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 (TB) Facts Testing for TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination
Tuberculosis (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
Tuberculosis (TB) Facts TB Can Be Treated What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination Page 1 of 2 TB Facts: TB ...
Tuberculosis (TB) Facts You Can Prevent TB What is TB? “TB” is short for a disease called tuberculosis. TB is spread through the air from one ... Viral Hepatitis, STD, and TB Prevention Division of Tuberculosis Elimination TB Facts: You Can Prevent TB What ...
... 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 ...
... or brain. If not treated, TB disease can cause death. HIV weakens the immune system , increasing the risk ... spine, or brain. If not treated, TB can cause death. How does TB spread from person to person? ...
Chambers, Mark A.; Crawshaw, Tim; Waterhouse, Sue; Delahay, Richard; Hewinson, R. Glyn; Lyashchenko, Konstantin P.
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
Shah, N. S.; Flood-Bryzman, A.; Jeffries, C.; Scott, J.
Objectives: To assess the magnitude of active TB disease and latent TB infection (LTBI) in young adults of college age. Participants: Individuals who were aged 18-24 years in 2011 were used as a proxy for college students. Methods: Active TB cases reported to the 2011 US National TB Surveillance System (NTSS) were included. LTBI prevalence was…
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 ...
Curran, Evonne T
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.
Systematic review on tuberculosis transmission on aircraft and update of the European Centre for Disease Prevention and Control risk assessment guidelines for tuberculosis transmitted on aircraft (RAGIDA-TB).
Kotila, Saara M; Payne Hallström, Lara; Jansen, Niesje; Helbling, Peter; Abubakar, Ibrahim
As a setting for potential tuberculosis (TB) transmission and contact tracing, aircraft pose specific challenges. Evidence-based guidelines are needed to support the related-risk assessment and contact-tracing efforts. In this study evidence of TB transmission on aircraft was identified to update the Risk Assessment Guidelines for TB Transmitted on Aircraft (RAGIDA-TB) of the European Centre for Disease Prevention and Control (ECDC). Electronic searches were undertaken from Medline (Pubmed), Embase and Cochrane Library until 19 July 2013. Eligible records were identified by a two-stage screening process and data on flight and index case characteristics as well as contact tracing strategies extracted. The systematic literature review retrieved 21 records. Ten of these records were available only after the previous version of the RAGIDA guidelines (2009) and World Health Organization guidelines on TB and air travel (2008) were published. Seven of the 21 records presented some evidence of possible in-flight transmission, but only one record provided substantial evidence of TB transmission on an aircraft. The data indicate that overall risk of TB transmission on aircraft is very low. The updated ECDC guidelines for TB transmission on aircraft have global implications due to inevitable need for international collaboration in contract tracing and risk assessment.
Shah, N S; Flood-Bryzman, A; Jeffries, C; Scott, J
To assess the magnitude of active TB disease and latent TB infection (LTBI) in young adults of college age. Individuals who were aged 18-24 years in 2011 were used as a proxy for college students. Active TB cases reported to the 2011 US National TB Surveillance System (NTSS) were included. LTBI prevalence was calculated from the 2011-2012 National Health and Nutrition Examination Survey. The 2011 American Community Survey was used to calculate population denominators. Analyses were stratified by nativity. Active TB disease incidence among persons aged 18-24 years was 2.82/100,000, 18.8/100,000 among foreign-born individuals and 0.9/100,000 among US-born individuals. In 2011, 878 TB cases were reported; 629 (71.6%) were foreign-born. LTBI prevalence among persons of 18-24 years was 2.5%: 8.7% and 1.3% among foreign-born and US-born, respectively. Active screening and treatment programs for foreign-born young adults could identify TB cases earlier and provide an opportunity for prevention efforts.
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 ...
... 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 ...
Gupta-Wright, Ankur; Tomlinson, Gillian S; Rangaka, Molebogeng X; Fletcher, Helen A
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).
Roy, Sukhendu; Rai, D R; Suresh, Gutta
In a landmark development, the Ministry of Health and Family Welfare, Government of India, has taken important steps to establish the compulsory notification of tuberculosis in the country. A Government Order to this effect was issued on 7 May 2012. In addition to this IMA passed a resolution on TB notification in CWC on 22nd April 2012 at Mumbai: "In conformity with the requirements of ISTC, Indian Medical Association (IMA) desires that Notification of TB patient to the National Programme be made mandatory. IMA also recommends to the medical practitioner to follow the ISTC guidelines in diagnosis and management of TB care". Notification of TB will facilitate early diagnosis and treatment, prevention of MDR and XDR, reduce TB deaths, better quality diagnostic and treatment services for the TB patients. RNTCP will realistically estimateTB burden, plan resources and control measures to commensurate with the actual burden of disease.
Coll, Francesc; Preston, Mark; Guerra-Assunção, José Afonso; Hill-Cawthorn, Grant; Harris, David; Perdigão, João; Viveiros, Miguel; Portugal, Isabel; Drobniewski, Francis; Gagneux, Sebastien; Glynn, Judith R; Pain, Arnab; Parkhill, Julian; McNerney, Ruth; Martin, Nigel; Clark, Taane G
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the second major cause of death from an infectious disease worldwide. Recent advances in DNA sequencing are leading to the ability to generate whole genome information in clinical isolates of M. tuberculosis complex (MTBC). The identification of informative genetic variants such as phylogenetic markers and those associated with drug resistance or virulence will help barcode Mtb in the context of epidemiological, diagnostic and clinical studies. Mtb genomic datasets are increasingly available as raw sequences, which are potentially difficult and computer intensive to process, and compare across studies. Here we have processed the raw sequence data (>1500 isolates, eight studies) to compile a catalogue of SNPs (n = 74,039, 63% non-synonymous, 51.1% in more than one isolate, i.e. non-private), small indels (n = 4810) and larger structural variants (n = 800). We have developed the PolyTB web-based tool (http://pathogenseq.lshtm.ac.uk/polytb) to visualise the resulting variation and important meta-data (e.g. in silico inferred strain-types, location) within geographical map and phylogenetic views. This resource will allow researchers to identify polymorphisms within candidate genes of interest, as well as examine the genomic diversity and distribution of strains. PolyTB source code is freely available to researchers wishing to develop similar tools for their pathogen of interest. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
Coll, Francesc; Preston, Mark; Guerra-Assunção, José Afonso; Hill-Cawthorn, Grant; Harris, David; Perdigão, João; Viveiros, Miguel; Portugal, Isabel; Drobniewski, Francis; Gagneux, Sebastien; Glynn, Judith R.; Pain, Arnab; Parkhill, Julian; McNerney, Ruth; Martin, Nigel; Clark, Taane G.
