-associated mutations in multidrug-resistant isolates in Nepal has been made, mutations in XDR isolates and their genotypes have not been reported previously. In this study, we identified and characterized 13 XDR Mycobacterium tuberculosis isolates from clinical isolates in Nepal. The most prevalent mutations involved in rifampicin, isoniazid, ofloxacin, and kanamycin/capreomycin resistance were Ser531Leu in rpoB gene (92.3%), Ser315Thr in katG gene (92.3%), Asp94Gly in gyrA gene (53.9%) and A1400G in rrs gene (61.5%), respectively. Spoligotyping and multilocus sequence typing revealed that 69% belonged to Beijing family, especially modern types. Further typing with 26-loci variable number of tandem repeats suggested the current spread of XDR M. tuberculosis. Our result highlights the need to reinforce the TB policy in Nepal with regard to control and detection strategies. Copyright © 2012 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

Advances in rapid diagnosis of tuberculosis disease and anti-tuberculous drug resistance.

PubMed

Alcaide, Fernando; Coll, Pere

2011-03-01

Rapid diagnosis of tuberculosis (TB) and multidrug-resistant (resistance to at least rifampin and isoniazid) Mycobacterium tuberculosis (MDR-TB) is one of the cornerstones for global TB control as it allows early epidemiological and therapeutic interventions. The slow growth of the tubercle bacillus is the greatest obstacle to rapid diagnosis of the disease. However, considerable progress has recently been made in developing novel diagnostic tools, especially molecular methods (commercial and 'in-house'), for direct detection in clinical specimens. These methods, based on nucleic acid amplification (NAA) of different targets, aim to identify the M. tuberculosis complex and detect the specific chromosome mutations that are most frequently associated with phenotypic resistance to multiple drugs. In general, commercial methods are recommended since they have a better level of standardization, reproducibility and automation. Although some aspects such as cost-efficiency and the appropriate setting for the implementation of these techniques are not yet well established, organizations such as the WHO are strongly supporting the implementation and universal use of these new molecular methods. This chapter summarizes current knowledge and the available molecular methods for rapid diagnosis of TB and anti-tuberculous drug resistance in clinical microbiology laboratories. Copyright © 2011 Elsevier España S.L. All rights reserved.

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

PubMed

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

2018-02-01

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

Perceptions and acceptability of short message services technology to improve treatment adherence amongst tuberculosis patients in Peru: a Focus Group Study.

PubMed

Albino, Sandra; Tabb, Karen M; Requena, David; Egoavil, Miguel; Pineros-Leano, Maria F; Zunt, Joseph R; García, Patricia J

2014-01-01

Tuberculosis (TB) is global health concern and a leading infectious cause of mortality. Reversing TB incidence and disease-related mortality is a major global health priority. Infectious disease mortality is directly linked to failure to adhere to treatments. Using technology to send reminders by short message services have been shown to improve treatment adherence. However, few studies have examined tuberculosis patient perceptions and attitudes towards using SMS technology to increase treatment adherence. In this study, we sought to investigate perceptions related to feasibility and acceptability of using text messaging to improve treatment adherence among adults who were receiving treatment for TB in Callao, Peru. We conducted focus group qualitative interviews with current TB positive and non-contagious participants to understand the attitudes, perceptions, and feasibility of using short message service (SMS) reminders to improve TB treatment adherence. Subjects receiving care through the National TB Program were recruited through public health centers in Ventanilla, Callao, Peru. In four focus groups, we interviewed 16 patients. All interviews were recorded and transcribed verbatim. Thematic network analysis and codebook techniques were used to analyze data. Three major themes emerged from the data: limits on health literacy and information posed challenges to successful TB treatment adherence, treatment motivation at times facilitated adherence to TB treatment, and acceptability of SMS including positive perceptions of SMS to improve TB treatment adherence. The majority of patients shared considerations about how to effectively and confidentially administer an SMS intervention with TB positive participants. The overall perceptions of the use of SMS were positive and indicated that SMS technology may be an efficient way to transmit motivational texts on treatment, health education information, and simple reminders to increase treatment adherence for low-income TB patients living in Peru.

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.

Tuberculosis in children and adolescents: Strategies for social workers' interventions.

PubMed

González, Norma E; Angueira, Luciana

2017-12-01

In the care of children and adolescents with tuberculosis (TB), it is necessary to know the difficulties that many families have in accessing health care, obtaining a diagnosis, and receiving a timely treatment. Social workers, along with other members of the health care team, assist in providing access to health care resources and benefits that may favor treatment compliance and strengthen the health of this vulnerable population. Although the purpose of social workers involvement in this disease is to reduce the risk of becoming infected, sick or dying from TB, the current epidemiological situation of this disease in Argentina has faced social workers with the challenge of reconsidering new intervention strategies and revising current objectives. This study addresses their role and proposes actions that may contribute to decreasing TB morbidity and mortality in children and adolescents. Sociedad Argentina de Pediatría.

[Current status of tuberculosis education in universities and future tasks].

PubMed

2000-02-01

Symposium Topics and Presenters: 1. Education of tuberculosis in medial school: Kaoru SHIMOKATA (Department of Clinical Preventive Medicine, Nagoya University Daiko Medical Center) 2. From Medical University holding Tuberculous ward: Shosaku ABE (Third Department of Internal Medicine, Sapporo Medical University School of Medicine), et al. 3. Necessity and Significance of Sanatorium ward associated with University Hospital: Saburo SONE, et al. (Third Department of Internal Medicine, The University of Tokushima School of Medicine) 4. A proposal on education and training for tuberculosis in medical school from aspect of sanitariums: Takeshi OGURA (Toneyama National Hospital) 5. How to avoid infecting TB and to prevent contracting TB while medical and nursing practices: Keiichi NAGAO (Health Sciences, Center, Chiba University), et al. 6. Special speech: A review of the year since TB patient rooms were included in a common ward as a part of ministry of welfare's model project: Shuji KURANE (Fourth Department of Internal Medicine, Nippon Medical School) Tuberculosis began to rank first in mortality rate in Japan in the Meiji Era, and especially since it did not conform to the "national wealth and military strength" that was the national policy of the time due to the high mortality rates in the early decades of life, it was referred to as the "disease that was destroying the country" and the "pandemic disease." Even after entering the Showa Era, tuberculosis long occupied first place as the cause of death in Japan, and it raged unchecked for a period after World War II. However, the prognosis of tuberculosis as a whole improved considerably as a result of the development of antituberculosis agents, such as streptomycin, and the advent of rifampicin made it a curable disease. Its rank as a cause of death subsequently fell precipitously, and many of the TB wards that had been established in university hospitals were closed as the numbers of patients rapidly declined. At the present time, only 22 of the 80 university hospitals in the country have TB wards or TB beds, and 18 of the hospitals that had TB wards have closed them. Two of them closed them prior to 1964, 6 between 1965 and 1974, 4 between 1975 and 1984, 4 between 1985 and 1994, and 2 since 1995. Thus, it would be no exaggeration to say that there has been a steady decline in the TB wards of university hospitals. It is fairly easy to surmise that the result has been a decrease in the opportunities and time available for educating medical students about tuberculosis. Today, university hospitals not only accept medical students, but 80% of clinical residents as well, and they too have lost opportunities for education concerning tuberculosis. We would hope that the concern of Japanese physicians regarding tuberculosis has not diminished in proportion to the decrease in TB wards in our university hospitals. However, as is truly revealed by the expression "doctor's delay" in the diagnosis and treatment of tuberculosis, it is a fact that physicians no longer bear pulmonary tuberculosis in mind when diagnosing and treating patients with respiratory disease, and that as a result diagnosis is delayed, treatment is drawn out, and in the worst-case scenario, we see scattered instances of a tragic outcome. When we consider the recent conditions in society, as reported in recent newspapers, tuberculosis is not a disease that is on the decline at all in Japan today. However, as stated above, but if the concern of ordinary physicians has drifted away from tuberculosis, it is fair to say that it is not only a major problem medically, but socially as well. Consideration of the tuberculosis education in university medical schools seems to be opportune at this time. Professor Shimokata of Nagoya University, who is chairperson of the Japan Tuberculosis Education Committee, outlined the problems of tuberculosis education in his speech at this symposium. (ABSTRACT TRUNCATED)

Mycobacterium tuberculosis causing tuberculous lymphadenitis in Maputo, Mozambique.

PubMed

Viegas, Sofia Omar; Ghebremichael, Solomon; Massawo, Leguesse; Alberto, Matos; Fernandes, Fabíola Couto; Monteiro, Eliane; Couvin, David; Matavele, José Maiane; Rastogi, Nalin; Correia-Neves, Margarida; Machado, Adelina; Carrilho, Carla; Groenheit, Ramona; Källenius, Gunilla; Koivula, Tuija

2015-11-21

The zoonosis bovine tuberculosis (TB) is known to be responsible for a considerable proportion of extrapulmonary TB. In Mozambique, bovine TB is a recognised problem in cattle, but little has been done to evaluate how Mycobacterium bovis has contributed to human TB. We here explore the public health risk for bovine TB in Maputo, by characterizing the isolates from tuberculous lymphadenitis (TBLN) cases, a common manifestation of bovine TB in humans, in the Pathology Service of Maputo Central Hospital, in Mozambique, during one year. Among 110 patients suspected of having TBLN, 49 had a positive culture result. Of those, 48 (98%) were positive for Mycobacterium tuberculosis complex and one for nontuberculous mycobacteria. Of the 45 isolates analysed by spoligotyping and Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR), all were M. tuberculosis. No M. bovis was found. Cervical TBLN, corresponding to 39 (86.7%) cases, was the main cause of TBLN and 66.7% of those where from HIV positive patients. We found that TBLN in Maputo was caused by a variety of M. tuberculosis strains. The most prevalent lineage was the EAI (n = 19; 43.2%). Particular common spoligotypes were SIT 48 (EAI1_SOM sublineage), SIT 42 (LAM 9), SIT 1 (Beijing) and SIT53 (T1), similar to findings among pulmonary cases. M. tuberculosis was the main etiological agent of TBLN in Maputo. M. tuberculosis genotypes were similar to the ones causing pulmonary TB, suggesting that in Maputo, cases of TBLN arise from the same source as pulmonary TB, rather than from an external zoonotic source. Further research is needed on other forms of extrapulmonary TB and in rural areas where there is high prevalence of bovine TB in cattle, to evaluate the risk of transmission of M. bovis from cattle to humans.

Current knowledge and pending challenges in zoonosis caused by Mycobacterium bovis: a review.

PubMed

Pérez-Lago, Laura; Navarro, Yurena; García-de-Viedma, Darío

2014-10-01

Mycobacterium bovis is both the causative agent of bovine tuberculosis (TB) and a zoonotic pathogen. In humans, considerably fewer cases of TB are caused by M. bovis than M. tuberculosis; nevertheless, diagnostic limitations mean that currently available data on prevalence grossly underestimate the true dimension of the problem. The routes of transmission from animals to humans are well known and include direct exposure to infected animals or consumption of contaminated animal products. Application of fingerprinting tools facilitates analysis of the molecular epidemiology of M. bovis in animal-to-human and human-to-human transmission. Apart from cattle and M. bovis, other animal species and members within the M. tuberculosis complex can contribute to the zoonosis. Improvements in diagnostic techniques, application of more advanced discriminatory genotyping tools, and collaboration between veterinary and human health care researchers are key to our understanding of this zoonosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

USDA-ARS?s Scientific Manuscript database

Background: Early and unambiguous detection of bovine tuberculosis (bTB), a significant disease of cattle worldwide, is necessary to control the spread of infection to other animals and humans. Current testing strategies are laborious, time consuming and heavily reliant on host responses that do n...

Transmission of Mycobacterium tuberculosis between Farmers and Cattle in Central Ethiopia

PubMed Central

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

2013-01-01

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

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

PubMed

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

2013-01-01

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

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).

Multidrug-resistant tuberculosis/rifampicin-resistant tuberculosis: Principles of management

PubMed Central

Prasad, Rajendra; Gupta, Nikhil; Banka, Amitabh

2018-01-01

Multidrug-resistant tuberculosis (MDR-TB)/rifampicin-resistant TB (RR-TB) is human-made problem and emerging due to poor management of TB and is a threat to control of TB. Early suspicion and diagnosis are important. Culture and drug susceptibility testing are gold standards, but newer molecular methods help in rapid diagnosis. Once diagnosed, prompt treatment should be started, preferably under direct observation. Treatment can be standardized or individualized. Conventional regimen takes up to 24 months but recently shorter regimen of up to 12 months was introduced in specific subset of MDR-TB/RR-TB patients. Management of MDR-TB/RR-TB is complicated, costlier, and challenging and is a concern for human health worldwide. It must be emphasized that optimal treatment of MDR-TB/RR-TB alone is not sufficient. Efforts must be made to ensure effective use of first- and second-line anti-TB drugs. PMID:29319042

Multidrug-resistant tuberculosis/rifampicin-resistant tuberculosis: Principles of management.

PubMed

Prasad, Rajendra; Gupta, Nikhil; Banka, Amitabh

2018-01-01

Multidrug-resistant tuberculosis (MDR-TB)/rifampicin-resistant TB (RR-TB) is human-made problem and emerging due to poor management of TB and is a threat to control of TB. Early suspicion and diagnosis are important. Culture and drug susceptibility testing are gold standards, but newer molecular methods help in rapid diagnosis. Once diagnosed, prompt treatment should be started, preferably under direct observation. Treatment can be standardized or individualized. Conventional regimen takes up to 24 months but recently shorter regimen of up to 12 months was introduced in specific subset of MDR-TB/RR-TB patients. Management of MDR-TB/RR-TB is complicated, costlier, and challenging and is a concern for human health worldwide. It must be emphasized that optimal treatment of MDR-TB/RR-TB alone is not sufficient. Efforts must be made to ensure effective use of first- and second-line anti-TB drugs.

Tuberculosis

MedlinePlus

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

Antimycobacterial and cytotoxic activity of selected medicinal plant extracts

PubMed Central

Nguta, Joseph M.; Appiah-Opong, Regina; Nyarko, Alexander K.; Yeboah-Manu, Dorothy; Addo, Phyllis G.A.; Otchere, Isaac; Kissi-Twum, Abena

2016-01-01

Ethnopharmacological relevance Tuberculosis (TB) caused by Mycobacterium tuberculosis remains an ongoing threat to human health. Several medicinal plants are used traditionally to treat tuberculosis in Ghana. The current study was designed to investigate the antimycobacterial activity and cytotoxicity of crude extracts from five selected medicinal plants. Material and methods The microplate alamar blue assay (MABA) was used for antimycobacterial studies while the CellTiter 96® AQueous Assay, which is composed of solutions of a novel tetrazolium compound [3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt; MTS] and an electron coupling reagent (phenazine methosulfate) PMS, was used for cytotoxic studies. Correlation coefficients were used to compare the activity of crude extracts against nonpathogenic strains and the pathogenic Mycobacterium tuberculosis subsp.tuberculosis. Results Results of the MIC determinations indicated that all the crude extracts were active on all the three tested mycobacterial strains. Minimum inhibitory concentration values as low as 156.3 µg/mL against M. tuberculosis; Strain H37Ra (ATCC® 25,177™) were recorded from the leaves of Solanum torvum Sw. (Solanaceae). Cytotoxicity of the extracts varied, and the leaves from S. torvum had the most promising selectivity index. Activity against M. tuberculosis; Strain H37Ra was the best predictor of activity against pathogenic Mycobacterium tuberculosis subsp.tuberculosis (correlation coefficient=0.8). Conclusion The overall results of the present study provide supportive data on the use of some medicinal plants for tuberculosis treatment. The leaves of Solanum torvum are a potential source of anti-TB natural products and deserve further investigations to develop novel anti-TB agents against sensitive and drug resistant strains of M. tuberculosis. PMID:26875647

Advances in diagnosis and treatment of latent tuberculosis infection.

PubMed

Chapman, Helena J; Lauzardo, Michael

2014-01-01

In the United States, latent tuberculosis infection (LTBI) affects between 10 and 15 million people, of whom 10% may develop active tuberculosis disease. People at increased risk for tuberculosis reactivation include recent immigrants from countries with a high incidence of tuberculosis, children younger than age 5, people who have been infected with Mycobacterium tuberculosis within the past 2 years, or people with immunosuppression for a variety of reasons. Appropriate diagnosis and treatment of LTBI are critical for controlling and eventually eliminating tuberculosis as a public health problem. Although the tuberculin skin test is the traditional diagnostic measure for LTBI, reduced specificity has promoted the development and utilization of the interferon-γ release assays as an in vitro blood test with specific antigens to M. tuberculosis (QuantiFERON-TB Gold In-Tube test and the T.SPOT-TB test are commercially available). Despite the rise of the new diagnostic tests, however, there is still no gold standard for diagnosing LTBI, and epidemiologic risks and comorbidities need to be taken into account before initiating therapy. Current diagnostic tests combined with recommended treatment regimens are valuable tools that, when used correctly, promise to hurry the elimination of tuberculosis. © Copyright 2014 by the American Board of Family Medicine.

Tuberculosis-resistant transgenic cattle

USDA-ARS?s Scientific Manuscript database

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

Integrating HIV testing and care into tuberculosis services in Benin: programmatic aspects.

PubMed

Ferroussier, O; Dlodlo, R A; Capo-Chichi, D; Boillot, F; Gninafon, M; Trébucq, A; Fujiwara, P I

2013-11-01

Between 2005 and 2008, the diagnosis and care of human immunodeficiency virus (HIV) infection and tuberculosis (TB) services were integrated in Benin. The appointment of a TB-HIV Coordinator by the National Tuberculosis Control Programme and quarterly supervisory visits to TB clinics have bolstered the implementation of integrated HIV-TB activities. HIV testing and cotrimoxazole preventive therapy were integrated smoothly into the TB services. The strategy chosen to facilitate access of HIV-positive TB patients to antiretroviral treatment contributed to greater integration over time, but perpetuated, for some, the burden of attending two facilities. The integration and decentralisation of TB and HIV care services at national level in Benin resulted in a high uptake of HIV services among TB patients.

Tuberculosis Data and Statistics

MedlinePlus

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

Field Application of Serodiagnostics To Identify Elephants with Tuberculosis prior to Case Confirmation by Culture

PubMed Central

Greenwald, Rena; Esfandiari, Javan; Mikota, Susan; Miller, Michele; Moller, Torsten; Vogelnest, Larry; Gairhe, Kamal P.; Robbe-Austerman, Suelee; Gai, Jackie; Waters, W. Ray

2012-01-01

Three serologic methods for antibody detection in elephant tuberculosis (TB), the multiantigen print immunoassay (MAPIA), ElephantTB STAT-PAK kit, and DPP VetTB test, were evaluated using serial serum samples from 14 captive elephants infected with Mycobacterium tuberculosis in 5 countries. In all cases, serological testing was performed prior to the diagnosis of TB by mycobacterial culture of trunk wash or tissue samples collected at necropsy. All elephants produced antibody responses to M. tuberculosis antigens, with 13/14 recognizing ESAT-6 and/or CFP10 proteins. The findings supported the high serodiagnostic test accuracy in detecting infections months to years before M. tuberculosis could be isolated from elephants. The MAPIA and/or DPP VetTB assay demonstrated the potential for monitoring antimycobacterial therapy and predicting TB relapse in treated elephants when continuously used in the posttreatment period. History of exposure to TB and past treatment information should be taken into consideration for proper interpretation of the antibody test results. Data suggest that the more frequent trunk wash culture testing of seropositive elephants may enhance the efficiency of the TB diagnostic algorithm, leading to earlier treatment with improved outcomes. PMID:22695162

Geographically weighted poisson regression semiparametric on modeling of the number of tuberculosis cases (Case study: Bandung city)

NASA Astrophysics Data System (ADS)

Octavianty, Toharudin, Toni; Jaya, I. G. N. Mindra

2017-03-01

Tuberculosis (TB) is a disease caused by a bacterium, called Mycobacterium tuberculosis, which typically attacks the lungs but can also affect the kidney, spine, and brain (Centers for Disease Control and Prevention). Indonesia had the largest number of TB cases after India (Global Tuberculosis Report 2015 by WHO). The distribution of Mycobacterium tuberculosis genotypes in Indonesia showed the high genetic diversity and tended to vary by geographic regions. For instance, in Bandung city, the prevalence rate of TB morbidity is quite high. A number of TB patients belong to the counted data. To determine the factors that significantly influence the number of tuberculosis patients in each location of the observations can be used statistical analysis tool that is Geographically Weighted Poisson Regression Semiparametric (GWPRS). GWPRS is an extension of the Poisson regression and GWPR that is influenced by geographical factors, and there is also variables that influence globally and locally. Using the TB Data in Bandung city (in 2015), the results show that the global and local variables that influence the number of tuberculosis patients in every sub-district.

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

Using cost and health impacts to prioritize the targeted testing of tuberculosis in the United States.

PubMed

Miller, Thaddeus L; Hilsenrath, Peter; Lykens, Kristine; McNabb, Scott J N; Moonan, Patrick K; Weis, Stephen E

2006-04-01

Evaluation improves efficiency and effectiveness. Current U.S. tuberculosis (TB) control policies emphasize the treatment of latent TB infection (LTBI). However, this policy, if not targeted, may be inefficient. We determined the efficiency of a state-law mandated TB screening program and a non state-law mandated one in terms of cost, morbidity, treatment, and disease averted. We evaluated two publicly funded metropolitan TB prevention and control programs through retrospective analyses and modeling. Main outcomes measured were TB incidence and prevalence, TB cases averted, and cost. A non state-law mandated TB program for homeless persons in Tarrant County screened 4.5 persons to identify one with LTBI and 82 persons to identify one with TB. A state-law mandated TB program for jail inmates screened 109 persons to identify one with LTBI and 3274 persons to identify one with TB. The number of patients with LTBI treated to prevent one TB case was 12.1 and 15.3 for the homeless and jail inmate TB programs, respectively. Treatment of LTBI by the homeless and jail inmate TB screening programs will avert 11.9 and 7.9 TB cases at a cost of 14,350 US dollars and 34,761 US dollars per TB case, respectively. Mandated TB screening programs should be risk-based, not population-based. Non mandated targeted testing for TB in congregate settings for the homeless was more efficient than state-law mandated targeted testing for TB among jailed inmates.

Chemokines additional to IFN-γ can be used to differentiate among Mycobacterium tuberculosis infection possibilities and provide evidence of an early clearance phenotype.

PubMed

Nonghanphithak, Ditthawat; Reechaipichitkul, Wipa; Namwat, Wises; Naranbhai, Vivek; Faksri, Kiatichai

2017-07-01

Current diagnostic tests for tuberculosis (TB) remain limited in their ability to discriminate between active TB (ATB) and latent TB infection (LTBI). Early clearance (EC) of TB by individuals exposed to Mycobacterium tuberculosis is a debated phenomenon for which evidence is lacking. We measured and compared secreted chemokines in the plasma fraction from 48 ATB, 38 LTBI, 162 presumed EC and 39 healthy controls (HC) using the QuantiFERON ® -TB Gold In-Tube assay. Single chemokine markers were limited in their ability to discriminate between ATB and LTBI: IFN-γ showed 16.7% sensitivity; CCL2 showed moderate sensitivity (70.8%) and specificity (74.4%); CXCL10 showed high sensitivity (87.5%) and specificity (78.9%). Compared to IFN-γ alone, IFN-γ combined with CXCL10 significantly improved (p < 0.001) the sensitivity and specificity to discriminate between ATB and HC (97.9% sensitivity and 94.9% specificity) and between ATB and LTBI (89.6% sensitivity and 71.1% specificity). Levels of CCL2 were very significantly lower (p < 0.0001) in EC compared to HC groups and hence CCL2 is a useful marker for EC. This study demonstrated the potential application of profiling using multiple chemokines for differentiating among the various M. tuberculosis infection possibilities. We also present evidence to support the EC phenomenon based on the decrease of CCL2 levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparison of the yield of tuberculosis among contacts of multidrug-resistant and drug-sensitive tuberculosis patients in Ethiopia using GeneXpert as a primary diagnostic test.

PubMed

Hiruy, Nebiyu; Melese, Muluken; Habte, Dereje; Jerene, Degu; Gashu, Zewdu; Alem, Genetu; Jemal, Ilili; Tessema, Belay; Belayneh, Beza; Suarez, Pedro G

2018-06-01

This study compared the yield of tuberculosis (TB) among contacts of multidrug-resistant tuberculosis (MDR-TB) index cases with that in drug-sensitive TB (DS-TB) index cases in a program setting. A comparative cross-sectional study was conducted among contacts of sputum smear-positive new DS-TB index cases and MDR-TB index cases. After contacts were screened, GeneXpert was used for the diagnosis of TB. The study included 111 MDR-TB and 119 DS-TB index cases. A total of 340 and 393 contacts of MDR-TB and DS-TB index cases, respectively, were traced, of whom 331 among MDR-TB contacts and 353 among DS-TB contacts were screened. There were 20 (6%) presumptive TB cases for MDR-TB contacts and 41 (11%) for DS-TB contacts. The prevalence of TB among MDR-TB contacts was 2.7% and among DS-TB contacts was 4.0%. The majority of the MDR-TB contacts diagnosed with TB had MDR-TB; the reverse was true for DS-TB. The yield of TB among contacts of MDR-TB and DS-TB patients using GeneXpert was high as compared to the population-level prevalence. The likelihood of diagnosing rifampicin-resistant TB among contacts of MDR-TB index cases was higher in comparison with contacts of DS-TB index cases. The use of GeneXpert in DS-TB contact investigation has the added advantage of diagnosing rifampicin-resistant TB cases when compared to the use of the nationally recommended acid-fast bacillus (AFB) microscopy for DS-TB contact investigation. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Knowledge and perceptions of national and provincial tuberculosis control programme managers in Pakistan about the WHO Stop TB strategy: a qualitative study

PubMed Central

Khan, Wasiq Mehmood; Smith, Helen; Qadeer, Ejaz

2016-01-01

Objective To understand how national and provincial tuberculosis programme managers in Pakistan perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. National and provincial tuberculosis programme managers play an important role in effective implementation of the Stop TB strategy. Design A qualitative interview study was conducted with 10 national and provincial tuberculosis programme managers to understand how they perceive and engage with the Stop TB strategy, its strengths, weaknesses and their experience in its implementation. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). Participants National and provincial tuberculosis programme managers in Pakistan. Managers were selected purposively; 10 managers were interviewed (six national staff and four from provincial level). Setting National and provincial tuberculosis programmes in Pakistan Main outcome measures 1. Knowledge and perceptions of national and provincial tuberculosis programme managers about the Stop TB strategy 2. Progress in implementing the strategy in Pakistan 3. Significant success factors 4. Significant implementation challenges 5. Lessons learnt to scale up successful implementation. Results The managers reported that most progress had been made in extending DOTS, health systems strengthening, public -private mixed interventions, MDR-TB care and TB/HIV care. The four factors that contributed significantly to progress were the availability of DOTS services, the public-private partnership approach, comprehensive guidance for TB control and government and donor commitment to TB control. Conclusion This study identified three main challenges as perceived by national and provincial tuberculosis programme managers in terms of implementing the Stop TB strategy: 1. Inadequate political commitment, 2. Issue pertaining to prioritisation of certain components in the TB strategy over others due to external influences and 3. Limitations in the overall health system. To improve the tuberculosis control programme in the country political commitment needs to be enhanced and public -private partnerships increased. This can be done through government prioritisation of TB control at both national and provincial levels; donor-funded components should not receive undue attention; and partnerships with the private health sector, health institutions not yet covered by DOTS services, non-governmental organisations and patient coalitions should be increased. PMID:28203383

Animal-adapted members of the Mycobacterium tuberculosis complex endemic to the southern African subregion.

PubMed

Clarke, Charlene; Van Helden, Paul; Miller, Michele; Parsons, Sven

2016-04-26

Members of the Mycobacterium tuberculosis complex (MTC) cause tuberculosis (TB) in both animals and humans. In this article, three animal-adapted MTC strains that are endemic to the southern African subregion - that is, Mycobacterium suricattae, Mycobacterium mungi, and the dassie bacillus - are reviewed with a focus on clinical and pathological presentations, geographic distribution, genotyping methods, diagnostic tools and evolution. Moreover, factors influencing the transmission and establishment of TB pathogens in novel host populations, including ecological, immunological and genetic factors of both the host and pathogen, are discussed. The risks associated with these infections are currently unknown and further studies will be required for greater understanding of this disease in the context of the southern African ecosystem.

Animal-adapted members of the Mycobacterium tuberculosis complex endemic to the southern African subregion.

PubMed

Clarke, Charlene; Van Helden, Paul; Miller, Michele; Parsons, Sven

2016-04-26

Members of the Mycobacterium tuberculosis complex (MTC) cause tuberculosis (TB) in both animals and humans. In this article, three animal-adapted MTC strains that are endemic to the southern African subregion - that is, Mycobacterium suricattae, Mycobacterium mungi, and the dassie bacillus - are reviewed with a focus on clinical and pathological presentations, geographic distribution, genotyping methods, diagnostic tools and evolution. Moreover, factors influencing the transmission and establishment of TB pathogens in novel host populations, including ecological, immunological and genetic factors of both the host and pathogen, are discussed. The risks associated with these infections are currently unknown and further studies will be required for greater understanding of this disease in the context of the southern African ecosystem.

A Study of the Patients Suffering from Tuberculosis and Tuberculosis-diabetes Comorbidity in Revised National Tuberculosis Control Program Centers of Northern Madhya Pradesh, India.

PubMed

Agarwal, Anil Kumar; Gupta, Ginisha; Marskole, Priyesh; Agarwal, Anju

2017-01-01

Diabetes mellitus (DM) is recognized as an important risk factor to tuberculosis (TB). India has high TB burden, along with rising DM prevalence. This study was conducted to document the coexistence of DM and TB in persons with established TB under the Revised National Tuberculosis Control Program. This was a cross-sectional, descriptive observational study conducted at selected Directly Observed Therapy center in Gwalior North Central India. A total of 550 patients with confirmed diagnosis of TB and on treatment were recruited. The study participants were screened for DM and diagnoses were made on the basis of the World Health Organization criteria. Clinical parameters were compared between persons with DM and those without DM. DM/TB co-morbidity was noted in 85 individuals and these made up 15.4% of the study population. The mean age was higher in DM patients with TB (43.4 ± 15.4 vs. 33.1 ± 16.2 years, P = 0.000); the mean duration of symptoms of TB with DM was more (124 ± 16.4 vs. 107.49 ± 10.3 days). Multinomial logistic regression analysis showed that increasing age, positive family history of diabetes, sedentary occupation, and presence of pulmonary TB were significantly associated with diabetes among TB patients. Diabetes is an important co-morbid feature to be sought in patients with TB. This study re-echo the need to raise awareness on screening for DM in persons with TB.

Delamanid Kills Dormant Mycobacteria In Vitro and in a Guinea Pig Model of Tuberculosis.

PubMed

Chen, Xiuhao; Hashizume, Hiroyuki; Tomishige, Tatsuo; Nakamura, Izuru; Matsuba, Miki; Fujiwara, Mamoru; Kitamoto, Ryuki; Hanaki, Erina; Ohba, Yoshio; Matsumoto, Makoto

2017-06-01

Tuberculosis (TB) treatment is long and requires multiple drugs, likely due to various phenotypes of TB bacilli with variable drug susceptibilities. Drugs with broad activity are urgently needed. This study aimed to evaluate delamanid's activity against growing or dormant bacilli in vitro as well as in vivo Cultures of Mycobacterium bovis BCG Tokyo under aerobic and anaerobic conditions were used to study the activity of delamanid against growing and dormant bacilli, respectively. Delamanid exhibited significant bactericidal activity against replicating and dormant bacilli at or above concentrations of 0.016 and 0.4 mg/liter, respectively. To evaluate delamanid's antituberculosis activity in vivo , we used a guinea pig model of chronic TB infection in which the lung lesions were similar to those in human TB disease. In the guinea pig TB model, a daily dose of 100 mg delamanid/kg of body weight for 4 or 8 weeks demonstrated strong bactericidal activity against Mycobacterium tuberculosis Importantly, histological examination revealed that delamanid killed TB bacilli within hypoxic lesions of the lung. The combination regimens containing delamanid with rifampin and pyrazinamide or delamanid with levofloxacin, ethionamide, pyrazinamide, and amikacin were more effective than the standard regimen (rifampin, isoniazid, and pyrazinamide). Our data show that delamanid is effective in killing both growing and dormant bacilli in vitro and in the guinea pig TB model. Adding delamanid to current TB regimens may improve treatment outcomes, as demonstrated in recent clinical trials with pulmonary multidrug-resistant (MDR) TB patients. Delamanid may be an important drug for consideration in the construction of new regimens to shorten TB treatment duration. Copyright © 2017 American Society for Microbiology.

The fourth national anti-tuberculosis drug resistance survey in Viet Nam.

PubMed

Nhung, N V; Hoa, N B; Sy, D N; Hennig, C M; Dean, A S

2015-06-01

Viet Nam's Fourth National Anti-Tuberculosis Drug Resistance Survey was conducted in 2011. To determine the prevalence of resistance to the four main first-line anti-tuberculosis drugs in Viet Nam. Eighty clusters were selected using a probability proportion to size approach. Drug susceptibility testing (DST) against the four main first-line anti-tuberculosis drugs was performed. A total of 1629 smear-positive tuberculosis (TB) patients were eligible for culture. Of these, DST results were available for 1312 patients, including 1105 new TB cases, 195 previously treated TB cases and 12 cases with an unknown treatment history. The proportion of cases with resistance to any drug was 32.7% (95%CI 29.1-36.5) among new cases and 54.2% (95%CI 44.3-63.7) among previously treated cases. The proportion of multidrug-resistant TB (MDR-TB) cases was 4.0% (95%CI 2.5-5.4) in new cases and 23.3 (95%CI 16.7-29.9) in previously treated cases. The fourth drug resistance survey in Viet Nam found that the proportion of MDR-TB among new and previously treated cases was not significantly different from that in the 2005 survey. The National TB Programme should prioritise the detection and treatment of MDR-TB to reduce transmission of MDR-TB in the community.

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)

Drug-Resistant Tuberculosis among Children, China, 2006–2015

PubMed Central

Tao, Ning-ning; He, Xiao-chun; Zhang, Xian-xin; Liu, Yao; Yu, Chun-bao

2017-01-01

Microbial drug resistance has become a major public health concern worldwide. To acquire epidemiologic data on drug-resistant tuberculosis (DR TB) among children, a major cause of illness and death for this population, we conducted a retrospective study of 2006–2015 data from 36 TB prevention and control institutions in Shandong Province, China. A total of 14,223 new TB cases, among which children (<18 years of age) accounted for only 5.5%, were caused by culture-confirmed Mycobacterium tuberculosis. Among children with TB, 18.9% had DR TB and 6.9% had multidrug-resistant TB. Over the past decade, the percentage of DR TB; multidrug-resistant TB; and overall first-line drug resistance for isoniazid, rifampin, ethambutol, and streptomycin among children increased significantly (at least 12%). Understanding the long-term trends of DR TB among children can shed light on the performance of TB control programs, thereby contributing to global TB control. PMID:29047424

Evaluation of the performance of two tuberculosis interferon gamma release assays (IGRA-ELISA and T-SPOT.TB) for diagnosing Mycobacterium tuberculosis infection.

PubMed

Wang, Linchuan; Tian, Xu-Dong; Yu, Yan; Chen, Wei

2018-04-01

The IGRA-ELISA and T-SPOT.TB are widely used in China. The aim of the study was to evaluate the performance of the two assays in diagnosis Mycobacterium tuberculosis infection. Of the 3727 patients in the study, 204 underwent testing using both the T-SPOT.TB and IGRA-ELISA, 1794 were tested using the T-SPOT.TB only, and 1729 were tested using the IGRA-ELISA only. The positive rate and consistency of the two assays were analyzed, and their sensitivity and specificity for diagnosing active tuberculosis were compared. There were no significant differences in the positive rate between the T-SPOT.TB test (25.8%) and IGRA-ELISA (28.6%), p = .065. The two assays were highly consistent, with a kappa value of 0.852 (p < .0001) and a total coincidence rate of 92.7%. For the diagnosis of active tuberculosis, the sensitivity and specificity values of the T-SPOT.TB test were 82.9% (107/129) and 78.6% (1309/1665), respectively, and those of IGRA-ELISA were 81.7% (94/115) and 75.2% (1214/1614), respectively. There were no significant differences in sensitivity (p > .05), but the specificity of the T-SPOT.TB test was slightly higher than that of IGRA-ELISA (p = .023). Both in terms of diagnosing M. tuberculosis infection and ruling out active tuberculosis, the performance of the IGRA-ELISA-a simple, almost labor-free assay that allows simultaneous processing of a very large number of samples-was well-matched with that of T-SPOT.TB test. However, IGRAs cannot be used as the only test to diagnose active tuberculosis. Copyright © 2018 Elsevier B.V. All rights reserved.

Validated methods for identifying tuberculosis patients in health administrative databases: systematic review.

PubMed

Ronald, L A; Ling, D I; FitzGerald, J M; Schwartzman, K; Bartlett-Esquilant, G; Boivin, J-F; Benedetti, A; Menzies, D

2017-05-01

An increasing number of studies are using health administrative databases for tuberculosis (TB) research. However, there are limitations to using such databases for identifying patients with TB. To summarise validated methods for identifying TB in health administrative databases. We conducted a systematic literature search in two databases (Ovid Medline and Embase, January 1980-January 2016). We limited the search to diagnostic accuracy studies assessing algorithms derived from drug prescription, International Classification of Diseases (ICD) diagnostic code and/or laboratory data for identifying patients with TB in health administrative databases. The search identified 2413 unique citations. Of the 40 full-text articles reviewed, we included 14 in our review. Algorithms and diagnostic accuracy outcomes to identify TB varied widely across studies, with positive predictive value ranging from 1.3% to 100% and sensitivity ranging from 20% to 100%. Diagnostic accuracy measures of algorithms using out-patient, in-patient and/or laboratory data to identify patients with TB in health administrative databases vary widely across studies. Use solely of ICD diagnostic codes to identify TB, particularly when using out-patient records, is likely to lead to incorrect estimates of case numbers, given the current limitations of ICD systems in coding TB.

Diabetes mellitus and tuberculosis facts and controversies

PubMed Central

2013-01-01

Tuberculosis (TB) and diabetes mellitus (DM) are both important health issues. A bidirectional association between them has been demonstrated by many researchers. The link of DM and TB is more prominent in developing countries where TB is endemic and the burden of diabetes mellitus is increasing. The association between diabetes and tuberculosis may be the next challenge for global tuberculosis control worldwide. Proper planning and collaboration are necessary to reduce the dual burden of diabetes and TB. One model similar to the TB-HIV program for prevention, screening and treatment of both diseases can be the best approach. In this paper, we review existing data and discuss the matters of controversy that would be helpful for determining research priorities in different countries. PMID:24360398

Completeness and timeliness of tuberculosis notification in Taiwan

PubMed Central

2011-01-01

Tuberculosis (TB) is a notifiable disease by the Communicable Disease Control Law in Taiwan. Several measures have been undertaken to improve reporting of TB but the completeness and timeliness of TB notification in Taiwan has not yet been systemically evaluated. Methods To assess completeness and timeliness of TB notification, potential TB cases diagnosed by health care facilities in the year 2005-2007 were identified using the reimbursement database of national health insurance (NHI), which has 99% population coverage in Taiwan. Potential TB patients required notification were defined as those who have TB-related ICD-9 codes (010-018) in the NHI reimbursement database in 2005-2007, who were not diagnosed with TB in previous year, and who have been prescribed with 2 or more types of anti-TB drugs. Each potential TB case was matched to the national TB registry maintained at Taiwan Centers for Disease Control (CDC) by using national identity number or, if non-citizen, passport number to determine whether the patients had been notified to local public health authorities and Taiwan CDC. The difference in the number of days between date of anti-tuberculosis treatment and date of notification was calculated to determine the timeliness of TB reporting. Results Of the 57,405 TB patients who were prescribed with 2 or more anti-tuberculosis drugs, 55,291 (96.3%) were notified to National TB Registry and 2,114 (3.7%) were not. Of the 55,291 notified cases, 45,250 (81.8%) were notified within 7 days of anti-tuberculosis treatment (timely reporting) and 10,041(18.2%) after 7 days (delayed reporting). Factors significantly associated with failure of notification are younger age, previously notified cases, foreigner, those who visited clinics and those who visited health care facilities only once or twice in 6 months. Conclusion A small proportion of TB cases were not notified and a substantial proportion of notified TB cases had delayed reporting, findings with implication for strengthening surveillance of tuberculosis in Taiwan. Countries where the completeness and timeliness of TB notification has not yet been evaluated should take similar action to strengthen surveillance of TB. PMID:22151346

Use of transrenal DNA for the diagnosis of extrapulmonary tuberculosis in children: a case of tubercular otitis media.

PubMed

Petrucci, Roberta; Lombardi, Giulia; Corsini, Ilaria; Visciotti, Francesca; Pirodda, Antonio; Cazzato, Salvatore; Landini, Maria Paola; Dal Monte, Paola

2015-01-01

The diagnosis of tuberculosis (TB) is difficult in children, especially for smear-negative pulmonary and extrapulmonary TB, which are common at this age. We report an 11-year-old girl with TB otitis media with negative smear microscopy and Xpert MTB/RIF but positive Mycobacterium tuberculosis-specific transrenal DNA (Tr-MTB-DNA) test results and culture for M. tuberculosis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Market size and sales pattern of tuberculosis drugs in the Philippines.