Summary Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is the second major cause of death from an infectious disease worldwide. Recent advances in DNA sequencing are leading to the ability to generate whole genome information in clinical isolates of M. tuberculosis complex (MTBC). The identification of informative genetic variants such as phylogenetic markers and those associated with drug resistance or virulence will help barcode Mtb in the context of epidemiological, diagnostic and clinical studies. Mtb genomic datasets are increasingly available as raw sequences, which are potentially difficult and computer intensive to process, and compare across studies. Here we have processed the raw sequence data (>1500 isolates, eight studies) to compile a catalogue of SNPs (n = 74,039, 63% non-synonymous, 51.1% in more than one isolate, i.e. non-private), small indels (n = 4810) and larger structural variants (n = 800). We have developed the PolyTB web-based tool (http://pathogenseq.lshtm.ac.uk/polytb) to visualise the resulting variation and important meta-data (e.g. in silico inferred strain-types, location) within geographical map and phylogenetic views. This resource will allow researchers to identify polymorphisms within candidate genes of interest, as well as examine the genomic diversity and distribution of strains. PolyTB source code is freely available to researchers wishing to develop similar tools for their pathogen of interest. PMID:24637013
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
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
Ennassiri, Wifak; Jaouhari, Sanae; Cherki, Wafa; Charof, Reda; Filali-Maltouf, Abdelkarim; Lahlou, Ouafae
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.
Xu, Jun-Chi; Li, Ze-Yi; Chen, Xin-Nian; Shi, Cui-Lin; Wu, Mei-Ying; Chen, Hui; Zhu, Xiao-Yan; Song, Hua-Feng; Wu, Min-Juan; Xu, Ping
Tuberculosis (TB)-interferon gamma release assay (IGRA) test has the characteristics of short time, high specificity, and high sensitivity, but it lacks the correlation research between TB-IGRA test results and body's immune cells, disease progression and prognosis, which is explored in this study. A retrospective study was carried out on positive TB-IGRA patients who were infected with TB and diagnosed at our hospital from January 2014 to June 2015. The TB-IGRA, routine blood test, T-cell subgroup data were collected for statistical analysis. TB-IGRA results were in positive proportion to the lymphocytes, CD4 + T cells and CD4 + CD28 + T cells, whereas negative to the Treg cells. Patient with unilateral pulmonary lesion had higher TB-IGRA than those with bilateral pulmonary lesions. After the stimulation of TB-specific antigen, the proportion of CD4 + IFN-γ + and CD8 + IFN-γ + T Tcells were both increased and the CD4 + IFN-γ + T had positive correlation with the value of TB-IGRA. IFN-γ was tested with TB-IGRA in patients with TB by the specific TB T cells and correlated with the lymphocytes, while the lymphocytes also closely related to the host's anti-TB immunity and disease outcome. Hence the result of TB-IGRA could reflect the specific anti-TB immunity ability of the host, disease progression and prognosis. This study further expands the application scope of TB-IGRA technology in the diagnosis of TB and lays a foundation for clinical practice to understand the immunity state of the patients with TB and the application of auxiliary clinical immunity regulators. © 2017 Wiley Periodicals, Inc.
Maitra, Arundhati; Danquah, Cynthia A; Scotti, Francesca; Howard, Tracey K; Kamil, Tengku K; Bhakta, Sanjib
Tuberculosis (TB) poses a grave predicament to the world as it is not merely a scientific challenge but a socio-economic burden as well. A prime cause of mortality in human due to an infectious disease; the malady and its cause, Mycobacterium tuberculosis have remained an enigma with many questions that remain unanswered. The ability of the pathogen to survive and switch between varied physiological states necessitates a protracted therapeutic regimen that exerts an excessive strain on low-resource countries. To complicate things further, there has been a significant rise of antimicrobial resistance. Existing control measures, including treatment regimens have remained fairly uniform globally for at least half a century and require reinvention. Overcoming the societal and scientific challenges requires an increase in dialog to identify key regions that need attention and effective partners with whom successful collaborations can be fostered. In this report, we explore the discussions held at the International TB Summit 2015 hosted by EuroSciCon, which served as an excellent platform for researchers to share their recent findings. Ground-breaking results require outreach to affect policy design, governance and control of the disease. Hence, we feel it is important that meetings such as these reach a wider, global audience. PMID:26151309
[Berlin Declaration on Tuberculosis: High Level Follow-Up of High Priority Countries for TB Control in the WHO-EURO Region 'Double Trouble or Double Success? Bringing Together Diseases and Programs' - a symposium report].
Castell, S; Hauer, B; Manissero, D; Ulrichs, T; Zaleskis, R; Loddenkemper, R
The global tuberculosis (TB) situation has deteriorated dramatically since the beginning of the 1990s. In 2007, the WHO identified 18 countries of the WHO European Region as 'high priority countries' and introduced a plan for these countries to improve the situation. To further promote solutions a WHO European Ministerial Forum 'All against Tuberculosis' took place in Berlin in 2007 and resulted in the 'Berlin Declaration' which was commonly endorsed. In October 2009 a meeting was organized by the German Ministry of Health under the title "Berlin Declaration on Tuberculosis: High Level Follow-Up of High Priority Countries for TB Control in the WHO-EURO Region 'Double Trouble or Double Success? Bringing together Diseases and Programs'". This article summarizes the symposium. Besides reporting on the recent epidemiological situation of the WHO-EURO Region (with partly dramatically developments) presentations on psychosocial issues, the role of the EU and the 'Global Fund to Fight AIDS, Tuberculosis and Malaria', the importance of new tools for the fight against tuberculosis and the need for further political commitment were given. Copyright Georg Thieme Verlag KG Stuttgart . New York.
Tarigan, A. P.; Pandia, P.; Eyanoer, P.; Tina, D.; Pratama, R.; Fresia, A.; Tamara; Silvanna
The case of post TB is a problem that arises in the community. Pulmonary tuberculosis (TB) can affect lung function. Therefore, we evaluated impaired pulmonary function in subjects with diagnosed prior pulmonary TB. A Case Series study, pulmonary function test was performed in subjects with a history of pulmonary tuberculosis; aged ≥18 years were included. Exclusion criteria was a subject who had asthma, obesity, abnormal thorax and smoking history. We measured FEV1 and FVC to evaluate pulmonary function. Airflow obstruction was FEV1/FVC%<75 and restriction was FVC<80% according to Indonesia’s pneumomobile project. This study was obtained from 23 patients with post pulmonary TB, 5 subjects (23%) had airflow obstruction with FEV1/FVC% value <75%, 15 subjects (71.4%) had abnormalities restriction with FVC value <80% and 3 subjects (5.6%) had normal lung function. Obstructive lung disease is one of the complications of impaired lung function in post pulmonary TB.
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
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: email@example.com
There is enough evidence to declare tuberculosis as an occupational disease among healthcare workers. In Peru, there are regulations granting employment rights regarding tuberculosis as an occupational disease, such as healthcare coverage for temporary or permanent disability. However, these rights have not been sufficiently socialized. This study presents information on the risk of acquiring tuberculosis in the workplace, and a review of the evidence to declare tuberculosis as an occupational disease among health care workers, presenting the current Peruvian law related.
Bates, Matthew; Marais, Ben J.; Zumla, Alimuddin
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
... TB Reference Laboratory Network, the National TB Surveillance System in the United States, the national reference laboratory of South Korea, and ... capacity in the U.S. and abroad; and Developing education, risk, and media communications ... – United States, 1993–2006 CDC. CDC’s Role in Preventing XDR ...
... prisons, or homeless shelters. If you work in hospitals or health-care settings where TB patients are likely to be seen, you should consult infection control or occupational health experts. Ask about administrative and ...
Aziz, Nazrina; Diah, Ijlal Mohd; Ahmad, Nazihah; Kasim, Maznah Mat
Tuberculosis (TB) occurs worldwide. It can be transmitted to others directly through air when active TB persons sneeze, cough or spit. In Malaysia, it was reported that TB cases had been recognized as one of the most infectious disease that lead to death. Disease mapping is one of the methods that can be used as the prevention strategies since it can displays clear picture for the high-low risk areas. Important thing that need to be considered when studying the disease occurrence is relative risk estimation. The transmission of TB disease is studied through mathematical model. Therefore, in this study, deterministic SLIR models are used to estimate relative risk for TB disease transmission.
Zhu, Feng; Ou, Qinfang; Zheng, Jian
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.
Lala, Sanjay G.; Little, Kristen M.; Tshabangu, Nkeko; Moore, David P.; Msandiwa, Reginah; van der Watt, Martin; Chaisson, Richard E.; Martinson, Neil A.
Background Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa. Methods Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts. Results Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART. Conclusion In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings–integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed
Anggriani, N.; Wicaksono, B. C.; Supriatna, A. K.
Tuberculosis (TB) is one of the deadliest infectious disease in the world which caused by Mycobacterium tuberculosis. The disease is spread through the air via the droplets from the infectious persons when they are coughing. The World Health Organization (WHO) has paid a special attention to the TB by providing some solution, for example by providing BCG vaccine that prevent an infected person from becoming an active infectious TB. In this paper we develop a mathematical model of the spread of the TB which assumes endogeneous reactivation and exogeneous reinfection factors. We also assume that some of the susceptible population are vaccinated. Furthermore we investigate the optimal vaccination level for the disease.
Mishra, Rahul; Shukla, Priyanka; Huang, Wei; Hu, Ning
Against a constant background of established infections, epidemics of new and old infectious diseases periodically emerge, greatly magnifying the global burden of infections. TB poses formidable challenges to the global health at the public health and scientific level by acquiring gene mutation into anti TB drugs specially rifampin and isoniazid which leads resistant to drug regime and treatment forms. Our tools to combat MDR (multidrug resistant) TB are dangerously out of date and ineffective. Besides new tools (TB drugs, vaccines, diagnostics), we also need new strategies to identify key Mycobacterium tuberculosis and human host interaction. It is all equally important that we build up high quality clinical trial capacity and bio banks for TB biomarkers identification. But most important is global commitment at all levels to roll back TB before it expose us again. Rapid development of drug resistance caused by M. tuberculosis has lead to measure resistance accurately and easily. This knowledge will certainly help us to understand how to prevent the occurrence of drug resistance as well as identifying genes associated with new drug resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.
Ntoumi, Francine; Kaleebu, Pontiano; Macete, Eusebio; Mfinanga, Sayoki; Chakaya, Jeremiah; Yeboah-Manu, Dorothy; Bates, Matthew; Mwaba, Peter; Maeurer, Markus; Petersen, Eskild; Zumla, Alimuddin
Tuberculosis (TB) remains a global emergency, with an estimated 9.6 million new TB cases worldwide reported in 2014. Twenty-eight percent of these cases were in the World Health Organization (WHO) Africa Region, where the annual case detection rate was 281 per 100000 population-more than double the global average of 133 per 100000. Of the 9.6 million people who developed TB, an estimated 1.2 million (12%) were HIV-positive, and the Africa Region accounted for 74% of these cases. Three million people with TB remain undiagnosed and untreated. Globally, an estimated 480000 had multidrug-resistant TB (MDR-TB). Whilst of the African countries, only South Africa has reported a high prevalence of MDR-TB, it is likely that all of Sub-Saharan Africa has an unreported high load of drug-resistant TB. Tragically, in 2014, only 48% of individuals diagnosed with MDR-TB had successful treatment and an estimated 190000 people died of MDR-TB. Of the global TB funding gap of US$ 0.8 billion, the largest funding gap was in the Africa Region, amounting to US$ 0.4 billion in 2015. The MDR-TB pandemic in particular now threatens to devastate entire regions and may fundamentally alter the life-expectancy and demographic profile of many countries in Sub-Saharan Africa. The theme designated for this year's World TB Day, March 24, 2016, is 'Unite to End TB'. From the Africa Region, there is an urgent need to seriously address the political, economic, and social factors that influence host-Mycobacterium tuberculosis interactions and result in disease. Recent political and funder initiatives that provide renewed hope for the alleviation of Africa's TB and TB/HIV problems are discussed. Copyright © 2016. Published by Elsevier Ltd.
Nkurunungi, Gyaviira; Lutangira, Jimreeves E.; Lule, Swaib A.; Akurut, Hellen; Kizindo, Robert; Fitchett, Joseph R.; Kizito, Dennison; Sebina, Ismail; Muhangi, Lawrence; Webb, Emily L.; Cose, Stephen; Elliott, Alison M.
Background Children with latent tuberculosis infection (LTBI) represent a huge reservoir for future disease. We wished to determine Mycobacterium tuberculosis (M.tb) infection prevalence among BCG-immunised five-year-old children in Entebbe, Uganda, but there are limited data on the performance of immunoassays for diagnosis of tuberculosis infection in children in endemic settings. We therefore evaluated agreement between a commercial interferon gamma release assay (T-SPOT.TB) and the tuberculin skin test (TST; 2 units RT-23 tuberculin; positive defined as diameter ≥10 mm), along with the reproducibility of T-SPOT.TB on short-term follow-up, in this population. Methodology/Principal Findings We recruited 907 children of which 56 were household contacts of TB patients. They were tested with T-SPOT.TB at age five years and then re-examined with T-SPOT.TB (n = 405) and TST (n = 319) approximately three weeks later. The principal outcome measures were T-SPOT.TB and TST positivity. At five years, 88 (9.7%) children tested positive by T-SPOT.TB. More than half of those that were T-SPOT.TB positive at five years were negative at follow-up, whereas 96% of baseline negatives were consistently negative. We observed somewhat better agreement between initial and follow-up T-SPOT.TB results among household TB contacts (κ = 0.77) than among non-contacts (κ = 0.39). Agreement between T-SPOT.TB and TST was weak (κ = 0.28 and κ = 0.40 for T-SPOT.TB at 5 years and follow-up, respectively). Of 28 children who were positive on both T-SPOT.TB tests, 14 (50%) had a negative TST. Analysis of spot counts showed high levels of instability in responses between baseline and follow-up, indicating variability in circulating numbers of T cells specific for certain M.tb antigens. Conclusions/Significance We found that T-SPOT.TB positives are unstable over a three-week follow-up interval, and that TST compares poorly with T-SPOT.TB, making the categorisation of
Ekins, Sean; Spektor, Anna Coulon; Clark, Alex M.; Dole, Krishna; Bunin, Barry A.