PubMed

Islam, T; van Weezenbeek, C; Vianzon, R; Garfin, A M C G; Hiatt, T; Lew, W J; Tisocki, K

2013-12-21

To identify the availability, types and quantity of anti-tuberculosis drugs in the public and private sectors from 2007 to 2011 in the Philippines. Analysis of the procurement of and sales data on anti-tuberculosis drugs from both the public and private sectors from 2007 to 2011. Publicly procured anti-tuberculosis drugs were sufficient to treat all reported new tuberculosis (TB) cases from 2007 to 2011 in the Philippines. Nevertheless, the volume of anti-tuberculosis drugs in the private sector would have sufficed for the intensive phase of treatment for an additional 250 000 TB patients annually, assuming compliance with national treatment guidelines. Fixed-dose combination drugs comprised the main bulk (81%) of private market sales, while sales of loose drugs decreased over the years. Combining public and private sales in 2011, 484 725 new TB patients, i.e., 2.4 times the number of notified cases, could have been placed on treatment and treated for at least the intensive phase. Key second-line drugs are not available in the private market, making it impossible to design an adequate treatment regimen for multidrug-resistant TB (MDR-TB) in the private sector. An enormous quantity of anti-tuberculosis drugs was channelled through the private market outside the purview of the Philippine National Tuberculosis Control Program, suggesting significant out-of-pocket expenditure, severe underreporting of TB cases and/or misuse of drugs due to overdiagnosis and overtreatment.

Direct and indirect costs of tuberculosis among immigrant patients in the Netherlands.

PubMed

Kik, Sandra V; Olthof, Sandra P J; de Vries, Jonie T N; Menzies, Dick; Kincler, Naomi; van Loenhout-Rooyakkers, Joke; Burdo, Conny; Verver, Suzanne

2009-08-05

In low tuberculosis (TB) incidence countries TB affects mostly immigrants in the productive age group. Little empirical information is available about direct and indirect TB-related costs that patients face in these high-income countries. We assessed the direct and indirect costs of immigrants with TB in the Netherlands. A cross-sectional survey at 14 municipal health services and 2 specialized TB hospitals was conducted. Interviews were administered to first or second generation immigrants, 18 years or older, with pulmonary or extrapulmonary TB, who were on treatment for 1-6 months. Out of pocket expenditures and time loss, related to TB, was assessed for different phases of the current TB illness. In total 60 patients were interviewed. Average direct costs spent by households with a TB patient amounted euro353. Most costs were spent when being hospitalized. Time loss (mean 81 days) was mainly due to hospitalization (19 days) and additional work days lost (60 days), and corresponded with a cost estimation of euro2603. Even in a country with a good health insurance system that covers medication and consultation costs, patients do have substantial extra expenditures. Furthermore, our patients lost on average 2.7 months of productive days. TB patients are economically vulnerable.

Impact of Euro-American sublineages of Mycobacterium tuberculosis on new infections among named contacts.

PubMed

Feng, J-Y; Jarlsberg, L G; Rose, J; Grinsdale, J A; Janes, M; Higashi, J; Osmond, D H; Nahid, P; Hopewell, P C; Kato-Maeda, M

2017-05-01

The impact of demographic, clinical, and bacterial factors on new infection by Euro-American lineage Mycobacterium tuberculosis among contacts of patients with tuberculosis (TB) has not been evaluated. To describe the risk factors for new infection by Euro-American M. tuberculosis sublineages in San Francisco, California. We included contacts of patients with TB due to Euro-American M. tuberculosis. Sublineages were determined by large-sequence polymorphisms. We used tuberculin skin testing or QuantiFERON®-TB Gold In-Tube to identify contacts with new infection. Regression models with generalized estimating equations were used to determine the risk factors for new infection. We included 1488 contacts from 134 patients with TB. There were 79 (5.3%) contacts with new infection. In adjusted analyses, contacts of patients with TB due to region of difference 219 M. tuberculosis sublineage were less likely to have new infection (OR 0.23, 95%CI 0.06-0.84) than those with other sublineages. Other risk factors for new infection were contacts exposed to more than one patient with TB, contacts exposed for 30 days, or contacts with a history of smoking or excessive alcohol consumption. In addition to well-known exposure and clinical characteristics, bacterial characteristics independently contribute to the transmissibility of TB in San Francisco.

Potential effect of ezetimibe against Mycobacterium tuberculosis infection in type II diabetes.

PubMed

Tsai, I-Fang; Kuo, Chiu-Ping; Lin, Andrew B; Chien, Ming-Nan; Ho, Hsin-Tsung; Wei, Tsai-Yin; Wu, Chien-Liang; Lu, Yen-Ta

2017-04-01

Tuberculosis (TB) risk might be increased in patients with diabetes by factors other than hyperglycaemia, such as dyslipidaemia. Host lipids are essential energy sources used by mycobacteria to persist in a latent TB state. A potential therapy targeting cholesterol catabolism of mycobacteria has been proposed, but the potential of cholesterol-lowering drugs as anti-TB therapy is unclear. The purpose of this study was to determine the effects of ezetimibe, a 2-azetidinone cholesterol absorption inhibitor, on intracellular mycobacteria survival and dormancy. Intracellular mycobacteria survival was determined by measurements of ATP activity and colony-formation units (CFUs). Gene expression profiles of hypoxia-induced dormant Mycobacterium tuberculosis (Mtb) were analysed by real-time PCR. Flow cytometry and microscopy analysis were used to measure the lipid loads of human macrophages with or without ezetimibe treatment. QuantiFERON-TB Gold In-Tube (QFT-G-IT) assays were performed to diagnose latent TB infection. The levels of intracellular cholesterol/ triglyceride were measured by an enzymatic fluorometric method. Ezetimibe was capable of effectively lowering intracellular growth of Mtb and hypoxia-induced dormant Mtb. There was a significant decrease in Mtb growth in leucocytes from ezetimibe-treated patients with diabetes in terms of ATP levels of intracellular mycobacteria and CFU formation. Also, patients receiving ezetimibe therapy had a lower prevalence of latent TB and had lower intracellular lipid contents. Ezetimibe, which is a currently marketed drug, could hold promise as an adjunctive, host-directed therapy for TB. © 2016 Asian Pacific Society of Respirology.

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.

A whole genome bioinformatic approach to determine potential latent phase specific targets in Mycobacterium tuberculosis.

PubMed

Defelipe, Lucas A; Do Porto, Dario Fernández; Pereira Ramos, Pablo Ivan; Nicolás, Marisa Fabiana; Sosa, Ezequiel; Radusky, Leandro; Lanzarotti, Esteban; Turjanski, Adrián G; Marti, Marcelo A

2016-03-01

Current Tuberculosis treatment is long and expensive, faces the increasing burden of MDR/XDR strains and lack of effective treatment against latent form, resulting in an urgent need of new anti-TB drugs. Key to TB biology is its capacity to fight the host's RNOS mediated attack. RNOS are known to display a concentration dependent mycobactericidal activity, which leads to the following hypothesis "if we know which proteins are targeted by RNOS and kill TB, we we might be able to inhibit them with drugs resulting in a synergistic bactericidal effect". Based on this idea, we performed an Mtb metabolic network whole proteome analysis of potential RNOS sensitive and relevant targets which includes target druggability and essentiality criteria. Our results, available at http://tuberq.proteinq.com.ar yield new potential TB targets, like I3PS, while also providing and updated view of previous proposals becoming an important tool for researchers looking for new ways of killing TB. Copyright © 2015 Elsevier Ltd. All rights reserved.

Non-Steroidal Anti-inflammatory Drugs As Host-Directed Therapy for Tuberculosis: A Systematic Review

PubMed Central

Kroesen, Vera M.; Gröschel, Matthias I.; Martinson, Neil; Zumla, Alimuddin; Maeurer, Markus; van der Werf, Tjip S.; Vilaplana, Cristina

2017-01-01

Lengthy, antimicrobial therapy targeting the pathogen is the mainstay of conventional tuberculosis treatment, complicated by emerging drug resistances. Host-directed therapies, including non-steroidal anti-inflammatory drugs (NSAIDs), in contrast, target host factors to mitigate disease severity. In the present Systematic Review, we investigate whether NSAIDs display any effects as therapy of TB and discuss possible mechanisms of action of NSAIDs as adjunctive therapy of TB. Ten studies, seven preclinical studies in mice and three clinical trials, were included and systematically reviewed. Our results point toward a beneficial effect of NSAIDs as adjunct to current TB therapy regimens, mediated by decreased lung pathology balancing host-immune reaction. The determination of the best timing for their administration in order to obtain the potential beneficial effects needs further investigation. Even if the preclinical evidence requires clinical evaluation, NSAIDs might represent a potential safe, simple, and cheap improvement in therapy of TB. PMID:28713389

Antiretroviral therapy and the control of HIV-associated tuberculosis. Will ART do it?

PubMed Central

Lawn, S. D.; Harries, A. D.; Williams, B. G.; Chaisson, R. E.; Losina, E.; De Cock, K. M.; Wood, R.

2014-01-01

SUMMARY The human immunodeficiency virus (HIV) associated tuberculosis (TB) epidemic remains an enormous challenge to TB control in countries with a high prevalence of HIV. In their 1999 article entitled ‘Will DOTS do it?’, De Cock and Chaisson questioned whether the World Health Organization’s DOTS Strategy could control this epidemic. Data over the past 10 years have clearly shown that DOTS is insufficient as a single TB control intervention in such settings because it does not address the fundamental epidemiological interactions between TB and HIV. Immunodeficiency is a principal river of this epidemic, and the solution must therefore include immune recovery using antiretroviral therapy (ART). Thus, in the era of global ART scale-up, we now ask the question, ‘Will ART do it?’ ART reduces the risk of TB by 67% (95%CI 61–73), halves TB recurrence rates, reduces mortality risk by 64–95% in cohorts and prolongs survival in patients with HIV-associated drug-resistant TB. However, the cumulative lifetime risk of TB in HIV infected individuals is a function of time spent at various CD4-defined levels of risk, both before and during ART. Current initiation of ART at low CD4 cell counts (by which time much HIV-associated TB has already occurred) and low effective coverage greatly undermine the potential impact of ART at a population level. Thus, while ART has proven a critical intervention for case management of HIV-associated TB, much of its preventive potential for TB control is currently being squandered. Much earlier ART initiation with high coverage is required if ART is to substantially influence the incidence of TB. PMID:21756508

Tuberculosis in Hispanics/Latinos

MedlinePlus

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

High Incidence of Tuberculosis, Low Sensitivity of Current Diagnostic Scheme and Prolonged Culture Positivity in Four Colombian Prisons. A Cohort Study

PubMed Central

Rueda, Zulma Vanessa; López, Lucelly; Vélez, Lázaro A.; Marín, Diana; Giraldo, Margarita Rosa; Pulido, Henry; Orozco, Luis Carlos; Montes, Fernando; Arbeláez, María Patricia

2013-01-01

Objective To determine the incidence of pulmonary tuberculosis (TB) in inmates, factors associated with TB, and the time to sputum smear and culture conversion during TB treatment. Methods Prospective cohort study. All prisoners with respiratory symptoms (RS) of any duration were evaluated. After participants signed consent forms, we collected three spontaneous sputum samples on consecutive days. We performed auramine-rhodamine staining, culturing with the thin-layer agar method, Löwestein-Jensen medium and MGIT, susceptibility testing for first-line drugs; and HIV testing. TB cases were followed, and the times to smear and culture conversion to negative were evaluated. Results Of 9,507 prisoners held in four prisons between April/30/2010 and April/30/2012, among them 4,463 were screened, 1,305 were evaluated for TB because of the lower RS of any duration, and 72 were diagnosed with TB. The annual incidence was 505 cases/100,000 prisoners. Among TB cases, the median age was 30 years, 25% had <15 days of cough, 12.5% had a history of prior TB, and 40.3% had prior contact with a TB case. TB-HIV coinfection was diagnosed in three cases. History of prior TB, contact with a TB case, and being underweight were risk factors associated with TB. Overweight was a protective factor. Almost a quarter of TB cases were detected only by culture; three cases were isoniazid resistant, and two resistant to streptomycin. The median times to culture conversion was 59 days, and smear conversion was 33. Conclusions The TB incidence in prisons is 20 times higher than in the general Colombian population. TB should be considered in inmates with lower RS of any duration. Our data demonstrate that patients receiving adequate anti-TB treatment remain infectious for prolonged periods. These findings suggest that current recommendations regarding isolation of prisoners with TB should be reconsidered, and suggest the need for mycobacterial cultures during follow-up. PMID:24278293

Polyclonal Pulmonary Tuberculosis Infections and Risk for Multidrug Resistance, Lima, Peru

PubMed Central

Shi, Cynthia X.; Chindelevitch, Leonid; Calderon, Roger; Zhang, Zibiao; Galea, Jerome T.; Contreras, Carmen; Yataco, Rosa; Lecca, Leonid; Becerra, Mercedes C.; Murray, Megan B.; Cohen, Ted

2017-01-01

Because within-host Mycobacterium tuberculosis diversity complicates diagnosis and treatment of tuberculosis (TB), we measured diversity prevalence and associated factors among 3,098 pulmonary TB patients in Lima, Peru. The 161 patients with polyclonal infection were more likely than the 115 with clonal or the 2,822 with simple infections to have multidrug-resistant TB. PMID:29048297

Spatial pattern and temporal trend of mortality due to tuberculosis 10

PubMed Central

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

2018-01-01

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

Understanding Latent Tuberculosis: A Moving Target

PubMed Central

Lin, Philana Ling; Flynn, JoAnne L.

2012-01-01

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

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

PubMed Central

Trollip, Andre; Erni, Donatelle; Kao, Kekeletso

2017-01-01

Background Quality-assured tuberculosis laboratory services are critical to achieve global and national goals for tuberculosis prevention and care. Implementation of a quality management system (QMS) in laboratories leads to improved quality of diagnostic tests and better patient care. The Strengthening Laboratory Management Toward Accreditation (SLMTA) programme has led to measurable improvements in the QMS of clinical laboratories. However, progress in tuberculosis laboratories has been slower, which may be attributed to the need for a structured tuberculosis-specific approach to implementing QMS. We describe the development and early implementation of the Strengthening Tuberculosis Laboratory Management Toward Accreditation (TB SLMTA) programme. Development The TB SLMTA curriculum was developed by customizing the SLMTA curriculum to include specific tools, job aids and supplementary materials specific to the tuberculosis laboratory. The TB SLMTA Harmonized Checklist was developed from the World Health Organisation Regional Office for Africa Stepwise Laboratory Quality Improvement Process Towards Accreditation checklist, and incorporated tuberculosis-specific requirements from the Global Laboratory Initiative Stepwise Process Towards Tuberculosis Laboratory Accreditation online tool. Implementation Four regional training-of-trainers workshops have been conducted since 2013. The TB SLMTA programme has been rolled out in 37 tuberculosis laboratories in 10 countries using the Workshop approach in 32 laboratories in five countries and the Facility-based approach in five tuberculosis laboratories in five countries. Conclusion Lessons learnt from early implementation of TB SLMTA suggest that a structured training and mentoring programme can build a foundation towards further quality improvement in tuberculosis laboratories. Structured mentoring, and institutionalisation of QMS into country programmes, is needed to support tuberculosis laboratories to achieve accreditation. PMID:28879165

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

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

Tuberculosis knowledge among injecting drug users visiting syringe exchange programme in Tallinn, Estonia.

PubMed

Rüütel, Kristi; Parker, R David; Sobolev, Igor; Loit, Helle-Mai

2012-12-01

The purpose of the current study was to describe tuberculosis (TB) knowledge, beliefs, and experience with TB services among injecting drug users. Participants for this anonymous, cross-sectional study were recruited from a community based syringe exchange programme in Tallinn, Estonia. A structured questionnaire was completed and included information on socio-demographics, health history, drug use, and knowledge about TB and HIV. The study included 407 people (79% male, mean age 27.9 years, mean injection drug use 9.4 years). 32.9% of participants reported HIV infection and 1.7% lifetime history of TB. 26.4% participants (n=106) reported symptoms suggestive of TB. 93% of participants recognized correctly that TB is air-borne infection and 91% that HIV is a risk factor for TB. Only 40% of the participants knew that TB diagnostics and treatment in Estonia are free of charge for everybody and 58% reported they knew where to get health care services in case they suspected that they had TB. TB transmission and treatment adherence knowledge was better among those in contact with either health care or harm reduction services, e.g the community based syringe exchange programme. Similar to HIV services, TB prevention and education should be integrated into harm reduction and drug treatment programmes to facilitate early diagnosis and treatment of TB among injecting drug users.

Factors that influence current tuberculosis epidemiology.

PubMed

Millet, Juan-Pablo; Moreno, Antonio; Fina, Laia; del Baño, Lucía; Orcau, Angels; de Olalla, Patricia García; Caylà, Joan A

2013-06-01

According to WHO estimates, in 2010 there were 8.8 million new cases of tuberculosis (TB) and 1.5 million deaths. TB has been classically associated with poverty, overcrowding and malnutrition. Low income countries and deprived areas, within big cities in developed countries, present the highest TB incidences and TB mortality rates. These are the settings where immigration, important social inequalities, HIV infection and drug or alcohol abuse may coexist, all factors strongly associated with TB. In spite of the political, economical, research and community efforts, TB remains a major global health problem worldwide. Moreover, in this new century, new challenges such as multidrug-resistance extension, migration to big cities and the new treatments with anti-tumour necrosis alpha factor for inflammatory diseases have emerged and threaten the decreasing trend in the global number of TB cases in the last years. We must also be aware about the impact that smoking and diabetes pandemics may be having on the incidence of TB. The existence of a good TB Prevention and Control Program is essential to fight against TB. The coordination among clinicians, microbiologists, epidemiologists and others, and the link between surveillance, control and research should always be a priority for a TB Program. Each city and country should define their needs according to the epidemiological situation. Local TB control programs will have to adapt to any new challenge that arises in order to respond to the needs of their population.

Tuberculosis: finding a new potential antimycobacterium derivative in a aldehyde-arylhydrazone-oxoquinoline series.

PubMed

da C Santos, Fernanda; Castro, Helena C; Lourenço, Maria Cristina S; Abreu, Paula A; Batalha, Pedro N; Cunha, Anna C; Carvalho, Guilherme S L; Rodrigues, Carlos R; Medeiros, Cid A; Souza, Simone D; Ferreira, Vitor F; de Souza, Maria C B V

2012-10-01

Tuberculosis (TB) is a contagious disease caused by Mycobacterium tuberculosis, which remains a serious public health problem. The emergence of resistant bacterial strains has continuously increased and new treatment options are currently in need. In this work, we identified a new potential aldehyde-arylhydrazone-oxoquinoline derivative (4e) with interesting chemical structural features that may be important for designing new anti-TB agents. This 1-ethyl-N'-[(1E)-(5-nitro-2-furyl)methylene]-4-oxo-1,4-dihydroquinoline-3-carbohydrazide (4e) presented an in vitro active profile against M. tuberculosis H37Rv strain (minimum inhibitory concentration, MIC = 6.25 μg/mL) better than other acylhydrazones described in the literature (MIC = 12.5 μg/mL) and close to other antitubercular agents currently on the market. The theoretical analysis showed the importance of several structural features that together with the 5-nitro-2-furyl group generated this active compound (4e). This new compound and the analysis of its molecular properties may be useful for designing new and more efficient antibacterial drugs.

HIV-Prevalence in Tuberculosis Patients in Germany, 2002–2009: An Estimation Based on HIV and Tuberculosis Surveillance Data

PubMed Central

Fiebig, Lena; Kollan, Christian; Hauer, Barbara; Gunsenheimer-Bartmeyer, Barbara; an der Heiden, Matthias; Hamouda, Osamah; Haas, Walter

2012-01-01

Tuberculosis (TB) and HIV comorbidity is a major challenge in TB prevention and control but difficult to assess in Germany as in other countries, where data confidentiality precludes notifying the HIV status of TB patients. We aimed to estimate the HIV-prevalence in TB patients in Germany, 2002–2009, and to characterize the HIV/TB patients demographically. Data from the long-term observational open multicentre cohort ClinSurv HIV were used to identify incident TB in HIV-positive individuals. We assessed the cohort’s coverage for the nationwide HIV-positive population by contrasting ClinSurv HIV patients under antiretroviral therapy (ART) with national HIV patient numbers derived from ART prescriptions (data by Insight Health; available for 2006–2009). The HIV-prevalence in TB patients was calculated as the number of HIV/TB cases projected for Germany over all culture-positive TB notifications. From 2002 to 2009, 298 of 15,531 HIV-positive patients enrolled in the ClinSurv HIV cohort were diagnosed with TB. A 21% cohort coverage was determined. The annual estimates of the HIV-prevalence in TB patients were on average 4.5% and ranged from 3.5% (95%CI 2.3–5.1%) in 2007 to 6.6% (95%CI 5.0–8.5%) in 2005. The most recent estimate for 2009 was 4.0% (95%CI 2.6–5.9%). The 298 HIV/TB patients were characterized by a male-to-female ratio of 2.1, by a median age of 38 years at TB diagnosis, and by 59% of the patients having a foreign origin, mainly from Subsahara Africa. We provide, to our knowledge, the first estimate of the HIV-prevalence in TB patients for Germany by joint evaluation of anonymous HIV and TB surveillance data sources. The identified level of HIV in TB patients approximates available surveillance data from neighbouring countries and indicates a non-negligible HIV/TB burden in Germany. Our estimation approach is valuable for epidemiological monitoring of HIV/TB within the current legal frameworks. PMID:23145087

Tuberculosis: The Connection between TB and HIV (the AIDS Virus)

MedlinePlus

... Task Force Tuberculosis: The Connection between TB and HIV Recommend on Facebook Tweet Share Compartir Order this ... if I am infected with both TB and HIV? If you have HIV, it is important to ...

TB-HIV co-infection among pregnant women in Karnataka, South India: A case series.

PubMed

Suresh, Shastri; Sharath, Burugina N; Anita, Shet; Lalitha, Ravindra; Prasad, Tripathy J; Rewari, Bharat B

2016-01-01

Tuberculosis (TB) is a significant contributor to mortality in HIV-infected patients. Concurrent TB infection is also a significant contributing factor to maternal mortality in human immunodeficiency virus (HIV)-infected pregnant women. Studies addressing the outcomes of TB and HIV co-infection among pregnant women are generally infrequent. Although limited, the records maintained by the Revised National Tuberculosis Control Programme (RNTCP) and the National AIDS Control Programme (NACP) in Karnataka State, Southern India provide information about the numbers of pregnant women who are co-infected with TB and HIV and their pregnancy outcomes. We reviewed the data and conducted this study to understand how TB-HIV co-infection influences the outcomes of pregnancy in this setting. We sought to determine the incidence and treatment and delivery outcomes of TB-HIV co-infected pregnant women in programmatic settings in Karnataka State in southern India. The study participants were all the HIV-infected pregnant women who were screened for tuberculosis under the NACP from 2008 to 2012. For the purposes of this study, the program staff in the field gathered the data regarding on treatment and delivery outcomes of pregnant women. A total of seventeen pregnant women with TB-HIV co-infection were identified among 3,165,729 pregnant women (for an incidence of 5.4 per million pregnancies). The median age of these pregnant women was 24 years, and majority were primiparous women with WHO HIV stage III disease and were on a stavudine-based ART regimen. The maternal mortality rates were 18% before delivery and 24% after delivery. The abortion rate was 24%, and the neonatal mortality rate was 10%. The anti-tuberculosis treatment and anti-retroviral treatment outcome mortality rates were 30% and 53%, respectively. Although the incidence of TB among the HIV-infected pregnant women was marginally less than that among the non-HIV-infected women, the delivery outcomes were relatively poorer. The current strategy for the management of TB among the HIV-positive pregnant women needs urgent review. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Tuberculosis attributed to household contacts in the Philippines.

PubMed

Sia, I G; Orillaza, R B; St Sauver, J L; Quelapio, I D; Lahr, B D; Alcañeses, R S; Wilson, W R; Cockerill, F R; Balane, G I; Mangubat, N V; Wengenack, N L; Tupasi, T E

2010-01-01

Data on the burden of disease from tuberculosis (TB) in Filipino households are limited. To determine the magnitude of undiagnosed TB in TB households, and the demographic and socio-economic factors associated with TB in the Philippines, household contacts of adult smear-positive TB patients seen from July 2001 to June 2003 were assessed based on interview, chest X-ray, tuberculin skin test and sputum examination. History of TB and older age were independently associated with TB disease, and age and duration of cohabitation with TB infection. TB and TB infection are highly prevalent in TB households in the Philippines.

Tuberculosis outbreak investigation of a U.S. Navy amphibious ship crew and the Marine expeditionary unit aboard, 1998.

PubMed

Lamar, James E; Malakooti, Mark A

2003-07-01

A Marine deployed aboard a U.S. Navy amphibious ship had smear-positive, cavitary pulmonary tuberculosis (TB). Contact investigation ultimately found 21 active cases of TB among sailors and Marines who were aboard the affected ship. Approximately 3 months lapsed between onset of the source patient's illness and appropriate diagnosis and treatment. During the contact investigation, 3,338 persons received tuberculin skin tests and 712 were identified as new latent tuberculosis infection cases. Four persons diagnosed with latent tuberculosis infection developed active TB because of poor compliance with treatment. After personnel disembarked from the ship, persistent efforts to identify persons with active disease and latent infections were successful in controlling further spread of tuberculosis in military units and local communities. The Mycobacterium tuberculosis bacteria isolated from the source patient and 16 of the other active cases were susceptible to all drugs commonly used to treat TB.

Vaccines for Leprosy and Tuberculosis: Opportunities for Shared Research, Development, and Application

PubMed Central

Coppola, Mariateresa; van den Eeden, Susan J. F.; Robbins, Naoko; Wilson, Louis; Franken, Kees L. M. C.; Adams, Linda B.; Gillis, Tom P.; Ottenhoff, Tom H. M.; Geluk, Annemieke

2018-01-01

Tuberculosis (TB) and leprosy still represent significant public health challenges, especially in low- and lower middle-income countries. Both poverty-related mycobacterial diseases require better tools to improve disease control. For leprosy, there has been an increased emphasis on developing tools for improved detection of infection and early diagnosis of disease. For TB, there has been a similar emphasis on such diagnostic tests, while increased research efforts have also focused on the development of new vaccines. Bacille Calmette–Guérin (BCG), the only available TB vaccine, provides insufficient and inconsistent protection to pulmonary TB in adults. The impact of BCG on leprosy, however, is significant, and the introduction of new TB vaccines that might replace BCG could, therefore, have serious impact also on leprosy. Given the similarities in antigenic makeup between the pathogens Mycobacterium tuberculosis (Mtb) and M. leprae, it is well possible, however, that new TB vaccines could cross-protect against leprosy. New TB subunit vaccines currently evaluated in human phase I and II studies indeed often contain antigens with homologs in M. leprae. In this review, we discuss pre-clinical studies and clinical trials of subunit or whole mycobacterial vaccines for TB and leprosy and reflect on the development of vaccines that could provide protection against both diseases. Furthermore, we provide the first preclinical evidence of such cross-protection by Mtb antigen 85B (Ag85B)-early secretory antigenic target (ESAT6) fusion recombinant proteins in in vivo mouse models of Mtb and M. leprae infection. We propose that preclinical integration and harmonization of TB and leprosy research should be considered and included in global strategies with respect to cross-protective vaccine research and development. PMID:29535713

Sensitivity, specificity, and confounding factors of novel serological tests used for the rapid diagnosis of bovine tuberculosis in farmed red deer (Cervus elaphus).

PubMed

Buddle, Bryce M; Wilson, Tania; Denis, Michel; Greenwald, Rena; Esfandiari, Javan; Lyashchenko, Konstantin P; Liggett, Simon; Mackintosh, Colin G

2010-04-01

In this study, novel serological tests were used to detect tuberculosis (TB) in groups of farmed red deer (Cervus elaphus) varying in disease status or possible confounding factors. Groups of deer naturally or experimentally infected with Mycobacterium bovis and animals vaccinated against paratuberculosis were studied, as were uninfected animals and animals naturally or experimentally infected with Mycobacterium avium subsp. paratuberculosis. Sera were assayed using two rapid lateral-flow tests, Chembio's CervidTB STAT-PAK and DPP VetTB tests, and results were compared to those from tuberculin skin tests. Both serological tests had a high sensitivity, but specificity was adversely affected after animals had received a vaccine against paratuberculosis and were subsequently skin tested. The specificity of the DPP VetTB test was higher than that of the CervidTB STAT-PAK test, with natural infection with M. avium subsp. paratuberculosis adversely affecting the specificity of only the CervidTB STAT-PAK test. The sera from M. avium subsp. paratuberculosis-infected deer that produced false-positive reactions in the CervidTB STAT-PAK test were retested with a multiantigen print immunoassay (MAPIA), and some of these sera were shown to react with the MPB83 antigen. Combining the results from the serological tests and the skin tests showed only a slight increase in the sensitivity of detection of M. bovis-infected animals. It is concluded that both the CervidTB STAT-PAK and DPP VetTB tests offer rapid, convenient, and easy detection of bovine tuberculosis in deer, albeit with significant interference from paratuberculosis vaccination status and subsequent skin testing. The latter finding illustrates one of the limitations of currently available vaccines against paratuberculosis.

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.

[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 mentioned, the course has been contributing to human resource capacity building including management of laboratory service to improve NTP in the resource-limited countries. Currently, expansion of technology transfer on culture examination for drug susceptibility test has been attempted to the resource-limited countries due to the occurrence of MDR-TB (Multi drug-resistant tuberculosis) and XDR-TB (Extensively drug-resistant tuberculosis) cases. However, since sputum smear examination is most effective method of detection of infectious TB, the writers believe it is still a core component of TB control, unless a new diagnostic tool that is practicable and effective in the resource-limited countries is developed. Therefore the course will keep focused on the smear examination as the basic curriculum. The course is highly appreciated by international experts and it is our responsibility to answer the expectation from them.

Enhanced tuberculosis case finding through advocacy and sensitisation meetings in prisons of Central India

PubMed Central

Mallick, G.; Agrawal, T. K.; Kumar, A. M. V.; Chadha, S. S.

2017-01-01

Tuberculosis (TB) in prisons is a major problem. The prisons in Chhattisgarh, India, are overcrowded, and there are no formal efforts to engage them in TB control. In 2014, the International Union Against Tuberculosis and Lung Disease and the state TB programme advocated with state prison authorities to implement an enhanced case-finding strategy in the prisons. Sensitisation meetings (one/quarter/prison) to improve awareness among prisoners about TB symptoms and services were coupled with improved access to diagnosis. Patients with presumptive TB who were examined by sputum microscopy increased by 39% per 100 000 prisoners, and TB case notification rates increased by 38%, in 2014 relative to 2013. PMID:28775946

A rare presentation of disseminated tuberculosis: Prostatic abscess.

PubMed

Verma, Ajay; Singh, Anubhuti; Kishore, Kislay; Kant, Surya

2017-10-01

Involvement of the prostate by tuberculosis (TB) occurs rarely and tuberculosis prostate abscess is an even rarer occurrence. It has been reported in immunocompromised patients, mainly human immunodeficiency virus seropositive individuals. We are reporting a case of tuberculosis prostatic abscess in an immunocompetent patient with relapse of TB. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Latent tuberculosis infection among close contacts of multidrug-resistant tuberculosis patients in central Taiwan.

PubMed

Huang, Y-W; Shen, G-H; Lee, J-J; Yang, W-T

2010-11-01

Both the tuberculin skin test (TST) and the QuantiFERON®-TB Gold In-Tube test (QFT-GIT) may be used to detect Mycobacterium tuberculosis infection. A positive reaction to either test can indicate latent tuberculosis infection (LTBI). These tests can be used to study the rate of infection in contacts of multidrug-resistant tuberculosis (MDR-TB) patients. To evaluate the transmission status of MDR-TB patients in Taiwan by examining their close contacts and to compare the efficiency of TST and QFT-GIT. Chest radiographs, TST and QFT-GIT were performed in household contacts of confirmed MDR-TB patients to determine their infection status. A total of 78 close contacts of confirmed MDR-TB patients were included in the study. The majority of the MDR-TB patients were parents of the close contacts and lived in the same building; 46% of the subjects were TST-positive and 19% were QFT-GIT-positive, indicating LTBI that was likely to develop into active MDR-TB. There was a lack of consistency between TST and QFT-GIT results in subjects with previous bacille Calmette-Guérin vaccination. Household contacts of MDR-TB patients are likely to develop LTBI; thus, follow-up and monitoring are mandatory to provide treatment and reduce the occurrence of active infection.

Predictive Role of ADA in Bronchoalveolar Lavage Fluid in Making the Diagnosis of Pulmonary Tuberculosis.

PubMed

Binesh, Fariba; Halvani, Abolhassan

2013-01-01

Current diagnostic tests for tuberculosis (TB) are time-consuming. The aim of this study was to evaluate the diagnostic usefulness of ADA in bronchoalveolar lavage fluid in patients with pulmonary TB. A cross-sectional study was performed in Yazd, Iran, between 2009 and 2010. Patients suspected of pulmonary TB with negative sputum smear for AFB were included in the study. Mean ADA levels in BAL fluids were measured and compared between study groups. Sixty-three patients were enrolled in the study among which 15 cases had pulmonary TB, 33 had pulmonary diseases other than TB, and 15 subjects with normal bronchoscopy results were considered as controls. Mean ADA levels in BAL fluid were 4.13 ± 2.55, 2.42 ± 1.06, and 1.93 ± 0.88, respectively. This rate was significantly higher in the pulmonary TB group compared to the other two groups (P = 0.001). Using ROC curve with a cut-off value of 3.5 IU/L, the highest sensitivity (57%) and specificity (84%) were obtained in diagnosis of TB. The results showed that although ADA activity in BAL fluid of pulmonary TB patients was higher than those seen in other diseases, a negative test does not rule out pulmonary TB.

[Tuberculosis care and new horizon of Japanese society].

PubMed

Ishikawa, Nobukatsu; Nagayama, Naohiro

2012-04-01

Current tuberculosis (TB) problems are reflections of Japanese society. Living or dying alone among the elderly, difficulty in finding jobs or withdrawal into themselves among the youths are features of modem society. The future needs for TB care were discussed on specific topics of TB among the elderly, foreigners and the homeless. Presenters showed the importance of the patient-centered care in collaboration with public health and welfare services. Both patients and staffs will see others shining, as they touch each other in the deep part of human existence. A diabetic ex-TB patient talked his experience in his treatment. His window of mind was gradually opened from inside with the continuous support in DOTS by the staff of the public health center. To accumulate these experiences of a heartwarming atmosphere will have the effective power on establishment of social supporting systems. This symposium can be a step towards humanized society or a new horizon of public health which can answer to another need of inner cry of a sick people particularly among the socially disadvantaged who are the victims of the weakness of society. 1. Current situation and issues of elderly tuberculosis patients: Eriko SHIGETO (NHO Higashihiroshima Medical Center). By the analysis of 102 tuberculosis patients of 70 years old and above who were registered at Hiroshima Prefectural Health Center in 2009, 41 patients had severe complications such as diabetes mellitus, renal insufficiency, malignancy or cerebrovascular disorder. Their prognosis was rather poor and the ADL tended to be worsened during hospitalization. Though 16 of the 34 deaths were caused with non-tuberculosis diseases, the ratio of the tuberculosis deaths was higher (4/17) among the patients living alone. Sufficient care of the elderly for early diagnosis, care system to treat various complications and patient support are required. 2. Provision of medical interpreters to help foreigners with tuberculosis in Tokyo: Takashi SAWADA (Services for Health in Asian & African Regions (SHARE)). In 2006, Tokyo Metropolitan Government started to dispatch interpreters for foreigners to strengthen DOTS program. Collaboration with NGOs made it possible to train 37 volunteer interpreters, and to provide services in 13 languages, as of 2010. In Japan, the treatment defaulter rate among non-Japanese tuberculosis patients had been remarkably high. But with having the assistance of interpreters, the treatment completion rate has become higher than 80%. It is recommended to expand a similar system to other part of Japan, as the proportion of foreigners among total tuberculosis cases keeps on increasing nationwide. 3. Tuberculosis problems in Japan from the view point of homelessness-through the activities of a NPO supporting the homeless in collaboration with a public health center: Sadako KANAZAWA (Volunteer, NPO Medical Care Team of Shinjuku Renraku-Kai). It has been 20 years since the issue of homelessness emerged in Japanese society. The people with a history of both tuberculosis and experience of homelessness tend to show a poor prognosis. Our team has played an active role, working with Shinjuku Public Health Center for conducting a screening for tuberculosis every year. It seems that the screening service itself does not make a fundamental solution for homeless people with tuberculosis. Developing a more basic system of 'from street to apartment' is more essential. We believe that understanding the importance of the system is most essential to the people who are involved in health and medical care. 4. What we have learned from DOTS--Toward care by cuddling the patient's mind: Kazuyo ARIMA (PHN, Osaka City Public Health Center). Osaka City has achieved the goals of DOTS set up by the City's TB Control Guidelines since 2001 such as 80% DOTS implementation rate, halving the defaulter rate and incidence rate. It was shown by analysis that the treatment success depends on 'patient's awareness of the disease', 'appropriate DOTS method for each patient', 'existence of side effects', or 'the relationship between treatment supporters'. Through working for the patients whose treatment management was difficult, we have learned that our attitude towards the patients is a most important first step to build a good relationship and mutual trust with the patients, and DOT is an important tool. For treatment supporters,'the patient-centered care', 'care by staying close to the patients' or 'cuddling the patient' s mind' is most necessary to lead the patients to cure. 5. Patient's view: Through DOTS, my life has been renewed: Kuniyoshi MAEDA (Himawari no kai; Ex-homeless TB patients self-help group). It is an unforgettable memory that I was hospitalized due to TB back in 2009. I was seriously ill with also diabetes mellitus. Because I had lost everything due to my friend's cheating, I could not trust anyone before the TB treatment. But I learned how to think of others through the daily communication with doctors, nurses, other staff at the hospital, and Public Health Center. They encouraged me every day and I came to desire to answer to their expectations. Public health nurses taught me that building the reliable relationship is so essential for humans, and I may not have realized this importance if I had not been treated for TB, or treated outside Shinjuku. I would rather say that I was lucky to have got TB, as I have become able to trust other people through DOTS TB care. DOTS is not only for medication, but also general health care and counseling. I hope that as many as poor people, especially homeless can have a similar experience by knowing more about TB and using a health service. I would like to cooperate with TB services if I can be useful. health: Toshio TAKATORIGE (Graduate School of Safety Science, Kansai University). Tuberculosis was ever the biggest health problem in Japan. Ministry of Health and Welfare and Public Health Centers were founded to push forward tuberculosis control. Local governments, companies and people had to follow the national tuberculosis control program uniformly without exception. Currently a new stream of tuberculosis control has been started by DOTS strategy. The aim of DOTS has made all patients take medicine regardless of their social conditions until cure. Every patient is snuggled up and supported whether he is homeless, criminal or a foreigner. The patients also participate in the program actively. The DOTS may be a new public health movement. The strong public health infrastructure is necessary to maintain tuberculosis control towards the low incidence situation. The role of the local government should be more important. This symposium has also shown that the tuberculosis services must be patients-centered and supported by the people, addressing a new horizon of public health in Japan through tuberculosis control.

Whole-Genome Sequencing of Mycobacterium tuberculosis Provides Insight into the Evolution and Genetic Composition of Drug-Resistant Tuberculosis in Belarus.

PubMed

Wollenberg, Kurt R; Desjardins, Christopher A; Zalutskaya, Aksana; Slodovnikova, Vervara; Oler, Andrew J; Quiñones, Mariam; Abeel, Thomas; Chapman, Sinead B; Tartakovsky, Michael; Gabrielian, Andrei; Hoffner, Sven; Skrahin, Aliaksandr; Birren, Bruce W; Rosenthal, Alexander; Skrahina, Alena; Earl, Ashlee M

2017-02-01

The emergence and spread of drug-resistant Mycobacterium tuberculosis (DR-TB) are critical global health issues. Eastern Europe has some of the highest incidences of DR-TB, particularly multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB. To better understand the genetic composition and evolution of MDR- and XDR-TB in the region, we sequenced and analyzed the genomes of 138 M. tuberculosis isolates from 97 patients sampled between 2010 and 2013 in Minsk, Belarus. MDR and XDR-TB isolates were significantly more likely to belong to the Beijing lineage than to the Euro-American lineage, and known resistance-conferring loci accounted for the majority of phenotypic resistance to first- and second-line drugs in MDR and XDR-TB. Using a phylogenomic approach, we estimated that the majority of MDR-TB was due to the recent transmission of already-resistant M. tuberculosis strains rather than repeated de novo evolution of resistance within patients, while XDR-TB was acquired through both routes. Longitudinal sampling of M. tuberculosis from 34 patients with treatment failure showed that most strains persisted genetically unchanged during treatment or acquired resistance to fluoroquinolones. HIV+ patients were significantly more likely to have multiple infections over time than HIV- patients, highlighting a specific need for careful infection control in these patients. These data provide a better understanding of the genomic composition, transmission, and evolution of MDR- and XDR-TB in Belarus and will enable improved diagnostics, treatment protocols, and prognostic decision-making. Copyright © 2017 Wollenberg et al.

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

PubMed

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

2012-01-01

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

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

PubMed Central

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

2012-01-01

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

Resistance pattern of multi-drug resistant strains of Mycobacterium tuberculosis and characteristics of patients with multi-drug resistant tuberculosis.

PubMed

Moisoiu, Adriana; Mitran, Cristina Iulia; Mitran, Mãdãlina Irina; Huhu, Mihaela Roxana; Ioghen, Octavian Costin; Gheorghe, Adelina-Silvana; Tampa, Mircea; Georgescu, Simona Roxana; Popa, Mircea Ioan

2016-01-01

Multi-drug resistant tuberculosis (MDR-TB) is a major concern in the medical community. Knowledge about the drug resistance pattern of Mycobacterium tuberculosis strains plays an essential role in the management of the disease. We conducted a retrospective, 3-year study (2009-2011), in an urban area. We collected data on the drug resistance for 497 M. tuberculosis strains, isolated from patients with pulmonary TB. Among the 497 strains, we identified 158 MDR strains. Eighty medical recorders of patients infected with MDR strains were available and we included those patients in the study group. Of the 497 analysed strains, 8% were resistant to a single anti-TB drug. We identified 5.2% polyresistant drug strains, the most frequent combination being INH+EMB (1.4%). Of the 158 MDR strains identified (31.8%), over 60% were resistant to all first line anti-TB drugs tested. Most of them presented resistance to STM (86.1%) and EMB (67.7%). With respect to second line anti-TB drugs resistance to KM (23.4%) was the most common, followed by OFX (8.2%). With respect to the patients with MDR-TB, a percentage of 61.2% of them had a history of anti-TB treatment. Regarding lifestyle habits, 61.2% of the patients were smokers and 18.8% were abusing alcohol. Out of 51 patients, for whom information was available regarding their occupation, only 33.3 % were employees. MDR strains of Mycobacterium tuberculosis display an increased resistance to first line anti-TB drugs. Extension of resistance to second line anti-TB drugs narrows the therapeutic options. Knowledge of MDR-TB risk factors is imperative for the correct and rapid initiation of the treatment.

Application of ImmunoScore Model for the Differentiation between Active Tuberculosis and Latent Tuberculosis Infection as Well as Monitoring Anti-tuberculosis Therapy.

PubMed

Zhou, Yu; Du, Juan; Hou, Hong-Yan; Lu, Yan-Fang; Yu, Jing; Mao, Li-Yan; Wang, Feng; Sun, Zi-Yong

2017-01-01

Tuberculosis (TB) is a leading global public health problem. To achieve the end TB strategy, non-invasive markers for diagnosis and treatment monitoring of TB disease are urgently needed, especially in high-endemic countries such as China. Interferon-gamma release assays (IGRAs) and tuberculin skin test (TST), frequently used immunological methods for TB detection, are intrinsically unable to discriminate active tuberculosis (ATB) from latent tuberculosis infection (LTBI). Thus, the specificity of these methods in the diagnosis of ATB is dependent upon the local prevalence of LTBI. The pathogen-detecting methods such as acid-fast staining and culture, all have limitations in clinical application. ImmunoScore (IS) is a new promising prognostic tool which was commonly used in tumor. However, the importance of host immunity has also been demonstrated in TB pathogenesis, which implies the possibility of using IS model for ATB diagnosis and therapy monitoring. In the present study, we focused on the performance of IS model in the differentiation between ATB and LTBI and in treatment monitoring of TB disease. We have totally screened five immunological markers (four non-specific markers and one TB-specific marker) and successfully established IS model by using Lasso logistic regression analysis. As expected, the IS model can effectively distinguish ATB from LTBI (with a sensitivity of 95.7% and a specificity of 92.1%) and also has potential value in the treatment monitoring of TB disease.

Correlations between major risk factors and closely related Mycobacterium tuberculosis isolates grouped by three current genotyping procedures: a population-based study in northeast Mexico.

PubMed

Peñuelas-Urquides, Katia; Martínez-Rodríguez, Herminia Guadalupe; Enciso-Moreno, José Antonio; Molina-Salinas, Gloria María; Silva-Ramírez, Beatriz; Padilla-Rivas, Gerardo Raymundo; Vera-Cabrera, Lucio; Torres-de-la-Cruz, Víctor Manuel; Martínez-Martínez, Yazmin Berenice; Ortega-García, Jorge Luis; Garza-Treviño, Elsa Nancy; Enciso-Moreno, Leonor; Saucedo-Cárdenas, Odila; Becerril-Montes, Pola; Said-Fernández, Salvador

2014-09-01

The characteristics of tuberculosis (TB) patients related to a chain of recent TB transmissions were investigated. Mycobacterium tuberculosis (MTB) isolates (120) were genotyped using the restriction fragment length polymorphism-IS6110 (R), spacer oligotyping (S) and mycobacterial interspersed repetitive units-variable number of tandem repeats (M) methods. The MTB isolates were clustered and the clusters were grouped according to the similarities of their genotypes. Spearman's rank correlation coefficients between the groups of MTB isolates with similar genotypes and those patient characteristics indicating a risk for a pulmonary TB (PTB) chain transmission were ana- lysed. The isolates showing similar genotypes were distributed as follows: SMR (5%), SM (12.5%), SR (1.67%), MR (0%), S (46.67%), M (5%) and R (0%). The remaining 35 cases were orphans. SMR exhibited a significant correlation (p < 0.05) with visits to clinics, municipalities and comorbidities (primarily diabetes mellitus). S correlated with drug consumption and M with comorbidities. SMR is needed to identify a social network in metropolitan areas for PTB transmission and S and M are able to detect risk factors as secondary components of a transmission chain of TB.

Correlations between major risk factors and closely related Mycobacterium tuberculosis isolates grouped by three current enotyping procedures: a population-based study in northeast Mexico

PubMed Central

Peñuelas-Urquides, Katia; Martínez-Rodríguez, Herminia Guadalupe; Enciso-Moreno, José Antonio; Molina-Salinas, Gloria María; Silva-Ramírez, Beatriz; Padilla-Rivas, Gerardo Raymundo; Vera-Cabrera, Lucio; Torres-de-la-Cruz, Víctor Manuel; Martínez-Martínez, Yazmin Berenice; Ortega-García, Jorge Luis; Garza-Treviño, Elsa Nancy; Enciso-Moreno, Leonor; Saucedo-Cárdenas, Odila; Becerril-Montes, Pola; Said-Fernández/, Salvador

2014-01-01

The characteristics of tuberculosis (TB) patients related to a chain of recent TB transmissions were investigated. Mycobacterium tuberculosis (MTB) isolates (120) were genotyped using the restriction fragment length polymorphism-IS6110 (R), spacer oligotyping (S) and mycobacterial interspersed repetitive units-variable number of tandem repeats (M) methods. The MTB isolates were clustered and the clusters were grouped according to the similarities of their genotypes. Spearman’s rank correlation coefficients between the groups of MTB isolates with similar genotypes and those patient characteristics indicating a risk for a pulmonary TB (PTB) chain transmission were ana- lysed. The isolates showing similar genotypes were distributed as follows: SMR (5%), SM (12.5%), SR (1.67%), MR (0%), S (46.67%), M (5%) and R (0%). The remaining 35 cases were orphans. SMR exhibited a significant correlation (p < 0.05) with visits to clinics, municipalities and comorbidities (primarily diabetes mellitus). S correlated with drug consumption and M with comorbidities. SMR is needed to identify a social network in metropolitan areas for PTB transmission and S and M are able to detect risk factors as secondary components of a transmission chain of TB. PMID:25317710

Infection of great apes and a zoo keeper with the same Mycobacterium tuberculosis spoligotype.

PubMed

Akkerman, Onno W; van der Werf, Tjip S; Rietkerk, Frank; Eger, Tony; van Soolingen, Dick; van der Loo, Kees; van der Zanden, Adri G M

2014-04-01

An animal keeper was diagnosed with pulmonary tuberculosis (TB) after bi-annual screening for latent TB infection in zoo employees. In the same period, several bonobos of the zoo were suffering from TB as well. The Mycobacterium tuberculosis strains from both the animal keeper and the bonobos appeared identical. We provide evidence that the animals infected their keeper.

Field application of serodiagnostics to identify elephants with Tuberculosis prior to case confirmation by culture

USDA-ARS?s Scientific Manuscript database

Three serologic methods for antibody detection in elephant tuberculosis (TB), multiantigen print immunoassay (MAPIA), ElephantTB STAT-PAK kit, and DPP VetTB test, were validated prospectively using serial serum samples from 14 captive elephants in 5 countries which were diagnosed with TB by positive...

Tuberculosis Outbreak in a Primary School, Milan, Italy

PubMed Central

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

2013-01-01

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

Opportunities and Challenges for Natural Products as Novel Antituberculosis Agents.

PubMed

Farah, Shrouq I; Abdelrahman, Abd Almonem; North, E Jeffrey; Chauhan, Harsh

2016-01-01

Current tuberculosis (TB) treatment suffers from complexity of the dosage regimens, length of treatment, and toxicity risks. Many natural products have shown activity against drug-susceptible, drug-resistant, and latent/dormant Mycobacterium tuberculosis, the pathogen responsible for TB infections. Natural sources, including plants, fungi, and bacteria, provide a rich source of chemically diverse compounds equipped with unique pharmacological, pharmacokinetic, and pharmacodynamic properties. This review focuses on natural products as starting points for the discovery and development of novel anti-TB chemotherapy and classifies them based on their chemical nature. The classes discussed are divided into alkaloids, chalcones, flavonoids, peptides, polyketides, steroids, and terpenes. This review also highlights the importance of collaboration between phytochemistry, medicinal chemistry, and physical chemistry, which is very important for the development of these natural compounds.

Comparison of TB-LAMP, GeneXpert MTB/RIF and culture for diagnosis of pulmonary tuberculosis in The Gambia.

PubMed

Bojang, Adama L; Mendy, Francis S; Tientcheu, Leopold D; Otu, Jacob; Antonio, Martin; Kampmann, Beate; Agbla, Schadrac; Sutherland, Jayne S

2016-03-01

Diagnosis of tuberculosis (TB) remains difficult, particularly in resource-limited settings. The development of nucleic acid-based tests for detection of Mycobacterium tuberculosis complex (MTBC) has significantly increased sensitivity compared to conventional smear microscopy and provides results within a matter of hours compared to weeks for the current gold-standard, liquid culture. In this study we performed side-by-side comparison of mycobacterial detection assays on sputum samples from 285 subjects presenting with symptoms suggestive of TB in The Gambia and a cross-sectional cohort of 156 confirmed TB patients with a median of 2 months of treatment. A novel assay, Loop-Mediated Amplification test for TB (TB-LAMP), was compared to smear microscopy, MGIT culture and GeneXpert MTB/RIF for all samples. When culture was used as the reference standard, we found an overall sensitivity for TB-LAMP of 99% (95% CI: 94.5-99.8) and specificity of 94% (95% CI: 89.3-96.7). When latent class analysis was performed, TB-LAMP had 98.6% (95% CI: 95.9-100) sensitivity and 99% (95% CI: 98.2-100) specificity compared to 91.1% (95% CI: 86.1-96) sensitivity and 100% (95% CI: 98.2-100) specificity for MGIT culture. GeneXpert had the highest sensitivity 99.1% (95% CI: 97.1-100) but the lowest specificity 96% (95% CI: 92.6-98.3). Both TB-LAMP and GeneXpert showed high sensitivity and specificity regardless of age or strain of infection. Our findings show the diagnostic utility of both GeneXpert and TB-LAMP in The Gambia. Whilst TB-LAMP requires less infrastructure, it is unable to detect drug-resistant patterns and therefore would be most suitable as a screening test for new TB cases in peripheral health clinics. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Leveraging tuberculosis case relative locations to enhance case detection and linkage to care in Swaziland.

PubMed

Brunetti, Marie; Rajasekharan, Sathyanath; Ustero, Piluca; Ngo, Katherine; Sikhondze, Welile; Mzileni, Buli; Mandalakas, Anna; Kay, Alexander W

2018-01-01

In Swaziland, as in many high HIV/TB burden settings, there is not information available regarding the household location of TB cases for identifying areas of increased TB incidence, limiting the development of targeted interventions. Data from "Butimba", a TB REACH active case finding project, was re-analyzed to provide insight into the location of TB cases surrounding Mbabane, Swaziland. The project aimed to identify geographical areas with high TB burdens to inform active case finding efforts. Butimba implemented household contact tracing; obtaining landmark based, informal directions, to index case homes, defined here as relative locations. The relative locations were matched to census enumeration areas (known location reference areas) using the Microsoft Excel Fuzzy Lookup function. Of 403 relative locations, an enumeration area reference was detected in 388 (96%). TB cases in each census enumeration area and the active case finders in each Tinkhundla, a local governmental region, were mapped using the geographic information system, QGIS 2.16. Urban Tinkhundla predictably accounted for most cases; however, after adjusting for population, the highest density of cases was found in rural Tinkhundla. There was no correlation between the number of active case finders currently assigned to the 7 Tinkhundla surrounding Mbabane and the total number of TB cases (Spearman rho = -0.57, p  = 0.17) or the population adjusted TB cases (Spearman rho = 0.14, p  = 0.75) per Tinkhundla. Reducing TB incidence in high-burden settings demands novel analytic approaches to study TB case locations. We demonstrated the feasibility of linking relative locations to more precise geographical areas, enabling data-driven guidance for National Tuberculosis Programs' resource allocation. In collaboration with the Swazi National Tuberculosis Control Program, this analysis highlighted opportunities to better align the active case finding national strategy with the TB disease burden.

Study of Mycobacterium tuberculosis drug resistance in the region of Galicia, Spain.

PubMed

Pérez del Molino Bernal, M L; Túñez, V; Cruz-Ferro, E; Fernández-Villar, A; Vázquez-Gallardo, R; Díaz-Cabanela, D; Anibarro, L

2005-11-01

Galicia, a region in north-east Spain with its own government and health system and a population of 2 695 880. To study the epidemiology of resistant tuberculosis (TB). A prospective, descriptive, and observational study of all Mycobacterium tuberculosis isolates processed by each of the laboratories in Galicia that perform mycobacterial cultures. The study followed the methodology recommended by the World Health Organization and the International Union Against Tuberculosis and Lung Disease, and included isolates processed between 1 November 2001 and 1 June 2002. Of 400 strains analysed, 360 corresponded to previously untreated cases and 40 to previously treated cases. Of the previously untreated cases, 88.3% contained strains susceptible to isoniazid, rifampicin, streptomycin and ethambutol, while 4.4% were resistant to isoniazid. The rate of susceptibility to the four drugs was 77.5% in the previously treated cases. Multidrug-resistant TB was detected in 1.4% of the previously untreated cases and in 7.5% of the previously treated cases. Although Galicia has a high incidence of TB (49.4 cases per 100 000 population in 2001), the resistance levels detected by the study do not currently pose a serious problem for the region.

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

PubMed Central

Good, Margaret; Duignan, Anthony

2011-01-01

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

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

PubMed

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

2016-01-01

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

Achievements in and Challenges of Tuberculosis Control in South Korea.

PubMed

Kim, Ji Han; Yim, Jae-Joon

2015-11-01

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

Trend of some Tuberculosis Indices in Iran during 25 yr Period (1990-2014).

PubMed

Khazaei, Salman; Ayubi, Erfan; Mansournia, Mohammad Ali; Rafiemanesh, Hossein

2016-01-01

Investigation of tuberculosis (TB)-specific indices including prevalence of TB, mortality of TB cases excluding HIV, HIV/TB mortality, incidence of TB (all forms), HIV/TB incidence as well as case detection and related trends is a crucial step in evaluation of program performance and strategies success. Besides, estimating the number and time of change points for TB incidence can help to detect effective factors in TB control. Therefore, the current study aimed to determine the trend of aforementioned indices in Iran during a 25 yr period (1990 to 2014). Data on trend of TB in Iran was extracted from WHO regional office reports during 1990-2014. For determining the trend of TB indices, Annual Percent Changes (APC) and Average Annual Percent Changes (AAPC) was estimated using segmented regression model. AAPC (95% CI) for HIV/TB mortality and HIV/TB incidence were 11.5 (9.3, 13.6) and 14.8 (13.6, 16.1), respectively, which are sign of increasing trend during the period (P<0.05). Other indices showed significantly decreasing trend (P<0.05), except for case detection rate (P =0.803). The incidence, prevalence, and death rates of TB had shown a decreasing trend in general population, regarded as a useful indicator of achievements of Millennium Development Goals (MDGs) and effectiveness of interventional programs. Increasing trend of incidence and mortality of TB in HIV infected patients, needs conducting more intervention strategies in health care programs.

Burden of tuberculosis in indigenous peoples globally: a systematic review.

PubMed

Tollefson, D; Bloss, E; Fanning, A; Redd, J T; Barker, K; McCray, E

2013-09-01

The burden of tuberculosis (TB) in the estimated 370 million indigenous peoples worldwide is unknown. To conduct a literature review to summarize the TB burden in indigenous peoples, identify gaps in current knowledge, and provide the foundation for a research agenda prioritizing indigenous health within TB control. A systematic literature review identified articles published between January 1990 and November 2011 quantifying TB disease burden in indigenous populations worldwide. Among the 91 articles from 19 countries included in the review, only 56 were from outside Australia, Canada, New Zealand and the United States. The majority of the studies showed higher TB rates among indigenous groups than non-indigenous groups. Studies from the Amazon generally reported the highest TB prevalence and incidence, but select populations from South-East Asia and Africa were found to have similarly high rates of TB. In North America, the Inuit had the highest reported TB incidence (156/100000), whereas the Metis of Canada and American Indians/Alaska Natives experienced rates of <10/100000. New Zealand's Maori and Pacific Islanders had higher TB incidence rates than Australian Aborigines, but all were at greater risk of developing TB than non-indigenous groups. Where data exist, indigenous peoples were generally found to have higher rates of TB disease than non-indigenous peoples; however, this burden varied greatly. The paucity of published information on TB burden among indigenous peoples highlights the need to implement and improve TB surveillance to better measure and understand global disparities in TB rates.

A novel automatic molecular test for detection of multidrug resistance tuberculosis in sputum specimen: A case control study.

PubMed

Li, Qiang; Ou, Xi C; Pang, Yu; Xia, Hui; Huang, Hai R; Zhao, Bing; Wang, Sheng F; Zhao, Yan L

2017-07-01

MiniLab tuberculosis (ML TB) assay is a new automatic diagnostic tool for diagnosis of multidrug resistance tuberculosis (MDR-TB). This study was conducted with aims to know the performance of this assay. Sputum sample from 224 TB suspects was collected from tuberculosis suspects seeking medical care at Beijing Chest hospital. The sputum samples were directly used for smear and ML TB test. The left sputum sample was used to conduct Xpert MTB/RIF, Bactec MGIT culture and drug susceptibility test (DST). All discrepancies between the results from DST, molecular and phenotypic methods were confirmed by DNA Sequencing. The sensitivity and specificity of ML TB test for detecting MTBC from TB suspects were 95.1% and 88.9%, respectively. The sensitivity for smear negative TB suspects was 64.3%. For detection of RIF resistance, the sensitivity and specificity of ML TB test were 89.2% and 95.7%, respectively. For detection of INH resistance, the sensitivity and specificity of ML TB test were 78.3% and 98.1%, respectively. ML TB test showed similar performance to Xpert MTB/RIF for detection of MTBC and RIF resistance. In addition, ML TB also had good performance for INH resistance detection. Copyright © 2017. Published by Elsevier Ltd.

Nosocomial tuberculosis prevention in Portuguese hospitals: a cross-sectional evaluation.

PubMed

Sousa, M; Gomes, M; Gaio, A R; Duarte, R

2017-08-01

Measures to control tuberculous infection are crucial to prevent nosocomial transmission and protect health care workers (HCWs). In Portugal, the extent of implementation of tuberculosis (TB) control measures in hospitals is not known. To determine the current implementation of preventive measures for tuberculous infection at administrative, environmental and personal levels in Portuguese hospitals. A cross-sectional evaluation was performed using two anonymous questionnaires: one sent to all the hospital infection control (IC) committees and the other sent to all pulmonologists and physicians specialising in infectious disease. Fourteen IC committees and 72 physicians responded. According to the IC committees, 92% of hospitals had a written TB control plan, but only 37% of the physicians said there was always/almost always a fast track for diagnosing suspected pulmonary TB cases. The majority of the hospitals had an isolation policy (85%) and these patients were always/almost always admitted in separate rooms, according to 70% of physicians. Both HCWs and TB patients used respiratory protection equipment (92%). These findings indicate that the most basic TB IC measures had been undertaken, but some TB IC measures were not fully implemented at all hospitals. An institutional effort should be made to solve this problem and strengthen TB prevention activities.

Persistent latent tuberculosis reactivation risk in United States immigrants.

PubMed

Walter, Nicholas D; Painter, John; Parker, Matthew; Lowenthal, Phillip; Flood, Jennifer; Fu, Yunxin; Asis, Redentor; Reves, Randall

2014-01-01

Current guidelines limit latent tuberculosis infection (LTBI) evaluation to persons in the United States less than or equal to 5 years based on the assumption that high TB rates among recent entrants are attributable to high LTBI reactivation risk, which declines over time. We hypothesized that high postarrival TB rates may instead be caused by imported active TB. Estimate reactivation and imported TB in an immigrant cohort. We linked preimmigration records from a cohort of California-bound Filipino immigrants during 2001-2010 with subsequent TB reports. TB was likely LTBI reactivation if the immigrant had no evidence of active TB at preimmigration examination, likely imported if preimmigration radiograph was abnormal and TB was reported less than or equal to 6 months after arrival, and likely reactivation of inactive TB if radiograph was abnormal but TB was reported more than 6 months after arrival. Among 123,114 immigrants, 793 TB cases were reported. Within 1 year of preimmigration examination, 85% of TB was imported; 6 and 9% were reactivation of LTBI and inactive TB, respectively. Conversely, during Years 2-9 after U.S. entry, 76 and 24% were reactivation of LTBI and inactive TB, respectively. The rate of LTBI reactivation (32 per 100,000) did not decline during Years 1-9. High postarrival TB rates were caused by detection of imported TB through active postarrival surveillance. Among immigrants without active TB at baseline, reported TB did not decline over 9 years, indicating sustained high risk of LTBI reactivation. Revised guidelines should support LTBI screening and treatment more than 5 years after U.S. arrival.

Tuberculosis epidemiology, diagnosis and infection control recommendations for dental settings: an update on the Centers for Disease Control and Prevention guidelines.

PubMed

Cleveland, Jennifer L; Robison, Valerie A; Panlilio, Adelisa L

2009-09-01

Although rates of tuberculosis (TB) in the United States have decreased in recent years, disparities in TB incidence still exist between U.S.-born and foreign-born people (people living in the United States but born outside it) and between white people and nonwhite people. In addition, the number of TB outbreaks among health care personnel and patients has decreased since the implementation of the 1994 Centers for Disease Control and Prevention (CDC) guidelines to prevent transmission of Mycobacterium tuberculosis. In this article, the authors provide updates on the epidemiology of TB, advances in TB diagnostic methods and TB infection control guidelines for dental settings. In 2008, 83 percent of all reported TB cases in the United States occurred in nonwhite people and 17 percent occurred in white people. Foreign-born people had a TB rate about 10 times higher than that of U.S.-born people. New blood assays for M. tuberculosis have been developed to diagnose TB infection and disease. Changes from the 1994 CDC guidelines incorporated into CDC's "Guidelines for Preventing the Transmission of Mycobacterium tuberculosis in Health-Care Settings, 2005" include revised risk classifications, new TB diagnostic methods, decreased frequencies of tuberculin skin testing in various settings and changes in terminology. Although the principles of TB infection control have remained the same, the changing epidemiology of TB and the advent of new diagnostic methods for TB led to the development of the 2005 update to the 1994 guidelines. Dental health care personnel should be aware of the modifications that are pertinent to dental settings and incorporate them into their overall infection control programs.

Characteristics and treatment outcomes of tuberculosis cases by risk groups, Japan, 2007-2010.

PubMed

Uchimura, Kazuhiro; Ngamvithayapong-Yanai, Jintana; Kawatsu, Lisa; Ohkado, Akihiro; Yoshiyama, Takashi; Shimouchi, Akira; Ito, Kunihiko; Ishikawa, Nobukatsu

2013-01-01

We studied the characteristics and treatment outcomes of the following risk groups for tuberculosis (TB): those with HIV and diabetes mellitus (DM), contact cases, the homeless, foreigners, health care workers (HCW) and the elderly. A descriptive cross-sectional study was conducted by analysing the Japanese tuberculosis surveillance data of all cases registered between 2007 and 2010 (n = 96 689). The annual proportion of TB cases by risk group was stable over the study period, although there was a slight but significant increase observed for foreigners and elderly cases. Homeless and elderly TB cases had the highest DM co-morbidity (16.6% and 15.3%). HIV co-infection was low in all TB cases (0.2%) yet highest in foreigners (1.3%). HIV status of 45% of TB cases was unknown. The proportion of multi drug resistant (MDR) TB was similar among all risk groups (0.0-0.9%) except foreigners, at 3.4%. Males in most risk groups had higher mortality than females; the mortality of all TB cases in all age groups for both males and females were 3.6-24 times higher than the general population. Reasons for the high proportion of "HIV status unknown" should be investigated and improved. Contact tracing among foreign cases with MDR-TB should be a priority. Homeless persons should be screened for DM together with TB. Programs to enhance health and nutrition status may benefit tuberculosis prevention among the elderly. Tuberculosis screening and TB education are important for HCW.

Drug-resistance patterns of Mycobacterium tuberculosis strains and associated risk factors among multi drug-resistant tuberculosis suspected patients from Ethiopia.

PubMed

Mesfin, Eyob Abera; Beyene, Dereje; Tesfaye, Abreham; Admasu, Addisu; Addise, Desalegn; Amare, Miskir; Dagne, Biniyam; Yaregal, Zelalem; Tesfaye, Ephrem; Tessema, Belay

2018-01-01

Multidrug drug-resistant tuberculosis (MDR-TB) is a major health problem and seriously threatens TB control and prevention efforts globally. Ethiopia is among the 30th highest TB burden countries for MDR-TB with 14% prevalence among previously treated cases. The focus of this study was on determining drug resistance patterns of Mycobacterium tuberculosis among MDR-TB suspected cases and associated risk factors. A cross-sectional study was conducted in Addis Ababa from June 2015 to December 2016. Sputum samples and socio-demographic data were collected from 358 MDR-TB suspected cases. Samples were analyzed using Ziehl-Neelsen technique, GeneXpert MTB/RIF assay, and culture using Lowenstein-Jensen and Mycobacterial growth indicator tube. Data were analyzed using SPSS version 23. A total of 226 the study participants were culture positive for Mycobacterium tuberculosis, among them, 133 (58.8%) participants were males. Moreover, 162 (71.7%) had been previously treated for tuberculosis, while 128 (56.6%) were TB/HIV co-infected. A majority [122 (54%)] of the isolates were resistant to any first-line anti-TB drugs. Among the resistant isolates, 110 (48.7%) were determined to be resistant to isoniazid, 94 (41.6%) to streptomycin, 89 (39.4%) to rifampicin, 72 (31.9%) to ethambutol, and 70 (30.9%) to pyrazinamide. The prevalence of MDR-TB was 89 (39.4%), of which 52/89 (58.4%) isolates were resistance to all five first-line drugs. Risk factors such as TB/HIV co-infection (AOR = 5.59, p = 0.00), cigarette smoking (AOR = 3.52, p = 0.045), alcohol drinking (AOR = 5.14, p = 0.001) hospital admission (AOR = 3.49, p = 0.005) and visiting (AOR = 3.34, p = 0.044) were significantly associated with MDR-TB. The prevalence of MDR-TB in the study population was of a significantly high level among previously treated patients and age group of 25-34. TB/HIV coinfection, smoking of cigarette, alcohol drinking, hospital admission and health facility visiting were identified as risk factors for developing MDR-TB. Therefore, effective strategies should be designed considering the identified risk factors for control of MDR-TB.

Target prioritization and strategy selection for active case-finding of pulmonary tuberculosis: a tool to support country-level project planning.

PubMed

Nishikiori, Nobuyuki; Van Weezenbeek, Catharina

2013-02-02

Despite the progress made in the past decade, tuberculosis (TB) control still faces significant challenges. In many countries with declining TB incidence, the disease tends to concentrate in vulnerable populations that often have limited access to health care. In light of the limitations of the current case-finding approach and the global urgency to improve case detection, active case-finding (ACF) has been suggested as an important complementary strategy to accelerate tuberculosis control especially among high-risk populations. The present exercise aims to develop a model that can be used for county-level project planning. A simple deterministic model was developed to calculate the number of estimated TB cases diagnosed and the associated costs of diagnosis. The model was designed to compare cost-effectiveness parameters, such as the cost per case detected, for different diagnostic algorithms when they are applied to different risk populations. The model was transformed into a web-based tool that can support national TB programmes and civil society partners in designing ACF activities. According to the model output, tuberculosis active case-finding can be a costly endeavor, depending on the target population and the diagnostic strategy. The analysis suggests the following: (1) Active case-finding activities are cost-effective only if the tuberculosis prevalence among the target population is high. (2) Extensive diagnostic methods (e.g. X-ray screening for the entire group, use of sputum culture or molecular diagnostics) can be applied only to very high-risk groups such as TB contacts, prisoners or people living with human immunodeficiency virus (HIV) infection. (3) Basic diagnostic approaches such as TB symptom screening are always applicable although the diagnostic yield is very limited. The cost-effectiveness parameter was sensitive to local diagnostic costs and the tuberculosis prevalence of target populations. The prioritization of appropriate target populations and careful selection of cost-effective diagnostic strategies are critical prerequisites for rational active case-finding activities. A decision to conduct such activities should be based on the setting-specific cost-effectiveness analysis and programmatic assessment. A web-based tool was developed and is available to support national tuberculosis programmes and partners in the formulation of cost-effective active case-finding activities at the national and subnational levels.

Tuberculosis at Raffic Hariri University Hospital (RHUH) during 10 years period 2005-2015, cross sectional, observational study.

PubMed

Zadeh, Catherina; Tayara, Loubna

2018-07-01

Tuberculosis is a contagious disease caused by Mycobacterium tuberculosis. It represents, according to WHO, one of the most leading causes of death worldwide. 1 BACKGROUND: Based on our regional conditions, such as Syrian immigration, poor nutritional status, are contributors for the development of the disease. This was a retrospective analytical cross sectional study done to review all cases of tuberculosis newly diagnosed at RHUH during 10 years period (2005-2015). 128 TB labeled patients were retrieved. A standardized checklist was used to collect data. Patients were then classified as TB diseased and TB infected. The total number of TB suspected patients was 128 over 10 years which represents 1.77% of all patients admitted to the medical floor. Among these, the total number of PPD positive patients was 40.6% from our study population (2005-2015), 48% were TB infected and 52% had positive CXR. Among those with positive CXR, 41% were confirmed TB disease and 59% not confirmed TB disease. There was significant variation in evolution through years (2005-2015). By comparing the socio-demographic findings between TB disease, TB infection and non-TB group no statistical significance was found. Same analysis were repeated between TB infection and TB disease groups showed one significant association between age and TB disease vs. TB infection (p=0.034), where the younger population belongs to TB infected group (42%), while 50% of TB diseased group were older. As for scoring severity index, ANOVA in the three groups showed a significant association with a p value of 0.046. The TB diseased patients have the highest severity score index. TB disease is still present in Lebanon with fluctuating level with the highest peak found in 2013 explained by the influx of Syrian refugee population. Followed by a gradual drop in the following years. The younger population belongs to TB infected group, while TB disease patients had the most severe clinical course compared to TB infected and non TB patients. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Guidance for National Tuberculosis Programmes on the management of tuberculosis in children. Chapter 1: introduction and diagnosis of tuberculosis in children.

PubMed

2006-10-01

About one million children develop tuberculosis (TB) annually worldwide, accounting for about 11% of all TB cases. Children with TB differ from adults in their immunological and pathophysiological response in ways that may have important implications for the prevention, diagnosis and treatment of TB in children. There is an urgent need to improve the diagnosis and management of children with TB, and the prevention of TB in children, by ensuring their inclusion under the implementation of the Stop TB strategy by National TB Programmes. Critical areas for further research include a better understanding of the epidemiology of childhood TB, vaccine development, the development of better diagnostic techniques, new drug development, and the optimal formulations and dosing of first- and second-line TB drugs in children. Specifically regarding the diagnosis of TB in children, this relies on a careful and thorough assessment of all the evidence derived from a careful history, clinical examination and relevant investigations, e.g., tuberculin skin test, chest radiograph and sputum smear microscopy. Although bacteriological confirmation of TB is not always possible, it should be sought whenever possible, e.g., by sputum microscopy in children with suspected pulmonary TB who are old enough to produce a sputum sample. A trial of treatment with TB medications is not generally recommended as a method to diagnose TB in children. New, improved diagnostic tests are urgently needed.

[Treatment of tuberculosis].

PubMed

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

2015-01-01

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

Inhibition of IL-17A by secukinumab shows no evidence of increased Mycobacterium tuberculosis infections

PubMed Central

Kammüller, Michael; Tsai, Tsen-Fang; Griffiths, Christopher EM; Kapoor, Nidhi; Kolattukudy, Pappachan E; Brees, Dominique; Chibout, Salah-Dine; Safi Jr, Jorge; Fox, Todd

2017-01-01

Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin-17A (IL-17A), has been shown to have significant efficacy in the treatment of moderate to severe psoriasis, psoriatic arthritis and ankylosing spondylitis. Blocking critical mediators of immunity may carry a risk of increased opportunistic infections. Here we present clinical and in vitro findings examining the effect of secukinumab on Mycobacterium tuberculosis infection. We re-assessed the effect of secukinumab on the incidence of acute tuberculosis (TB) and reactivation of latent TB infection (LTBI) in pooled safety data from five randomized, double-blind, placebo-controlled, phase 3 clinical trials in subjects with moderate to severe plaque psoriasis. No cases of TB were observed after 1 year. Importantly, in subjects with a history of pulmonary TB (but negative for interferon-γ release and receiving no anti-TB medication) or positive for latent TB (screened by interferon-γ release assay and receiving anti-TB medication), no cases of active TB were reported. Moreover, an in vitro study examined the effect of the anti-tumor necrosis factor-α (TNFα) antibody adalimumab and secukinumab on dormant M. tuberculosis H37Rv in a novel human three-dimensional microgranuloma model. Auramine-O, Nile red staining and rifampicin resistance of M. tuberculosis were measured. In vitro, anti-TNFα treatment showed increased staining for Auramine-O, decreased Nile red staining and decreased rifampicin resistance, indicative of mycobacterial reactivation. In contrast, secukinumab treatment was comparable to control indicating a lack of effect on M. tuberculosis dormancy. To date, clinical and preclinical investigations with secukinumab found no evidence of increased M. tuberculosis infections. PMID:28868144

Tuberculosis in recipients of solid-organ transplants during 1995-2015 in Cali, Colombia.

PubMed

García-Goez, J F; Munera, G A; Rojas, V; Pacheco, R; Caylá, J A; Miro, J M

2017-11-01

Tuberculosis (TB) in solid-organ transplants (SOTs) is an important opportunistic infection associated with mortality and graft loss. SOT recipients carry a higher risk of contracting active TB than the general population. Clinical and radiographic presentations are non-specific, and sputum smear and culture have low yields. TB patients with SOTs require standard anti-tuberculosis treatment. However, rifampicin (RMP) use is associated with a 30% rate of acute graft rejection (AGR) and a 20% rate of transplant loss. To determine treatment outcomes in SOT recipients with active TB. A retrospective study of clinical and microbiological data and TB treatment outcomes. Among the 2349 transplants assessed, active TB was detected in 31 recipients; 55% had pulmonary TB and 40% were sputum smear-positive. In 32% of the patients, TB was diagnosed 30 days after symptom onset, 77% of the patients were cured and 10% died. AGR occurred in 13%. TB was diagnosed in <30 days. Anti-tuberculosis treatment without RMP (80% vs. 67%; P = 0.48, OR 0.5, 95%CI 0.07-3.55) and with moxifloxacin yielded higher treatment success rates and a lower risk of AGR.

T Cell Production of GM-CSF Protects the Host during Experimental Tuberculosis.

PubMed

Robinson, Richard T

2017-12-12

Although classically associated with myelopoiesis, granulocyte-macrophage colony-stimulating factor (GM-CSF) is increasingly recognized as being important for tuberculosis (TB) resistance. GM-CSF is expressed by nonhematopoietic and hematopoietic lineages following infection with Mycobacterium tuberculosis and is necessary to restrict M. tuberculosis growth in experimental models. Until the recent study by Rothchild et al. (mBio 8:e01514-17, 2017, https://doi.org/10.1128/mBio.01514-17), it was unknown whether GM-CSF-producing T cells contribute to TB resistance. Rothchild et al. identify which conventional and nonconventional T cell subsets produce GM-CSF during experimental TB, establish their protective nature using a variety of approaches, and provide a mechanistic basis for their ability to restrict M. tuberculosis growth. This commentary discusses the significance of these findings to basic and applied TB research. As translated to human disease, these findings suggest vaccine-mediated expansion of GM-CSF-producing T cells could be an effective prophylactic or therapeutic TB strategy. Copyright © 2017 Robinson.

Human genetic factors in tuberculosis: an update.

PubMed

van Tong, Hoang; Velavan, Thirumalaisamy P; Thye, Thorsten; Meyer, Christian G

2017-09-01

Tuberculosis (TB) is a major threat to human health, especially in many developing countries. Human genetic variability has been recognised to be of great relevance in host responses to Mycobacterium tuberculosis infection and in regulating both the establishment and the progression of the disease. An increasing number of candidate gene and genome-wide association studies (GWAS) have focused on human genetic factors contributing to susceptibility or resistance to TB. To update previous reviews on human genetic factors in TB we searched the MEDLINE database and PubMed for articles from 1 January 2014 through 31 March 2017 and reviewed the role of human genetic variability in TB. Search terms applied in various combinations were 'tuberculosis', 'human genetics', 'candidate gene studies', 'genome-wide association studies' and 'Mycobacterium tuberculosis'. Articles in English retrieved and relevant references cited in these articles were reviewed. Abstracts and reports from meetings were also included. This review provides a recent summary of associations of polymorphisms of human genes with susceptibility/resistance to TB. © 2017 John Wiley & Sons Ltd.

Microbe Profile: Mycobacterium tuberculosis: Humanity's deadly microbial foe.

PubMed

Gordon, Stephen V; Parish, Tanya

2018-04-01

Mycobacterium tuberculosis is an expert and deadly pathogen, causing the disease tuberculosis (TB) in humans. It has several notable features: the ability to enter non-replicating states for long periods and cause latent infection; metabolic remodelling during chronic infection; a thick, waxy cell wall; slow growth rate in culture; and intrinsic drug resistance and antibiotic tolerance. As a pathogen, M. tuberculosis has a complex relationship with its host, is able to replicate inside macrophages, and expresses diverse immunomodulatory molecules. M. tuberculosis currently causes over 1.8 million deaths a year, making it the world's most deadly human pathogen.

Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011

PubMed Central

Tran, Huong Thi Giang; Bui, Quyen Thi Tu

2016-01-01

Introduction Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. Methods Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. Results A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. Conclusion This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance. PMID:27508089

Prevalence of resistance to second-line tuberculosis drug among multidrug-resistant tuberculosis patients in Viet Nam, 2011.

PubMed

Nguyen, Hoa Binh; Nguyen, Nhung Viet; Tran, Huong Thi Giang; Nguyen, Hai Viet; Bui, Quyen Thi Tu

2016-01-01

Extensively drug-resistant tuberculosis (XDR-TB) represents an emerging public health problem worldwide. According to the World Health Organization, an estimated 9.7% of multidrug-resistant TB (MDR-TB) cases are defined as XDR-TB globally. The objective of this study was to determine the prevalence of drug resistance to second-line TB drugs among MDR-TB cases detected in the Fourth National Anti-Tuberculosis Drug Resistance Survey in Viet Nam. Eighty clusters of TB cases were selected using a probability-proportion-to-size approach. To identify MDR-TB cases, drug susceptibility testing (DST) was performed for the four major first-line TB drugs. DST of second-line drugs (ofloxacin, amikacin, kanamycin, capreomycin) was performed on isolates from MDR-TB cases to identify pre-XDR and XDR cases. A total of 1629 smear-positive TB cases were eligible for culture and DST. Of those, DST results for first-line drugs were available for 1312 cases, and 91 (6.9%) had MDR-TB. Second-line DST results were available for 84 of these cases. Of those, 15 cases (17.9%) had ofloxacin resistance and 6.0% were resistant to kanamycin and capreomycin. Five MDR-TB cases (6.0%) met the criteria of XDR-TB. This survey provides the first estimates of the proportion of XDR-TB among MDR-TB cases in Viet Nam and provides important information for local policies regarding second-line DST. Local policies and programmes that are geared towards TB prevention, early diagnosis and treatment with effective regimens are of high importance.

2-Thiophenecarboxylic acid hydrazide Derivatives: Synthesis and Anti-Tuberculosis Studies

NASA Astrophysics Data System (ADS)

Fahmi, M. R. G.; Khumaidah, L.; Ilmiah, T. K.; Fadlan, A.; Santoso, M.