Neglected disease drug discovery is generally poorly funded compared with major diseases and hence there is an increasing focus on collaboration and precompetitive efforts such as public–private partnerships (PPPs). The More Medicines for Tuberculosis (MM4TB) project is one such collaboration funded by the EU with the goal of discovering new drugs for tuberculosis. Collaborative Drug Discovery has provided a commercial web-based platform called CDD Vault which is a hosted collaborative solution for securely sharing diverse chemistry and biology data. Using CDD Vault alongside other commercial and free cheminformatics tools has enabled support of this and other large collaborative projects, aiding drug discovery efforts and fostering collaboration. We will describe CDD's efforts in assisting with the MM4TB project. PMID:27884746
Yerlikaya, Seda; Broger, Tobias; MacLean, Emily; Pai, Madhukar; Denkinger, Claudia M
New diagnostic innovations for tuberculosis (TB), including point-of-care solutions, are critical to reach the goals of the End TB Strategy. However, despite decades of research, numerous reports on new biomarker candidates, and significant investment, no well-performing, simple and rapid TB diagnostic test is yet available on the market, and the search for accurate, non-DNA biomarkers remains a priority. To help overcome this 'biomarker pipeline problem', FIND and partners are working on the development of a well-curated and user-friendly TB biomarker database. The web-based database will enable the dynamic tracking of evidence surrounding biomarker candidates in relation to target product profiles (TPPs) for needed TB diagnostics. It will be able to accommodate raw datasets and facilitate the verification of promising biomarker candidates and the identification of novel biomarker combinations. As such, the database will simplify data and knowledge sharing, empower collaboration, help in the coordination of efforts and allocation of resources, streamline the verification and validation of biomarker candidates, and ultimately lead to an accelerated translation into clinically useful tools. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Di, Li; Li, Yan
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.
... 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 ...
Asha, T.; Natarajan, S.; Murthy, K. N. B.
Tuberculosis (TB) is a disease caused by bacteria called Mycobacterium tuberculosis. It usually spreads through the air and attacks low immune bodies such as patients with Human Immunodeficiency Virus (HIV). This work focuses on finding close association rules, a promising technique in Data Mining, within TB data. The proposed method first normalizes of raw data from medical records which includes categorical, nominal and continuous attributes and then determines Association Rules from the normalized data with different support and confidence. Association rules are applied on a real data set containing medical records of patients with TB obtained from a state hospital. The rules determined describes close association between one symptom to another; as an example, likelihood that an occurrence of sputum is closely associated with blood cough and HIV.
Suwanpimolkul, Gompol; Kawkitinarong, Kamon; Manosuthi, Weerawat; Sophonphan, Jiratchaya; Gatechompol, Sivaporn; Ohata, Pirapon June; Ubolyam, Sasiwimol; Iampornsin, Thatri; Katerattanakul, Pairaj; Avihingsanon, Anchalee; Ruxrungtham, Kiat
To evaluate the applicability and accuracy of the urine lipoarabinomannan (LAM) test in tuberculosis (TB)/HIV co-infected patients and HIV-negative patients with disseminated TB. Frozen urine samples obtained at baseline from patients in the TB research cohort with proven culture-positive TB were selected for blinded urine LAM testing. One hundred and nine patients were categorized into four groups: (1) HIV-positive patients with TB; (2) HIV-negative patients with disseminated TB; (3) HIV-negative immunocompromised patients with TB; and (4) patients with diseases other than TB. The sensitivity of urine LAM testing for culture-positive TB, specificity of urine LAM testing for patients without TB, positive predictive value (PPV), and negative predictive value (NPV) were assessed. The sensitivity of the urine LAM test in group 1 patients with a CD4 T-cell count of >100, ≤100, and ≤50 cells/mm 3 was 38.5%, 40.6%, and 45%, respectively. The specificity and PPV of the urine LAM test were >80%. The sensitivity of the test was 20% in group 2 and 12.5% in group 3, and the specificity and PPV were 100% for both groups. A positive urine LAM test result was significantly associated with death. This promising diagnostic tool could increase the yield of TB diagnosis and may predict the mortality rate of TB infection, particularly in TB/HIV co-infected patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
Okimoto, Niro; Kurihara, Takeyuki; Miyashita, Naoyuki
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.
Perumal, Rubeshan; Naidoo, Kogieleum; Padayatchi, Nesri
The global predominance of tuberculosis in men has received significant attention. However, epidemiological studies now demonstrate that there is an increased representation of young women with tuberculosis, especially in high HIV burden settings where young women bear a disproportionate burden of HIV. The role of the HIV epidemic, as well as changes in behavioural, biological, and structural risk factors are explored as potential explanations for the increasing burden of tuberculosis in young women. As young women are particularly vulnerable to HIV infection in sub-Saharan Africa, it is unsurprising that the TB epidemic in this setting has become increasingly feminised. This age-sex trend of TB in South Africa is similar to WHO estimates for other countries with a high HIV prevalence where there are more female than male cases notified up to the age of 25 years. The high prevalence of anaemia of chronic disease in young women with HIV is an additional potential reason for their increased TB risk. The widespread use of injectable medroxyprogesterone acetate contraception, which has been shown to possess selective glucocorticoid effect and oestrogen suppression, in young women may be an important emerging biological risk factor for tuberculosis in young women. Behavioural factors such as alcohol use and tobacco smoking patterns are further factors which may be responsible for the narrowing of the sex gap in TB epidemiology. In comparison to the significantly higher alcohol consumption rates in men globally, there is a narrowing gap in alcohol consumption between the sexes in South Africa with alarming rates of alcohol abuse in young women. There is a similar narrowing of the tobacco smoking gap between the sexes in South Africa, with increasing smoking prevalence in young women. With nearly 70% of all TB patients being co-infected with HIV in our setting, it is not surprising that the age and sex distribution of TB is increasingly resembling the distribution of HIV
Rahman, Md Arifur; Sarkar, Atanu
Extensively Drug-resistant Tuberculosis (XDR-TB) has emerged as one of the most formidable challenges to the End TB Strategy that has targeted a 95% reduction in TB deaths and 90% reduction in cases by 2035. Globally, there were an estimated 55,100 new XDR-TB cases in 2015 in 117 countries. However, only one in 30 XDR-TB cases had been reported so far. Drug susceptibility test (DST) is the mainstay for diagnosing XDR-TB, but the lack of laboratory facilities in the resource-limited endemic countries limit its uses. A few new drugs including bedaquiline and delamanid, have the potential to improve the efficiency of XDR-TB treatment, but the drugs have been included in 39 countries only. The costs of XDR-TB treatment are several folds higher than that of the MDR-TB. Despite the financing from the donors, there is an urgent need to fill the current funding gap of US$ 2 billion to ensure effective treatment and robust surveillance. In the review article we have addressed current update on XDR-TB, including surveillance, diagnosis and the interventions needed to treat and limit its spread, emphasis on extensive financial support for implementing of current recommendations to meet the goals of End TB Strategy. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.
Pan, Sheng-Wei; Yen, Yung-Feng; Feng, Jia-Yih; Su, Vincent Yi-Fong; Kou, Yu Ru; Su, Wei-Juin
Abstract Tuberculosis (TB) disease may be transmitted to close contacts of index cases, causing physical illness. No studies have investigated the risk of developing depressive disorder among TB contacts in a TB-endemic area. Adult participants with a new diagnosis of TB contact (ICD-9-CM codes V01.1 plus chest radiographic order) since January 1, 2008, were identified from the National Health Insurance Research Database in Taiwan. A control cohort matched for age (±5 y), sex, enrolled years, and income level was selected. These 2 cohorts were followed until December 31, 2012, and observed for the development of depressive disorder. The Kaplan-Meier method and the log-rank test were used to examine the difference in cumulative incidences of depressive disorder between groups. Cox proportional-hazard models were used to calculate adjusted hazard ratios (aHRs) for depressive disorder. The TB contact cohort consisted of 9046 patients and matched controls of 36,184 ones. The mean age of TB contacts was 44.7 years, and 56.0% of them were women. During a mean follow-up period of 2.5 years, 127 (1.40%) TB contacts and 521 (1.44%) matched controls developed depressive disorder. TB exposure was found to be an independent risk factor of depressive disorder in women (aHR 1.34, 95% confidence interval [CI] 1.07–1.68), but not in men (aHR 0.71, 95% CI 0.48–1.06) after adjusting for age, comorbidities, and income levels. The risk of depression was significantly higher for female TB contacts than for matched controls in the first and second years (aHR 1.49, 95% CI 1.03–2.14; and aHR 1.53, 95% CI 1.05–2.23, respectively), but not thereafter. Of note, 67 (0.74%) TB contacts and 88 (0.24%) matched controls developed active TB, but none of them had subsequent depressive disorder during follow-up periods. Female TB contacts had an increased risk of depression within the first 2 years after exposure. Clinicians should consider conducting depression evaluations in addition to
Harrington-Kandt, Rachel; Stylianou, Elena; Eddowes, Lucy A.; Lim, Pei Jin; Stockdale, Lisa; Pinpathomrat, Nawamin; Bull, Naomi; Pasricha, Janet; Ulaszewska, Marta; Beglov, Yulia; Vaulont, Sophie
Tuberculosis (TB), caused by the macrophage-tropic pathogen Mycobacterium tuberculosis (M.tb) is a highly prevalent infectious disease. Since an immune correlate of protection or effective vaccine have yet to be found, continued research into host-pathogen interactions is important. Previous literature reports links between host iron status and disease outcome for many infections, including TB. For some extracellular bacteria, the iron regulatory hormone hepcidin is essential for protection against infection. Here, we investigated hepcidin (encoded by Hamp1) in the context of murine M.tb infection. Female C57BL/6 mice were infected with M.tb Erdman via aerosol. Hepatic expression of iron-responsive genes was measured by qRT-PCR and bacterial burden determined in organ homogenates. We found that hepatic Hamp1 mRNA levels decreased post-infection, and correlated with a marker of BMP/SMAD signalling pathways. Next, we tested the effect of Hamp1 deletion, and low iron diets, on M.tb infection. Hamp1 knockout mice did not have a significantly altered M.tb mycobacterial load in either the lungs or spleen. Up to 10 weeks of dietary iron restriction did not robustly affect disease outcome despite causing iron deficiency anaemia. Taken together, our data indicate that unlike with many other infections, hepcidin is decreased following M.tb infection, and show that hepcidin ablation does not influence M.tb growth in vivo. Furthermore, because even severe iron deficiency did not affect M.tb mycobacterial load, we suggest that the mechanisms M.tb uses to scavenge iron from the host must be extremely efficient, and may therefore represent potential targets for drugs and vaccines. PMID:29324800
Boggiano, Cesar; Eichelberg, Katrin; Ramachandra, Lakshmi; Shea, Jaqueline; Ramakrishnan, Lalita; Behar, Samuel; Ernst, Joel D; Porcelli, Steven A; Maeurer, Markus; Kornfeld, Hardy
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.
Chen, Qiaopei; Guo, Xuxiao; Wang, Xinfeng; Wang, Maoshui
Interferon-gamma release assays have not been validated in active TB among pregnant women. Therefore, the objective of this retrospective study was to estimate the diagnostic value of T-SPOT.TB in active TB among pregnant women. Between May 2012 and May 2015, 26 consecutive pregnant women with suspected TB were enrolled in our study. The clinicopathological characteristics and T-SPOT.TB results were reviewed and analyzed. Pregnant patients were divided into a TB group (n=21) and a Non-TB group (n=5). In the TB group, 5 patients had pulmonary TB, 5 had pulmonary TB+ extrapulmonary TB, and 11 had exclusively extrapulmonary TB. The most common site of extrapulmonary TB was pleural (n=11). Statistical analysis showed that the lymphocyte count in the TB group was lower than in the Non-TB group (P<0.05). For detection of active TB during pregnancy, T-SPOT.TB had a high sensitivity of 100.0% (84.5%-100.0%) and a specificity of 80.0% (37.6-96.4%). T-SPOT.TB shows good performance in detection of active tuberculosis during pregnancy. Interferon gamma release assay for TB screening of pregnant women is recommended in clinical practice because it may be a more appropriate diagnostic tool than the tuberculin skin test.
Du, Fengjiao; Xie, Li; Zhang, Yonghong; Gao, Fei; Zhang, Huibin; Chen, Wei; Sun, Bingqi; Sha, Wei; Fang, Yong; Jia, Hongyan; Xing, Aiying; Du, Boping; Zheng, Li; Gao, Mengqiu; Zhang, Zongde
T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests, as two commercial blood assays for diagnosing active tuberculosis (ATB), are not yet fully validated. Especially, there are no reports on comparing the efficacy between the two tests in the same population in China. A multicenter, prospective comparison study was undertaken at four hospitals specializing in pulmonary diseases. A total of 746 suspected pulmonary TB were enrolled and categorized, including 185 confirmed TB, 298 probable TB and 263 non-TB. Of 32 patients with indeterminate test results (ITRs), age and underlying disease were associated with the rate of ITRs. Furthermore, the rate of ITRs determined by T-SPOT.TB was lower than QFT-GIT (0.4% vs. 4.3%, P < 0.01). When excluding ITRs, the sensitivities of T-SPOT.TB and QFT-GIT were 85.2% and 84.8%, and specificities of 63.4% and 60.5%, respectively in the diagnosis of ATB. The two assays have an overall agreement of 92.3%, but exhibited a poor linear correlation (r 2 = 0.086) between the levels of interferon-γ release detected by the different assays. Although having some heterogeneity in detecting interferon-γ release, both the QFT-GIT and T-SPOT.TB demonstrated high concordance in diagnosing ATB. However, neither of them showed suitability in the definitive diagnosis of the disease.