2018-04-01

One of the most frequent and widespread infectious diseases especially in developing countries is tuberculosis (TB). The number of TB drug resistant tend to increase, and there has been no new TB drug introduce since the 1960s. Six 2-Thiophenecarboxylic acid hydrazide derivatives were synthesized in 90-97% yields, and 2-thiophenecarbonylhydrazone-5, 7-dibromoisatin showed the highest activity in inhibiting M. tuberculosis H37Rv.

Knowledge and Attitudes About Tuberculosis Among U.S.-Born Blacks and Whites with Tuberculosis.

PubMed

Howley, Meredith M; Rouse, Chaturia D; Katz, Dolores J; Colson, Paul W; Hirsch-Moverman, Yael; Royce, Rachel A

2015-10-01

Non-Hispanic blacks represent 13% of the U.S.-born population but account for 37% of tuberculosis (TB) cases reported in U.S.-born persons. Few studies have explored whether this disparity is associated with differences in TB-related knowledge and attitudes. Interviews were conducted with U.S.-born, non-Hispanic blacks and whites diagnosed with TB from August 2009 to December 2010 in cities and states that accounted for 27% of all TB cases diagnosed in these racial groups in the U.S. during that time period. Of 477 participants, 368 (77%) were non-Hispanic black and 109 (23%) were non-Hispanic white. Blacks had significantly less knowledge and more misconceptions about TB transmission and latent TB infection than whites. Most TB patients in both groups recalled being given TB information; having received such information was strongly correlated with TB knowledge. Providing information to U.S.-born TB patients significantly increased their knowledge and understanding of TB. More focused efforts are needed to provide TB information to U.S.-born black TB patients.

Tuberculosis care for pregnant women: a systematic review.

PubMed

Nguyen, Hang Thanh; Pandolfini, Chiara; Chiodini, Peter; Bonati, Maurizio

2014-11-19

Tuberculosis (TB) during pregnancy may lead to severe consequences affecting both mother and child. Prenatal care could be a very good opportunity for TB care, especially for women who have limited access to health services. The aim of this review was to gather and evaluate studies on TB care for pregnant women. We used a combination of the terms "tuberculosis" and "pregnancy", limited to human, to search for published articles. Studies reflecting original data and focusing on TB care for pregnant women were included. All references retrieved were collected using the Reference Manager software (Version 11). Thirty five studies were selected for review and their data showed that diagnosis was often delayed because TB symptoms during pregnancy were not typical. TB prophylaxis and anti-TB therapy appeared to be safe and effective for pregnant women and their babies when suitable follow up and early initiation were present, but the compliance rate to TB prophylaxis is still low due to lack of follow up and referral services. TB care practices in the reviewed studies were in line in principle with the WHO International Standards for Tuberculosis Care (ISTC). Integration of TB care within prenatal care would improve TB diagnosis and treatment for pregnant women. To improve the quality of TB care, it is necessary to develop national level guidelines based on the ISTC with detailed guidelines for pregnant women.

Tuberculous cold abscess of breast: an unusual presentation in a male patient.

PubMed

Brown, Sarah; Thekkinkattil, Dinesh K

2016-06-01

Tuberculosis (TB) of breast is a rare condition especially presentation as a cold abscess. We present a case of male patient with TB of lung and meninges with a cold abscess in the breast. The abscess was incidental finding on the computed tomography (CT) scan. This was further managed by a combination of anti-tuberculous chemotherapy treatment and surgical drainage. We reviewed the current literature related to mammary TB, its presentations and treatment.

Tuberculous cold abscess of breast: an unusual presentation in a male patient

PubMed Central

Brown, Sarah

2016-01-01

Tuberculosis (TB) of breast is a rare condition especially presentation as a cold abscess. We present a case of male patient with TB of lung and meninges with a cold abscess in the breast. The abscess was incidental finding on the computed tomography (CT) scan. This was further managed by a combination of anti-tuberculous chemotherapy treatment and surgical drainage. We reviewed the current literature related to mammary TB, its presentations and treatment. PMID:27294045

"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.

[The Enhanceing effect of IL-12 on phagocytosis and killing of Mycobacterium tuberculosis by neutrophils in tuberculosis patients].

PubMed

Jiang, Li-na; Yao, Chun-yan; Jin, Qi-li; He, Wen-xin; Li, Bai-qing

2011-11-01

To explore the effects of IL-12 on phagocytosis and killing of Mycobacterium tuberculosis by neutrophils or polymorphonuclear cells (PMNs) in tuberculosis patients. The fresh peripheral blood samples from TB patients and healthy adults were incubated with M.tb labeled with FITC, and the percentages of phagocytosis of M.tb by PMNs was measured by flow cytometry (FCM). The fresh peripheral blood samples were incubated with DCFH-DA, and with or without M.tb for different times, the percentage of activation and the ROS production of PMNs were measured by FCM. Whole blood samples were pretreated with IL-12, the changes of phagocytosis, activation and ROS production of PMNs were measured by FCM. The percentages of phagocytosis by PMNs, activation and ROS production of PMNs in both TB patients and healthy adults increased dependent on the time of incubation with M.tb. Only the phagocytosis of M.tb by PMNs at 5 min in TB patients of tuberculosis patients (51.82±6.93)% was obviously higher than that in healthy adults (47.20±4.26)%, (P<0.05). Pretreatment of whole blood with IL-12 before incubation with M.tb, the percentages of phagocytosis, activation and ROS production of PMNs in both TB patients and healthy adults increased in dose dependent manner, but no significant difference was found between both groups. The results indicated that the phagocytosis of M.tb and ROS production by PMNs in TB patients were almost the same as that in healthy controls, except for phagocytosis is higher at early stage. Furthermore, IL-12 can enhance the responsiveness to the phagocytosis and ROS production of PMNs.

Genotypic characteristics of Mycobacterium tuberculosis circulating in Xinjiang, China.

PubMed

Yuan, Li; Mi, Ligu; Li, Yongxiang; Zhang, Hui; Zheng, Fang; Li, Zhuoya

2016-02-01

Tuberculosis (TB), a chronic infectious disease caused by Mycobacterium tuberculosis (MTB), poses a serious threat to human health. We investigated the genotypes of MTB in the high prevalence province Xinjiang, China. From March 2010 to May 2013, 381 MTB isolates from patients with pulmonary TB were analyzed by molecular typing of 24 mycobacterial interspersed repetitive unit-variable number tandem repeat loci and PCR detection of the deleted regions of difference of the Beijing/W lineage and its sublineages. These isolates were shown to be highly polymorphic and to be composed of 345 unique genotypes, including 30 genotype clusters consisting of 2 or 3 strains and 315 individual genotypes. The genotype clustering rate was 17.32% and recent transmission index was low (9.45%). The Beijing/W lineage strains accounted for 57.48% of the isolates, and this predominant family strain was further subdivided into four sublineages: 181 (69.86%), 207 (14.61%), 105 (10.96%), and 150 (4.56%). The Beijing/W lineage (especially sublineage 181) strains were predominant and were associated with the transmissibility of TB in Xinjiang. Based on our data, we hypothesize that the circulating MTB strains in Xinjiang have significant genetic diversity and that the majority of the TB in Xinjiang may be explained by non-recent transmission emerging by endogenous reactivation. The possibility of outbreak is low, and current measures to control TB should first focus on standardized treatment of TB patients to prevent reactivation of latent infections.

Prevalence of latent tuberculosis infection among tuberculosis laboratory workers in Iran.

PubMed

Nasehi, Mahshid; Hashemi-Shahraki, Abdolrazagh; Doosti-Irani, Amin; Sharafi, Saeed; Mostafavi, Ehsan

2017-01-01

The risk of transmission of Mycobacterium tuberculosis from patients to health care workers (HCWs) is a neglected problem in many countries, including Iran. The aim of this study was to estimate the prevalence of latent tuberculosis (TB) infection (LTBI) among TB laboratory staff in Iran, and to elucidate the risk factors associated with LTBI. All TB laboratory staff (689 individuals) employed in the TB laboratories of 50 Iranian universities of medical sciences and a random sample consisting of 317 low-risk HCWs were included in this cross-sectional study. Participants with tuberculin skin test indurations of 10 mm or more were considered to have an LTBI. The prevalence of LTBI among TB laboratory staff and low-risk HCWs was 24.83% (95% confidence interval [CI], 21.31 to 27.74%) and 14.82% (95% CI, 11.31 to 19.20%), respectively. No active TB cases were found in either group. After adjusting for potential confounders, TB laboratory staff were more likely to have an LTBI than low-risk HCWs (prevalence odds ratio, 2.06; 95% CI, 1.35 to 3.17). This study showed that LTBI are an occupational health problem among TB laboratory staff in Iran. This study reinforces the need to design and implement simple, effective, and affordable TB infection control programs in TB laboratories in Iran.

High prevalence of multidrug-resistant tuberculosis among patients with rifampicin resistance using GeneXpert Mycobacterium tuberculosis/rifampicin in Ghana.

PubMed

Boakye-Appiah, Justice K; Steinmetz, Alexis R; Pupulampu, Peter; Ofori-Yirenkyi, Stephen; Tetteh, Ishmael; Frimpong, Michael; Oppong, Patrick; Opare-Sem, Ohene; Norman, Betty R; Stienstra, Ymkje; van der Werf, Tjip S; Wansbrough-Jones, Mark; Bonsu, Frank; Obeng-Baah, Joseph; Phillips, Richard O

2016-06-01

Drug-resistant strains of tuberculosis (TB) represent a major threat to global TB control. In low- and middle-income countries, resource constraints make it difficult to identify and monitor cases of resistance using drug susceptibility testing and culture. Molecular assays such as the GeneXpert Mycobacterium tuberculosis/rifampicin may prove to be a cost-effective solution to this problem in these settings. The objective of this study is to evaluate the use of GeneXpert in the diagnosis of pulmonary TB since it was introduced into two tertiary hospitals in Ghana in 2013. A 2-year retrospective audit of clinical cases involving patients who presented with clinically suspected TB or documented TB not improving on standard therapy and had samples sent for GeneXpert testing. GeneXpert identified 169 cases of TB, including 17 cases of rifampicin-resistant TB. Of the seven cases with final culture and drug susceptibility testing results, six demonstrated further drug resistance and five of these were multidrug-resistant TB. These findings call for a scale-up of TB control in Ghana and provide evidence that the expansion of GeneXpert may be an optimal means to improve case finding and guide treatment of drug-resistant TB in this setting. Copyright © 2016. Published by Elsevier Ltd.

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.

[Tuberculosis among the socially vulnerable populations; perspectives from human security concept].

PubMed

Ishikawa, Nobukatsu

2009-07-01

Tuberculosis (TB) has been and will continue to be the disease of the poor and the socially vulnerable. Current TB epidemiology in Japan shows increasing proportion of TB among the economically and socially poor or vulnerable populations. Though there is no universally recognized set of the definitions, the economically poor who are covered under the social security services including the homeless, foreign migrants, or the aged over 80 years may be considered as consisting the "socially vulnerable population" for TB in Japan. TB among the socially vulnerable has several characteristics, for example, patients are often detected with severe conditions due to delayed diagnosis, and have high defaulter rate during treatment, which causes immature death, or drug-resistant disease. Stop TB Strategy by WHO, responding to the Millennium Development Goals, proposes a new approach which focuses on empowering the patients and the community. Observations from various studies show that DOTS contributes to empowering the patients and the communities. Further effort will be needed to reorient TB programs towards the perspective of patients' empowerment. Solely relying on static analyses of TB among the socially vulnerable has its limitations. Dynamic approach, which utilizes human security concepts such as empowerment and patients' perspective, will be required not only to control TB among the socially vulnerable population but also to holistically tackle the problem of TB for Japan.

Impact of community tracer teams on treatment outcomes among tuberculosis patients in South Africa.

PubMed

Bronner, Liza E; Podewils, Laura J; Peters, Annatjie; Somnath, Pushpakanthi; Nshuti, Lorna; van der Walt, Martie; Mametja, Lerole David

2012-08-07

Tuberculosis (TB) indicators in South Africa currently remain well below global targets. In 2008, the National Tuberculosis Program (NTP) implemented a community mobilization program in all nine provinces to trace TB patients that had missed a treatment or clinic visit. Implementation sites were selected by TB program managers and teams liaised with health facilities to identify patients for tracing activities. The objective of this analysis was to assess the impact of the TB Tracer Project on treatment outcomes among TB patients. The study population included all smear positive TB patients registered in the Electronic TB Registry from Quarter 1 2007-Quarter 1 2009 in South Africa. Subdistricts were used as the unit of analysis, with each designated as either tracer (standard TB program plus tracer project) or non-tracer (standard TB program only). Mixed linear regression models were utilized to calculate the percent quarterly change in treatment outcomes and to compare changes in treatment outcomes from Quarter 1 2007 to Quarter 1 2009 between tracer and non-tracer subdistricts. For all provinces combined, the percent quarterly change decreased significantly for default treatment outcomes among tracer subdistricts (-0.031%; p < 0.001) and increased significantly for successful treatment outcomes among tracer subdistricts (0.003%; p = 0.03). A significant decrease in the proportion of patient default was observed for all provinces combined over the time period comparing tracer and non-tracer subdistricts (p = 0.02). Examination in stratified models revealed the results were not consistent across all provinces; significant differences were observed between tracer and non-tracer subdistricts over time in five of nine provinces for treatment default. Community mobilization of teams to trace TB patients that missed a clinic appointment or treatment dose may be an effective strategy to mitigate default rates and improve treatment outcomes. Additional information is necessary to identify best practices and elucidate discrepancies across provinces; these findings will help guide the NTP in optimizing the adoption of tracing activities for TB control.

Perceptions and Acceptability of Short Message Services Technology to Improve Treatment Adherence amongst Tuberculosis Patients in Peru: A Focus Group Study

PubMed Central

Albino, Sandra; Tabb, Karen M.; Requena, David; Egoavil, Miguel; Pineros-Leano, Maria F.; Zunt, Joseph R.; García, Patricia J.

2014-01-01

Background Tuberculosis (TB) is global health concern and a leading infectious cause of mortality. Reversing TB incidence and disease-related mortality is a major global health priority. Infectious disease mortality is directly linked to failure to adhere to treatments. Using technology to send reminders by short message services have been shown to improve treatment adherence. However, few studies have examined tuberculosis patient perceptions and attitudes towards using SMS technology to increase treatment adherence. In this study, we sought to investigate perceptions related to feasibility and acceptability of using text messaging to improve treatment adherence among adults who were receiving treatment for TB in Callao, Peru. Methods We conducted focus group qualitative interviews with current TB positive and non-contagious participants to understand the attitudes, perceptions, and feasibility of using short message service (SMS) reminders to improve TB treatment adherence. Subjects receiving care through the National TB Program were recruited through public health centers in Ventanilla, Callao, Peru. In four focus groups, we interviewed 16 patients. All interviews were recorded and transcribed verbatim. Thematic network analysis and codebook techniques were used to analyze data. Results Three major themes emerged from the data: limits on health literacy and information posed challenges to successful TB treatment adherence, treatment motivation at times facilitated adherence to TB treatment, and acceptability of SMS including positive perceptions of SMS to improve TB treatment adherence. The majority of patients shared considerations about how to effectively and confidentially administer an SMS intervention with TB positive participants. Conclusion The overall perceptions of the use of SMS were positive and indicated that SMS technology may be an efficient way to transmit motivational texts on treatment, health education information, and simple reminders to increase treatment adherence for low-income TB patients living in Peru. PMID:24828031

A cross sectional study of knowledge and attitudes towards tuberculosis amongst front-line tuberculosis personnel in high burden areas of Lima, Peru.

PubMed

Minnery, Mark; Contreras, Carmen; Pérez, Rosa; Solórzano, Ninfa; Tintaya, Karen; Jimenez, Judith; Soto, Silvia; Lecca, Leonid

2013-01-01

Tuberculosis, reported as the second most common infectious cause of death worldwide, is a key mortality contributor in developing countries and globally. The disease is endemic in Peru and while relative success was achieved during the 1990s in its control, this slowed as new complications, such as multi drug resistant TB arose. Health centre workers participating in the national DOTS program, create the front-line TB work-force in Peru meaning their knowledge and attitudes about the disease are key in its control. A Spanish language, multiple choice knowledge and attitudes survey was designed based on previous successful studies and the national Peruvian TB control guidelines. It was applied to two health networks in Lima, Peru amongst 301 health workers participating in the national TB control program from 66 different health centres. The study results were analysed to test mean knowledge scores amongst different groups, overall gaps in key areas of TB treatment and control knowledge, and attitudes towards the disease and the national TB control program. A mean knowledge score of 10.1 (+/- 1.7) out of 15 or 67.3% correct was shown. Demographics shown to have an effect on knowledge score were age and level of education. Major knowledge gaps were noted primarily in themes relating to treatment and diagnostics. Greater community involvement including better patient education about TB was seen as important in implementing the national TB control program. Participants were in disagreement about the current distribution of health resources throughout the study area. Discussion Serious knowledge gaps were identified from the survey; these reflect findings from a previous study in Lima and other studies from TB endemic areas throughout the world. Understanding these gaps and observations made by front-line TB workers in Lima may help to improve the national TB control program and other control efforts globally.

The Impact and Cost-Effectiveness of a Four-Month Regimen for First-Line Treatment of Active Tuberculosis in South Africa

PubMed Central

Knight, Gwenan M.; Gomez, Gabriela B.; Dodd, Peter J.; Dowdy, David; Zwerling, Alice; Wells, William A.; Cobelens, Frank; Vassall, Anna; White, Richard G.

2015-01-01

Background A 4-month first-line treatment regimen for tuberculosis disease (TB) is expected to have a direct impact on patient outcomes and societal costs, as well as an indirect impact on Mycobacterium tuberculosis transmission. We aimed to estimate this combined impact in a high TB-burden country: South Africa. Method An individual based M. tb transmission model was fitted to the TB burden of South Africa using a standard TB natural history framework. We measured the impact on TB burden from 2015–2035 of introduction of a non-inferior 4-month regimen replacing the standard 6-month regimen as first-line therapy. Impact was measured with respect to three separate baselines (Guidelines, Policy and Current), reflecting differences in adherence to TB and HIV treatment guidelines. Further scenario analyses considered the variation in treatment-related parameters and resistance levels. Impact was measured in terms of differences in TB burden and Disability Adjusted Life Years (DALYs) averted. We also examined the highest cost at which the new regimen would be cost-effective for several willingness-to-pay thresholds. Results It was estimated that a 4-month regimen would avert less than 1% of the predicted 6 million person years with TB disease in South Africa between 2015 and 2035. A similarly small impact was seen on deaths and DALYs averted. Despite this small impact, with the health systems and patient cost savings from regimen shortening, the 4-month regimen could be cost-effective at $436 [NA, 5983] (mean [range]) per month at a willingness-to-pay threshold of one GDP per capita ($6,618). Conclusion The introduction of a non-inferior 4-month first-line TB regimen into South Africa would have little impact on the TB burden. However, under several scenarios, it is likely that the averted societal costs would make such a regimen cost-effective in South Africa. PMID:26717007

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 normalize during microbiological TB cure. The depression of both IFN-γ production and IFN-γR signaling may synergize in contributing to defective host control in active TB. PMID:17145950

Addressing poverty through disease control programmes: examples from Tuberculosis control in India

PubMed Central

2012-01-01

Introduction Tuberculosis remains a major public health problem in India with the country accounting for one-fifth or 21% of all tuberculosis cases reported globally. The purpose of the study was to obtain an understanding on pro-poor initiatives within the framework of tuberculosis control programme in India and to identify mechanisms to improve the uptake and access to TB services among the poor. Methodology A national level workshop was held with participation from all relevant stakeholder groups. This study conducted during the stakeholder workshop adopted participatory research methods. The data was elicited through consultative and collegiate processes. The research study also factored information from primary and secondary sources that included literature review examining poverty headcount ratios and below poverty line population in the country; and quasi-profiling assessments to identify poor, backward and tribal districts as defined by the TB programme in India. Results Results revealed that current pro-poor initiatives in TB control included collaboration with private providers and engaging community to improve access among the poor to TB diagnostic and treatment services. The participants identified gaps in existing pro-poor strategies that related to implementation of advocacy, communication and social mobilisation; decentralisation of DOT; and incentives for the poor through the available schemes for public-private partnerships and provided key recommendations for action. Synergies between TB control programme and centrally sponsored social welfare schemes and state specific social welfare programmes aimed at benefitting the poor were unclear. Conclusion Further in-depth analysis and systems/policy/operations research exploring pro-poor initiatives, in particular examining service delivery synergies between existing poverty alleviation schemes and TB control programme is essential. The understanding, reflection and knowledge of the key stakeholders during this participatory workshop provides recommendations for action, further planning and research on pro-poor TB centric interventions in the country. PMID:22449205

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.

Bovine tuberculosis in Europe from the perspective of an officially tuberculosis free country: Trade, surveillance, and diagnostics

USDA-ARS?s Scientific Manuscript database

Switzerland is officially free of bovine tuberculosis (OTF) since 1960. A mandatory eradication program had been launched in 1950. Since 1980 the control of bovine tuberculosis (bTB) has been reduced to passive abattoir surveillance. Single cases of bTB, partly due to reactivation of human Mycobacte...

Outcomes from patients with presumed drug resistant tuberculosis in five reference centers in Brazil.

PubMed

Ramalho, D M P; Miranda, P F C; Andrade, M K; Brígido, T; Dalcolmo, M P; Mesquita, E; Dias, C F; Gambirasio, A N; Ueleres Braga, J; Detjen, A; Phillips, P P J; Langley, I; Fujiwara, P I; Squire, S B; Oliveira, M M; Kritski, A L

2017-08-15

The implementation of rapid drug susceptibility testing (DST) is a current global priority for TB control. However, data are scarce on patient-relevant outcomes for presumptive diagnosis of drug-resistant tuberculosis (pDR-TB) evaluated under field conditions in high burden countries. Observational study of pDR-TB patients referred by primary and secondary health units. TB reference centers addressing DR-TB in five cities in Brazil. Patients age 18 years and older were eligible if pDR-TB, culture positive results for Mycobacterium tuberculosis and, if no prior DST results from another laboratory were used by a physician to start anti-TB treatment. The outcome measures were median time from triage to initiating appropriate anti-TB treatment, empirical treatment and, the treatment outcomes. Between February,16th, 2011 and February, 15th, 2012, among 175 pDR TB cases, 110 (63.0%) confirmed TB cases with DST results were enrolled. Among study participants, 72 (65.5%) were male and 62 (56.4%) aged 26 to 45 years. At triage, empirical treatment was given to 106 (96.0%) subjects. Among those, 85 were treated with first line drugs and 21 with second line. Median time for DST results was 69.5 [interquartile - IQR: 35.7-111.0] days and, for initiating appropriate anti-TB treatment, the median time was 1.0 (IQR: 0-41.2) days. Among 95 patients that were followed-up during the first 6 month period, 24 (25.3%; IC: 17.5%-34.9%) changed or initiated the treatment after DST results: 16/29 MDRTB, 5/21 DR-TB and 3/45 DS-TB cases. Comparing the treatment outcome to DS-TB cases, MDRTB had higher proportions changing or initiating treatment after DST results (p = 0.01) and favorable outcomes (p = 0.07). This study shows a high rate of empirical treatment and long delay for DST results. Strategies to speed up the detection and early treatment of drug resistant TB should be prioritized.

Community knowledge, attitudes and practices in relation to tuberculosis in Cameroon.

PubMed

Kwedi Nolna, S; Kammogne, I D; Ndzinga, R; Afanda, B; Ntonè, R; Boum, Y; Nolna, D

2016-09-01

With 15 080 new cases in 2013, Cameroon is a country with high tuberculosis (TB) incidence and prevalence. Understanding the community's knowledge, attitude and practice (KAP) about TB is key to TB control in such endemic settings. To assess TB-related KAP in Cameroon by describing the sociodemographics of respondents, to identify barriers to seeking care and to explore attitudes and experiences of stigma and discrimination related to TB in communities. We conducted a cross-sectional descriptive study using structured questionnaires to assess and compare TB KAP in the entire territory. The results showed that Cameroonians have insufficient understanding of TB, numerous erroneous health assumptions and beliefs concerning TB, and erroneous information about the symptoms and mode of transmission of the disease. Negative attitudes and poor practices are obstacles to elimination and control efforts. The National Tuberculosis Control Programme should generate more effective strategies to reach the populations, paying particular attention to rural populations.

Multidrug-resistant Pulmonary Tuberculosis Among Young Korean Soldiers in a Communal Setting

PubMed Central

Lee, Sei Won; Kim, Kwang Hyun; Min, Kyung Hoon

2009-01-01

The goal of this study was to evaluate the prevalence of first-line anti-tuberculosis drug resistance and risk factors associated with multidrug-resistant tuberculosis (MDR TB) among young soldiers in the Korean military, which has a strict tuberculosis control program. All patients with culture-confirmed pulmonary tuberculosis during their service at the Armed Forces Capital Hospital from January 2001 to December 2006 were enrolled in the study. Drug resistant Mycobacterium tuberculosis was isolated from 18 patients (12.2%) and multidrug-resistant M. tuberculosis was isolated from 12 patients (8.1%). Previous treatment of tuberculosis and the presence of a cavity on the patient's chest computed tomography scan were associated with MDR TB; military rank, smoking habits, and positive acid-fast bacilli smears were not associated with MDR TB. In a multiple logistic regression analysis, previous treatment of tuberculosis was a significant independent risk factor for MDR TB (odds ratio 6.12, 95% confidence interval 1.53-24.46). The prevalence of drug resistant tuberculosis among young soldiers in the Korean military was moderately high and the majority of resistant cases were found in patients who had undergone previous treatment of tuberculosis. Based on our results, we suggest that relapsed tuberculosis cases within communal settings should be cautiously managed until the drug susceptibility tests report is completed, even if previous treatment results were satisfactory. PMID:19654938

Synthesis of biocompatible nanoparticle drug complexes for inhibition of mycobacteria

NASA Astrophysics Data System (ADS)

Bhave, Tejashree; Ghoderao, Prachi; Sanghavi, Sonali; Babrekar, Harshada; Bhoraskar, S. V.; Ganesan, V.; Kulkarni, Anjali

2013-12-01

Tuberculosis (TB) is one of the most critical infectious diseases affecting the world today. Current TB treatment involves six months long daily administration of four oral doses of antibiotics. Due to severe side effects and the long treatment, a patient's adherence is low and this results in relapse of symptoms causing an alarming increase in the prevalence of multi-drug resistant (MDR) TB. Hence, it is imperative to develop a new drug delivery technology wherein these effects can be reduced. Rifampicin (RIF) is one of the widely used anti-tubercular drugs (ATD). The present study discusses the development of biocompatible nanoparticle-RIF complexes with superior inhibitory activity against both Mycobacterium smegmatis (M. smegmatis) and Mycobacterium tuberculosis (M. tuberculosis). Iron oxide nanoparticles (NPs) synthesized by gas phase condensation and NP-RIF complexes were tested against M. smegmatis SN2 strain as well as M. tuberculosis H37Rv laboratory strain. These complexes showed significantly better inhibition of M. smegmatis SN2 strain at a much lower effective concentration (27.5 μg ml-1) as compared to neat RIF (125 μg ml-1). Similarly M. tuberculosis H37Rv laboratory strain was susceptible to both nanoparticle-RIF complex and neat RIF at a minimum inhibitory concentration of 0.22 and 1 μg ml-1, respectively. Further studies are underway to determine the efficacy of NPs-RIF complexes in clinical isolates of M. tuberculosis as well as MDR isolates.

[Clinical, microbiological and evolutionary profile of patients experiencing failures and relapses of tuberculosis in Ivory Coast].

PubMed

Kouamé-N'Takpé, N; Horo, K; Koné, A; N'guessan, K R; Touré, K; Kouadio, C; Assi, D; Coulibaly, I; Kouakou, A

2015-02-01

Multidrug-resistant tuberculosis (MDR-TB) is a major obsession for TB control. The main risk factor for MDR-TB remains a history of TB treatment especially bad conduct. The objective of this study is to describe the profile of patients in situations of failure and relapse of tuberculosis. We performed a retrospective survey of the analysis of records of patients starting TB retreatment for failure or relapse of tuberculosis. We used 193 cases with results of culture-sensitivity. The proportion of failure is 59/193 (30.6 %) and cases of relapse are 134/193 (69.4 %). The proportion of married life is 23.4 % (11/47) in chess against 41.5 % (51/123) in relapse of TB [P=0.021, OR=0.431 (0.201 to 0.927)]. Patients failing therapy have more chest pain [5.8 % (3/52) versus 0 % (0/126) with P=0.024]. The proportion of MDR-TB was 61.4 (38/59) in case of failure against 41 % (55/134) in case of relapse [P=0.002, OR=2.599 (1.378 to 4.902)]. The evolution is the same whatever the indication of reprocessing. The proportion of MDR-TB is very important in case of reprocessing failure and relapse of tuberculosis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Polymorphisms of SP110 are associated with both pulmonary and extra-pulmonary tuberculosis among the Vietnamese.

PubMed

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

2014-01-01

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

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

PubMed

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

2015-12-21

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

Evaluation of Xpert MTB/RIF assay performance in the diagnosis of abdominal tuberculosis.

PubMed

Kumar, Suraj; Bopanna, Sawan; Kedia, Saurabh; Mouli, Pratap; Dhingra, Rajan; Padhan, Rajesh; Kohli, Mikashmi; Chaubey, Jigyasa; Sharma, Rohini; Das, Prasenjit; Dattagupta, S; Makharia, Govind; Sharma, S K; Ahuja, Vineet

2017-04-01

The use of genetic probes for the diagnosis of pulmonary tuberculosis (TB) has been well described. However, the role of these assays in the diagnosis of intestinal tuberculosis is unclear. We therefore assessed the diagnostic utility of the Xpert Mycobacterium tuberculosis /rifampicin (MTB/RIF) assay, and estimated the prevalence of multidrug-resistant (MDR) TB in the Indian population. Of 99 patients recruited, 37 had intestinal TB; two control groups comprised 43 with Crohn's disease (CD) and 19 with irritable bowel syndrome. Colonoscopy was performed before starting any therapy; mucosal biopsies were subjected to histopathology, acid-fast bacilli staining, Lowenstein-Jensen culture, and nucleic acid amplification testing using the Xpert MTB/RIF assay. Patients were followed up for 6 months to confirm the diagnosis and response to therapy. A composite reference standard was used for diagnosis of TB and assessment of the diagnostic utility of the Xpert MTB/RIF assay. Of 37 intestinal TB patients, the Xpert MTB/RIF assay was positive in three of 37 (8.1%), but none had MDR-TB. The sensitivity, specificity, positive predictive value, and negative predictive value of the Xpert MTB/RIF assay was 8.1%, 100%, 100%, and, 64.2%, respectively. The Xpert MTB/RIF assay has low sensitivity but high specificity for intestinal TB, and may be helpful in endemic tuberculosis areas, when clinicians are faced with difficulty differentiating TB and CD. Based on the Xpert MTB/RIF assay, the prevalence of intestinal MDR-TB is low in the Indian population.

Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia.

PubMed

Ahmad, Riris Andono; Matthys, Francine; Dwihardiani, Bintari; Rintiswati, Ning; de Vlas, Sake J; Mahendradhata, Yodi; van der Stuyft, Patrick

2012-02-15

Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities. We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results), and final diagnosis were collected. Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC). Diagnostic delays were significantly longer in health centres compared to lung clinics. The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care.

Wild boar tuberculosis in Iberian Atlantic Spain: a different picture from Mediterranean habitats

PubMed Central

2013-01-01

Background Infections with Mycobacterium bovis and closely related members of the Mycobacterium tuberculosis complex (MTC) are shared between livestock, wildlife and sporadically human beings. Wildlife reservoirs exist worldwide and can interfere with bovine tuberculosis (TB) eradication efforts. The Eurasian wild boar (Sus scrofa) is a MTC maintenance host in Mediterranean Iberia (Spain and Portugal). However, few systematic studies in wild boar have been carried out in Atlantic regions. We describe the prevalence, distribution, pathology and epidemiology of MTC and other mycobacteria from wild boar in Atlantic Spain. A total of 2,067 wild boar were sampled between 2008 and 2012. Results The results provide insight into the current status of wild boar as MTC and Mycobacterium avium complex (MAC) hosts in temperate regions of continental Europe. The main findings were a low TB prevalence (2.6%), a low proportion of MTC infected wild boar displaying generalized TB lesions (16.7%), and a higher proportion of MAC infections (4.5%). Molecular typing revealed epidemiological links between wild boar and domestic – cattle, sheep and goat – and other wildlife – Eurasian badger (Meles meles) and red fox (Vulpes vulpes) – hosts. Conclusions This study shows that the likelihood of MTC excretion by wild boar in Atlantic habitats is much lower than in Mediterranean areas. However, wild boar provide a good indicator of MTC circulation and, given the current re-emergence of animal TB, similar large-scale surveys would be advisable in other Atlantic regions of continental Europe. PMID:24010539

Cost-effectiveness of interferon-γ release assay versus chest X-ray for tuberculosis screening of employees.

PubMed

Kowada, Akiko

2011-12-01

Currently, an annual chest X-ray examination (CXR) for detection of active tuberculosis (TB) in employees aged ≥40 years is recommended in the guidelines of the Japan Industrial Safety and Health Law. Interferon-γ release assays are new alternatives to the tuberculin skin test for detecting Mycobacterium tuberculosis infection, with higher specificity than the tuberculin skin test and without cross-reactivity with the Bacille Calmette-Guérin vaccine. This study aimed to assess the cost-effectiveness of employee TB screening using QuantiFERON-TB Gold In-Tube (QFT) versus CXR. Markov models were constructed. The target population was a hypothetical cohort of immunocompetent 40-year-old individuals, using a societal perspective and a lifetime horizon. All costs and clinical benefits were discounted at a fixed annual rate of 3%. In a base-case analysis, the QFT strategy was the most cost-effective ($US 262.84; 22.87049 quality-adjusted life-years [QALYs]) compared with no screening ($448.38; 22.85452 QALYs) and CXR ($543.50; 22.85453 QALYs) [year 2009 values]. The QFT strategy is currently robust for screening Bacille Calmette-Guérin- vaccinated employees in Japan. There appears to be little role for CXR. These findings may be applicable to other countries in terms of choosing optimal TB screening for employees. Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.

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

Phenotypic and genotypic characteristics of drug resistance in Mycobacterium tuberculosis isolates from pediatric population of Chennai, India.

PubMed

Therese, K Lily; Gayathri, R; Balasubramanian, S; Natrajan, S; Madhavan, H N

2012-01-01

Multidrug-resistant TB (MDR-TB) has been reported in almost all parts of the world. Childhood TB is accorded low priority by national TB control programs. Probable reasons include diagnostic difficulties, limited resources, misplaced faith in BCG and lack of data on treatment. Good data on the burden of all forms of TB among children in India are not available. To study the drug sensitivity pattern of tuberculosis in children aged from 3 months to 18 years and the outcome of drug-resistant tuberculosis by BACTEC culture system and PCR-based DNA sequencing technique. This is a retrospective study. One hundred and fifty-nine clinical specimens were processed for Ziehl-Neelsen stain, Mycobacterial culture by BACTEC method, phenotypic DST for first-line drugs for Mycobacterium tuberculosis (M. tuberculosis) isolates and PCR-based DNA sequencing was performed for the M. tuberculosis isolates targeting rpoB, katG, inhA, oxyR-ahpC, rpsL, rrs and pncA. Out of the 159 Mycobacterial cultures performed during the study period, 17 clinical specimens (10.7%) were culture positive for M. tuberculosis. Among the 17 M. tuberculosis isolates, 2 were multidrug-resistant TB. PCR-based DNA sequencing revealed the presence of many novel mutations targeting katG, inhA, oxyR-ahpC and pncA and the most commonly reported mutation Ser531Leu in the rpoB gene. This study underlines the urgent need to take efforts to develop methods for rapid detection and drug susceptibility of tubercle bacilli in the pediatric population.

The Activity of a Hexameric M17 Metallo-Aminopeptidase Is Associated With Survival of Mycobacterium tuberculosis

PubMed Central

Correa, Andre F.; Bastos, Izabela M. D.; Neves, David; Kipnis, Andre; Junqueira-Kipnis, Ana P.; de Santana, Jaime M.

2017-01-01

Mycobacterium tuberculosis is one of the most prevalent human pathogens causing millions of deaths in the last years. Moreover, tuberculosis (TB) treatment has become increasingly challenging owing to the emergence of multidrug resistant M. tuberculosis strains. Thus, there is an immediate need for the development of new anti-TB drugs. Proteases appear to be a promising approach and may lead to shortened and effective treatments for drug-resistant TB. Although the M. tuberculosis genome predicts more than 100 genes encoding proteases, only a few of them have been studied. Aminopeptidases constitute a set of proteases that selectively remove amino acids from the N-terminus of proteins and peptides and may act as virulence factors, essential for survival and maintenance of many microbial pathogens. Here, we characterized a leucine aminopeptidase of M. tuberculosis (MtLAP) as a cytosolic oligomeric metallo-aminopeptidase. Molecular and enzymatic properties lead us to classify MtLAP as a typical member of the peptidase family M17. Furthermore, the aminopeptidase inhibitor bestatin strongly inhibited MtLAP activity, in vitro M. tuberculosis growth and macrophage infection. In murine model of TB, bestatin treatment reduced bacterial burden and lesion in the lungs of infected mice. Thus, our data suggest that MtLAP participates in important metabolic pathways of M. tuberculosis necessary for its survival and virulence and consequently may be a promising target for new anti-TB drugs. PMID:28396657

Comparison of cortisol and thyroid hormones between tuberculosis-suspect and healthy elephants of Nepal.

PubMed

Paudel, Sarad; Brown, Janine L; Thapaliya, Sharada; Dhakal, Ishwari P; Mikota, Susan K; Gairhe, Kamal P; Shimozuru, Michito; Tsubota, Toshio

2016-12-01

We compared cortisol and thyroid hormone (T3 and T4) concentrations between tuberculosis (TB)-suspected (n=10) and healthy (n=10) elephants of Nepal. Whole blood was collected from captive elephants throughout Nepal, and TB testing was performed using the ElephantTB STAT-PAK ® and DPP VetTB ® serological assays that detect antibodies against Mycobacterium tuberculosis and M. bovis in elephant serum. Cortisol, T3 and T4 were quantified by competitive enzyme immunoassays, and the results showed no significant differences in hormone concentrations between TB-suspect and healthy elephants. These preliminary data suggest neither adrenal nor thyroid function is altered by TB disease status. However, more elephants, including those positively diagnosed for TB by trunk wash cultures, need to be evaluated over time to confirm results.

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

PubMed

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

2015-01-01

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

Vitamin D: Immuno-modulation and tuberculosis treatment.

PubMed

Selvaraj, Paramasivam; Harishankar, Murugesan; Afsal, Kolloli

2015-05-01

Tuberculosis (TB) is a major global health problem and often coincides with vitamin D deficiency. High doses of vitamin D were widely used to treat TB during the pre-antibiotic era. Vitamin D exerts its action through vitamin D receptor (VDR), and VDR gene polymorphisms are associated with susceptibility or resistance to tuberculosis as well as sputum smear and culture conversion during anti-TB treatment. In-vitro studies have revealed that 1,25-dihydroxyvitamin D3 enhances innate immunity by increased expression of various antimicrobial peptides, including cathelicidin, and induction of autophagy of the infected cells thus restricts the intracellular growth of Mycobacterium tuberculosis in macrophages. On the other hand, vitamin D has been shown to suppress the pro-inflammatory cytokine response and enhance the anti-inflammatory response. Supplementation with vitamin D in concert with treatment for TB may be beneficial with respect to minimizing the excessive tissue damage that occurs during the active stage of tuberculosis disease. Several clinical trials have evaluated vitamin D supplementation as an adjunct therapy in the treatment for tuberculosis. However, results are conflicting, owing to variations in dose regimens and outcomes. Further investigations are needed to find the optimal concentration of vitamin D for supplementation with standard anti-TB drugs to optimize treatment, which could help to effectively manage both drug-sensitive and drug-resistant tuberculosis.

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.

Pediatric tuberculosis at Beijing Children's Hospital: 2002-2010.

PubMed

Wu, Xi-Rong; Yin, Qing-Qin; Jiao, An-Xia; Xu, Bao-Ping; Sun, Lin; Jiao, Wei-Wei; Xiao, Jing; Miao, Qing; Shen, Chen; Liu, Fang; Shen, Dan; Shen, Adong

2012-12-01

Our aim was to describe the patient characteristics, clinical-epidemiological profile, and treatment outcome of childhood tuberculosis (TB). A retrospective, descriptive study was undertaken of 1212 children aged 0 to 18 years admitted to Beijing Children's Hospital for the treatment of TB from January 2002 to December 2010. Statistical significance of category variables was evaluated by using Fisher's exact test. Fifty-four percent of patients had extrapulmonary tuberculosis (EPTB), 38.8% had tuberculous meningitis, and 31.3% had disseminated TB. The last 2 types were defined as severe TB. Most patients with TB (81.6%) were cured or completed treatment. There were more patients aged <5 years and from rural areas with EPTB than with pulmonary tuberculosis. More severe cases of TB were found in patients aged <1 year than other less severe types of TB. Patients with no bacille Calmette-Guérin vaccination and a contact history at home had a significantly risk of contracting severe TB. Children aged <1 year and those with severe TB were more likely to have poor treatment outcomes (failed to improve or died). Among those with EPTB, only 61.3% and 61.1% had positive results on the purified protein derivative tuberculin skin test and chest radiograph, respectively. In this referral hospital setting, more pediatric EPTB and severe TB patients were found among children aged <1 year. Age <1 year and having severe TB were risk factors for treatment failure. Thus, prevention and health care in pediatric TB should focus on both EPTB and severe TB.