Henostroza, German; Topp, Stephanie M.; Hatwiinda, Sisa; Maggard, Katie R.; Phiri, Winifreda; Harris, Jennifer B.; Krüüner, Annika; Kapata, Nathan; Ayles, Helen; Chileshe, Chisela; Reid, Stewart E.
Background Tuberculosis (TB) and human immunodeficiency virus (HIV) represent two of the greatest health threats in African prisons. In 2010, collaboration between the Centre for Infectious Disease Research in Zambia, the Zambia Prisons Service, and the National TB Program established a TB and HIV screening program in six Zambian prisons. We report data on the prevalence of TB and HIV in one of the largest facilities: Lusaka Central Prison. Methods Between November 2010 and April 2011, we assessed the prevalence of TB and HIV amongst inmates entering, residing, and exiting the prison, as well as in the surrounding community. The screening protocol included complete history and physical exam, digital radiography, opt-out HIV counseling and testing, sputum smear and culture. A TB case was defined as either bacteriologically confirmed or clinically diagnosed. Results A total of 2323 participants completed screening. A majority (88%) were male, median age 31 years and body mass index 21.9. TB symptoms were found in 1430 (62%). TB was diagnosed in 176 (7.6%) individuals and 52 people were already on TB treatment at time of screening. TB was bacteriologically confirmed in 88 cases (3.8%) and clinically diagnosed in 88 cases (3.8%). Confirmed TB at entry and exit interventions were 4.6% and 5.3% respectively. Smear was positive in only 25% (n = 22) of bacteriologically confirmed cases. HIV prevalence among inmates currently residing in prison was 27.4%. Conclusion Ineffective TB and HIV screening programs deter successful disease control strategies in prison facilities and their surrounding communities. We found rates of TB and HIV in Lusaka Central Prison that are substantially higher than the Zambian average, with a trend towards concentration and potential transmission of both diseases within the facility and to the general population. Investment in institutional and criminal justice reform as well as prison-specific health systems is urgently required. PMID
Henostroza, German; Topp, Stephanie M; Hatwiinda, Sisa; Maggard, Katie R; Phiri, Winifreda; Harris, Jennifer B; Krüüner, Annika; Kapata, Nathan; Ayles, Helen; Chileshe, Chisela; Reid, Stewart E
Tuberculosis (TB) and human immunodeficiency virus (HIV) represent two of the greatest health threats in African prisons. In 2010, collaboration between the Centre for Infectious Disease Research in Zambia, the Zambia Prisons Service, and the National TB Program established a TB and HIV screening program in six Zambian prisons. We report data on the prevalence of TB and HIV in one of the largest facilities: Lusaka Central Prison. Between November 2010 and April 2011, we assessed the prevalence of TB and HIV amongst inmates entering, residing, and exiting the prison, as well as in the surrounding community. The screening protocol included complete history and physical exam, digital radiography, opt-out HIV counseling and testing, sputum smear and culture. A TB case was defined as either bacteriologically confirmed or clinically diagnosed. A total of 2323 participants completed screening. A majority (88%) were male, median age 31 years and body mass index 21.9. TB symptoms were found in 1430 (62%). TB was diagnosed in 176 (7.6%) individuals and 52 people were already on TB treatment at time of screening. TB was bacteriologically confirmed in 88 cases (3.8%) and clinically diagnosed in 88 cases (3.8%). Confirmed TB at entry and exit interventions were 4.6% and 5.3% respectively. Smear was positive in only 25% (n = 22) of bacteriologically confirmed cases. HIV prevalence among inmates currently residing in prison was 27.4%. Ineffective TB and HIV screening programs deter successful disease control strategies in prison facilities and their surrounding communities. We found rates of TB and HIV in Lusaka Central Prison that are substantially higher than the Zambian average, with a trend towards concentration and potential transmission of both diseases within the facility and to the general population. Investment in institutional and criminal justice reform as well as prison-specific health systems is urgently required.
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
Gonzalez, Jesus M.; Francis, Bryan; Burda, Sherri; Hess, Kaitlyn; Behera, Digamber; Gupta, Dheeraj; Agarwal, Ashutosh Nath; Verma, Indu; Verma, Ajoy; Myneedu, Vithal Prasad; Niedbala, Sam; Laal, Suman
The need for an accurate, rapid, simple and affordable point-of-care (POC) test for Tuberculosis (TB) that can be implemented in microscopy centers and other peripheral health-care settings in the TB-endemic countries remains unmet. This manuscript describes preliminary results of a new prototype rapid lateral flow TB test based on detection of antibodies to immunodominant epitopes (peptides) derived from carefully selected, highly immunogenic M. tuberculosis cell-wall proteins. Peptide selection was initially based on recognition by antibodies in sera from TB patients but not in PPD-/PPD+/BCG-vaccinated individuals from TB-endemic settings. The peptides were conjugated to BSA; the purified peptide-BSA conjugates striped onto nitrocellulose membrane and adsorbed onto colloidal gold particles to devise the prototype test, and evaluated for reactivity with sera from 3 PPD-, 29 PPD+, 15 PPD-unknown healthy subjects, 10 patients with non-TB lung disease and 124 smear-positive TB patients. The assay parameters were adjusted to determine positive/negative status within 15 minutes via visual or instrumented assessment. There was minimal or no reactivity of sera from non-TB subjects with the striped BSA-peptides demonstrating the lack of anti-peptide antibodies in subjects with latent TB and/or BCG vaccination. Sera from most TB patients demonstrated reactivity with one or more peptides. The sensitivity of antibody detection ranged from 28–85% with the 9 BSA-peptides. Three peptides were further evaluated with sera from 400 subjects, including additional PPD-/PPD+/PPD-unknown healthy contacts, close hospital contacts and household contacts of untreated TB patients, patients with non-TB lung disease, and HIV+TB- patients. Combination of the 3 peptides provided sensitivity and specificity>90%. While the final fully optimized lateral flow POC test for TB is under development, these preliminary results demonstrate that an antibody-detection based rapid POC lateral flow test
Scriba, Thomas J; Carpenter, Chelsea; Pro, Sebastian Carrasco; Sidney, John; Musvosvi, Munyaradzi; Rozot, Virginie; Seumois, Grégory; Rosales, Sandy L; Vijayanand, Pandurangan; Goletti, Delia; Makgotlho, Edward; Hanekom, Willem; Hatherill, Mark; Peters, Bjoern; Sette, Alessandro; Arlehamn, Cecilia S Lindestam
Individuals with a history of tuberculosis (TB) disease are at elevated risk of disease recurrence. The underlying cause is not known, but one explanation is that previous disease results in less-effective immunity against Mycobacterium tuberculosis (Mtb). We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection differs as a function of previous diagnosis of active TB disease. T-cell responses to peptide pools in samples collected from an adult screening and an adolescent validation cohort were measured by IFN-γ enzyme-linked immunospot assay or intracellular cytokine staining. We identified a set of "type 2" T-cell epitopes that were recognized at 10-fold-lower levels in Mtb-infected individuals with a history of TB disease less than 6 years ago than in those without previous TB. By contrast, "type 1" epitopes were recognized equally well in individuals with or without previous TB. The differential epitope recognition was not due to differences in HLA class II binding, memory phenotypes, or gene expression in the responding T cells. Instead, "TB disease history-sensitive" type 2 epitopes were significantly (P < 0.0001) more homologous to sequences from bacteria found in the human microbiome than type 1 epitopes. Preferential loss of T-cell reactivity to Mtb epitopes that are homologous to bacteria in the microbiome in persons with previous TB disease may reflect long-term effects of antibiotic TB treatment on the microbiome.