Gamma delta T cell responses associated with the development of tuberculosis in health care workers.

PubMed

Ordway, Diane J; Pinto, Luisa; Costa, Leonor; Martins, Marta; Leandro, Clara; Viveiros, Miguel; Amaral, Leonard; Arroz, Maria J; Ventura, Fernando A; Dockrell, Hazel M

2005-03-01

This study evaluated T cell immune responses to purified protein derivative (PPD) and Mycobacterium tuberculosis (Mtb) in health care workers who remained free of active tuberculosis (HCWs w/o TB), health care workers who went on to develop active TB (HCWs w/TB), non-health care workers who were TB free (Non-HCWs) and tuberculosis patients presenting with minimal (Min TB) or advanced (Adv TB) disease. Peripheral blood mononuclear cells (PBMC) were stimulated with Mtb and PPD and the expression of T cell activation markers CD25+ and HLA-DR+, intracellular IL-4 and IFN-gamma production and cytotoxic responses were evaluated. PBMC from HCWs who developed TB showed decreased percentages of cells expressing CD8+CD25+ in comparison to HCWs who remained healthy. HCWs who developed TB showed increased gammadelta TCR+ cell cytotoxicity and decreased CD3+gammadelta TCR- cell cytotoxicity in comparison to HCWs who remained healthy. PBMC from TB patients with advanced disease showed decreased percentages of CD25+CD4+ and CD25+CD8+ T cells that were associated with increased IL-4 production in CD8+ and gammadelta TCR+ phenotypes, in comparison with TB patients presenting minimal disease. TB patients with advanced disease showed increased gammadelta TCR+ cytotoxicity and reduced CD3+gammadelta TCR- cell cytotoxicity. Our results suggest that HCWs who developed TB show an early compensatory mechanism involving an increase in lytic responses of gammadelta TCR+ cells which did not prevent TB.

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.

What's new in tuberculosis vaccines?

PubMed Central

Ginsberg, Ann M.

2002-01-01

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

Breath-based biomarkers for tuberculosis

NASA Astrophysics Data System (ADS)

Kolk, Arend H. J.; van Berkel, Joep J. B. N.; Claassens, Mareli M.; Walters, Elisabeth; Kuijper, Sjoukje; Dallinga, Jan W.; van Schooten, Fredrik-Jan

2012-06-01

We investigated the potential of breath analysis by gas chromatography - mass spectrometry (GC-MS) to discriminate between samples collected prospectively from patients with suspected tuberculosis (TB). Samples were obtained in a TB endemic setting in South Africa where 28% of the culture proven TB patients had a Ziehl-Neelsen (ZN) negative sputum smear. A training set of breath samples from 50 sputum culture proven TB patients and 50 culture negative non-TB patients was analyzed by GC-MS. A classification model with 7 compounds resulted in a training set with a sensitivity of 72%, specificity of 86% and accuracy of 79% compared with culture. The classification model was validated with an independent set of breath samples from 21 TB and 50 non-TB patients. A sensitivity of 62%, specificity of 84% and accuracy of 77% was found. We conclude that the 7 volatile organic compounds (VOCs) that discriminate breath samples from TB and non-TB patients in our study population are probably host-response related VOCs and are not derived from the VOCs secreted by M. tuberculosis. It is concluded that at present GC-MS breath analysis is able to differentiate between TB and non-TB breath samples even among patients with a negative ZN sputum smear but a positive culture for M. tuberculosis. Further research is required to improve the sensitivity and specificity before this method can be used in routine laboratories.

Comparison of Mycobacterium tuberculosis culture using liquid culture medium and Lowenstein Jensen medium in abdominal tuberculosis.

PubMed

Shah, Sudeep R; Shenai, Shubhada; Desai, Devendra C; Joshi, Anand; Abraham, Philip; Rodrigues, Camilla

2010-11-01

Traditionally, the Lowenstein Jensen (LJ) medium has been used for culturing Mycobacterium tuberculosis. In abdominal tuberculosis (TB), the reported yield from tissue culture is between 20% and 60%. Liquid cultures are reported to give a higher yield but there is little data available in abdominal TB. To compare the yield of TB culture with BACTEC 460TB liquid medium and LJ medium for patients with suspected abdominal TB and determine cost effectiveness. This prospective study was done in consecutive cases with clinical, radiological, endoscopic/surgical, and histological suspicion of abdominal TB. Tissue biopsies obtained at colonoscopy or surgery were processed and plated on LJ medium as well as the BACTEC 460TB system. NAP (ρ-nitro-α-acetylamino-β-hydroxy-propiophenone) differentiation was carried out to determine species. The cost of each method and cost per yield were calculated. Of the 29 cases, 22 cases (76%) were positive on BACTEC 460TB culture while 14 (48%) were positive on LJ medium giving a 64% increment in yield. However, the culture of one patient grew on LJ medium, where the BACTEC 460TB was negative. The additional cost of BACTEC 460TB is Rs. 460 and LJ is Rs. 40. Samples from patients with abdominal TB should be processed on both liquid and LJ medium. For high yield, the use of a liquid culture medium system is essential.

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 scale study on the genotyping of Mycobacterium tuberculosis in Ethiopia is crucial to understand transmission dynamics, identification of drug resistant strains and design preventive strategies. PMID:22414165

Collaboration between the national tuberculosis programme and a non governmental organisation in TB/HIV care at a district level: experience from Tanzania.

PubMed

Wandwalo, Eliud; Kapalata, Neema; Tarimo, Edith; Corrigan, C Brigid; Morkve, Odd

2004-08-01

The increase in tuberculosis and HIV/AIDS patients in many countries in Africa including Tanzania, is outstripping the ability of public health services to cope. This calls for a closer collaboration between tuberculosis programmes and other stakeholders involved in HIV/AIDS care. To determine the feasibility of establishing collaboration between the tuberculosis programme and an NGO in TB/ HIV care at a district level in Tanzania. Quantitative and qualitative study designs involving TB as well as HIV suspects and patients together with health workers, were conducted between December, 2001 and September, 2002. A total of 72 patients and 28 key informants were involved. The collaboration was in the following areas; voluntary counselling and testing for HIV, diagnosis and treatment of TB, referral and follow up of patients and suspects, home based care, psychological support and training. Both the tuberculosis programme and NGO benefited from the collaboration. TB case detection among PLWA increased more than three folds and TB treatment was integrated in home based care of NGO. The main barriers identified in this study were; poor communication, poor referral system and lack of knowledge and skills among health staff. The study has shown that it is possible for a tuberculosis programme and a non governmental organisation to collaborate in TB/HIV care. The study has also identified potential areas of collaboration and barriers that needed to be overcome in order to provide such comprehensive services at a district level.

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

PubMed

Chyczewska, Elzbieta

2008-01-01

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

Current perspectives in drug discovery against tuberculosis from natural products.

PubMed

Nguta, Joseph Mwanzia; Appiah-Opong, Regina; Nyarko, Alexander K; Yeboah-Manu, Dorothy; Addo, Phyllis G A

2015-09-01

Currently, one third of the world's population is latently infected with Mycobacterium tuberculosis (MTB), while 8.9-9.9 million new and relapse cases of tuberculosis (TB) are reported yearly. The renewed research interests in natural products in the hope of discovering new and novel antitubercular leads have been driven partly by the increased incidence of multidrug-resistant strains of MTB and the adverse effects associated with the first- and second-line antitubercular drugs. Natural products have been, and will continue to be a rich source of new drugs against many diseases. The depth and breadth of therapeutic agents that have their origins in the secondary metabolites produced by living organisms cannot be compared with any other source of therapeutic agents. Discovery of new chemical molecules against active and latent TB from natural products requires an interdisciplinary approach, which is a major challenge facing scientists in this field. In order to overcome this challenge, cutting edge techniques in mycobacteriology and innovative natural product chemistry tools need to be developed and used in tandem. The present review provides a cross-linkage to the most recent literature in both fields and their potential to impact the early phase of drug discovery against TB if seamlessly combined. Copyright © 2015 Asian African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Preliminary investigation of human exhaled breath for tuberculosis diagnosis by multidimensional gas chromatography - Time of flight mass spectrometry and machine learning.

PubMed

Beccaria, Marco; Mellors, Theodore R; Petion, Jacky S; Rees, Christiaan A; Nasir, Mavra; Systrom, Hannah K; Sairistil, Jean W; Jean-Juste, Marc-Antoine; Rivera, Vanessa; Lavoile, Kerline; Severe, Patrice; Pape, Jean W; Wright, Peter F; Hill, Jane E

2018-02-01

Tuberculosis (TB) remains a global public health malady that claims almost 1.8 million lives annually. Diagnosis of TB represents perhaps one of the most challenging aspects of tuberculosis control. Gold standards for diagnosis of active TB (culture and nucleic acid amplification) are sputum-dependent, however, in up to a third of TB cases, an adequate biological sputum sample is not readily available. The analysis of exhaled breath, as an alternative to sputum-dependent tests, has the potential to provide a simple, fast, and non-invasive, and ready-available diagnostic service that could positively change TB detection. Human breath has been evaluated in the setting of active tuberculosis using thermal desorption-comprehensive two-dimensional gas chromatography-time of flight mass spectrometry methodology. From the entire spectrum of volatile metabolites in breath, three random forest machine learning models were applied leading to the generation of a panel of 46 breath features. The twenty-two common features within each random forest model used were selected as a set that could distinguish subjects with confirmed pulmonary M. tuberculosis infection and people with other pathologies than TB. Copyright © 2018 Elsevier B.V. All rights reserved.

Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis

PubMed Central

Serra-Vidal, Mᵃdel Mar; Latorre, Irene; Franken, Kees L. C. M.; Díaz, Jéssica; de Souza-Galvão, Maria Luiza; Casas, Irma; Maldonado, José; Milà, Cèlia; Solsona, Jordi; Jimenez-Fuentes, M. Ángeles; Altet, Neus; Lacoma, Alícia; Ruiz-Manzano, Juan; Ausina, Vicente; Prat, Cristina; Ottenhoff, Tom H. M.; Domínguez, José

2014-01-01

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates. PMID:25339944

Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis.

PubMed

Serra-Vidal, Mᵃdel Mar; Latorre, Irene; Franken, Kees L C M; Díaz, Jéssica; de Souza-Galvão, Maria Luiza; Casas, Irma; Maldonado, José; Milà, Cèlia; Solsona, Jordi; Jimenez-Fuentes, M Ángeles; Altet, Neus; Lacoma, Alícia; Ruiz-Manzano, Juan; Ausina, Vicente; Prat, Cristina; Ottenhoff, Tom H M; Domínguez, José

2014-01-01

The aim of our work here was to evaluate the immunogenicity of 60 mycobacterial antigens, some of which have not been previously assessed, notably a novel series of in vivo-expressed Mycobacterium tuberculosis (IVE-TB) antigens. We enrolled 505 subjects and separated them in individuals with and without latent tuberculosis infection (LTBI) vs. patients with active tuberculosis (TB). Following an overnight and 7 days stimulation of whole blood with purified recombinant M. tuberculosis antigens, interferon-γ (IFN-γ) levels were determined by ELISA. Several antigens could statistically significantly differentiate the groups of individuals. We obtained promising antigens from all studied antigen groups [dormancy survival regulon (DosR regulon) encoded antigens; resuscitation-promoting factors (Rpf) antigens; IVE-TB antigens; reactivation associated antigens]. Rv1733, which is a probable conserved transmembrane protein encoded in DosR regulon, turned out to be very immunogenic and able to discriminate between the three defined TB status, thus considered a candidate biomarker. Rv2389 and Rv2435n, belonging to Rpf family and IVE-TB group of antigens, respectively, also stood out as LTBI biomarkers. Although more studies are needed to support our findings, the combined use of these antigens would be an interesting approach to TB immunodiagnosis candidates.

WHO Treatment Guidelines for Drug-Resistant Tuberculosis, 2016 Update: Applicability in South Korea

PubMed Central

2017-01-01

Despite progress made in tuberculosis control worldwide, the disease burden and treatment outcome of multidrug-resistant tuberculosis (MDR-TB) patients have remained virtually unchanged. In 2016, the World Health Organization released new guidelines for the management of MDR-TB. The guidelines are intended to improve detection rate and treatment outcome for MDR-TB through novel, rapid molecular testing and shorter treatment regimens. Key changes include the introduction of a new, shorter MDR-TB treatment regimen, a new classification of medicines and updated recommendations for the conventional MDR-TB regimen. This paper will review these key changes and discuss the potential issues with regard to the implementation of these guidelines in South Korea. PMID:28905529

Multidrug-resistant tuberculosis with a history of nontuberculous Mycobacteriosis: a brief report of two cases.

PubMed

Morimoto, Kozo; Yoshiyama, Takashi; Okumura, Masao; Hoshino, Yoshihiko; Yoshimori, Kozo; Ogata, Hideo; Kurashima, Atsuyuki; Gemma, Akihiko; Kudoh, Shoji

2012-01-01

We herein report two cases of multidrug-resistant tuberculosis (MDR-TB) in patients with a history of pulmonary nontuberculous mycobacteriosis (PNTM). A 50-year-old man was diagnosed with MDR-TB five years after receiving treatment for pulmonary Mycobacterium kansasii infection. In the second patient, a 72-year-old woman, the diagnosis of PNTM was confirmed twice with two bronchial washings; she was diagnosed with MDR-TB 29 months after presenting with PNTM. It is highly possible that these two patients were already infected with tuberculosis (TB) at the time of PNTM diagnosis and acquired resistance to anti-TB drugs as a result of undergoing treatment for PNTM.

In vivo inhibition of tryptophan catabolism reorganizes the tuberculoma and augments immune-mediated control of Mycobacterium tuberculosis

PubMed Central

Gautam, Uma S.; Foreman, Taylor W.; Bucsan, Allison N.; Veatch, Ashley V.; Alvarez, Xavier; Adekambi, Toidi; Golden, Nadia A.; Gentry, Kaylee M.; Doyle-Meyers, Lara A.; Didier, Peter J.; Blanchard, James L.; Kousoulas, K. Gus; Lackner, Andrew A.; Kalman, Daniel; Rengarajan, Jyothi; Khader, Shabaana A.; Kaushal, Deepak

2018-01-01

Mycobacterium tuberculosis continues to cause devastating levels of mortality due to tuberculosis (TB). The failure to control TB stems from an incomplete understanding of the highly specialized strategies that M. tuberculosis utilizes to modulate host immunity and thereby persist in host lungs. Here, we show that M. tuberculosis induced the expression of indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan catabolism, in macrophages and in the lungs of animals (mice and macaque) with active disease. In a macaque model of inhalation TB, suppression of IDO activity reduced bacterial burden, pathology, and clinical signs of TB disease, leading to increased host survival. This increased protection was accompanied by increased lung T cell proliferation, induction of inducible bronchus-associated lymphoid tissue and correlates of bacterial killing, reduced checkpoint signaling, and the relocation of effector T cells to the center of the granulomata. The enhanced killing of M. tuberculosis in macrophages in vivo by CD4+ T cells was also replicated in vitro, in cocultures of macaque macrophages and CD4+ T cells. Collectively, these results suggest that there exists a potential for using IDO inhibition as an effective and clinically relevant host-directed therapy for TB. PMID:29255022

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

PubMed Central

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

2011-01-01

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

Design of the Anti-tuberculosis Drugs induced Adverse Reactions in China National Tuberculosis Prevention and Control Scheme Study (ADACS)

PubMed Central

2010-01-01

Background More than 1 million tuberculosis (TB) patients are receiving the standard anti-TB treatment provided by China National Tuberculosis Prevention and Control Scheme (CNTS) in China every year. Adverse reactions (ADRs) induced by anti-TB drugs could both do harm to patients and lead to anti-TB treatment failure. The ADACS aimed to explore ADRs' incidences, prognoses, economical and public health impacts for TB patients and TB control, and build a DNA bank of TB patients. Methods/Design Multiple study designs were adopted. Firstly, a prospective cohort with 4488 sputum smears positive pulmonary tuberculosis patients was established. Patients were followed up for 6-9 months in 52 counties of four regions. Those suspected ADRs should be checked and confirmed by Chinese State Food and Drug Administration (SFDA). Secondly, if the suspected ADR was anti-TB drug induced liver injury (ATLI), a nested case-control study would be performed which comprised choosing a matched control and doing a plus questionnaire inquiry. Thirdly, health economical data of ADRs would be collected to analyze financial burdens brought by ADRs and cost-effectiveness of ADRs' treatments. Fourthly, a drop of intravenous blood for each patient was taken and saved in FTA card for DNA banking and genotyping. Finally, the demographic, clinical, environmental, administrative and genetic data would be merged for the comprehensive analysis. Discussion ADACS will give an overview of anti-TB drugs induced ADRs' incidences, risk factors, treatments, prognoses, and clinical, economical and public health impacts for TB patients applying CNTS regimen in China, and provide suggestions for individualized health care and TB control policy. PMID:20492672

Drug Resistance Profiles of Mycobacterium tuberculosis Complex and Factors Associated with Drug Resistance in the Northwest and Southwest Regions of Cameroon

PubMed Central

Meriki, Henry D.; Tufon, Kukwah A.; Atanga, Pascal N.; Ane-Anyangwe, Irene N.; Anong, Damian N.; Cho-Ngwa, Fidelis; Nkuo-Akenji, Theresa

2013-01-01

Background Anti-tuberculosis drug resistance continues to be a major obstacle to tuberculosis (TB) control programmes with HIV being a major risk factor in developing TB. We investigated anti-TB drug resistance profiles and the impact of socioeconomic as well as behavioural factors on the prevalence of TB and drug resistance in two regions of Cameroon with such data paucity. Methods This was a hospital-based study in which 1706 participants, comprising 1133 females and 573 males consecutively enrolled from selected TB and HIV treatment centres of the Northwest and Southwest regions. Demographic, clinical and self-reported risk behaviours and socioeconomic data were obtained with the consent of participants using questionnaires. Culture and drug resistance testing were performed according to standard procedures. Results The prevalence of resistance to at least one anti-TB drug was 27.7% and multi-drug resistance was 5.9%. Smoking, concurrent alcohol consumption and smoking, being on antiretroviral therapy for ≤ 12 months and previous household contact with TB patient were independently associated with tuberculosis prevalence, while only previous tuberculosis infection was associated with drug resistance in a univariate analysis. Conclusion The study showed a high prevalence of drug resistance TB in the study population with only previous TB infection associated with drug resistance in a univariate analysis. It also provides evidence in our context, of the role of alcohol and smoking in increasing the risk of developing TB, which is more likely in people living with HIV/AIDS. Therefore, it is important for public health authorities to integrate and intensify alcohol/smoking abstention interventions in TB and HIV control programs in Cameroon. PMID:24146991

Rapid molecular diagnostics for multi-drug resistant tuberculosis in India.

PubMed

Ramachandran, Rajeswari; Muniyandi, M

2018-03-01

Rapid molecular diagnostic methods help in the detection of TB and Rifampicin resistance. These methods detect TB early, are accurate and play a crucial role in reducing the burden of drug resistant tuberculosis. Areas covered: This review analyses rapid molecular diagnostic tools used in the diagnosis of MDR-TB in India, such as the Line Probe Assay and GeneXpert. We have discussed the burden of MDR-TB and the impact of recent diagnostic tools on case detection and treatment outcomes. This review also discusses the costs involved in establishing these new techniques in India. Expert commentary: Molecular methods have considerable advantages for the programmatic management of drug resistant TB. These include speed, standardization of testing, potentially high throughput and reduced laboratory biosafety requirements. There is a desperate need for India to adopt modern, rapid, molecular tools with point-of-care tests being currently evaluated. New molecular diagnostic tests appear to be cost effective and also help in detecting missing cases. There is enough evidence to support the scaling up of these new tools in India.

The research agenda for improving health policy, systems performance, and service delivery for tuberculosis control: a WHO perspective.

PubMed Central

Nunn, Paul; Harries, Anthony; Godfrey-Faussett, Peter; Gupta, Raj; Maher, Dermot; Raviglione, Mario

2002-01-01

The development of WHO's DOTS strategy for the control of tuberculosis (TB) in 1995 led to the expansion, adaptation and improvement of operational research in this area. From being a patchwork of small-scale studies concerned with aspects of service delivery, TB operational research shifted to larger-scale, often multicountry projects that were also concerned with health policy and the needs of health systems. The results are now being put into practice by national TB control programmes. In 1998 an ad hoc committee identified the chief factors inhibiting the expansion of DOTS: lack of political will and commitment, poor financial support for TB control, poor organization and management of health services, inadequate human resources, irregular drug supplies, the HIV epidemic, and the rise of multidrug resistance. An analysis of current operational research on TB is presented on the basis of these constraints, and examples of successful projects are outlined in the article. We discuss the prerequisites for success, the shortcomings of this WHO- supported programme, and future challenges and needs. PMID:12132005

Risk and Timing of Tuberculosis Among Close Contacts of Persons with Infectious Tuberculosis.

PubMed

Reichler, Mary R; Khan, Awal; Sterling, Timothy R; Zhao, Hui; Moran, Joyce; McAuley, James; Bessler, Patricia; Mangura, Bonita

2018-05-15

The risk and timing of tuberculosis (TB) among recently exposed close contacts of patients with infectious TB is not well established. We prospectively enrolled culture-confirmed pulmonary TB patients ≥15 years of age and their close contacts at nine health departments in the United States and Canada. Close contacts were screened and cross-matched with TB registries to identify those who developed TB. TB was diagnosed in 158 (4%) of 4490 contacts to 718 index TB patients. Of those with TB, cumulative totals of 81 (51%), 119 (75%), 128 (81%) and 145 (92%) were diagnosed by 1, 3, 6, and 12 months after index case diagnosis, respectively. TB rates among contacts were 2644, 115, 46, 69, and 25 per 100,000 persons, respectively, in the five consecutive years after index patient diagnosis. Of the TB cases among contacts, 121 (77%) were identified by contact investigation and 37 (23%) by TB registry cross-match. Close contacts to infectious TB patients had high rates of TB, with most disease diagnosed before or within 3 months after index patient diagnosis. Contact investigations need to be prompt to detect TB and maximize the opportunity to identify and treat latent infection in order to prevent disease.

Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons.

PubMed

Quiroga, Maria Florencia; Angerami, Matias Tomas; Santucci, Natalia; Ameri, Diego; Francos, Jose Luis; Wallach, Jorge; Sued, Omar; Cahn, Pedro; Salomón, Horacio; Bottasso, Oscar

2012-01-01

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.

Dynamics of Adrenal Steroids Are Related to Variations in Th1 and Treg Populations during Mycobacterium tuberculosis Infection in HIV Positive Persons

PubMed Central

Quiroga, Maria Florencia; Angerami, Matias Tomas; Santucci, Natalia; Ameri, Diego; Francos, Jose Luis; Wallach, Jorge; Sued, Omar; Cahn, Pedro; Salomón, Horacio; Bottasso, Oscar

2012-01-01

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS. PMID:22431997

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

PubMed

Mascart, Françoise; Locht, Camille

2015-01-01

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

Perinatal tuberculosis: new challenges in the diagnosis and treatment of tuberculosis in infants and the newborn.

PubMed

Whittaker, Elizabeth; Kampmann, Beate

2008-12-01

With increasing rates of tuberculosis (TB) infection and disease worldwide, the rate of perinatal TB is also affected. A high index of suspicion by health professionals, in both the developed and developing world, is required to detect and manage tuberculosis in pregnancy and the early newborn period. Differences in immune responses in the fetus and neonate add to the diagnostic difficulties already recognised in young children. Although specific guidelines for the treatment of this potentially devastating disease are lacking due to paucity of experience, outcome is favourable, if the condition is recognised and treated according to existing TB protocols. HIV co-infection, multi- and extensively-drug resistant (MDR/XDR) TB contribute to the challenges. New diagnostic and vaccine developments hold future promise, but much work is needed to completely understand the complex immune responses to tuberculosis and control this disease.

Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines.

PubMed

Caccamo, Nadia; Pietra, Gabriella; Sullivan, Lucy C; Brooks, Andrew G; Prezzemolo, Teresa; La Manna, Marco P; Di Liberto, Diana; Joosten, Simone A; van Meijgaarden, Krista E; Di Carlo, Paola; Titone, Lucina; Moretta, Lorenzo; Mingari, Maria C; Ottenhoff, Tom H M; Dieli, Francesco

2015-04-01

CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mycobacterial diversity causing multi- and extensively drug-resistant tuberculosis in Djibouti, Horn of Africa.

PubMed

Millán-Lou, M I; Ollé-Goig, J E; Tortola, M T; Martin, C; Samper, S

2016-02-01

On detecting a high prevalence of multidrug-resistant tuberculosis (TB) in Djibouti, 32 Mycobacterium tuberculosis isolates of patients hospitalised in the TB referral centre of the capital were genotyped. A high variety of M. tuberculosis lineages, including lineage 1, Indo-Oceanic, lineage 2, East-Asian, lineage 3, East-African Indian and lineage 4, Euro-American, were detected.

Experiences in anti-tuberculosis treatment in patients with multiple previous treatments and its impact on drug resistant tuberculosis epidemics

PubMed Central

Xu, Biao; Zhao, Qi; Hu, Yi; Shi, Ying; Wang, Weibing; Diwan, Vinod K.

2014-01-01

Background Tuberculosis (TB) patients with a history of multiple anti-TB treatments are the ‘neglected’ group to the free anti-TB treatment policy in China. Objective To understand the experiences of TB patients with multiple previous treatments with regard to bacteriological diagnosis and treatment regimens, especially for second-line anti-TB drugs, and how this might influence the risks of multidrug and extensively drug-resistant TB (M/XDR-TB). Design A cross-sectional study was conducted in 10 county/district TB clinics in five provinces of China. The study participants were TB patients that had at least two previous treatment episodes that lasted longer than 1 month each. Face-to-face interviews and drug susceptibility testing (DST) were conducted with the consenting participants. Results A total of 328 TB patients were recruited. The proportion of multidrug-resistant tuberculosis (MDR-TB) was 58.2% in the 287 DST-confirmed patients. Forty-two percent of the patients did not complete their first treatment course. About 23.8% of the participants had a history of taking second-line drugs, and more than 77.8% of them were treated in county TB dispensaries where only sputum microscopy was applied. Multivariate analysis found that the use of second-line drugs was significantly associated with frequency of previous treatments (p<0.01), but not with drug resistance profiles of patients. Conclusions Patients with multiple previous treatments are at extremely high risk of MDR-TB in China. The unregulated use of second-line drugs bring about the threat of XDR-TB epidemic. DST-guided treatment and strict regulations of anti-TB treatment should be assured for the high-risk TB patients for the prevention and control of M/XDR-TB. PMID:25138531

Alarming levels of drug-resistant tuberculosis in HIV-infected patients in metropolitan Mumbai, India.

PubMed

Isaakidis, Petros; Das, Mrinalini; Kumar, Ajay M V; Peskett, Christopher; Khetarpal, Minni; Bamne, Arun; Adsul, Balkrishna; Manglani, Mamta; Sachdeva, Kuldeep Singh; Parmar, Malik; Kanchar, Avinash; Rewari, B B; Deshpande, Alaka; Rodrigues, Camilla; Shetty, Anjali; Rebello, Lorraine; Saranchuk, Peter

2014-01-01

Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%-40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with 'presumptive TB' rather than 'presumptive DR-TB' and tailor the treatment regimen based on the resistance patterns.

Multidrug-resistant tuberculosis (MDR-TB) in India: an attempt to link biosocial determinants.

PubMed

Atre, Sachin R; Mistry, Nerges F

2005-04-01

Multidrug-resistant tuberculosis (MDR-TB) has emerged as a possible threat to global tuberculosis control efforts in recent years. It is a challenge not only from a public health point of view but also in the context of global economy, especially in the absence of treatment for MDR-TB at national-level programs in developing countries. Biological accounts are insufficient to understand the emergence and dynamics of drug resistance. This article focuses essentially on the need for a holistic perspective, linking biosocial determinants that would probably lead to better insights into MDR-TB control strategies.

Achievements in and Challenges of Tuberculosis Control in South Korea

PubMed Central

Kim, Ji Han

2015-01-01

After the Korean War (1950–1953), nearly 6.5% of South Korea’s population had active tuberculosis (TB). In response, South Korea implemented the National Tuberculosis Program in 1962. From 1965 to 1995, the prevalence of bacteriologically confirmed pulmonary TB in South Korea decreased from 940 to 219 cases per 100,000 population. Astounding economic growth might have contributed to this result; however, TB incidence in South Korea remains the highest among high-income countries. The rate of decrease in TB incidence seems to have slowed over the past 15 years. A demographic shift toward an older population, many of whom have latent TB and various concurrent conditions, is challenging TB control efforts in South Korea. The increasing number of immigrants also plays a part in the prolonged battle against TB. A historical review of TB in South Korea provides an opportunity to understand national TB control efforts that are applicable to other parts of the world. PMID:26485188

Occupational exposure to Mycobacterium tuberculosis. Legal issues in workers' compensation.

PubMed

Evenson, W

1999-08-01

Occupational exposure to TB remains a significant threat in select high risk occupations despite 5 years of declining disease incidence rates in the United States. TB kills more people on a global scale than any other infectious disease. One third of the global population is currently infected with TB. Workers' compensation insurance may be inadequate to cover lost wages and medical bills in cases of occupational exposure to TB if the source patient is unknown. There is a need to reform state laws for workers' compensation so TB infections in high risk employees are presumed to be work related unless a community exposure to the disease is identified.

Persistent Latent Tuberculosis Reactivation Risk in United States Immigrants

PubMed Central

Painter, John; Parker, Matthew; Lowenthal, Phillip; Flood, Jennifer; Fu, Yunxin; Asis, Redentor; Reves, Randall

2014-01-01

Rationale: Current guidelines limit latent tuberculosis infection (LTBI) evaluation to persons in the United States less than or equal to 5 years based on the assumption that high TB rates among recent entrants are attributable to high LTBI reactivation risk, which declines over time. We hypothesized that high postarrival TB rates may instead be caused by imported active TB. Objectives: Estimate reactivation and imported TB in an immigrant cohort. Methods: We linked preimmigration records from a cohort of California-bound Filipino immigrants during 2001–2010 with subsequent TB reports. TB was likely LTBI reactivation if the immigrant had no evidence of active TB at preimmigration examination, likely imported if preimmigration radiograph was abnormal and TB was reported less than or equal to 6 months after arrival, and likely reactivation of inactive TB if radiograph was abnormal but TB was reported more than 6 months after arrival. Measurements and Main Results: Among 123,114 immigrants, 793 TB cases were reported. Within 1 year of preimmigration examination, 85% of TB was imported; 6 and 9% were reactivation of LTBI and inactive TB, respectively. Conversely, during Years 2–9 after U.S. entry, 76 and 24% were reactivation of LTBI and inactive TB, respectively. The rate of LTBI reactivation (32 per 100,000) did not decline during Years 1–9. Conclusions: High postarrival TB rates were caused by detection of imported TB through active postarrival surveillance. Among immigrants without active TB at baseline, reported TB did not decline over 9 years, indicating sustained high risk of LTBI reactivation. Revised guidelines should support LTBI screening and treatment more than 5 years after U.S. arrival. PMID:24308495

Evaluation of the interferon-γ assay on blood collected at exsanguination of cattle under field conditions for surveillance of bovine tuberculosis.

PubMed

Okafor, C C; Grooms, D L; Bolin, S R; Averill, J J; Kaneene, J B

2014-12-01

Development of point of concentration (POC) surveillance strategies for bovine tuberculosis (bTB) would facilitate global efforts to eradicate bTB. The interferon-gamma (IFNγ) assay can detect IFNγ responses to Mycobacterium bovis in blood collected at commencement of exsanguination (COE) of experimentally challenged cattle but has not been evaluated under field conditions. The current study was aimed at determining (i) whether blood collected at COE of cattle at slaughter, under field conditions, is practical to obtain and useful for identifying cattle as IFNγ positive for bTB, (ii) whether the results of the IFNγ assay obtained at COE reliably compare with results obtained from live animals in the field, and (iii) whether the identified animal(s) originated from bTB-infected or bTB-exposed herds. Cattle from three risk groups were used: the highest risk group consisted of 49 cattle from 3 bTB-infected herds; the medium risk group consisted of 24 cattle from a potentially exposed herd; and the lowest risk group consisted of 60 cattle from herds with no known history of bTB exposure. The IFNγ assay was performed on blood collected both before stunning and at COE of cattle at slaughter. An enhanced slaughter inspection for gross lesions consistent with bTB was performed on all cattle. In addition, lymph nodes were cultured for M. bovis for cattle that tested positive for bTB via the IFNγ assay and for most cattle that tested negative for bTB. Cattle, both with and without lesions consistent with bTB, were identified as positive for bTB by the IFNγ assay using blood collected at COE, but none of the positive cattle originated from the lowest risk group. The current study demonstrates that blood collected at COE of cattle is both a practical and moderately reliable sample for accessing bTB infection using the IFNγ assay. © 2013 Blackwell Verlag GmbH.

Tuberculosis: a new vision for the 21st century.

PubMed

Small, Peter M

2009-11-01

Tuberculosis is a global problem that we can't afford to keep ignoring. In 2006, tuberculosis killed 1.7 million people--almost twice as many people as malaria--and it is the leading cause of death among people living with HIV/AIDS. This is all the more tragic because these deaths are preventable. For a long time the world thought that we had defeated tuberculosis, but just because tuberculosis doesn't make headlines doesn't mean it has gone away. The fact is that tuberculosis is getting worse, as complacency and lack of adequate tools and funding fuel the disease and the spread of drug resistance. Drug resistant tuberculosis is the wake-up call, it is an airborne epidemic of increasingly untreatable disease. Drug resistant tuberculosis develops when tuberculosis patients take low-quality drugs, do not finish their full course of treatment, or pass drug resistant tuberculosis from one person to another. In 2007, there were approximately 500,000 cases of drug resistant tuberculosis globally. MDR-TB is resistant to the two most commonly used first-line TB drugs, and requires long, complex and expensive treatment. XDR-TB is resistant to first- and second-line drugs, severely limiting treatment options. While progress is being made, much more is needed. Basic tuberculosis control is one of the most cost-effective interventions in global health. Appropriate treatment can save a life and stop the spread of disease for US$14. It is essential that countries implement the World Health Organization's (WHO) internationally recommended Stop TB strategy, which includes DOTS. But due to outdated tools and methods, DOTS alone is not enough. The remarkable fact is that global control of tuberculosis, a disease that kills someone every 20 seconds, depends upon a 125-year-old test, an 85-year-old vaccine and drugs that take six months to cure and haven't changed in four decades. To successfully treat tuberculosis and prevent resistance, we need to use current tools better and accelerate the development of new tools for the future. Simple improvements in tuberculosis control, such as expanding the use of under-utilized technologies, can have enormous impact. Fixed-dose combinations have existed for over 25 years, and could help ensure that more patients complete treatment; yet globally, only 15 percent of patients are using them. We also need new drugs, vaccines and diagnostics, as well as innovations in tuberculosis control and case management. Better diagnostics are already available, and new drugs and vaccines are coming. But more commitment and resources are needed. Better prevention and control of tuberculosis is the surest way to stop drug resistance. To ensure that drug resistance does not pose a wider threat, we need to employ a number of equally important approaches. These include improved basic tuberculosis control, increased use of underutilized technologies such as fixed-dose combinations, and new technologies and health systems innovations. At the same time, we should expand access to M/XDR-TB treatment and diagnostics for those who already have drug resistant tuberculosis. Some of the most innovative solutions can come from the private sector and through partnerships. An untapped market of two billion people carries the tuberculosis bacterium. Since tuberculosis requires a comprehensive approach, companies should also explore opportunities to work together and pool complementary technologies to ensure new tools are used most effectively. Japan is poised to play a leading role in the discovery, development and delivery of tuberculosis solutions in the 21st century.

Optimal control of a two-strain tuberculosis-HIV/AIDS co-infection model.

PubMed

Agusto, F B; Adekunle, A I

2014-05-01

Tuberculosis is a bacterial disease caused by Mycobacterium tuberculosis (TB). The risk for TB infection greatly increases with HIV infection; TB disease occurs in 7-10% of patients with HIV infection each year, increasing the potential for transmission of drug-resistant Mycobacterium tuberculosis strains. In this paper a deterministic model is presented and studied for the transmission of TB-HIV/AIDS co-infection. Optimal control theory is then applied to investigate optimal strategies for controlling the spread of the disease using treatment of infected individuals with TB as the system control variables. Various combination strategies were examined so as to investigate the impact of the controls on the spread of the disease. And incremental cost-effectiveness ratio (ICER) was used to investigate the cost effectiveness of all the control strategies. Our results show that the implementation of the combination strategy involving the prevention of treatment failure in drug-sensitive TB infectious individuals and the treatment of individuals with drug-resistant TB is the most cost-effective control strategy. Similar results were obtained with different objective functionals involving the minimization of the number of individuals with drug-sensitive TB-only and drug-resistant TB-only with the efforts involved in applying the control. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Common errors in multidrug-resistant tuberculosis management.

PubMed

Monedero, Ignacio; Caminero, Jose A

2014-02-01

Multidrug-resistant tuberculosis (MDR-TB), defined as being resistant to at least rifampicin and isoniazid, has an increasing burden and threatens TB control. Diagnosis is limited and usually delayed while treatment is long lasting, toxic and poorly effective. MDR-TB management in scarce-resource settings is demanding however it is feasible and extremely necessary. In these settings, cure rates do not usually exceed 60-70% and MDR-TB management is novel for many TB programs. In this challenging scenario, both clinical and programmatic errors are likely to occur. The majority of these errors may be prevented or alleviated with appropriate and timely training in addition to uninterrupted procurement of high-quality drugs, updated national guidelines and laws and an overall improvement in management capacities. While new tools for diagnosis and shorter and less toxic treatment are not available in developing countries, MDR-TB management will remain complex in scarce resource settings. Focusing special attention on the common errors in diagnosis, regimen design and especially treatment delivery may benefit patients and programs with current outdated tools. The present article is a compilation of typical errors repeatedly observed by the authors in a wide range of countries during technical assistant missions and trainings.

Latent tuberculous infection in household contacts of multidrug-resistant and newly diagnosed tuberculosis.

PubMed

Fox, G J; Anh, N T; Nhung, N V; Loi, N T; Hoa, N B; Ngoc Anh, L T; Cuong, N K; Buu, T N; Marks, G B; Menzies, D

2017-03-01

Differences in the prevalence of latent tuberculous infection (LTBI) and tuberculosis (TB) disease among contacts of patients with multidrug-resistant TB (MDR-TB) and drug-susceptible TB are not well understood. To compare the prevalence of tuberculin skin test (TST) positivity in household contacts of patients with MDR-TB and in contacts of patients never previously treated for TB ('new TB'). Consecutive patients with MDR-TB and their household contacts at nine urban district clinics in Viet Nam were screened for TB and LTBI, and followed up for 6 months. LTBI was defined as a TST result of at least 10 mm. A total of 167 patients with TB and their 337 household contacts were recruited. A total of 167/180 (25.8%) contacts of new TB patients and 60/147 (40.8%) contacts of MDR-TB patients were TST-positive (odds ratio [OR] 2.0, 95%CI 1.3-3.2). Contacts of MDR-TB patients were more likely to have baseline chest radiograph findings consistent with TB (OR 2.6, 95%CI 1.4-5.0). Contacts of MDR-TB patients have a high risk of developing TB. Measures to reduce Mycobacterium tuberculosis transmission and accelerate the detection of disease among high-risk contacts should be prioritised to curb the MDR-TB epidemic.

High laboratory cost predicted per tuberculosis case diagnosed with increased case finding without a triage strategy.

PubMed

Dunbar, R; Naidoo, P; Beyers, N; Langley, I

2017-09-01

Cape Town, South Africa. To model the effects of increased case finding and triage strategies on laboratory costs per tuberculosis (TB) case diagnosed. We used a validated operational model and published laboratory cost data. We modelled the effect of varying the proportion with TB among presumptive cases and Xpert cartridge price reductions on cost per TB case and per additional TB case diagnosed in the Xpert-based vs. smear/culture-based algorithms. In our current scenario (18.3% with TB among presumptive cases), the proportion of cases diagnosed increased by 8.7% (16.7% vs. 15.0%), and the cost per case diagnosed increased by 142% (US$121 vs. US$50). The cost per additional case diagnosed was US$986. This would increase to US$1619 if the proportion with TB among presumptive cases was 10.6%. At 25.9-30.8% of TB prevalence among presumptive cases and a 50% reduction in Xpert cartridge price, the cost per TB case diagnosed would range from US$50 to US$59 (comparable to the US$48.77 found in routine practice with smear/culture). The operational model illustrates the effect of increased case finding on laboratory costs per TB case diagnosed. Unless triage strategies are identified, the approach will not be sustainable, even if Xpert cartridge prices are reduced.

The impact of migration on tuberculosis epidemiology and control in high-income countries: a review.