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
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
Sharma, Surendra K.; Ryan, H.; Khaparde, Sunil; Sachdeva, K. S.; Singh, Achintya D.; Mohan, Alladi; Sarin, Rohit; Paramasivan, C N; Kumar, Prahlad; Nischal, Neeraj; Khatiwada, Saurav; Garner, Paul; Tharyan, Prathap
Extrapulmonary tuberculosis (EPTB) is frequently a diagnostic and therapeutic challenge. It is a common opportunistic infection in people living with HIV/AIDS and other immunocompromised states such as diabetes mellitus and malnutrition. There is a paucity of data from clinical trials in EPTB and most of the information regarding diagnosis and management is extrapolated from pulmonary TB. Further, there are no formal national or international guidelines on EPTB. To address these concerns, Indian EPTB guidelines were developed under the auspices of Central TB Division and Directorate of Health Services, Ministry of Health and Family Welfare, Government of India. The objective was to provide guidance on uniform, evidence-informed practices for suspecting, diagnosing and managing EPTB at all levels of healthcare delivery. The guidelines describe agreed principles relevant to 10 key areas of EPTB which are complementary to the existing country standards of TB care and technical operational guidelines for pulmonary TB. These guidelines provide recommendations on three priority areas for EPTB: (i) use of Xpert MTB/RIF in diagnosis, (ii) use of adjunct corticosteroids in treatment, and (iii) duration of treatment. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, which were evidence based, and due consideration was given to various healthcare settings across India. Further, for those forms of EPTB in which evidence regarding best practice was lacking, clinical practice points were developed by consensus on accumulated knowledge and experience of specialists who participated in the working groups. This would also reflect the needs of healthcare providers and develop a platform for future research. PMID:28862176
Khan, Koushambhi Basu
There have been few ethnographic studies on gender aspects of tuberculosis (TB). In this article, drawing on a qualitative study on TB in Delhi slums and through an intersectional analysis of group interviews and personal narratives of women living with TB, I bring forth the "genderization" of TB and the associated sufferings for women. With my findings I demonstrate how gender, in conjunction with other social forces, influences the disease outcomes and stigmatizes women, how lives in slums are uniquely organized by multiple discourses that contribute to the gender makings of TB, and, finally, how women strategize to reduce their burden of illness.
Olowe, Olugbenga A; Makanjuola, Olufunmilola B; Adekanmi, Adeniyi S; Adefioye, Olusola J; Olowe, Rita A
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.
Chabala, Chishala; Turkova, Anna; Thomason, Margaret J; Wobudeya, Eric; Hissar, Syed; Mave, Vidya; van der Zalm, Marieke; Palmer, Megan; Kapasa, Monica; Bhavani, Perumal K; Balaji, Sarath; Raichur, Priyanka A; Demers, Anne-Marie; Hoddinott, Graeme; Owen-Powell, Ellen; Kinikar, Aarti; Musoke, Philippa; Mulenga, Veronica; Aarnoutse, Rob; McIlleron, Helen; Hesseling, Anneke; Crook, Angela M; Cotton, Mark; Gibb, Diana M
Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug
Background An increasing number of researchers are focused on strategies for developing inhibitors of Mycobacterium tuberculosis (Mtb) as tuberculosis (TB) drugs. Results In order to learn from prior work we have collated information on molecules screened versus Mtb and their targets which has been made available in the Collaborative Drug Discovery (CDD) database. This dataset contains published data on target, essentiality, links to PubMed, TBDB, TBCyc (which provides a pathway-based visualization of the entire cellular biochemical network) and human homolog information. The development of mobile cheminformatics apps could lower the barrier to drug discovery and promote collaboration. Therefore we have used this set of over 700 molecules screened versus Mtb and their targets to create a free mobile app (TB Mobile) that displays molecule structures and links to the bioinformatics data. By input of a molecular structures and performing a similarity search within the app we can infer potential targets or search by targets to retrieve compounds known to be active. Conclusions TB Mobile may assist researchers as part of their workflow in identifying potential targets for hits generated from phenotypic screening and in prioritizing them for further follow-up. The app is designed to lower the barriers to accessing this information, so that all researchers with an interest in combatting this deadly disease can use it freely to the benefit of their own efforts. PMID:23497706
Bam, Kiran; Bhatt, Lokesh Prasad; Thapa, Rajshree; Dossajee, Hussein Karimjee; Angdembe, Mirak Raj
Combating tuberculosis (TB) in urban slums is more complex than in rural areas due to reasons such as over-crowding, unhygienic living conditions and poverty. This study aimed to assess illness perception of TB and identify barriers and facilitators for health seeking practice among the residents of Badda slum, Dhaka, Bangladesh. The Badda slum was purposively selected. Convenience sampling was carried out to select participants aged 18 years and above. Twenty two in-depth interviews, two key informants' interviews and participatory rapid appraisal (PRA) were conducted. Data were analyzed manually by using defined a priori codes and color coding of the quotes in data matrix table. TB was commonly recognized as Jokkha (pulmonary TB), Sas rog (disease associated to breathing) followed by TB. More females than males had knowledge about TB related illness. Very few perceived of being at risk of TB despite the high risk behavior and environment. Prime barriers for health seeking practice of TB were cost along with other barriers like prevailing stigma on TB, lack of information on service sites and unavailability of accompanying person. Training and orientation to community organizations and people, awareness on TB and free treatment through advertisements/media, community level diagnostic and home based care were identified as the facilitators for the health seeking practice of TB. Perceptions of TB and knowledge associated with the disease shape the health seeking practice, therefore promotion of media awareness campaign, targeting the people of urban slums for reducing misconceptions and promotion of home based service is needed to encourage health seeking practice in the future.