PubMed

Pareek, Manish; Greenaway, Christina; Noori, Teymur; Munoz, Jose; Zenner, Dominik

2016-03-23

Tuberculosis (TB) causes significant morbidity and mortality in high-income countries with foreign-born individuals bearing a disproportionate burden of the overall TB case burden in these countries. In this review of tuberculosis and migration we discuss the impact of migration on the epidemiology of TB in low burden countries, describe the various screening strategies to address this issue, review the yield and cost-effectiveness of these programs and describe the gaps in knowledge as well as possible future solutions.The reasons for the TB burden in the migrant population are likely to be the reactivation of remotely-acquired latent tuberculosis infection (LTBI) following migration from low/intermediate-income high TB burden settings to high-income, low TB burden countries.TB control in high-income countries has historically focused on the early identification and treatment of active TB with accompanying contact-tracing. In the face of the TB case-load in migrant populations, however, there is ongoing discussion about how best to identify TB in migrant populations. In general, countries have generally focused on two methods: identification of active TB (either at/post-arrival or increasingly pre-arrival in countries of origin) and secondly, conditionally supported by WHO guidance, through identifying LTBI in migrants from high TB burden countries. Although health-economic analyses have shown that TB control in high income settings would benefit from providing targeted LTBI screening and treatment to certain migrants from high TB burden countries, implementation issues and barriers such as sub-optimal treatment completion will need to be addressed to ensure program efficacy.

Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis in children: a prospective, multi-centre evaluation.

PubMed

Reither, Klaus; Manyama, Christina; Clowes, Petra; Rachow, Andrea; Mapamba, Daniel; Steiner, Andreas; Ross, Amanda; Mfinanga, Elirehema; Sasamalo, Mohamed; Nsubuga, Martin; Aloi, Francesco; Cirillo, Daniela; Jugheli, Levan; Lwilla, Fred

2015-04-01

Following endorsement by the World Health Organisation, the Xpert MTB/RIF assay has been widely incorporated into algorithms for the diagnosis of adult tuberculosis (TB). However, data on its performance in children remain scarce. This prospective, multi-centre study evaluated the performance of Xpert MTB/RIF to diagnose pulmonary tuberculosis in children. Children older than eight weeks and younger than 16 years with suspected pulmonary tuberculosis were enrolled at three TB endemic settings in Tanzania and Uganda, and assigned to five well-defined case definition categories: culture-confirmed TB, highly probable TB, probable TB, not TB, or indeterminate. The diagnostic accuracy of Xpert MTB/RIF was assessed using culture-confirmed TB cases as reference standard. In total, 451 children were enrolled. 37 (8%) had culture-confirmed TB, 48 (11%) highly probably TB and 62 probable TB (13%). The Xpert MTB/RIF assay had a sensitivity of 68% (95% CI, 50%-82%) and specificity of 100% (95% CI, 97%-100%); detecting 1.7 times more culture-confirmed cases than smear microscopy with a similar time to detection. Xpert MTB/RIF was positive in 2% (1/48) of highly probable and in 3% (2/62) of probable TB cases. Xpert MTB/RIF provided timely results with moderate sensitivity and excellent specificity compared to culture. Low yields in children with highly probable and probable TB remain problematic. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

School-based Study to Identify and Treat Adolescent Students at Risk for Tuberculosis Infection.

PubMed

Hatzenbuehler, Lindsay A; Starke, Jeffrey R; Graviss, Edward A; Smith, E O'Brian; Cruz, Andrea T

2016-07-01

Screening for and treating tuberculosis (TB) infection in children and adolescents is an effective way of decreasing future TB cases. However, current approaches leave many children at risk for TB unidentified. We recruited adolescent students from 2 public high schools (a magnet and a low-income) in the Houston Independent School District. Compared with the magnet school, the student population at the low-income school was larger, primarily Hispanic and economically disadvantaged. Students were educated about TB, and parents completed a risk factor questionnaire. Students with TB risk factors were tested using 2 interferon gamma release assays (IGRAs). Those with a positive IGRA received a 12-dose regimen of weekly isoniazid/rifapentine (3HP) administered via direct observation at school. Nine hundred twenty-five students received TB education; 73% of their parents submitted the TB questionnaire. Eighty-six percent of students (n = 415) with a TB risk factor identified on the study questionnaire agreed to IGRA testing. Sixteen students had at least one positive IGRA (1% [magnet], 4.1% [low-income]; P = 0.005). Recent student travel to a high-risk country (7) or contact with TB disease (2) were associated with IGRA positivity (P < 0.05). All students with a positive IGRA accepted, tolerated and completed 3HP treatment at school. School-based TB education, screening, testing using IGRAs and administration of 3HP treatment is feasible to improve the identification and treatment of adolescent students at risk for TB.

[The Spanish AIDS Study Group and Spanish National AIDS Plan (GESIDA/Secretaría del Plan Nacional sobre el Sida) recommendations for the treatment of tuberculosis in HIV-infected individuals (Updated January 2013)].

PubMed

Rivero, Antonio; Pulido, Federico; Caylá, Joan; Iribarren, José A; Miró, José M; Moreno, Santiago; Pérez-Camacho, Inés

2013-12-01

This consensus document was prepared by an expert panel of the Grupo de Estudio de Sida (GESIDA [Spanish AIDS Study Group]) and the Plan Nacional sobre el Sida (PNS [Spanish National AIDS Plan]). The document updates current guidelines on the treatment of tuberculosis (TB) in HIV-infected individuals contained in the guidelines on the treatment of opportunistic infections published by GESIDA and PNS in 2008. The document aims to facilitate the management and treatment of HIV-infected patients with TB in Spain, and includes specific sections and recommendations on the treatment of drug-sensitive TB, multidrug-resistant TB, and extensively drug-resistant TB, in this population. The consensus guidelines also make recommendations on the treatment of HIV-infected patients with TB in special situations, such as chronic liver disease, pregnancy, kidney failure, and transplantation. Recommendations are made on the timing and initial regimens of antiretroviral therapy in patients with TB, and on immune reconstitution syndrome in HIV-infected patients with TB who are receiving antiretroviral therapy. The document does not cover the diagnosis of TB, diagnosis/treatment of latent TB, or treatment of TB in children. The quality of the evidence was evaluated and the recommendations graded using the approach of the Grading of Recommendations Assessment, Development and Evaluation Working Group. Copyright © 2013 Elsevier España, S.L. All rights reserved.

Enhancing the role of private practitioners in tuberculosis prevention and care activities in India.

PubMed

Anand, Tanu; Babu, Ranjith; Jacob, Anil G; Sagili, Karuna; Chadha, Sarabjit S

2017-01-01

India accounts for the highest number of incident tuberculosis (TB) cases globally. Hence, to impact the TB incidence world over, there is an urgent need to address and accelerate TB control activities in the country. Nearly, half of the TB patients first seek TB care in private sector. However, the participation of private practitioners (PPs) has been patchy in TB prevention and care and distrust exists between public and private sector. PPs usually have varied diagnostic and treatment practices that are inadequate and amplify the risk of drug resistance. Hence, their regulation and involvement as key stakeholders are important in TB prevention and care in India if we are to achieve TB control at global level. However, there remain certain barriers and gaps, which are preventing their upscaling. The current paper aims to discuss the status of private sector involvement in TB prevention and care in India. The paper also discusses the strategies and initiatives taken by the government in this regard as evidence shows that the involvement of private sector in co-opting directly observed treatment short-course (DOTS) helps to enhance case finding and treatment outcomes; it improves the accessibility of quality TB care with greater geographic coverage. Besides public-private mix, DOTS has been found more cost-effective and reduces financial burden of patients. The paper also offers to present some more solutions both at policy and program level for upscaling the engagement of PPs in the national TB control program.

Enhancing the role of private practitioners in tuberculosis prevention and care activities in India

PubMed Central

Anand, Tanu; Babu, Ranjith; Jacob, Anil G.; Sagili, Karuna; Chadha, Sarabjit S.

2017-01-01

India accounts for the highest number of incident tuberculosis (TB) cases globally. Hence, to impact the TB incidence world over, there is an urgent need to address and accelerate TB control activities in the country. Nearly, half of the TB patients first seek TB care in private sector. However, the participation of private practitioners (PPs) has been patchy in TB prevention and care and distrust exists between public and private sector. PPs usually have varied diagnostic and treatment practices that are inadequate and amplify the risk of drug resistance. Hence, their regulation and involvement as key stakeholders are important in TB prevention and care in India if we are to achieve TB control at global level. However, there remain certain barriers and gaps, which are preventing their upscaling. The current paper aims to discuss the status of private sector involvement in TB prevention and care in India. The paper also discusses the strategies and initiatives taken by the government in this regard as evidence shows that the involvement of private sector in co-opting directly observed treatment short-course (DOTS) helps to enhance case finding and treatment outcomes; it improves the accessibility of quality TB care with greater geographic coverage. Besides public-private mix, DOTS has been found more cost-effective and reduces financial burden of patients. The paper also offers to present some more solutions both at policy and program level for upscaling the engagement of PPs in the national TB control program. PMID:29099000

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.

[Reform of Japan's NTP and its technical perspectives].

PubMed

Mori, Toru

2004-10-01

The 1951 Tuberculosis Control Law of Japan is now faced with tremendous changes that have occurred during the last 50 years in tuberculosis epidemiology and in the environment in tuberculosis control implementation. The law is also challenged with the shift of the paradigm for the National Tuberculosis (TB) Programme. In order to respond properly to these changes, the Tuberculosis Panel of the Health Science Council of the Ministry of Health, Labor and Welfare submitted its report for the amendment of the law in March 2002. Based on this report, a new Tuberculosis Control Law was passed in Parliament last June, and related decrees of the Cabinet and the Ministry are now being revised in preparation for it's enactment in April 2005. In this special lecture, the main points and framework of the revisions were discussed with the perspective of the development of new technical innovations relevant to each area of the revised TB control legislation. 1. Case detection. There will be a shift from the current "indiscriminate" screening scheme to a selective one regarding periodic mass health examination. Only subjects aged 65 or older will be eligible for the screening, supplemented with selected occupational groups who are considered to be at a higher risk of TB, or may be a danger to others if they develop TB, such as health-care providers and school teachers. In addition, local autonomies are responsible for offering screening to the socio-economic high-risk populations, such as homeless people, slum residents, day laborers, and/or workers in small businesses. This means that the efforts of the autonomies are critical for the new system to be effective. The extra-ordinary examination will be limited to only the patient's contacts, and will be mandatory for those contacts so they cannot refuse to be examined by the Health Center. The public services used in the contact investigations will be greatly facilitated by such new technologies as DNA fingerprinting of TB bacilli and a new diagnostic of TB infection using whole-blood interferon-gamma determination (QuantiFERON). The quality of clinical diagnosis and monitoring of treatment should also be improved by introducing an external quality assurance system of commercial laboratory services. 2. Chemoprophylaxis. Although not explicitly defined in the new legislation, the expansion and improvement of chemoprophylaxis to cover anyone with any risk of clinical development of TB would have a tremendous effect in Japan, especially since 90% of patients who developed TB were infected tens of years ago. These technical innovations in diagnosis of TB infection will be very helpful. Development of new drug regimens for the preventive treatment is also badly needed. 3. Immunization. Prior to the amendment of the Law, the BCG vaccination of students entering primary and junior high schools has been already abandoned. In order to encourage the early primary vaccination for infants, the new Law will adopt the direct vaccination scheme in which babies will be given the BCG vaccine without tuberculin testing. This program will be implemented safely, only if it is given to young babies, e.g., less than one year old, as defined by the decree. It is essential to maintain the high level of vaccination coverage under the new program. The autonomy may encounter difficulty mobilizing client babies shortly after their birth (only one year, as compared with the current four years). To avoid the possible, though very rare, adverse health effects due to the vaccination of infected babies, careful questioning should be conducted regarding the risk of exposure to infection prior to vaccination. A ready course of treatment and examinations for abnormal reactions after vaccination (Koch's phenomenon) is also warranted. 4. Treatment and patient care: The revised Law clearly states the governmental responsibility for treating TB patients in close cooperation with a doctor. This is an important legal basis for the expansion of the DOTS Japan version. While the development of new anti-tuberculosis drugs will be realized in the near future, Japan still has to overcome the issue of improper practice of treatment, as well as the government's slow process for approving new drugs to be used for multi-drug resistant TB and non-tuberculous mycobacterioses. 5. Prefectural TB Control Plan: In order to resolve the problems specific to the respective prefectures in terms of epidemiological parameters or available resources, the new Law requests every prefecture to develop its own TB control plan. In order for the new TB Control Law to be effective, strong government commitment supported by technological innovation is mandatory. It is for that reason that the Japanese Society of Tuberculosis should aggressively join the global movement to stop TB along with the general public of Japan.

A case risk study of lactic acidosis risk by metformin use in type 2 diabetes mellitus tuberculosis coinfection patients.

PubMed

Novita, Bernadette Dian; Pranoto, Agung; Wuryani; Soediono, Endang Isbandiati; Mertaniasih, Ni Made

2018-07-01

Metformin (MET) has possibilities to be utilized as an adjunct of tuberculosis (TB) therapy for controlling the growth of Mycobacterium tuberculosis (M. tuberculosis). MET enhances the production of mitochondrial reactive oxygen species and facilitates phagosome-lysosome fusion; those mechanism are important in M. tuberculosis elimination. Moreover, MET-associated lactic acidosis (MALA) needs to be considered and the incidence of MALA in patients with type 2 DM-TB coinfection remains unknown. This result contributes much to our understanding about the clinical effect of MET use in type 2 DM-TB coinfection. For the purpose of understanding the MET effect as an adjuvant therapy in TB therapy and insulin simultaneous therapy, an observational clinical study was done in type 2 DM newly TB coinfection outpatients at Surabaya Paru Hospital. Patients were divided into two groups. First group was MET group, in which the patients were given MET accompanying insulin and TB treatment regimens, the golden standard therapy of DM-TB coinfection. MET therapy was given for at least 2 months. Second group was non-MET group, in which the patients were given insulin and TB treatment regimens. The lactate levels in both groups were measured after 2 months. Among 42 participants, there was no case of lactic acidosis during this study period. Data were normally distributed; thus, we continued analysis of the difference using paired T-test with 95% confidence. There was no difference in lactate levels (p=0.396) after MET therapy compared to non-MET group. In this study involving patients with TB pulmonary diseases, there is neither evidence that MET therapy induced lactic acidosis event nor that it increased lactate blood level. Thus, we concluded that MET use in type 2 DM-TB coinfection did not induce lactic acidosis. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Factors associated with tuberculosis treatment outcomes among tuberculosis patients attending tuberculosis treatment centres in 2016-2017 in Mogadishu, Somalia.

PubMed

Ali, Marian Khalif; Karanja, Simon; Karama, Mohammed

2017-01-01

World Health Organization (WHO) reported that tuberculosis (TB) was a major health problem and the second leading cause of mortality globally. An estimated 1.8 million TB deaths were reported in 2015. In Somalia, the average TB incidence was 274 cases per 100,000 people in 2014; prevalence was 513 per 100,000 population; and mortality rate excluding human immune deficiency virus (HIV)/TB co-infection was 64/100,000. In addition, the prevalence rates of multi-drug resistant (MDR)-TB are still high, 5.2% among new cases and 40.7% for retreatment cases. The objective of this study was to determine individual and institutional level factors associated with TB treatment outcomes (TB-TOs) among patients attending TBTCs in Mogadishu. The study design was cross-sectional, using quantitative and qualitative methods. Data was collected using interviewer administered semi-structured questionnaires and key in-depth interviews in 2016/2017. Qualitative data was coded using NVIVO8 and quantitative data analyzed using descriptive and inferential statistics at 95% confidence interval using SPSS20 software. The study used a sample of 385 TB patients. There were 315(81.8%) successful TB-TOs. Individual level factors-marital status, education level, HIV status, treatment category and knowledge on TB influenced TB-TOs (p-value < 0.05). Being married, educated, HIV-negative, new treatment case and knowledgeable on TB increased odds of successful TB-TOs (OR > 0, p value < 0.05) compared to other patients. TBTCs factors did not influence TB-TOs (p-value > 0.05). TB-TOs were mainly affected by patient individual factors. There was need for patient education on TB management and treatment; and improved patient-health provider relationship.

Factors associated with tuberculosis treatment outcomes among tuberculosis patients attending tuberculosis treatment centres in 2016-2017 in Mogadishu, Somalia

PubMed Central

Ali, Marian Khalif; Karanja, Simon; Karama, Mohammed

2017-01-01

Introduction World Health Organization (WHO) reported that tuberculosis (TB) was a major health problem and the second leading cause of mortality globally. An estimated 1.8 million TB deaths were reported in 2015. In Somalia, the average TB incidence was 274 cases per 100,000 people in 2014; prevalence was 513 per 100,000 population; and mortality rate excluding human immune deficiency virus (HIV)/TB co-infection was 64/100,000. In addition, the prevalence rates of multi-drug resistant (MDR)-TB are still high, 5.2% among new cases and 40.7% for retreatment cases. The objective of this study was to determine individual and institutional level factors associated with TB treatment outcomes (TB-TOs) among patients attending TBTCs in Mogadishu. Methods The study design was cross-sectional, using quantitative and qualitative methods. Data was collected using interviewer administered semi-structured questionnaires and key in-depth interviews in 2016/2017. Qualitative data was coded using NVIVO8 and quantitative data analyzed using descriptive and inferential statistics at 95% confidence interval using SPSS20 software. Results The study used a sample of 385 TB patients. There were 315(81.8%) successful TB-TOs. Individual level factors-marital status, education level, HIV status, treatment category and knowledge on TB influenced TB-TOs (p-value < 0.05). Being married, educated, HIV-negative, new treatment case and knowledgeable on TB increased odds of successful TB-TOs (OR > 0, p value < 0.05) compared to other patients. TBTCs factors did not influence TB-TOs (p-value > 0.05). Conclusion TB-TOs were mainly affected by patient individual factors. There was need for patient education on TB management and treatment; and improved patient-health provider relationship. PMID:29610635

How much is tuberculosis screening worth? Estimating the value of active case finding for tuberculosis in South Africa, China, and India.

PubMed

Azman, Andrew S; Golub, Jonathan E; Dowdy, David W

2014-10-30

Current approaches are unlikely to achieve the aggressive global tuberculosis (TB) control targets set for 2035 and beyond. Active case finding (ACF) may be an important tool for augmenting existing strategies, but the cost-effectiveness of ACF remains uncertain. Program evaluators can often measure the cost of ACF per TB case detected, but how this accessible measure translates into traditional metrics of cost-effectiveness, such as the cost per disability-adjusted life year (DALY), remains unclear. We constructed dynamic models of TB in India, China, and South Africa to explore the medium-term impact and cost-effectiveness of generic ACF activities, conceptualized separately as discrete (2-year) campaigns and as continuous activities integrated into ongoing TB control programs. Our primary outcome was the cost per DALY, measured in relationship to the cost per TB case actively detected and started on treatment. Discrete campaigns costing up to $1,200 (95% uncertainty range [UR] 850-2,043) per case actively detected and started on treatment in India, $3,800 (95% UR 2,706-6,392) in China, and $9,400 (95% UR 6,957-13,221) in South Africa were all highly cost-effective (cost per DALY averted less than per capita gross domestic product). Prolonged integration was even more effective and cost-effective. Short-term assessments of ACF dramatically underestimated potential longer term gains; for example, an assessment of an ACF program at 2 years might find a non-significant 11% reduction in prevalence, but a 10-year evaluation of that same intervention would show a 33% reduction. ACF can be a powerful and highly cost-effective tool in the fight against TB. Given that short-term assessments may dramatically underestimate medium-term effectiveness, current willingness to pay may be too low. ACF should receive strong consideration as a basic tool for TB control in most high-burden settings, even when it may cost over $1,000 to detect and initiate treatment for each extra case of active TB.

Electronic recording and reporting system for tuberculosis in China: experience and opportunities

PubMed Central

Huang, Fei; Cheng, ShiMing; Du, Xin; Chen, Wei; Scano, Fabio; Falzon, Dennis; Wang, Lixia

2014-01-01

Tuberculosis (TB) surveillance in China is organized through a nationwide network of about 3200 hospitals and health facilities. In 2005, an electronic Tuberculosis Information Management System (TBIMS) started to be phased in to replace paper recording. The TBIMS collects key information on TB cases notified in TB care facilities, and exchanges real-time data with the Infectious Disease Reporting System, which covers the country’s 37 notifiable diseases. The system is accessible to authorized users at every level of the TB network through a password-protected website. By 2009 the TBIMS achieved nationwide coverage. Completeness of data on patient bacteriological end points improved remarkably over time. Data on about a million active TB cases, including drug-resistant TB, are included each year. The sheer scale of the data handling and the intricate functions that the China TBIMS performs makes it stand apart from the electronic information systems for TB adopted in other countries. PMID:24326537

Childhood tuberculosis: progress requires an advocacy strategy now

PubMed Central

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

2012-01-01

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

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

PubMed

Yükseltürk, Neriman; Dinç, Leyla

2013-02-01

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

[Tuberculous abscess of the thoracic wall secondary to nodular tuberculosis: Atypical presentation in an older adult].

PubMed

Cajuste-Sequeira, Fritz; Bueno-Wong, Juan Luis; Rosas-Carrasco, Óscar; González-Vergara, Carolina; Bieletto-Trejo, Olivia

2017-01-01

Tuberculosis (tb) of the chest wall is uncommon and it represents less than 5% of all cases of musculoskeletal tb and only 1-2% of tb. We present the case of an elderly woman with tb of the chest wall secondary to a nodal tb with an unusual presentation. The diagnosis of this entity is difficult because the disease often mimics other diseases such as pyogenic abscess, chest wall.

Extensively Drug-Resistant Tuberculosis in Women, KwaZulu-Natal, South Africa

PubMed Central

Zelnick, Jennifer; Werner, Lise; Master, Iqbal; Loveday, Marian; Horsburgh, C. Robert; Padayatchi, Nesri

2011-01-01

To determine whether women in KwaZulu-Natal, South Africa, with drug-resistant tuberculosis (TB) were more likely than men to have extensively drug-resistant TB, we reviewed 4,514 adults admitted during 2003–2008 for drug-resistant TB. Female sex independently predicted extensively drug-resistant TB, even after we controlled for HIV infection. This association needs further study. PMID:22000378

Vaccination of white-tailed deer (Odocoileus virginianus) for protection against bovine tuberculosis

USDA-ARS?s Scientific Manuscript database

Bovine tuberculosis (bTB), caused by Mycobacterium bovis and other related species in the M. tuberculosis complex, pose a serious continual threat to the health and economic wellbeing of wildlife, livestock, and humans worldwide. Wildlife reservoirs of bTB play a very important role in the epidemio...

Utility of Th1-cell immune responses for distinguishing active tuberculosis from non-active tuberculosis: A case-control study

PubMed Central

Zhang, Lifan; Cheng, Xinhe; Bian, Sainan; Song, Yanhua; Li, Qiang; Gao, Mengqiu; Zhang, Yueqiu; Shi, Xiaochun

2017-01-01

Currently available Interferon-γ release assay (IGRA) cannot reliably differentiate active TB (ATB) from non-active TB (non-ATB). A study was performed to evaluate the value of Mycobacterium tuberculosis (MTB) specific Th1 cell immune responses which test IFN-γ and IL-2 simultaneous for differentiating ATB from non-ATB. Forty-nine newly diagnosed inpatients with ATB (26 pulmonary TB and 23 extrapulmonary TB) were enrolled as the ATB group. Forty-five volunteers with latent tuberculosis infection (LTBI) and twenty with evidence of previous TB were enrolled during the same period as the non-ATB group. Clinical examination and MTB specific Th1 cell immune responses were performed for all participants. After being stimulated with ESAT-6 and CFP-10, the median frequencies of single IL-2-, single IFN-γ-, and dual IFN-γ/IL-2-secreting T-cells were all higher in the ATB group than in the non-ATB group (20(8–45) vs. 7(3–13), P<0.001;131(44–308) vs. 10(6–27), P<0.001;25(9–74) vs. 7(3–23), P = 0.001, respectively). Evaluation of the diagnostic performance of detecting single IFN-γ-secreting T cells for pulmonary TB employed a cutoff value of 35 iSFCs/250,000 PBMC. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) were 92.3%, 80.0%, 64.9%, 96.3%, 4.62, and 0.10, respectively. For extrapulmonary TB, using a cutoff value of 23 iSFCs/ 250,000 PBMC, the sensitivity, specificity, PPV, NPV, PLR, and NLR were 91.3%, 76.9%, 58.3%, 96.2%, 3.96, and 0.11, respectively. When combining frequencies and proportion of single IFN-γ-secreting T cells, the test sensitivity was 100% in parallel tests and the specificity was 87.7% in serial tests for pulmonary TB. MTB specific Th1 cell immune responses (FluoroSpot) had value for the differentiation of ATB and non-ATB. Further confirmatory studies are indicated. PMID:28531231

Use of anti-tuberculosis drugs among newly diagnosed pulmonary tuberculosis inpatients in China: a retrospective study.

PubMed

Huang, Fei; Zhang, Hui; Lv, Qing; Sato, Kaori D; Qu, Yan; Huan, Shitong; Cheng, Jun; Zhao, Fei; Wang, Lixia

2016-01-21

China's national tuberculosis control program (NTP) provides free, first-line anti-tuberculosis (TB) drugs to pulmonary TB patients. This treatment regimen follows the World Health Organization's (WHO) guideline. The objective of this paper is to evaluate the current status of anti-TB drug use for newly diagnosed pulmonary TB inpatients treated in prefecture- and county-level designated hospitals. Three prefecture-level hospitals and nine county-level hospitals were selected for the study. All newly diagnosed pulmonary TB inpatient medical records from 2012 were reviewed and doubly examined by two national senior physicians. The rational use of anti-TB drugs was evaluated based on criteria in line with WHO's guideline. Of the 2,060 total treatment regimens for TB, 53.1 % were found to be rational (1093/2060). The percentages in prefecture-level and county-level hospitals were 50.3 % (761/1513) and 60.7 % (332/547), respectively. The difference between the two levels of hospitals was statistically significant (Chi-square value = 17.44, P < 0.01). The percentages of rational treatment regimens for first-time hospitalizations and for two or more hospitalizations were 59.5 % (983/1653) and 27.0 % (110/407), respectively, with a statistically significant difference (Chi-square value = 138.00, P < 0.01). The overall use of second-line drugs (SLD) was 54.9 % (1131/2060). The percentages for prefecture-level and county-level hospitals were 50.6 % (766/1513) and 66.7 % (365/547), respectively. A statistically significant difference was found (Chi-square value = 42.06, P < 0.01). The use of SLD for inpatients hospitalized once and inpatients hospitalized twice or more was 58.4 % (966/1653) and 40.5 % (165/407), respectively, with a statistically significant difference (Chi-square value = 42.26, P < 0.01). Half of inpatients might be treated with irrational regimens, and the use of SLD was more appropriately dispensed in city-level hospitals than in county-level hospitals. Trainings and guidelines for health personnel, supervision led by health authorities and increased investment to designated hospitals may help to improve the rational use of anti-TB drugs.

Diagnostic dilemma of pulmonary tuberculosis among adults with severe mental illness in Beijing, China.

PubMed

Wang, Li; Zhang, Zhiguo; Yan, Qiuli; Lu, Jie; Gao, Baoyin; Zhao, Yanlin; Pang, Yu

2017-01-18

Although the prevalence of tuberculosis has decreased significantly over the past decades, the certain populations with mental illness are at increased risk for tuberculosis infection and transmission. However, no studies have examined the performance of different laboratory examination methods among people with severe mental illness in China. In this study, we firstly performed a retrospective study to evaluate the feasibility of three routine laboratory methods, including sputum microscopy, solid culture and GeneXpert, to diagnose tuberculosis patients with mental illness. During August 2010 and March 2013, a total of 251 TB patients based on clinical and radiographic criteria with severe mental illness were enrolled in this study. The majority of patients was homeless (97/251, 38.6%), and the other 62 (24.7%) and 92 (36.7%) were from urban and rural region, respectively. The most frequently diagnosed mental illness was schizophrenia, accounting for 84.1% (211/251) of patients available for analysis. In addition, the laboratory received 753 sputum samples collected from these 251 TB patients, of which 76.0% (572/753) of samples were classified as salivary sputum, which were unqualified for microscopy and culture. When the test results were analyzed by patients, the positive numbers of TB patients detected by sputum microscopy, solid culture and GeneXpert were 3 (1.2%), 5 (2.0%) and 5 (2.0%), respectively. In conclusion, our findings reveal that the current laboratory examinations based on sputum samples seem not to be suitable for the diagnosis of active TB in the persons with severe mental illness. The products using a non-invasive specimen such as urine deserve further evaluation, which may generate benefit for the early diagnosis of TB in this special population.

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 Global Fund and tuberculosis in Nicaragua: building sustainable capacity?

PubMed

Plamondon, Katrina M; Hanson, Lori; Labonté, Ronald; Abonyi, Sylvia

2008-01-01

The purpose of the study was to explore and provide feedback on local stakeholders' experiences with the Global Fund to Fight AIDS, Tuberculosis and Malaria (GFATM) as it related to capacity building for tuberculosis (TB) services in Nicaragua. An ethnomethodological approach was used to capture the experiences of three different groups: service providers, service recipients, and decision-makers. Data collection involved reviewing secondary texts and records, participant observation, and in-depth interviews and focus groups in both rural and urban municipalities. Stakeholders felt that Nicaragua's Global Fund project improved TB control, built human resource capacity and strengthened community involvement in TB programming; however, they noted several contextual and structural threats to sustainable capacity development. The nature of the GFATM's performance-based evaluation de-emphasized qualitative assessment and, at times, created pressure to meet numeric targets at the risk of decreasing quality. Contextual challenges often determined or limited the potential sustainability of activities. Two examples (training volunteer health workers and establishing TB Clubs) from the broader study are offered here to highlight these challenges from health systems and community perspectives. Current approaches to GFATM evaluation and accountability may compromise its positive impacts on capacity building in Nicaragua. Greater consideration needs to be given to ensuring more comprehensive evaluation of project implementation.

Alteration in the Gut Microbiota Provokes Susceptibility to Tuberculosis.

PubMed

Khan, Nargis; Vidyarthi, Aurobind; Nadeem, Sajid; Negi, Shikha; Nair, Girish; Agrewala, Javed N

2016-01-01

The microbiota that resides in the gastrointestinal tract provides essential health benefits to the host. In particular, they regulate immune homeostasis. Recently, several evidences indicate that alteration in the gut microbial community can cause infectious and non-infectious diseases. Tuberculosis (TB) is the most devastating disease, inflicting mortality and morbidity. It remains unexplored, whether changes in the gut microbiota can provoke or prevent TB. In the current study, we have demonstrated the antibiotics driven changes in the gut microbial composition and their impact on the survival of Mycobacterium tuberculosis ( Mtb ) in the lungs, liver, and spleen of infected mice, compared to those with intact microbiota. Interestingly, dysbiosis of microbes showed significant increase in the bacterial burden in lungs and dissemination of Mtb to spleen and liver. Furthermore, elevation in the number of Tregs and decline in the pool of IFN-γ- and TNF-α-releasing CD4 T cells was noticed. Interestingly, fecal transplantation in the gut microbiota disrupted animals exhibited improved Th1 immunity and lesser Tregs population. Importantly, these animals displayed reduced severity to Mtb infection. This study for the first time demonstrated the novel role of gut microbes in the susceptibility to TB and its prevention by microbial implants. In future, microbial therapies may help in treating patients suffering from TB.

QSAR-driven design, synthesis and discovery of potent chalcone derivatives with antitubercular activity.

PubMed

Gomes, Marcelo N; Braga, Rodolpho C; Grzelak, Edyta M; Neves, Bruno J; Muratov, Eugene; Ma, Rui; Klein, Larry L; Cho, Sanghyun; Oliveira, Guilherme R; Franzblau, Scott G; Andrade, Carolina Horta

2017-09-08

New anti-tuberculosis (anti-TB) drugs are urgently needed to battle drug-resistant Mycobacterium tuberculosis strains and to shorten the current 6-12-month treatment regimen. In this work, we have continued the efforts to develop chalcone-based anti-TB compounds by using an in silico design and QSAR-driven approach. Initially, we developed SAR rules and binary QSAR models using literature data for targeted design of new heteroaryl chalcone compounds with anti-TB activity. Using these models, we prioritized 33 compounds for synthesis and biological evaluation. As a result, 10 heteroaryl chalcone compounds (4, 8, 9, 11, 13, 17-20, and 23) were found to exhibit nanomolar activity against replicating mycobacteria, low micromolar activity against nonreplicating bacteria, and nanomolar and micromolar against rifampin (RMP) and isoniazid (INH) monoresistant strains (rRMP and rINH) (<1 μM and <10 μM, respectively). The series also show low activity against commensal bacteria and generally show good selectivity toward M. tuberculosis, with very low cytotoxicity against Vero cells (SI = 11-545). Our results suggest that our designed heteroaryl chalcone compounds, due to their high potency and selectivity, are promising anti-TB agents. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Alarming Levels of Drug-Resistant Tuberculosis in HIV-Infected Patients in Metropolitan Mumbai, India

PubMed Central

Isaakidis, Petros; Das, Mrinalini; Kumar, Ajay M V; Peskett, Christopher; Khetarpal, Minni; Bamne, Arun; Adsul, Balkrishna; Manglani, Mamta; Sachdeva, Kuldeep Singh; Parmar, Malik; Kanchar, Avinash; Rewari, B.B.; Deshpande, Alaka; Rodrigues, Camilla; Shetty, Anjali; Rebello, Lorraine; Saranchuk, Peter

2014-01-01

Background Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. Methods A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Results Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%–40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. Conclusion The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with ‘presumptive TB’ rather than ‘presumptive DR-TB’ and tailor the treatment regimen based on the resistance patterns. PMID:25333696

Can Intensified Tuberculosis Case Finding Efforts at Nutrition Rehabilitation Centers Lead to Pediatric Case Detection in Bihar, India?

PubMed Central

Mishra, Bal Krishna; Moonan, Patrick K.; Nair, Sreenivas A.; Kumar, Ajay M. V.; Gandhi, Mohit P.; Mannan, Shamim

2016-01-01

Introduction Seven district-level Nutritional Rehabilitation Centres (NRCs) in Bihar, India provide clinical and nutritional care for children with severe acute malnutrition (SAM). Aim To assess whether intensified case finding (ICF) strategies at NRCs can lead to pediatric case detection among SAM children and link them to TB treatment under the Revised National Tuberculosis Control Programme (RNTCP). Materials and Methods A retrospective cohort study was conducted that included medical record reviews of SAM children registered for TB screening and RNTCP care during July–December 2012. Results Among 440 SAM children screened, 39 (8.8%) were diagnosed with TB. Among these, 34 (87%) initiated TB treatment and 18 (53%) were registered with the RNTCP. Of 16 children not registered under the RNTCP, nine (56%) weighed below six kilograms—the current weight requirement for receiving drugs under RNTCP. Conclusion ICF approaches are feasible at NRCs; however, screening for TB entails diagnostic challenges, especially among SAM children. However, only half of the children diagnosed with TB were treated by the RNTCP. More effort is needed to link this vulnerable population to TB services in addition to introducing child-friendly drug formulations for covering children weighing less than six kilograms. PMID:27066518

[Outbreaks of tuberculosis in facilities used by an unspecified number of people near a train station - problems regarding tuberculosis in urban areas ].

PubMed

Kinoshita, Setsuko; Ohmori, Masako; Tsukamoto, Kazuhide; Ohtsuka, Goro; Mashiko, Mari; Fujiu, Michiko; Takahashi, Tsukasa; Hoshino, Hitoshi

2007-10-01

To report on the mass outbreak of tuberculosis (TB) in an urban area and to discuss current issues regarding the problem of TB in the metropolis. Case studies were mainly carried out. Discussions on the route of infection are based on the results of DNA fingerprinting analysis for M. tuberculosis and on information obtained by epidemiological research. In an approximately 500-meter vicinity around Kawasaki Station in Kawasaki City, nine incidences of people contracting TB were reported during the period of one year and five months starting February 2005. Seven of the nine patients were resistant for streptomycin, and the tubercle bacilli of five patients showed identical patterns based on DNA fingerprinting analysis. These nine patients were relatively young, ranging from 16 years to 55 years in age, and three of the patients were homeless. The area for daily activities for all nine patients is a neighborhood of Kawasaki Station. Based on results from an epidemiologic survey, it is suspected that nine patients had come into contact with each other TB patient in places such as "Net cafes" before they developed TB. Based on the epidemiological and bacteriological results, the route of infection related to this series of TB outbreak is considered to be facilities used by an unspecified number of people such as "Net cafes." Such "Net cafes" are open 24 hours a day and are used by an unspecified number of people, who go to such places to Internet or enjoy comic books. Recently, there are many "Net cafes" in the city, and has become to be used as temporary places to sleep, not only by young people but also by socially vulnerable people, such as the homeless. This study suggests that infection can happen easily once someone begins to discharge TB bacilli in such environments, due to young people, who for the most part are not infected with TB bacilli, and high-risk people, who have higher probability of developing the disease, sharing a closed space for a long period of time. Such social environments may also affect the distribution of TB to lean towards urban areas. The TB control program in the metropolis should be planned and carried out giving consideration to social aspects.

Direct Application of the INNO-LiPA Rif.TB Line-Probe Assay for Rapid Identification of Mycobacterium tuberculosis Complex Strains and Detection of Rifampin Resistance in 360 Smear-Positive Respiratory Specimens from an Area of High Incidence of Multidrug-Resistant Tuberculosis

PubMed Central

Viveiros, Miguel; Leandro, Clara; Rodrigues, Liliana; Almeida, Josefina; Bettencourt, Rosário; Couto, Isabel; Carrilho, Lurdes; Diogo, José; Fonseca, Ana; Lito, Luís; Lopes, João; Pacheco, Teresa; Pessanha, Mariana; Quirim, Judite; Sancho, Luísa; Salfinger, Max; Amaral, Leonard

2005-01-01

The INNO-LiPA Rif.TB assay for the identification of Mycobacterium tuberculosis complex strains and the detection of rifampin (RIF) resistance has been evaluated with 360 smear-positive respiratory specimens from an area of high incidence of multidrug-resistant tuberculosis (MDR-TB). The sensitivity when compared to conventional identification/culture methods was 82.2%, and the specificity was 66.7%; the sensitivity and specificity were 100.0% and 96.9%, respectively, for the detection of RIF resistance. This assay has the potential to provide rapid information that is essential for the effective management of MDR-TB. PMID:16145166

Structural basis for catalysis of a tetrameric, class IIa fructose 1,6-bisphosphate aldolase from M. tuberculosis

PubMed Central

Pegan, Scott D.; Rukseree, Kamolchanok; Franzblau, Scott G.; Mesecar, Andrew D.

2009-01-01

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), currently infects one third of the world’s population in its latent form. The emergence of multidrug resistant strains, MDR-TB and XDR-TB has highlighted the need for new pharmacological targets within M. tuberculosis. The Class IIa fructose 1,6-bisphosphate aldolase (FBA) enzyme from M. tuberculosis (MtFBA) has been proposed as one such target since its upregulated in latent TB. Since the structure of MtFBA had not been determined and since there was little information available on its reaction mechanism, we sought to determine the X-ray structure of MtFBA in complex with its substrates. By lowering the pH of the enzyme in the crystalline state, we were able to determine a series of high-resolution X-ray structures of MtFBA bound to dihydroxyacetonephosphate (DHAP), glyceraldehyde-3-phosphate (G3P), and fructose 1,6-bisphosphate (FBP) at 1.5 Å, 2.1 Å, and 1.3 Å respectively. Through these structures it was discovered that MtFBA belongs to a novel tetrameric class of the type IIa FBAs. The molecular details at the interface of the tetramer revealed important information for being able to better predict the quaternary structures among the FBAs based on their primary sequences. These X-ray structures also provide interesting and new details on the reaction mechanism of class II FBAs. Not only were the substrates and products observed in geometries poised for catalysis, but unexpectedly the hydroxyl enolate intermediate of DHAP was also captured and resolved structurally. These concise new details provide a better understanding of the reaction mechanisms for FBAs in general and provide a structural basis for inhibitor design efforts aimed at this class of enzymes. PMID:19167403

Miliary tuberculosis: a severe opportunistic infection in juvenile systemic lupus erythematosus patients.

PubMed

Freire, Priscilla S; Montoni, João D; Ribeiro, Aline S M; Marques, Heloísa H; Mauad, Thais; Silva, Clovis A

2016-01-01

One of the main issues in juvenile systemic lupus erythematosus (JSLE) patients is infection, such as tuberculosis (TB). Of note, SLE patients are susceptible to pulmonary and extrapulmonary TB. However, to our knowledge, this contagious disease was rarely reported in pediatric lupus population, particularly diffuse or miliary TB. Therefore, from January 1983 to December 2011, 5,635 patients were followed-up at our Pediatric Rheumatology Unit and 285 (5%) of them met the American College of Rheumatology classification criteria for SLE. Four (1.4%) of our JSLE patients had disseminated TB and were described herein. All of them were female gender, received BCG vaccination and did not have a history of TB household contact. The median of current age at TB diagnosis and the period between JSLE and TB diagnosis were 17 years old (range 14-20) and 5.5 years (range 2-7), respectively. All patients developed miliary TB during the course of the disease. The median of SLE Disease Activity Index 2000 (SLEDAI-2K) was 4 (2-16) and the patients were treated with immunosuppressive agents (glucocorticoid, azathioprine and/or intravenous cyclophosphamide). Two of them presented sepsis and TB diagnosis was only established at autopsy, especially with lungs, central nervous system and abdominal involvements. Anti-TB therapy (isoniazid, rifampicin and pyrazinamide) was indicated in the other two TB cases, however they deceased. Miliary TB is a rare and severe opportunist infection in pediatric lupus population. This study reinforces the importance of routine searches for TB in JSLE patients. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

High levels of vulnerability and anticipated stigma reduce the impetus for tuberculosis diagnosis in Cape Town, South Africa.

PubMed

Murray, Emma J; Bond, Virginia A; Marais, Ben J; Godfrey-Faussett, Peter; Ayles, Helen M; Beyers, Nulda

2013-07-01

Prolonged diagnostic and treatment delays, particularly in settings experiencing concomitant human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics, undermine global TB control efforts. Current TB control policy in South Africa, as organized through the National TB Control Programme (NTP), relies on the voluntary presentation of TB suspects to local clinics for diagnosis, i.e. passive case finding (PCF). In 2005 a participatory study suggested that popular interpretation and perception of TB within eight South African township sites in and around Cape Town, all carrying a high burden of HIV and undiagnosed TB, undermine PCF. Both people's association of TB with dirt and squalor, and the anticipation of HIV-related stigma, combine to impede TB diagnosis. Respondents conveyed TB as unavoidable; this perception is expressed in the context of vulnerability where so much-including dirt-is largely beyond the control of local residents. The lack of control has a disempowering effect, reducing the drive for seeking treatment. In addition, low confidence in patient confidentiality and anticipated HIV-related stigma act as direct deterrents to TB diagnosis and treatment. In conclusion, we wish to draw attention to high levels of disease stigma and vulnerability, and how these undermine PCF. Public health interventions that wish to improve case detection should aim to: (1) emphasize how early treatment improves outcome and can curb ongoing transmission; (2) combat a sense of communal vulnerability to TB; (3) address anticipated HIV-TB stigma; and (4) improve the quality of care provided at local diagnostic services, addressing low levels of patient confidentiality.

Multidrug-resistant tuberculosis in Lisbon, Portugal: a molecular epidemiological perspective.

PubMed

Perdigão, João; Macedo, Rita; João, Inês; Fernandes, Elisabete; Brum, Laura; Portugal, Isabel

2008-06-01

Portugal has the fourth highest tuberculosis (TB) incidence rate in the European Union (EU). Thirty-nine percent of all cases originate in Lisbon Health Region. Portugal also presents high levels of multidrug-resistant tuberculosis (MDR-TB) (1.5%, primary rate and 2.4%, in retreatment cases). In the present study we have characterized 58 MDR-TB clinical isolates by: (i) determining the resistance profile to first- and second-line drugs used in the treatment of tuberculosis; (ii) genotyping all isolates by MIRU-VNTR; (iii) analyzing mutations conferring resistance to isoniazid, rifampicin, streptomycin, and ethambutol, in katG, mabA-inhA, rpoB, rpsL, rrs, and pncA genes. We have therefore established the prevalence of the most common mutations associated with drug resistance in the Lisbon Health Region: C-15T in mabA-inhA for isoniazid; S531L in rpoB for rifampicin; K43R in rpsL for streptomycin; and V125G in pncA for pyrazinamide. By genotyping all isolates and combining with the mutational results, we were able to assess the isolates' genetic relatedness and determine possible transmission events. Strains belonging to family Lisboa, characterized several years ago, are still responsible for the majority of the MDR-TB. Even more alarming is the high prevalence of extensive drug-resistant tuberculosis (XDR-TB) among the MDR-TB isolates, which was found to be 53%. The TB status in Portugal therefore requires urgent attention to contain the strains continuously responsible for MDR-TB and now, XDR-TB.

Diagnostic work-up and loss of tuberculosis suspects in Jogjakarta, Indonesia

PubMed Central

2012-01-01

Background Early and accurate diagnosis of pulmonary tuberculosis (TB) is critical for successful TB control. To assist in the diagnosis of smear-negative pulmonary TB, the World Health Organisation (WHO) recommends the use of a diagnostic algorithm. Our study evaluated the implementation of the national tuberculosis programme's diagnostic algorithm in routine health care settings in Jogjakarta, Indonesia. The diagnostic algorithm is based on the WHO TB diagnostic algorithm, which had already been implemented in the health facilities. Methods We prospectively documented the diagnostic work-up of all new tuberculosis suspects until a diagnosis was reached. We used clinical audit forms to record each step chronologically. Data on the patient's gender, age, symptoms, examinations (types, dates, and results), and final diagnosis were collected. Results Information was recorded for 754 TB suspects; 43.5% of whom were lost during the diagnostic work-up in health centres, 0% in lung clinics. Among the TB suspects who completed diagnostic work-ups, 51.1% and 100.0% were diagnosed without following the national TB diagnostic algorithm in health centres and lung clinics, respectively. However, the work-up in the health centres and lung clinics generally conformed to international standards for tuberculosis care (ISTC). Diagnostic delays were significantly longer in health centres compared to lung clinics. Conclusions The high rate of patients lost in health centres needs to be addressed through the implementation of TB suspect tracing and better programme supervision. The national TB algorithm needs to be revised and differentiated according to the level of care. PMID:22333111

Plan to combat extensively drug-resistant tuberculosis: recommendations of the Federal Tuberculosis Task Force.

PubMed

2009-02-13

An estimated one third of the world's population is infected with Mycobacterium tuberculosis, and nearly 9 million persons develop disease caused by M. tuberculosis each year. Although tuberculosis (TB) occurs predominantly in resource-limited countries, it also occurs in the United States. During 1985-1992, the United States was confronted with an unprecedented TB resurgence. This resurgence was accompanied by a rise in multidrug-resistant TB (MDR TB), which is defined as TB that is resistant to the two most effective first-line therapeutic drugs, isoniazid and rifampin. In addition, virtually untreatable strains of M. tuberculosis are emerging globally. Extensively drug-resistant (XDR) TB is defined as MDR TB that also is resistant to the most effective second-line therapeutic drugs used commonly to treat MDR TB: fluoroquinolones and at least one of three injectable second-line drugs used to treat TB (amikacin, kanamycin, or capreomycin). XDR TB has been identified in all regions of the world, including the United States. In the United States, the cost of hospitalization for one XDR TB patient is estimated to average $483,000, approximately twice the cost for MDR TB patients. Because of the limited responsiveness of XDR TB to available antibiotics, mortality rates among patients with XDR TB are similar to those of TB patients in the preantibiotic era. In January 1992, CDC convened a Federal TB Task Force to draft an action plan to improve prevention and control of drug-resistant TB in the United States (CDC. National action plan to combat multidrug-resistant tuberculosis. MMWR 1992;41([No. RR-11]). In November 2006, CDC reconvened the Task Force to draft an updated action plan to address the issue of MDR TB and XDR TB. Task Force members were divided into nine response areas and charged with articulating the most pressing problems, identifying barriers to improvement, and recommending specific action steps to improve prevention and control of XDR TB within their respective areas. Although the first priority of the Federal TB Task Force convened in 2006 was to delineate objectives and action steps to address MDR TB and XDR TB domestically, members recognized the necessity for TB experts in the United States to work with the international community to help strengthen TB control efforts globally. TB represents a substantial public health problem in low- and middle-income countries, many of which might benefit from assistance by the United States. In addition, the global TB epidemic directly affects the United States because the majority of all cases of TB and 80% of cases of MDR TB reported in the United States occur among foreign-born persons. For these reasons, the Action Plan also outlines potential steps that U.S. government agencies can take to help solve global XDR TB problems. Unless the fundamental causes of MDR TB and XDR TB are addressed in the United States and internationally, the United States is likely to experience a growing number of cases of MDR TB and XDR TB that will be difficult, if not impossible, to treat or prevent. The recommendations provided in this report include specific action steps and new activities that will require additional funding and a renewed commitment by government and nongovernment organizations involved in domestic and international TB control efforts to be implemented effectively. The Federal TB Task Force will coordinate activities of various federal agencies and partner with state and local health departments, nonprofit and TB advocacy organizations in implementing this plan to control and prevent XDR TB in the United States and to contribute to global efforts in the fight against this emerging public health crisis.

Tuberculosis among the homeless, United States, 1994-2010.

PubMed

Bamrah, S; Yelk Woodruff, R S; Powell, K; Ghosh, S; Kammerer, J S; Haddad, M B

2013-11-01

1) To describe homeless persons diagnosed with tuberculosis (TB) during the period 1994-2010, and 2) to estimate a TB incidence rate among homeless persons in the United States. TB cases reported to the National Tuberculosis Surveillance System were analyzed by origin of birth. Incidence rates were calculated using the US Department of Housing and Urban Development homeless population estimates. Analysis of genotyping results identified clustering as a marker for transmission among homeless TB patients. Of 270,948 reported TB cases, 16,527 (6%) were homeless. The TB incidence rate among homeless persons ranged from 36 to 47 cases per 100,000 population in 2006-2010. Homeless TB patients had over twice the odds of not completing treatment and of belonging to a genotype cluster. US- and foreign-born homeless TB patients had respectively 8 and 12 times the odds of substance abuse. Compared to the general population, homeless persons had an approximately 10-fold increase in TB incidence, were less likely to complete treatment and more likely to abuse substances. Public health outreach should target homeless populations to reduce the excess burden of TB in this population.

LOWER LEVELS OF INTERLEUKIN-12 PRECEDE THE DEVELOPMENT OF TUBERCULOSIS AMONG HIV-INFECTED WOMEN

PubMed Central

Bordón, José; Plankey, Michael W.; Young, Mary; Greenblatt, Ruth M.; Villacres, Maria C.; French, Audrey L.; Zhang, Jie; Brock, Guy; Appana, Savitri; Herold, Betsy; Durkin, Helen; Golub, Jonathan E.; Fernandez-Botran, Rafael

2012-01-01

Tuberculosis (TB) is the worldwide leading cause of death among HIV-infected individuals, accounting for more than half of AIDS-related deaths. A high risk of tuberculosis (TB) has been shown in early stages of the HIV disease, even in the presence of normal CD4+ cell counts. Moreover, the factors that determine protective immunity vs. susceptibility to M. tuberculosis cannot be fully explained by simple changes in IFNγ levels or a shift from Th1 to Th2 cytokines. This work investigated the relationship between cytokine expression profiles in peripheral blood mononuclear cells (PBMC) and susceptibility to M. tuberculosis in ten HIV+ women who went on to develop TB. RNA transcripts for IL-4, IL-4δ2, IL-10, IL-12(p35), IL-13, IL-17A, IFNγ and TNFα were measured by real-time quantitative PCR in unstimulated or TB peptide antigen-stimulated PBMCs from ten HIV+ women with positive tuberculin skin tests (TST) and compared with HIV-seropositive and seronegative women without previous TB and negative TST. Stimulated PBMC cultures showed significantly lower expression of IL-12p35 (p=0.004) and IL-10 (p=0.026) in the HIV+TB+ group six to twelve months before onset of TB compared to HIV+TB− women. Unstimulated PBMC from HIV+TB+ women also had lower expression of Th2 cytokines [IL-4 (p=0.056) and IL-13 (p=0.050)] compared to HIV+TB− women. These results suggest that lower IL-12 production by PBMC in response to TB antigens and lower levels of both Th1 and Th2 cytokines by PBMC correlate with future development of TB in HIV-infected women and may be responsible for their increased susceptibility. PMID:21880503

Is systematic screening and treatment for latent tuberculosis infection in HIV patients useful in a low endemic setting?

PubMed

Maniewski, Ula; Payen, Marie-Christine; Delforge, Marc; De Wit, Stephane

2017-08-01

A decreasing incidence of tuberculosis (TB) among HIV patients has been documented in high-income settings and screening for tuberculosis is not systematically performed in many clinics (such as ours). Our objectives are to evaluate whether a same decline of incidence was seen in our Belgian tertiary center and to evaluate whether systematic screening and prophylaxis of tuberculosis should remain part of routine practice. Between 2005 and 2012, the annual incidence of tuberculosis among adult HIV patients was measured. The impact of demographic characteristics and CD 4 nadir on the incidence of active TB was evaluated. Among the 1167 patients who entered the cohort, 42 developed active TB with a significant decrease of annual incidence from 28/1000 patient-years in 2005 to 3/1000 patient-years in 2012. Among the 42 cases, 83% were of sub-Saharan origin. Median CD4 cell count upon HIV diagnosis was significantly lower in TB cases and 60% had a nadir CD4 below 200/μl. Thirty-six percent of incident TB occurred within 14 days after HIV diagnosis. A significant decline of TB incidence in HIV patients was observed. Incident TB occurred mainly in African patients, with low CD4 upon HIV diagnosis. A significant proportion of TB cases were discovered early in follow-up which probably reflects TB already present upon HIV diagnosis. In a low endemic setting, exclusion of active TB upon HIV diagnosis remains a priority and screening for LTBI should focus on HIV patients from high risk groups such as migrants from endemic regions, especially in patients with low CD4 nadir.

Evaluation of two line probe assays for rapid detection of Mycobacterium tuberculosis, tuberculosis (TB) drug resistance, and non-TB Mycobacteria in HIV-infected individuals with suspected TB.

PubMed

Luetkemeyer, Anne F; Kendall, Michelle A; Wu, Xingye; Lourenço, Maria Cristina; Jentsch, Ute; Swindells, Susan; Qasba, Sarojini S; Sanchez, Jorge; Havlir, Diane V; Grinsztejn, Beatriz; Sanne, Ian M; Firnhaber, Cynthia

2014-04-01

Limited performance data from line probe assays (LPAs), nucleic acid tests used for the rapid diagnosis of tuberculosis (TB), nontuberculosis mycobacteria (NTM), and Mycobacterium tuberculosis drug resistance are available for HIV-infected individuals, in whom paucibacillary TB is common. In this study, the strategy of testing sputum with GenoType MTBDRplus (MTBDR-Plus) and GenoType Direct LPA (Direct LPA) was compared to a gold standard of one mycobacterial growth indicator tube (MGIT) liquid culture. HIV-positive (HIV(+)) individuals with suspected TB from southern Africa and South America with <7 days of TB treatment had 1 sputum specimen tested with Direct LPA, MTBDR-Plus LPA, smear microscopy, MGIT, biochemical identification of mycobacterial species, and culture-based drug-susceptibility testing (DST). Of 639 participants, 59.3% were MGIT M. tuberculosis culture positive, of which 276 (72.8%) were acid-fast bacillus (AFB) smear positive. MTBDR-Plus had a sensitivity of 81.0% and a specificity of 100%, with sensitivities of 44.1% in AFB smear-negative versus 94.6% in AFB smear-positive specimens. For specimens that were positive for M. tuberculosis by MTBDR-Plus, the sensitivity and specificity for rifampin resistance were 91.7% and 96.6%, respectively, and for isoniazid (INH) they were 70.6% and 99.1%. The Direct LPA had a sensitivity of 88.4% and a specificity of 94.6% for M. tuberculosis detection, with a sensitivity of 72.5% in smear-negative specimens. Ten of 639 MGIT cultures grew Mycobacterium avium complex or Mycobacterium kansasii, half of which were detected by Direct LPA. Both LPA assays performed well in specimens from HIV-infected individuals, including in AFB smear-negative specimens, with 72.5% sensitivity for M. tuberculosis identification with the Direct LPA and 44.1% sensitivity with MTBDR-Plus. LPAs have a continued role for use in settings where rapid identification of INH resistance and clinically relevant NTM are priorities.

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

PubMed

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

2016-01-01

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

Nontuberculous Mycobacteria (NTM)

MedlinePlus

... human disease. NTM is an infectious disease like tuberculosis (TB), but it does not cause TB. There ... founded more than 100 years ago as a tuberculosis hospital. Since that time, we have grown to ...

Assessing the quality of tuberculosis evaluation for children with prolonged cough presenting to routine community health care settings in rural Uganda.

PubMed

Marquez, Carina; Davis, J Lucian; Katamba, Achilles; Haguma, Priscilla; Ochom, Emmanuel; Ayakaka, Irene; Chamie, Gabriel; Dorsey, Grant; Kamya, Moses R; Charlebois, Edwin; Havlir, Diane V; Cattamanchi, Adithya

2014-01-01

Improving childhood tuberculosis (TB) evaluation and care is a global priority, but data on performance at community health centers in TB endemic regions are sparse. To describe the current practices and quality of TB evaluation for children with cough ≥2 weeks' duration presenting to community health centers in Uganda. Cross-sectional analysis of children (<15 years) receiving care at five Level IV community health centers in rural Uganda for any reason between 2009-2012. Quality of TB care was assessed using indicators derived from the International Standards of Tuberculosis Care (ISTC). From 2009-2012, 1713 of 187,601 (0.9%, 95% CI: 0.4-1.4%) children presenting to community health centers had cough ≥ 2 weeks' duration. Of those children, only 299 (17.5%, 95% CI: 15.7-19.3%) were referred for sputum microscopy, but 251 (84%, 95% CI: 79.8-88.1%) completed sputum examination if referred. The yield of sputum microscopy was only 3.6% (95% CI: 1.3-5.9%), and only 55.6% (95% CI: 21.2-86.3%) of children with acid-fast bacilli positive sputum were started on treatment. Children under age 5 were less likely to be referred for sputum examination and to receive care in accordance with ISTC. The proportion of children evaluated in accordance with ISTC increased over time (4.6% in 2009 to 27.9% in 2012, p = 0.03), though this did not result in increased case-detection. The quality of TB evaluation was poor for children with cough ≥2 weeks' duration presenting for health care. Referrals for sputum smear microscopy and linkage to TB treatment were key gaps in the TB evaluation process, especially for children under the age of five.

Output-driven feedback system control platform optimizes combinatorial therapy of tuberculosis using a macrophage cell culture model.

PubMed

Silva, Aleidy; Lee, Bai-Yu; Clemens, Daniel L; Kee, Theodore; Ding, Xianting; Ho, Chih-Ming; Horwitz, Marcus A

2016-04-12

Tuberculosis (TB) remains a major global public health problem, and improved treatments are needed to shorten duration of therapy, decrease disease burden, improve compliance, and combat emergence of drug resistance. Ideally, the most effective regimen would be identified by a systematic and comprehensive combinatorial search of large numbers of TB drugs. However, optimization of regimens by standard methods is challenging, especially as the number of drugs increases, because of the extremely large number of drug-dose combinations requiring testing. Herein, we used an optimization platform, feedback system control (FSC) methodology, to identify improved drug-dose combinations for TB treatment using a fluorescence-based human macrophage cell culture model of TB, in which macrophages are infected with isopropyl β-D-1-thiogalactopyranoside (IPTG)-inducible green fluorescent protein (GFP)-expressing Mycobacterium tuberculosis (Mtb). On the basis of only a single screening test and three iterations, we identified highly efficacious three- and four-drug combinations. To verify the efficacy of these combinations, we further evaluated them using a methodologically independent assay for intramacrophage killing of Mtb; the optimized combinations showed greater efficacy than the current standard TB drug regimen. Surprisingly, all top three- and four-drug optimized regimens included the third-line drug clofazimine, and none included the first-line drugs isoniazid and rifampin, which had insignificant or antagonistic impacts on efficacy. Because top regimens also did not include a fluoroquinolone or aminoglycoside, they are potentially of use for treating many cases of multidrug- and extensively drug-resistant TB. Our study shows the power of an FSC platform to identify promising previously unidentified drug-dose combinations for treatment of TB.

Acquaintance to Artificial Neural Networks and use of artificial intelligence as a diagnostic tool for tuberculosis: A review.

PubMed

Dande, Payal; Samant, Purva

2018-01-01

Tuberculosis [TB] has afflicted numerous nations in the world. As per a report by the World Health Organization [WHO], an estimated 1.4 million TB deaths in 2015 and an additional 0.4 million deaths resulting from TB disease among people living with HIV, were observed. Most of the TB deaths can be prevented if it is detected at an early stage. The existing processes of diagnosis like blood tests or sputum tests are not only tedious but also take a long time for analysis and cannot differentiate between different drug resistant stages of TB. The need to find newer prompt methods for disease detection has been aided by the latest Artificial Intelligence [AI] tools. Artificial Neural Network [ANN] is one of the important tools that is being used widely in diagnosis and evaluation of medical conditions. This review aims at providing brief introduction to various AI tools that are used in TB detection and gives a detailed description about the utilization of ANN as an efficient diagnostic technique. The paper also provides a critical assessment of ANN and the existing techniques for their diagnosis of TB. Researchers and Practitioners in the field are looking forward to use ANN and other upcoming AI tools such as Fuzzy-logic, genetic algorithms and artificial intelligence simulation as a promising current and future technology tools towards tackling the global menace of Tuberculosis. Latest advancements in the diagnostic field include the combined use of ANN with various other AI tools like the Fuzzy-logic, which has led to an increase in the efficacy and specificity of the diagnostic techniques. Copyright © 2017 Elsevier Ltd. All rights reserved.

First national survey of anti-tuberculosis drug resistance in Azerbaijan and risk factors analysis

PubMed Central

Akhundova, I.; Seyfaddinova, M.; Mammadbayov, E.; Mirtskulava, V.; Rüsch-Gerdes, S.; Bayramov, R.; Suleymanova, J.; Kremer, K.; Dadu, A.; Acosta, C. D.; Harries, A. D.; Dara, M.

2014-01-01

Setting: Civilian population of the Republic of Azerbaijan. Objectives: To determine patterns of anti-tuberculosis drug resistance among new and previously treated pulmonary tuberculosis (TB) cases, and explore their association with socio-demographic and clinical characteristics. Design: National cross-sectional survey conducted in 2012–2013. Results: Of 789 patients (549 new and 240 previously treated) who met the enrolment criteria, 231 (42%) new and 146 (61%) previously treated patients were resistant to any anti-tuberculosis drug; 72 (13%) new and 66 (28%) previously treated patients had multidrug-resistant TB (MDR-TB). Among MDR-TB cases, 38% of new and 46% of previously treated cases had pre-extensively drug-resistant TB (pre-XDR-TB) or XDR-TB. In previously treated cases, 51% of those who had failed treatment had MDR-TB, which was 15 times higher than in relapse cases (OR 15.2, 95%CI 6–39). The only characteristic significantly associated with MDR-TB was a history of previous treatment (OR 3.1, 95%CI 2.1–4.7); for this group, history of incarceration was an additional risk factor for MDR-TB (OR 2.8, 95%CI 1.1–7.4). Conclusion: Azerbaijan remains a high MDR-TB burden country. There is a need to implement countrywide control and innovative measures to accelerate early diagnosis of drug resistance in individual patients, improve treatment adherence and strengthen routine surveillance of drug resistance. PMID:26393092

Characterisation of Mycobacterium tuberculosis isolates lacking IS6110 in Viet Nam.

PubMed

Huyen, M N T; Tiemersma, E W; Kremer, K; de Haas, P; Lan, N T N; Buu, T N; Sola, C; Cobelens, F G J; van Soolingen, D

2013-11-01

The molecular diagnosis of tuberculosis (TB) in Viet Nam is often based on the detection of insertion sequence (IS) 6110 in Mycobacterium tuberculosis. However, 8-11% of M. tuberculosis strains in South-East Asia do not contain this target and this undermines the validity of these molecular tests. We quantified the frequency of M. tuberculosis strains lacking IS6110 in rural Viet Nam and studied their epidemiological and clinical characteristics. Consecutively diagnosed adult TB patients in rural Southern Viet Nam submitted two sputum samples for culture, IS6110 restriction fragment length polymorphism (RFLP) spoligotyping and 15-loci variable number tandem repeat typing. Polymerase chain reaction (PCR) was performed to confirm the absence of IS6110 elements in strains lacking IS6110 hybridisation in RFLP. Among 2664 TB patient isolates examined, 109 (4.1%) had no IS6110 element. Compared to other strains, these no-copy strains were less often resistant to anti-tuberculosis drugs, particularly to streptomycin (adjusted OR 0.2, 95%CI 0.1-0.5), and showed significant geographic variation. No associations with TB history or demographic factors were found. Strains without the IS6110 target pose a problem in Viet Nam as regards false-negative molecular TB diagnosis in PCR. Compared to other strains circulating in Viet Nam, no-copy strains are more susceptible to anti-tuberculosis drugs.

Tuberculosis in the elderly: Why inflammation matters.

PubMed

Piergallini, Tucker J; Turner, Joanne

2018-05-01

Growing old is associated with an increase in the basal inflammatory state of an individual and susceptibility to many diseases, including infectious diseases. Evidence is growing to support the concept that inflammation and disease susceptibility in the elderly is linked. Our studies focus on the infectious disease tuberculosis (TB), which is caused by Mycobacterium tuberculosis (M.tb), a pathogen that infects approximately one fourth of the world's population. Aging is a major risk factor for developing TB, and inflammation has been strongly implicated. In this review we will discuss the relationship between inflammation in the lung and susceptibility to develop and succumb to TB in old age. Further understanding of the relationship between inflammation, age, and M.tb will lead to informed decisions about TB prevention and treatment strategies that are uniquely designed for the elderly. Copyright © 2017 Elsevier Inc. All rights reserved.

TB Anywhere Is TB Everywhere: The Intersection of U.S. Immigration Enforcement Policy and TB

DTIC Science & Technology

2016-09-01

born population.40 One region of special concern in the United States is the area along the border with Mexico . Tuberculosis rates in the border ...Controlling Tuberculosis along the US- Mexico Border ,” Morbidity and Mortality Weekly Report 50, no. RR1 (2001): 1–2, http://www.cdc.gov/mmwr/ preview/mmwrhtml...Ramirez, “Health Departments Fight Tuberculosis on both Sides of the U.S. Border with Mexico : Mexican Immigrants Often Contract the Disease before

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

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

PubMed Central

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

2015-01-01

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

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

PubMed Central

Kozakiewicz, Lee; Phuah, Jiayao; Flynn, JoAnne

2014-01-01

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

Prevalence of Pulmonary Tuberculosis among Prison Inmates in Ethiopia, a Cross-Sectional Study

PubMed Central

Ali, Solomon; Haileamlak, Abraham; Wieser, Andreas; Pritsch, Michael; Heinrich, Norbert; Loscher, Thomas; Hoelscher, Michael; Rachow, Andrea

2015-01-01

Setting Tuberculosis (TB) is one of the major health problems in prisons. Objective This study was done to assess the prevalence and determinants of active tuberculosis in Ethiopian prisons. Design A cross-sectional study was conducted from January 2013 to December 2013 in 13 zonal prisons. All incarcerated inmates underwent TB symptom screening according to WHO criteria. From identified TB-suspects two sputum samples were analyzed using smear microscopy and solid culture. A standardized questionnaire assessing TB risk factors was completed for each TB suspect. Results 765 (4.9%) TB suspects were identified among 15,495 inmates. 51 suspects were already on anti-TB treatment (6.67%) and 20 (2.8%) new culture-confirmed TB cases were identified in the study, resulting in an overall TB prevalence of 458.1/100,000 (95%CI: 350-560/100,000). Risk factors for active TB were alcohol consumption, contact with a TB case before incarceration and no window in prison cell. HIV prevalence was not different between TB suspects and active TB cases. Further, the TB burden in prisons increased with advancing distance from the capital Addis Ababa. Conclusions The overall TB prevalence in Ethiopian prisons was high and extremely variable among different prisons. TB risk factors related to conditions of prison facilities and the impact of implemented TB control measures need to be further studied in order to improve TB control among inmates. PMID:26641654

Recent technological advancements in tuberculosis diagnostics - A review.

PubMed

Gupta, Shagun; Kakkar, Vipan

2018-09-15

Early diagnosis and on-time effective treatment are indispensable for Tuberculosis (TB) control - a life threatening infectious communicable disease. The conventional techniques for diagnosing TB normally take two to three weeks. This delay in diagnosis and further increase in detection complexity due to the emerging risks of XDR-TB (Extensively drug Resistant-TB) and MDR-TB (Multidrug Resistant-TB) are evoking interest of researchers in the field of developing rapid TB detection techniques such as biosensing and other point-of-care (POC) techniques. Biosensing technologies along with the collaboration with nanotechnology have enormous potential to boost the MTB detection and for overall management in clinical diagnosis. A diverse range of portable, sensitive and rapid biosensors based on different signal transducer principles and with different biomarkers detection capabilities have been developed for TB detection in the early stages. Further, a lot of progress has been achieved over the years in developing various point-of-care diagnostic tools including non-molecular methods and molecular techniques. The objective of this study is to present a succinct review of the available TB detection techniques that are either in use or under development. The focus of this review is on the current developments occurred in nano-biosensing technologies. A synopsis of ameliorations in different non-molecular diagnostic tools and progress in the field of molecular techniques along with the role of emerging Lab-on-Chip technology for diagnosing and mitigating the TB consequences have also been presented. Copyright © 2018 Elsevier B.V. All rights reserved.

The prevalence and factors associated for anti-tuberculosis treatment non-adherence among pulmonary tuberculosis patients in public health care facilities in South Ethiopia: a cross-sectional study.

PubMed

Woimo, Tadele Teshome; Yimer, Wondwossen Kassahun; Bati, Temesgen; Gesesew, Hailay Abrha

2017-03-20

Evidence exists pointing out how non-adherence to treatment remains a major hurdle to efficient tuberculosis control in developing countries. Many tuberculosis (Tb) patients do not complete their six-month course of anti-tuberculosis medications and are not aware of the importance of sputum re-examinations, thereby putting themselves at risk of developing multidrug-resistant and extensively drug-resistant forms of tuberculosis and relapse. However, there is a dearth of publications about non-adherence towards anti-Tb medication in these settings. We assessed the prevalence of and associated factors for anti-Tb treatment non-adherence in public health care facilities of South Ethiopia. This was a cross-sectional survey using both quantitative and qualitative methods. The quantitative study was conducted among 261 Tb patients from 17 health centers and one general hospital. The qualitative aspect included an in-depth interview of 14 key informants. For quantitative data, the analysis of descriptive statistics, bivariate and multiple logistic regression was carried out, while thematic framework analysis was applied for the qualitative data. The prevalence of non-adherence towards anti-Tb treatment was 24.5%. Multiple logistic regression analysis demonstrated that poor knowledge towards tuberculosis and its treatment (AOR = 4.6, 95%CI: 1.4-15.6), cost of medication other than Tb (AOR = 4.7, 95%CI: 1.7-13.4), having of health information at every visit (AOR = 3, 95% CI: 1.1-8.4) and distance of DOTS center from individual home (AOR = 5.7, 95%CI: 1.9-16.8) showed statistically significant association with non-adherence towards anti- tuberculosis treatment. Qualitative study also revealed that distance, lack of awareness about importance of treatment completion and cost of transportation were the major barriers for adherence. A quarter of Tb patients interrupted their treatment due to knowledge, availability and accessibility of DOTS service. We recommend creating awareness about anti-Tb treatment, and decentralization of drug pick-ups to the lowest level of health institutions.

Improving quality of tuberculosis care in India.

PubMed

Pai, Madhukar; Satyanarayana, Srinath; Hopewell, Phil

2014-01-01

In India, the quality of care that tuberculosis (TB) patients receive varies considerably and is often not in accordance with the national and international standards. In this article, we provide an overview of the third (latest) edition of the International Standards of Tuberculosis Care (ISTC). These standards are supported by the existing World Health Organization guidelines and policy statements pertaining to TB care and have been endorsed by a number of international organizations. We call upon all health care providers in the country to practice TB care that is consistent with these standards, as well as the upcoming Standards for TB Care in India (STCI).

Survey of rheumatologists on the use of the Philippine Guidelines on the Screening for Tuberculosis prior to use of Biologic Agents.

PubMed

Aquino-Villamin, Melissa; Tankeh-Torres, Sandra; Lichauco, Juan Javier

2016-11-01

The use of biologic agents has become an important option in treating patients with rheumatoid arthritis. However, these drugs have been associated with an increased risk of tuberculosis (TB) reactivation. Local guidelines for TB screening prior to the use of biologic agents were developed to address this issue. This study is a survey describing the compliance of Filipino rheumatologists to these guidelines. Eighty-seven rheumatologists in the Philippines were given the questionnaire and responses from 61 rheumatologists were included in the analysis. All respondents agree that patients should be screened prior to giving the biologic agents. Local guidelines recommend screening with tuberculin skin test (TST) and chest radiograph. However, cut-off values considered for a positive TST and timing of initiation of biologic agents after starting TB prophylaxis and treatment varied among respondents. In addition, screening of close household contacts were only performed by 41 (69.5%) respondents. There were 11 respondents who reported 16 patients developing TB during or after receiving biologic agents, despite adherence to the guidelines. This survey describes the compliance rate of Filipino rheumatologists in applying current local recommendations for TB screening prior to initiating biologic agents. The incidence of new TB cases despite the current guidelines emphasizes the importance of compliance and the need to revise the guidelines based on updated existing literature. © 2015 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Evaluation of a Tuberculosis Skin Testing Program

ERIC Educational Resources Information Center

Kahn, Pamela

2009-01-01

There has been a recent slowdown in the decline of rates of tuberculosis (TB) in the United States. However, there are disparities in TB diagnosis between U.S.-born and foreign-born persons and between Whites and minorities. Measures for achieving TB elimination include identification of high-risk persons, including children and adolescents, at…

Multidrug-resistant tuberculosis, Somalia, 2010-2011.

PubMed

Sindani, Ireneaus; Fitzpatrick, Christopher; Falzon, Dennis; Suleiman, Bashir; Arube, Peter; Adam, Ismail; Baghdadi, Samiha; Bassili, Amal; Zignol, Matteo

2013-03-01

In a nationwide survey in 2011, multidrug-resistant tuberculosis (MDR TB) was found in 5.2% and 40.8% of patients with new and previously treated TB, respectively. These levels of drug resistance are among the highest ever documented in Africa and the Middle East. This finding presents a serious challenge for TB control in Somalia.

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

PubMed

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

2007-02-01

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

Community empowerment program for increasing knowledge and awareness of tuberculosis patients, cadres and community in Medan city

NASA Astrophysics Data System (ADS)

Harahap, J.; Amelia, R.; Wahyuni, A. S.; Andayani, L. S.

2018-03-01

Tuberculosis is one of a major health problem in Indonesia. WHO expressed the need for the participation of various stakeholders in addition to government. TB CEPAT Program aimed to increase knowledge and awareness in combating tuberculosis. This study aimed to compare the knowledge and awareness of community, cadres and TB patients in the program areas and non-program areas, and assess the role of the program in combating tuberculosis in Medan. The study used quantitative and qualitative methods, where 300 people (community, cadres, TB patients) as respondents and three key persons as informants. The findings revealed that in the program areas the knowledge, attitude and practice of the respondents generally are better compare to those in the non-program areas. There was a significant difference in knowledge and practice for community, cadres, and TB patients (p<0.05) and there was a significant difference in attitude for community, cadres (p<0.05), but no significant difference for TB patients (p>0.05) in program areas and non-program areas. The community empowerment through TB CEPAT Program plays an important role in improving knowledge, attitude, and practice of community, cadres, and TB patients. It would help the effort of TB control and prevention in Medan City.

Challenges to the global control of tuberculosis.

PubMed

Chiang, Chen-Yuan; Van Weezenbeek, Catharina; Mori, Toru; Enarson, Donald A

2013-05-01

Diagnosis and treatment of tuberculosis (TB) will likely navigate a historical turning point in the 2010s with a new management paradigm emerging. However, global control of TB remains a formidable challenge for the decades to come. The estimated case detection rate of TB globally was 66%, and there were 310 000 estimated multidrug-resistant TB (MDR-TB) cases among the 6.2 million TB patients notified in 2011. Although new tools are being introduced for the diagnosis of MDR-TB, there are operational and cost issues related to their use that require urgent attention, so that the poor and vulnerable can benefit. World Health Organization (WHO) estimated that globally, 3.7% of new cases and 20% of previously treated cases have MDR-TB. However, the scale-up of programmatic management of drug-resistant TB is slow, with only 60 000 MDR-TB cases notified to WHO in 2011. The overall proportion of treatment success of MDR-TB notified globally in 2009 was 48%, far below the global target of 75% success rate. Although new tools and drugs have the potential to significantly improve both case detection and treatment outcome, adequate health systems and human resources are needed for rapid uptake and proper implementation to have the impact required to eliminate TB. Hence, the global TB community should broaden its scope, seek intersectoral collaboration and advocate for cost reduction of new tools, while ensuring that the basics of TB control are implemented to reduce the TB burden through the current 'prevention through case management' paradigm. Respirology © 2013 Asian Pacific Society of Respirology. The World Health Organization retains copyright and all other rights in the manuscript as submitted for publication and has granted the Publisher permission for the reproduction of this article.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries.

PubMed

Getahun, Haileyesus; Matteelli, Alberto; Abubakar, Ibrahim; Aziz, Mohamed Abdel; Baddeley, Annabel; Barreira, Draurio; Den Boon, Saskia; Borroto Gutierrez, Susana Marta; Bruchfeld, Judith; Burhan, Erlina; Cavalcante, Solange; Cedillos, Rolando; Chaisson, Richard; Chee, Cynthia Bin-Eng; Chesire, Lucy; Corbett, Elizabeth; Dara, Masoud; Denholm, Justin; de Vries, Gerard; Falzon, Dennis; Ford, Nathan; Gale-Rowe, Margaret; Gilpin, Chris; Girardi, Enrico; Go, Un-Yeong; Govindasamy, Darshini; D Grant, Alison; Grzemska, Malgorzata; Harris, Ross; Horsburgh, C Robert; Ismayilov, Asker; Jaramillo, Ernesto; Kik, Sandra; Kranzer, Katharina; Lienhardt, Christian; LoBue, Philip; Lönnroth, Knut; Marks, Guy; Menzies, Dick; Migliori, Giovanni Battista; Mosca, Davide; Mukadi, Ya Diul; Mwinga, Alwyn; Nelson, Lisa; Nishikiori, Nobuyuki; Oordt-Speets, Anouk; Rangaka, Molebogeng Xheedha; Reis, Andreas; Rotz, Lisa; Sandgren, Andreas; Sañé Schepisi, Monica; Schünemann, Holger J; Sharma, Surender Kumar; Sotgiu, Giovanni; Stagg, Helen R; Sterling, Timothy R; Tayeb, Tamara; Uplekar, Mukund; van der Werf, Marieke J; Vandevelde, Wim; van Kessel, Femke; van't Hoog, Anna; Varma, Jay K; Vezhnina, Natalia; Voniatis, Constantia; Vonk Noordegraaf-Schouten, Marije; Weil, Diana; Weyer, Karin; Wilkinson, Robert John; Yoshiyama, Takashi; Zellweger, Jean Pierre; Raviglione, Mario

2015-12-01

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone. Copyright ©ERS 2015.

Spoligotyping of Mycobacterium tuberculosis isolates at a tertiary care hospital in India.

PubMed

Suzana, Shirly; Shanmugam, Sivakumar; Uma Devi, K R; Swarna Latha, P N; Michael, Joy S

2017-06-01

Spoligotyping is a valuable genotyping tool to study the genetic diversity and molecular epidemiology of Mycobacterium tuberculosis (M. tb). The aim of this study was to analyse different spoligotype patterns of M. tb strains isolated from patients with tuberculosis from different parts of India. A total of 163 M. tb isolates were spoligotyped between January 2014 and January 2015. About 47% (n = 77) were from patients with extrapulmonary tuberculosis; of these, 10 were MDR, and seven were Pre-XDR. Of the 86 M. tb isolates from patients with pulmonary tuberculosis, 25 were MDR, and 25 were Pre-XDR. We found 61 spoligo patterns, 128 clusters in the spoligotype data base (spoldb4 data base) with spoligo international type (SIT) number and 35 true unique isolates. The most pre-dominant spoligotype was EAI lineage (56), followed by Beijing (28), CAS (20), T(9), U(7), X(3), H(3), BOVIS_1 BCG(1) and LAM(1). Although our study identified EAI, CAS and Beijing strain lineages as pre-dominant, we also found a large number of orphan strains (20%) in our study. Beijing strains were more significantly associated with MDR TB than CAS and EAI lineages. Further studies on large sample sizes would help to clearly describe the epidemiology of M. tb in India. © 2017 John Wiley & Sons Ltd.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

PubMed Central

Matteelli, Alberto; Abubakar, Ibrahim; Aziz, Mohamed Abdel; Baddeley, Annabel; Barreira, Draurio; Den Boon, Saskia; Borroto Gutierrez, Susana Marta; Bruchfeld, Judith; Burhan, Erlina; Cavalcante, Solange; Cedillos, Rolando; Chaisson, Richard; Chee, Cynthia Bin-Eng; Chesire, Lucy; Corbett, Elizabeth; Dara, Masoud; Denholm, Justin; de Vries, Gerard; Falzon, Dennis; Ford, Nathan; Gale-Rowe, Margaret; Gilpin, Chris; Girardi, Enrico; Go, Un-Yeong; Govindasamy, Darshini; D. Grant, Alison; Grzemska, Malgorzata; Harris, Ross; Horsburgh Jr, C. Robert; Ismayilov, Asker; Jaramillo, Ernesto; Kik, Sandra; Kranzer, Katharina; Lienhardt, Christian; LoBue, Philip; Lönnroth, Knut; Marks, Guy; Menzies, Dick; Migliori, Giovanni Battista; Mosca, Davide; Mukadi, Ya Diul; Mwinga, Alwyn; Nelson, Lisa; Nishikiori, Nobuyuki; Oordt-Speets, Anouk; Rangaka, Molebogeng Xheedha; Reis, Andreas; Rotz, Lisa; Sandgren, Andreas; Sañé Schepisi, Monica; Schünemann, Holger J.; Sharma, Surender Kumar; Sotgiu, Giovanni; Stagg, Helen R.; Sterling, Timothy R.; Tayeb, Tamara; Uplekar, Mukund; van der Werf, Marieke J.; Vandevelde, Wim; van Kessel, Femke; van't Hoog, Anna; Varma, Jay K.; Vezhnina, Natalia; Voniatis, Constantia; Vonk Noordegraaf-Schouten, Marije; Weil, Diana; Weyer, Karin; Wilkinson, Robert John; Yoshiyama, Takashi; Zellweger, Jean Pierre; Raviglione, Mario

2015-01-01

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone. PMID:26405286

Structural measurements and cell line studies of the copper-PEG-Rifampicin complex against Mycobacterium tuberculosis.

PubMed

Manning, Thomas; Mikula, Rachel; Wylie, Greg; Phillips, Dennis; Jarvis, Jackie; Zhang, Fengli

2015-02-01

The bacterium responsible for tuberculosis is increasing its resistance to antibiotics resulting in new multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). In this study, several analytical techniques including NMR, FT-ICR, MALDI-MS, LC-MS and UV/Vis are used to study the copper-Rifampicin-Polyethylene glycol (PEG-3350) complex. The copper (II) cation is a carrier for the antibiotic Rifampicin as well as nutrients for the bacterium. The NIH-NIAID cell line containing several Tb strains (including antibiotic resistant strains) is tested against seven copper-PEG-RIF complex variations. Copyright © 2014 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 informed the first South African HIV and TB Investment Cases and successfully leveraged additional resources from the National Treasury at a time of austerity. In Ghana, a long-term TIME model-centred interaction with the NTP provided new insights into the local epidemiology and guided resource allocation decisions to improve impact.

Performance of tests for latent tuberculosis in different groups of immunocompromised patients.

PubMed

Richeldi, Luca; Losi, Monica; D'Amico, Roberto; Luppi, Mario; Ferrari, Angela; Mussini, Cristina; Codeluppi, Mauro; Cocchi, Stefania; Prati, Francesca; Paci, Valentina; Meacci, Marisa; Meccugni, Barbara; Rumpianesi, Fabio; Roversi, Pietro; Cerri, Stefania; Luppi, Fabrizio; Ferrara, Giovanni; Latorre, Irene; Gerunda, Giorgio E; Torelli, Giuseppe; Esposito, Roberto; Fabbri, Leonardo M

2009-07-01

Immunocompromised persons infected with Mycobacterium tuberculosis (MTB) have increased risk of tuberculosis (TB) reactivation, but their management is hampered by the occurrence of false-negative results of the tuberculin skin test (TST). The T-cell interferon (IFN)-gamma release blood assays T-SPOT.TB (TS.TB) [Oxford Immunotec; Abingdon, UK] and QuantiFERON-TB Gold In-Tube (QFT-IT) [Cellestis Ltd; Carnegie, VIC, Australia] might improve diagnostic accuracy for latent TB infection (LTBI) in high-risk persons, although their performance in different groups of immunocompromised patients is largely unknown. Over a 1-year period, we prospectively enrolled patients in three different immunosuppressed groups, as follows: 120 liver transplantation candidates (LTCs); 116 chronically HIV-infected persons; and 95 patients with hematologic malignancies (HMs). TST, TS.TB, and QFT-IT were simultaneously performed, their results were compared, and intertest agreement was evaluated. Overall, TST provided fewer positive results (10.9%) than TS.TB (18.4%; p < 0.001) and QFT-IT (15.1%; p = 0.033). Significantly fewer HIV-infected individuals had at least one positive test (9.5%) compared with LTCs (35.8%; p < 0.001) and patients with HMs (29.5%; p < 0.001). Diagnostic agreement between tests was moderate (kappa = 0.40 to 0.65) and decreased in the HIV-infected group when the results of the TS.TB were compared with either TST (kappa = 0.16) or QFT-IT (kappa = 0.19). Indeterminate blood test results due to low positive control values were significantly more frequent with QFT-IT (7.2%) than with TS.TB (0.6%; p < 0.001). Blood tests identified significantly more patients as being infected with MTB than TST, although diagnostic agreement varied across groups. Based on these results, we recommend tailoring application of the new blood IFN-gamma assays for LTBI in different high-risk groups and advise caution in their current use in immunosuppressed patients.

Framework for Establishment of a Comprehensive and Standardized Administration System for Prevention and Control of Tuberculosis in College Student Community in China.

PubMed

Zhang, Shaoru; Li, Xiaohong; Zhang, Tianhua; Wang, Xiangni; Liu, Weiping; Ma, Xuexue; Li, Yuelu; Fan, Yahui

2016-10-01

College student community is the one with high risk of tuberculosis (TB). A systemic and standardized administration model for prevention and control of TB is significance in controlling TB spread in universities. Currently, the universities in China have not established the comprehensive and standardized administration system for TB prevention and control in college student community. Firstly, the literature research and brainstorming method (n=13) were used to construct the clause and sub-clause pool for the administration of TB prevention and control within college student community in 2014. Secondly, a total of twenty experts in the field of TB prevention and control who are representatives of the east, west, south and north parts of China were selected and invited to participate the Delphi letter-inquiry. After two rounds of letter-inquiry, the opinions of the experts reached a consensus and the framework for the administration system was constructed. A framework for the administration system was constructed, which included 8 first class indexes, 26 second class indexes and 104 third class indexes. The results are highly scientific and reliable, which can be helpful for improving the systemic and standardized levels for the administration of TB prevention and control in universities in China and perhaps in other developing counties with high TB burden as well.

Factors associated with tuberculosis cases in Semarang District, Indonesia: case-control study performed in the area where case detection rate was extremely low.

PubMed

Rahayu, Sri Ratna; Katsuyama, Hironobu; Demura, Masashi; Katsuyama, Midori; Ota, Yoko; Tanii, Hideji; Higashi, Tomomi; Semadi, Ngakan Putu Djaja; Saijoh, Kiyofumi

2015-07-01

Indonesia is ranked as the 4th highest contributor to tuberculosis (TB) in the world. Semarang District in Central Java displays extremely low case detection rate (CDR), possibly contributing to the local prevalence of TB. A case-control study was performed to explore the factors that cause such low CDR. We recruited 129 TB cases and 83 controls that visited the same centers and were not diagnosed with TB. The cases had 7.5 ± 2.3 symptoms/person on average, indicating the delay in diagnosis because the controls only displayed 1.0 ± 1.7. The multiple logistic regression analysis comparing the cases/controls extracted following factors as a risk to have TB: farmer, close contact with TB patients, ignorance of whether Bacillus Calmette-Guérin (BCG) was accepted or no, smoking, low income, a lot of people living in the same room, irregular hand wash before meals, not wash hands after blow, soil floor, and no sunlight and no ventilation in the house. Neither the cases nor the controls knew the symptoms and how to avoid TB infection, which probably caused the delay in diagnosis. It is difficult to change the current living conditions. Thus, the amendment of the community-based education program of TB seems to be required.

Framework for Establishment of a Comprehensive and Standardized Administration System for Prevention and Control of Tuberculosis in College Student Community in China

PubMed Central

ZHANG, Shaoru; LI, Xiaohong; ZHANG, Tianhua; WANG, Xiangni; LIU, Weiping; MA, Xuexue; LI, Yuelu; FAN, Yahui

2016-01-01

Background: College student community is the one with high risk of tuberculosis (TB). A systemic and standardized administration model for prevention and control of TB is significance in controlling TB spread in universities. Currently, the universities in China have not established the comprehensive and standardized administration system for TB prevention and control in college student community. Methods: Firstly, the literature research and brainstorming method (n=13) were used to construct the clause and sub-clause pool for the administration of TB prevention and control within college student community in 2014. Secondly, a total of twenty experts in the field of TB prevention and control who are representatives of the east, west, south and north parts of China were selected and invited to participate the Delphi letter-inquiry. After two rounds of letter-inquiry, the opinions of the experts reached a consensus and the framework for the administration system was constructed. Results: A framework for the administration system was constructed, which included 8 first class indexes, 26 second class indexes and 104 third class indexes. Conclusion: The results are highly scientific and reliable, which can be helpful for improving the systemic and standardized levels for the administration of TB prevention and control in universities in China and perhaps in other developing counties with high TB burden as well. PMID:27957436

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

[Management of multidrug-resistant tuberculosis].

PubMed

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

2015-01-01

The emergence of drug-resistant TB in many countries has become a major public health problem and an obstacle to effective tuberculosis control. Multidrug-resistant tuberculosis (MDR-TB), which is most often the result of poor adherence, is a particularly dangerous form of tuberculosis because it is caused by bacilli resistant to at least isoniazid and rifampicin, the two most effective anti-tuberculosis drugs. Techniques for rapid diagnosis of resistance have greatly improved the care of patients by allowing early treatment which remains complex and costly establishment, and requires skills and resources. The treatment is not standardized but it includes in all cases attack phase with five drugs (there must be an injectable agent and a fluoroquinolone that form the basis of the regimen) for eight months and a maintenance phase (without injectable agent) with a total duration of 20 months on average. Surgery may be beneficial as long as the lesions are localized and the patient has a good cardiorespiratory function. Evolution of MDR-TB treated is less favorable than tuberculosis with germ sensitive. The cure rate varies from 60 to 75% for MDR-TB, and drops to 30 to 40% for XDR-TB. Mortality remains high, ranging from 20 to 40% even up to 70-90% in people co-infected with HIV. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Humoral immune profiling of mycobacterial antigen recognition in sarcoidosis and Löfgren's syndrome using high-content peptide microarrays.

PubMed

Ferrara, Giovanni; Valentini, Davide; Rao, Martin; Wahlström, Jan; Grunewald, Johan; Larsson, Lars-Olof; Brighenti, Susanna; Dodoo, Ernest; Zumla, Alimuddin; Maeurer, Markus

2017-03-01

Sarcoidosis is considered an idiopathic granulomatous disease, although similar immunological and clinical features with tuberculosis (TB) suggest mycobacterial involvement in its pathogenesis. High-content peptide microarrays (HCPM) may help to decipher mycobacteria-specific antibody reactivity in sarcoidosis. Serum samples from patients with sarcoidosis, Löfgren's syndrome, and TB, as well as from healthy individuals (12/group), were tested on HCPM containing 5964 individual peptides spanning 154 Mycobacterium tuberculosis proteins displayed as 15-amino acid stretches. Inclusion/exclusion and significance analyses were performed according to published methods. Each study group recognized 68-78% M. tuberculosis peptides at least once. M. tuberculosis epitope recognition by sarcoidosis patient sera was 42.7%, and by TB patient sera was 39.1%. Seven and 16 peptides were recognized in 9/12 (75%) and 8/12 (67%) sarcoidosis patient sera but not in TB patient sera, respectively. Nine (75%) and eight (67%) out of twelve TB patient sera, respectively recognized M. tuberculosis peptides that were not recognized in sarcoidosis patient sera. Specific IgG recognition patterns for M. tuberculosis antigens in sarcoidosis patients re-affirm mycobacterial involvement in sarcoidosis, providing biologically relevant targets for future studies pertaining to diagnostics and immunotherapy. Copyright © 2017. Published by Elsevier Ltd.

Immunology of bovine tuberculosis: Perspectives on one health approaches and defining correlates of protection versus infection

USDA-ARS?s Scientific Manuscript database

Tuberculosis (TB), primarily due to Mycobacterium tuberculosis in humans and Mycobacterium bovis in cattle, is an exemplary model of the One Health Concept. The human TB vaccine, M. bovis bacille Calmette-Guerin (BCG), was first proven effective in cattle prior to use in humans. Recent experimental ...

Treatment compliance and challenges among tuberculosis patients across selected health facilities in Osun State Nigeria.

PubMed

Ajao, K O; Ogundun, O A; Afolabi, O T; Ojo, T O; Atiba, B P; Oguntunase, D O

2014-12-01

Tuberculosis (TB) is a major public health problem in the world and Africa has approximately one quarter of the world's cases. One of the greatest challenges facing most TB programmes is the non-compliance to TB treatment among TB patients. This study aimed at determining the challenges of management of tuberculosis (TB) across selected Osun State health facilities. The study employed a descriptive cross-sectional design. A semi-structured questionnaire was used to collect data from 102 TB patients in the health facilities. The instrument measured socio-demographic variables, patient related factors, socio-economic variables, health care system related factors to TB disease and treatment. Data were analysed and summarized using descriptive and inferential statistics. Statistical significance was placed at p < 0.05. TB patients who had no formal education (χ2 = 12.941, p < 0.05), who were smoking during treatment (χ2 = 13.194, p < 0.001), who consumed alcohol during TB treatment (χ2 = 6.371, p < 0.05) and those who were HIV positive (χ2 = 23.039, p < 0.001) significantly failed to comply with TB treatment. TB patients who waited for one hour or more at heath facilities (χ2 = 21.761, p < 0.001), who reported that TB treatment should be stopped before six month (χ2 = 9.804, p < 0.05) or when patient felt better (χ2 = 35.185, p < 0.001) and travelled for 10 km or more (χ2 = 13.610, p < 0.001) significantly failed to comply with TB treatment. This study concluded that non-compliance rate to tuberculosis treatment among TB patients in this study is high. Both health facility and patient-related factors were largely responsible.

Performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.

PubMed

Manga, Selene; Perales, Rocio; Reaño, Maria; D'Ambrosio, Lia; Migliori, Giovanni Battista; Amicosante, Massimo

2016-11-01

Tuberculosis (TB) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. Serological tests have the potentially to impact TB diagnosis, in particular in extreme clinical settings. The diagnostic performances of the TB-XT HEMA EXPRESS (HEMA-EXPRESS) immunochromatographic rapid test for active TB diagnosis, based on use of multiple Mycobacterium tuberculosis (MTB) specific antigens, have been evaluated in a large study multicentre TB case-finding study, in populations with different exposure level to TB. A total of 1,386 subjects were enrolled in the six participating centres in Peru: 290 active-TB and 1,096 unaffected subjects. The TB prevalence (overall 20.5%) varied between 4.0% and 41.1% in the different study groups. Overall, the HEMA-EXPRESS test had 30.6% sensitivity (range 3.9-77.9%) and 84.6% specificity (range 51.6-97.3%). A significant inverse correlation between test accuracy (overall 73.5%, range 40.4-96.4%) and TB prevalence in the various study populations was observed (Pearson's r=-0.7985; P=0.05). HEMA-EXPRESS, is rapid and relatively inexpensive test suitable for routine use in TB diagnosis. In low TB prevalence conditions, test performance appears in line with WHO Target Product Profile for TB diagnostics. Performances appear suboptimal in high TB prevalence settings. Appropriate set-up in operative clinical settings has to be considered for novel serological tests for TB diagnosis, particularly for formats suitable for point-of-care use.

Tuberculosis Treatment Outcome and Drug Resistance in Lambaréné, Gabon: A Prospective Cohort Study

PubMed Central

Bélard, Sabine; Remppis, Jonathan; Bootsma, Sanne; Janssen, Saskia; Kombila, Davy U.; Beyeme, Justin O.; Rossatanga, Elie G.; Kokou, Cosme; Osbak, Kara K.; Obiang Mba, Régis M.; Kaba, Harry M.; Traoré, Afsatou N.; Ehrhardt, Jonas; Bache, Emmanuel B.; Flamen, Arnaud; Rüsch-Gerdes, Sabine; Frank, Matthias; Adegnika, Ayôla A.; Lell, Bertrand; Niemann, Stefan; Kremsner, Peter G.; Loembé, Marguerite M.; Alabi, Abraham S.; Grobusch, Martin P.

2016-01-01

Despite overall global progress in tuberculosis (TB) control, TB remains one of the deadliest communicable diseases. This study prospectively assessed TB epidemiology in Lambaréné, Gabon, a Central African country ranking 10th in terms of TB incidence rate in the 2014 World Health Organization TB report. In Lambaréné, between 2012 and 2014, 201 adult and pediatric TB patients were enrolled and followed up; 66% had bacteriologically confirmed TB and 95% had pulmonary TB. The human immunodeficiency virus (HIV) coinfection rate was 42% in adults and 16% in children. Mycobacterium tuberculosis and Mycobacterium africanum were identified in 82% and 16% of 108 culture-confirmed TB cases, respectively. Isoniazid (INH) and streptomycin yielded the highest resistance rates (13% and 12%, respectively). The multidrug resistant TB (MDR-TB) rate was 4/91 (4%) and 4/13 (31%) in new and retreatment TB cases, respectively. Treatment success was achieved in 53% of patients. In TB/HIV coinfected patients, mortality rate was 25%. In this setting, TB epidemiology is characterized by a high rate of TB/HIV coinfection and low treatment success rates. MDR-TB is a major public health concern; the need to step-up in-country diagnostic capacity for culture and drug susceptibility testing as well as access to second-line TB drugs urgently requires action. PMID:27352879

Research on tuberculosis in tribal areas in India: A systematic review.

PubMed

Rao, V G; Muniyandi, M; Bhat, J; Yadav, R; Sharma, R

2018-01-01

Tuberculosis (TB) remains a major public health problem in resource-poor countries including India. Scientific knowledge is used to guide policy and practice. There is however, a limited, systematically collected data required for guiding the scale-up of interventions particularly amongst vulnerable populations including tribal groups in the country. In view of this, a systematic review of the TB research studies carried out in tribal areas of different parts of the country was undertaken. To undertake a systematic review of the TB research studies carried out in tribal areas of India between 1996 and 2016. A systematic review of English articles published between 1996 and 2016 on any aspect of TB was done through internet searches using Literature search EndNote programme. The words used for searching were tuberculosis, India, tribal, indigenous, disadvantaged, adivasi. The most common topics classified as annual risk of tuberculosis infection (ARTI), prevalence of TB, laboratory studies, clinical symptoms of TB, risk factors for TB, knowledge attitude practice, community Directly Observed Treatment (DOT) providers, performance of Revised National Tuberculosis Control Programme (RNTCP), and drug resistant TB. Classification was also done on the basis of the type of tribe studied and place of study conducted. A total of 47 studies identified through the search were included in the review. Of the 47 studies reviewed, 12 were on TB prevalence, 7 were laboratory studies, four on ARTI and 5 on performance of RNTCP in tribal areas. Among these, majority (23 studies) of the tribal studies did not mention the type of tribe. Ten studies were conducted among Saharia, a particularly vulnerable tribal group in the Indian state of Madhya Pradesh mainly by the National Institute for Research on Tribal Health, five were among the mixed tribes and very few on other tribes. The systematic review indicates that the research studies on TB among tribal population are very few. There is a need to invest and encourage researcher to work on the research plans for the control of TB in tribal areas. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Exogenous reinfection of tuberculosis in a low-burden area.

PubMed

Schiroli, Consuelo; Carugati, Manuela; Zanini, Fabio; Bandera, Alessandra; Di Nardo Stuppino, Silvia; Monge, Elisa; Morosi, Manuela; Gori, Andrea; Matteelli, Alberto; Codecasa, Luigi; Franzetti, Fabio

2015-12-01

Recurrence of tuberculosis (TB) can be the consequence of relapse or exogenous reinfection. The study aimed to assess the factors associated with exogenous TB reinfection. Prospective cohort study based on the TB database, maintained at the Division of Infectious Diseases, Luigi Sacco Hospital (Milan, Italy). Time period: 1995-2010. (1) ≥2 episodes of culture-confirmed TB; (2) cure of the first episode of TB; (3) availability of one Mycobacterium tuberculosis isolate for each episode. Genotyping of the M. tuberculosis strains to differentiate relapse and exogenous reinfection. Logistic regression analysis was used to assess the influence of risk factors on exogenous reinfections. Of the 4682 patients with TB, 83 were included. Of these, exogenous reinfection was diagnosed in 19 (23 %). It was independently associated with absence of multidrug resistance at the first episode [0, 10 (0.01-0.95), p = 0.045] and with prolonged interval between the first TB episode and its recurrence [7.38 (1.92-28.32) p = 0.004]. However, TB relapses occurred until 4 years after the first episode. The risk associated with being foreign born, extrapulmonary site of TB, and HIV infection was not statistically significant. In the relapse and re-infection cohort, one-third of the patients showed a worsened drug resistance profile during the recurrent TB episode. Exogenous TB reinfections have been documented in low endemic areas, such as Italy. A causal association with HIV infection could not be confirmed. Relapses and exogenous reinfections shared an augmented risk of multidrug resistance development, frequently requiring the use of second-line anti-TB regimens.

Direct Detection by the Xpert MTB/RIF Assay and Characterization of Multi and Poly Drug-Resistant Tuberculosis in Guinea-Bissau, West Africa

PubMed Central

Ponce, Gema; Sanca, Lilica; Mané, Morto; Armada, Ana; Machado, Diana; Vieira, Fina; Gomes, Victor F.; Martins, Elisabete; Colombatti, Raffaella; Riccardi, Fabio; Perdigão, João; Sotero, Joana; Portugal, Isabel; Couto, Isabel; Atouguia, Jorge; Rodrigues, Amabélia; Viveiros, Miguel

2015-01-01

Background This study aimed to evaluate the usefulness of the Xpert MTB/RIF assay for the rapid direct detection of M. tuberculosis complex (MTBC) strains and rifampicin resistance associated mutations in a resource-limited setting such as Guinea-Bissau and its implications in the management of tuberculosis (TB) and drug resistant tuberculosis, complementing the scarce information on resistance and genotypic diversity of MTBC strains in this West African country. Methods and Results This cross-sectional prospective study included 100 consecutive TB patients with positive acid-fast smears at two months of anti-tuberculosis treatment or in a re-treatment situation, between May and December 2012. Resistance to rifampicin was detected using the GeneXpert system and the Xpert MTB/RIF assay. MTBC isolates obtained with the BACTEC MGIT 960 system were tested for susceptibility to first- and second-line anti-tuberculosis drugs. Overall, the prevalence of multidrug-resistant tuberculosis (MDR-TB) was found to be 9 cases. Of these, 67% (6 patients) of confirmed MDR-TB cases had no past history of TB treatment and 33% (3 patients) were previously treated cases. Extensively drug-resistant TB was not found. Molecular typing of the MDR-TB strains revealed recent transmission patterns of imported MDR strains. Conclusions The Xpert MTB/RIF assay was reliable for the detection of rifampicin resistant MTBC strains directly from sputum samples of patients undergoing first-line treatment for two months, being more trustworthy than the simple presence of acid-fast bacilli in the smear. Its implementation is technically simple, does not require specialized laboratory infrastructures and is suitable for resource-limited settings when a regular source of electricity and maintenance is available as well as financial and operation sustainability is guaranteed by the health authorities. A high prevalence of MDR-TB among patients at risk of MDR-TB after two months of first-line treatment was found, in support of the WHO recommendations for its use in the management of this risk group. PMID:26017968

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

Dietary Intake of Antioxidant Vitamins and Carotenoids and Risk of Developing Active Tuberculosis in a Prospective Population-Based Cohort Study.

PubMed

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

2017-08-15

Antioxidants may protect against oxidative stress, which is associated with tuberculosis (TB) disease. However, direct evidence for a protective association between dietary antioxidants and TB incidence in humans has been lacking. The relationship between intake of antioxidant vitamins (vitamins A, C, D, and E) and individual carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and lutein) and TB incidence was examined in the Singapore Chinese Health Study, a prospective cohort study of 63,257 adults aged 45-74 years enrolled during 1993-1998. Baseline intake of these antioxidants was estimated using a validated semiquantitative food frequency questionnaire including questions on use of dietary supplements. After an average of 16.9 years of follow-up, 1,186 incident active TB cases were identified among cohort participants. Compared with the lowest quartile, reduced risk of active TB was observed for the highest quartile of vitamin A intake (hazard ratio = 0.71, 95% confidence interval: 0.59, 0.85; P-trend < 0.01) and β-carotene intake (hazard ratio = 0.76, 95% confidence interval: 0.63, 0.91; P-trend < 0.01), regardless of smoking status. Lower TB risk was seen for vitamin C intake among current smokers only. Other vitamins and carotenoids were not associated with TB risk. These results suggest that vitamin C may reduce TB risk among current smokers by ameliorating oxidative stress, while vitamin A and β-carotene may have additional antimycobacterial properties. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Under-reporting of tuberculosis in Praia, Cape Verde, from 2006 to 2012.

PubMed

Furtado da Luz, E; Braga, J U

2018-03-01

According to World Health Organization (WHO) estimates, the under-reporting rate for tuberculosis (TB) in Cape Verde between 2006 and 2012 was 49%. However, the WHO recognises the challenges associated with this estimation process and recommends implementing other methods, such as record linkage, to combat TB under-reporting. To estimate and analyse under-reporting of cases by TB surveillance health units and to evaluate TB cases retrieved from other TB diagnostic sources in Praia, Cape Verde, from 2006 to 2012. This cross-sectional study evaluated under-reporting using the following data: 1) the under-reporting index from TB reporting health units (RHUs), where the number of validated TB cases from RHUs was compared with data from the National Programme for the Fight against Tuberculosis and Leprosy (NPFTL); and 2) the under-reporting index among overall data sources, or a comparison of the number of all validated TB cases from all sources with NPFTL data. The TB under-reporting rate was 40% in Praia during the study period, and results were influenced by laboratory findings. The TB under-reporting rate was very similar to the rate estimated by the WHO. TB surveillance must be improved to reduce under-reporting.

Tuberculosis: Is the landscape changing?

PubMed

Khatua, Sutapa; Geltemeyer, Abby M; Gourishankar, Anand

2017-01-01

Robert Heinrich Herman Koch, a German physician and microbiologist, received Nobel Prize in 1905 for identifying the specific causative agent of tuberculosis (TB). During his time it was believed that TB was an inherited disease. However he was convinced that the disease was caused by a bacterium and was infectious, tested his postulates using guinea pigs, and found the causative agent to be slow growing mycobacterium tuberculosis. TB is the second most common cause of death from infectious diseases after HIV/AIDS. Drug-resistant TB poses serious challenge to effective management of TB worldwide. Multidrug-resistant TB accounted for about half a million new cases and over 200,000 deaths in 2013. Whole-genome sequencing (first done in 1998) technologies have provided new insight into the mechanism of drug resistance. For the first time in 50 y, new anti TB drugs have been developed. The World Health Organization (WHO) has recently revised their treatment guidelines based on 32 studies. In United States, latent TB affects between 10 and 15 million people, 10% of whom may develop active TB disease. QuantiFERON TB Gold and T-SPOT.TB test are used for diagnosis. Further research will look into the importance of newly discovered gene mutations in causing drug resistance.

Learning from epidemiological, clinical, and immunological studies on Mycobacterium africanum for improving current understanding of host-pathogen interactions, and for the development and evaluation of diagnostics, host-directed therapies, and vaccines for tuberculosis.

PubMed

Zumla, Alimuddin; Otchere, Isaac Darko; Mensah, Gloria Ivy; Asante-Poku, Adwoa; Gehre, Florian; Maeurer, Markus; Bates, Matthew; Mwaba, Peter; Ntoumi, Francine; Yeboah-Manu, Dorothy

2017-03-01

Mycobacterium africanum comprises two phylogenetic lineages within the Mycobacterium tuberculosis complex (MTBC). M. africanum was first described and isolated in 1968 from the sputum of a Senegalese patient with pulmonary tuberculosis (TB) and it has been identified increasingly as an important cause of human TB, particularly prevalent in West Africa. The restricted geographical distribution of M. africanum, in contrast to the widespread global distribution of other species of MTBC, requires explanation. Available data indicate that M. africanum may also have important differences in transmission, pathogenesis, and host-pathogen interactions, which could affect the evaluation of new TB intervention tools (diagnostics and vaccines)-those currently in use and those under development. The unequal geographical distribution and spread of MTBC species means that individual research findings from one country or region cannot be generalized across the continent. Thus, generalizing data from previous and ongoing research studies on MTBC may be inaccurate and inappropriate. A major rethink is required regarding the design and structure of future clinical trials of new interventions. The West, Central, East, and Southern African EDCTP Networks of Excellence provide opportunities to take forward these pan-Africa studies. More investments into molecular, epidemiological, clinical, diagnostic, and immunological studies across the African continent are required to enable further understanding of host-M. africanum interactions, leading to the development of more specific diagnostics, biomarkers, host-directed therapies, and vaccines for TB. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Rapid detection of Mycobacterium tuberculosis complex in sputum Samples using PURE TB-LAMP assay.

PubMed

N'guessan, K; Horo, K; Coulibaly, I; Adegbele, J; Kouame-Adjei, N; Seck-Angu, H; Guei, A; Kouakou, J; Dosso, M

2016-12-01

Lack of rapid and accurate diagnostic testing is a critical obstacle to global tuberculosis (TB) control. Sensitivity of sputum smear microscopy (SSM) is not optimal; however, it remains the most prevalent tool for TB confirmation in poor countries. As a part of passive case finding of TB detection, this study was conducted to determine the clinical performance of PURE TB-LAMP assay using liquid culture medium as the gold standard. Centre Antituberculeux de Yopougon is one of the 17 intermediate Tuberculosis centers in Côte d'Ivoire. A standardized questionnaire was submitted to patients with signs and symptoms consistent with tuberculosis by a trained caregiver. After obtaining signed consent forms, sputum samples were collected according to National TB Control Programme guidelines (spot-morning). SSM after Ziehl-Neelsen staining and TB-LAMP assay were blindly performed on the first sample. Samples transported to Institut Pasteur de Côte d'Ivoire were decontaminated according to the N-acetyl-L-Cystein method. In Mycobacteria Growth Indicator Tube (MGIT), 500mL of pellets were inoculated and incubated in the MGIT 960 system. MPT64 antigen was detected in positive cultures. Of the 500 patients enrolled, 469 (232men and 239 women) patients were included. The mean ages of men and women were 36.9 (15-86) and 37.3 (15-37.3) years, respectively. There were 56 (12.2%) HIV-infected patients, including 14 women. Clinical isolates of M. tuberculosis complex were detected for 157 (33.5%) patients. Compared with culturing, the overall sensitivity and specificity of SSM were 86% (95% confidence interval [CI]=81-91) and 96% (95% CI=94-98), respectively. The overall sensitivity and specificity for TB-LAMP was 92% (95% CI=0.88-0.96) and 94% (95% CI=0.91-0.97), respectively. Positive likelihood ratios for TB-LAMP and SSM were 15.3 and 21.5, respectively, and negative likelihood ratios for TB-LAMP and SSM were 0.09 and 0.15, respectively. Among the 469 patients, active tuberculosis was detected using TB-LAMP assay and SSM in 162 (34.5%) and 147 (31.3%) patients, respectively. For accurate diagnostic of pulmonary TB, TB-LAMP could be used as a tool of the first intention. Copyright © 2016.

High Rates of Mycobacterium tuberculosis among Socially Marginalized Immigrants in Low-Incidence Area, 1991–2010, Italy

PubMed Central

Mercadante, Silvio; Pareek, Manish; Lalvani, Ajit; Bugiani, Massimiliano

2013-01-01

Migration from low- and middle-income countries to high-income countries increasingly determines the severity of tuberculosis (TB) cases in the adopted country. Socially marginalized groups, about whom little is known, may account for a reservoir of TB among the immigrant populations. We investigated the rates of and risk factors for Mycobacterium tuberculosis transmission, infection, and disease in a cohort of 27,358 socially marginalized immigrants who were systematically screened (1991–2010) in an area of Italy with low TB incidence. Overall TB and latent TB infection prevalence and annual tuberculin skin testing conversion rates (i.e., incidence of new infection) were 2.7%, 34.6%, and 1.7%, respectively. Prevalence of both TB and latent TB infection and incidence of infection increased as a function of the estimated TB incidence in the immigrants’ countries of origin. Annual infection incidence decreased with time elapsed since immigration. These findings have implications for control policy and immigrant screening in countries with a low prevalence of TB. PMID:23965807

Mobility patterns of persons at risk for drug-resistant tuberculosis in Mumbai, India.

PubMed

Conners, E; Garfein, R S; Rodwell, T C; Udwadia, Z F; Catanzaro, D G

2016-12-01

Tuberculosis (TB) hospital in Mumbai, India. To describe the mobility patterns of persons with suspected drug-resistant tuberculosis (DR-TB) and to assess whether there were significant differences in demographic or risk characteristics based on mobility. Observational cohort study of TB clinic patients at risk for DR-TB. Among 602 participants, 37% had ever moved from their place of birth; 14% were local movers (within state), and 23% were distant movers, between states or countries. Univariate multinomial logistic regression models showed that distant movers were more likely than non-movers to have lower income, less education, a greater number of previous TB episodes, and to have ever smoked. Compared to non-movers, local movers were more likely to have lower income and were more likely to have seen a doctor in the past 2 years. Clinical outcomes, including DR-TB, diabetes, and human immunodeficiency virus (HIV), did not differ between the three mobility groups. Mobility was common among patients at risk for DR-TB in Mumbai. TB programs should consider the implications of mobility on the protracted treatment for DR-TB in India.

Emerging technologies for monitoring drug-resistant tuberculosis at the point-of-care.

PubMed

Mani, Vigneshwaran; Wang, ShuQi; Inci, Fatih; De Libero, Gennaro; Singhal, Amit; Demirci, Utkan

2014-11-30

Infectious diseases are the leading cause of death worldwide. Among them, tuberculosis (TB) remains a major threat to public health, exacerbated by the emergence of multiple drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (Mtb). MDR-Mtb strains are resistant to first-line anti-TB drugs such as isoniazid and rifampicin; whereas XDR-Mtb strains are resistant to additional drugs including at least to any fluoroquinolone and one of the second-line anti-TB injectable drugs such as kanamycin, capreomycin, or amikacin. Clinically, these strains have significantly impacted the management of TB in high-incidence developing countries, where systemic surveillance of TB drug resistance is lacking. For effective management of TB on-site, early detection of drug resistance is critical to initiate treatment, to reduce mortality, and to thwart drug-resistant TB transmission. In this review, we discuss the diagnostic challenges to detect drug-resistant TB at the point-of-care (POC). Moreover, we present the latest advances in nano/microscale technologies that can potentially detect TB drug resistance to improve on-site patient care. Copyright © 2014 Elsevier B.V. All rights reserved.

Emerging Technologies for Monitoring Drug-Resistant Tuberculosis at the Point-of-Care

PubMed Central

Mani, Vigneshwaran; Wang, ShuQi; Inci, Fatih; De Libero, Gennaro; Singhal, Amit; Demirci, Utkan

2014-01-01

Infectious diseases are the leading cause of death worldwide. Among them, tuberculosis (TB) remains a major threat to public health, exacerbated by the emergence of multiple drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (Mtb). MDR-Mtb strains are resistant to first-line anti-TB drugs such as isoniazid and rifampicin; whereas XDR-Mtb strains are resistant to additional drugs including at least to any fluoroquinolone and at least one of the second-line anti-TB injectable drugs such as kanamycin, capreomycin, or amikacin. Clinically, these strains have significantly impacted the management of TB in high-incidence developing countries, where systemic surveillance of TB drug resistance is lacking. For effective management of TB on-site, early detection of drug resistance is critical to initiate treatment, to reduce mortality, and to thwart drug-resistant TB transmission. In this review, we discuss the diagnostic challenges to detect drug-resistant TB at the point-of-care (POC). Moreover, we present the latest advances in nano/microscale technologies that can potentially detect TB drug resistance to improve on-site patient care. PMID:24882226

Mycobacterial lipolytic enzymes: a gold mine for tuberculosis research.

PubMed

Dedieu, L; Serveau-Avesque, C; Kremer, L; Canaan, S

2013-01-01

Tuberculosis (TB) is one of the deadliest infectious diseases worldwide with a strong impact in developing countries. Mycobacterium tuberculosis, the etiological agent of TB, has a high capacity to evade the host immune system and establish a chronic, asymptomatic and latent infection. In a latent TB infection, persistent bacilli are present in a non-replicating dormant state within host granulomas. During reactivation, bacilli start replicating again leading to an active TB infection that can be highly contagious. Mycobacterial lipids and lipolytic enzymes are thought to play important physiological roles during dormancy and reactivation. The role of lipolytic enzymes in the physiology of M. tuberculosis and physiopathology of the disease will be discussed in this review, with an emphasis on the secreted or cell wall-associated, surface exposed lipolytic enzymes characterized to date. Studies on the localization, enzymatic activity and immunological properties of these enzymes highlighted their possible usefulness as new diagnostic markers in the fight against TB. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Fast and efficient detection of tuberculosis antigens using liposome encapsulated secretory proteins of Mycobacterium tuberculosis.

PubMed

Tiwari, Dileep; Haque, Shafiul; Tiwari, Ram P; Jawed, Arshad; Govender, Thavendran; Kruger, Hendrik G

2017-04-01

A rapid and efficient diagnostic test was developed for the detection of Mycobacterium tuberculosis antigens in serum samples of active tuberculosis (TB) and extrapulmonary TB patients via a liposomal agglutination-based method. A rapid card test has been developed to facilitate the recognition of high-affinity binding rabbit raised purified culture filtrate protein antibodies coupled on the surface of activated liposomal preparation. In the presence of TB antigens, the polyclonal antibodies bound to the liposomal particles demonstrate a visible agglutination reaction. The developed assay was simple, rapid, reliable, sensitive, and specific as a diagnostic test for the detection of antigens in serum samples of clinically confirmed cases of TB within 4-5 minutes' duration. The test was evaluated at different hospitals, medical colleges, and pathology centers, and involved 1483 participants. This investigation was conducted to detect the presence of these antigens during the period of active growth of the microorganism in serum samples for pulmonary TB and processed tissue biopsy for other extrapulmonary TB. Results obtained using this test were compared with acid-fast bacilli smear and culture results. Our study demonstrated that the newly developed liposome tuberculosis antigen card test detected antigens in our study population with approximately 97.48% sensitivity and 95.79% specificity. This is the first study to report the liposomal encapsulation of culture filtrate proteins from M. tuberculosis for diagnostic application. Copyright © 2015. Published by Elsevier B.V.

Drug Resistance in Newly Presenting and Previously Treated Tuberculosis Patients in Guangxi Province, People's Republic of China.

PubMed

Luo, Dan; Zhao, Jinming; Lin, Mei; Liu, Feiying; Huang, Shuhai; Zhang, Yingkun; Huang, Minying; Li, Juan; Zhou, Yang; Lan, Rushu; Zhao, Yanlin

2017-05-01

Drug-resistant Mycobacterium tuberculosis strains are a major threat to the control of tuberculosis (TB), but the prevalence of drug-resistant TB is still unknown in the southern ethnic region of China. A cluster-randomized sampling method was used to include the study population. Isolates were tested for resistance to 6 antituberculosis drugs, and genotyped to identify Beijing strains. Overall, 11.3% (139/1229) of new cases and 33.0% (126/382) of retreated cases had drug-resistant tuberculosis. Multiple previous TB treatment episodes and multiple treatment interruptions were risk factors for both drug-resistant and multidrug-resistant TB among retreated cases. A total of 53.2% of the patients were infected with a Beijing strain of M tuberculosis. Infection with a Beijing strain was significantly associated with drug resistance among new cases (odds ratio, 1.44; 95% CI, 1.01-2.07). Novel strategies to rapid diagnosis and effective treatment are urgently needed to prevent the development of drug resistance.

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.

Assessing the consequences of stigma for tuberculosis patients in urban Zambia.

PubMed

Cremers, Anne Lia; de Laat, Myrthe Manon; Kapata, Nathan; Gerrets, Rene; Klipstein-Grobusch, Kerstin; Grobusch, Martin Peter

2015-01-01

Stigma is one of the many factors hindering tuberculosis (TB) control by negatively affecting hospital delay and treatment compliance. In Zambia, the morbidity and mortality due to TB remains high, despite extended public health attempts to control the epidemic and to diminish stigma. To enhance understanding of TB-related stigmatizing perceptions and to describe TB patients' experiences of stigma in order to point out recommendations to improve TB policy. We conducted a mixed method study at Kanyama clinic and surrounding areas, in Lusaka, Zambia; structured interviews with 300 TB patients, multiple in-depth interviews with 30 TB patients and 10 biomedical health workers, 3 focus group discussions with TB patients and treatment supporters, complemented by participant observation and policy analysis of the TB control program. Predictors of stigma were identified by use of multivariate regression analyses; qualitative analysis of the in-depth interviews, focus group discussions and participant observation was used for triangulation of the study findings. We focused on the 138/300 patients that described TB-related perceptions and attitudes, of whom 113 (82%) reported stigma. Stigma provoking TB conceptions were associated with human immunodeficiency virus (HIV)-infection, alleged immoral behaviour, (perceived) incurability, and (traditional) myths about TB aetiology. Consequences of stigma prevailed both among children and adults and included low self-esteem, insults, ridicule, discrimination, social exclusion, and isolation leading to a decreased quality of life and social status, non-disclosure, and/or difficulties with treatment compliance and adherence. Women had significantly more stigma-related problems than men. The findings illustrate that many TB patients faced stigma-related issues, often hindering effective TB control and suggesting that current efforts to reduce stigma are not yet optimal. The content and implementation of sensitization programs should be improved and more emphasis needs to be placed on women and children.