Background Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of Mycobacterium tuberculosis may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data. Results We developed inTB, a web-based system for integrated warehousing and analysis of clinical, socio-demographic and molecular data for Mycobacterium sp. isolates. As a database it can organize and display data from any of the standard genotyping methods (SNP, MIRU-VNTR, RFLP and spoligotype), as well as an extensive array of clinical and socio-demographic variables that are used in multiple countries to characterize the disease. Through the inTB interface it is possible to insert and download data, browse the database and search specific parameters. New isolates are automatically classified into strains according to an internal reference, and data uploaded or typed in is checked for internal consistency. As an analysis framework, the system provides simple, point and click analysis tools that allow multiple types of data plotting, as well as simple ways to download data for external analysis. Individual trees for each genotyping method are available, as well as a super tree combining all of them. The integrative nature of inTB grants the user the ability to generate trees for filtered subsets of data crossing molecular and clinical/socio-demografic information. inTB is built on open source software, can be easily installed locally and easily adapted to other diseases. Its design allows for use by research
Soares, Patrícia; Alves, Renato J; Abecasis, Ana B; Penha-Gonçalves, Carlos; Gomes, M Gabriela M; Pereira-Leal, José B
Tuberculosis is currently the second highest cause of death from infectious diseases worldwide. The emergence of multi and extensive drug resistance is threatening to make tuberculosis incurable. There is growing evidence that the genetic diversity of Mycobacterium tuberculosis may have important clinical consequences. Therefore, combining genetic, clinical and socio-demographic data is critical to understand the epidemiology of this infectious disease, and how virulence and other phenotypic traits evolve over time. This requires dedicated bioinformatics platforms, capable of integrating and enabling analyses of this heterogeneous data. We developed inTB, a web-based system for integrated warehousing and analysis of clinical, socio-demographic and molecular data for Mycobacterium sp. isolates. As a database it can organize and display data from any of the standard genotyping methods (SNP, MIRU-VNTR, RFLP and spoligotype), as well as an extensive array of clinical and socio-demographic variables that are used in multiple countries to characterize the disease. Through the inTB interface it is possible to insert and download data, browse the database and search specific parameters. New isolates are automatically classified into strains according to an internal reference, and data uploaded or typed in is checked for internal consistency. As an analysis framework, the system provides simple, point and click analysis tools that allow multiple types of data plotting, as well as simple ways to download data for external analysis. Individual trees for each genotyping method are available, as well as a super tree combining all of them. The integrative nature of inTB grants the user the ability to generate trees for filtered subsets of data crossing molecular and clinical/socio-demografic information. inTB is built on open source software, can be easily installed locally and easily adapted to other diseases. Its design allows for use by research laboratories, hospitals or
Jagodziński, Jacek; Zielonka, Tadeusz M
Migration of population contributes to the transmission of tuberculosis (TB), particularly multidrug-resistant tuberculosis. In the countries of Western Europe, the immigrants' inflow contributes to the deterioration of the epidemiological situation. Majority of newly detected TB cases in some countries were affirmed among immigrant and foreign born population. In Poland, this problem has not been investigated up to 2005. The aim of the study was the assessment of the occurrence of tuberculosis in foreigners treated in the Mazovian Centre for Treatment of Lung Diseases and Tuberculosis in Otwock. This work had a retrospective character. The number of cases of tuberculosis in foreigners admitted between 2002 and 2007 was calculated from the data base of the Mazovian Centre for Treatment of Lung Diseases and Tuberculosis; 125 patients, whose basic demographic data, bacteriological status and the radiological changes suggested TB, were included in the study. The foreigners made up to 0.5-1.7% all tuberculosis cases treated in Mazovian Centre for Treatment of Lung Diseases and Tuberculosis. Among confirmed cases, twenty four nationalities were seen. Nationals of the Russian Federation (coming from the Republic of Chechnya) formed the biggest group (24%), followed by the Vietnamese (21%) and the Ukrainians (12%). Most of all cases were young men (77%; average age - 34 years). Children made up to 12% of all cases. Tuberculosis of lungs was predominating, and there were culture confirmed extrapulmonary locations in 13.6% of cases. Bacteriological confirmation was achieved in 53% of cases, but up to 22.7% cases were resistant to one of the antituberculosis medicines and 13.6% was multidrug-resistant. Despite the fact, that foreigners made up a small proportion among all the patient treated for tuberculosis in Mazovia, their number systematically increases. High proportion of multidrug-resistant tuberculosis reported in foreign-born cases is a concern.
Ordway, Diane J; Martins, Marta S; Costa, Leonor M; Freire, Mónica S; Arroz, Maria J; Dockrell, Hazel M; Ventura, Fernando A
The study was designed to compare immune responses to Mycobacterium tuberculosis bacilli and antigens in healthy Portuguese subjects and pulmonary tuberculosis patients (TB), and to correlate immune status with clinical severity of tuberculosis disease. PBMC were cultured and stimulated with live and killed M. tuberculosis H37Rv and purified protein derivative (PPD) and lymphoproliferation and production of IFN-gamma and IL-5/IL-4 by these cultures were evaluated by the use of ELISA and multi-parameter flow cytometry. PBMC from 30 tuberculosis patients demonstrated significantly reduced amounts of proliferation and IFN-gamma when stimulated with live M. tuberculosis compared the control group. Of 15 tuberculosis patients tested for intracellular IL-4 following stimulation with M. tuberculosis, 7 showed greatly increased IL-4 production in CD8+ and gammadelta+ T cells. Tuberculosis patients demonstrated an increase of intracellular IL-4 after PBMC were stimulated with live M. tuberculosis in the CD4+ phenotype, but more notably in CD8+ and gammadelta TCR+ subsets. Increased production of IL-4 in tuberculosis patients was primarily in individuals with advanced involvement of lung parenchymal with high bacterial loads in sputum. These results suggest that an alteration in type 1 and type 2 cytokine balance can occur in patients with tuberculosis at an advanced clinical stage of disease.
Paul, Sukanta; Akter, Rahima; Aftab, Afzal; Khan, Antora M; Barua, Mrittika; Islam, Shayla; Islam, Akramul; Husain, Ashaque; Sarker, Malabika
Bangladesh National Tuberculosis (TB) Control Programme adopted a number of strategies to facilitate TB diagnosis and treatment. 'Advocacy, Communication and Social Mobilization' (ACSM) was one of the key strategies implemented by BRAC (Bangladesh Rural Advancement Committee, a non-governmental development organization) TB control program. The purpose of this study is to assess the knowledge and attitudes of the key community members (KCMs) participated in ACSM in BRAC TB control areas. This study combined quantitative and qualitative methods using a mixed method approach. KCMs in three districts with low TB case detection rates were targeted to assess the ACSM program. The quantitative survey using a multi-stage random-sampling strategy was conducted among 432 participants. The qualitative study included in-depth interviews (IDIs) of a sub sample of 48 respondents. For quantitative analysis, descriptive statistics were reported using frequencies, percentages, and Chi square tests, while thematic analysis was used for qualitative part. Most (99%) of the participants had heard about TB, and almost all knew that TB is a contagious yet curable disease. More than half (53%) of the KCMs had good knowledge regarding TB, but BRAC workers were found to be more knowledgeable compared to other KCMs. However, considerable knowledge gaps were observed among BRAC community health workers. Qualitative results revealed that the majority of the KCMs were aware about the signs, symptoms and transmission pathways of TB and believed that smoking and addiction were the prime causes of transmission of TB. The knowledge about child TB was poor even among BRAC health workers. Stigma associated with TB was not uncommon. Almost all respondents expressed that young girls diagnosed with TB. This study finding has revealed varying levels of knowledge and mixed attitudes about TB among the KCMs. It also provides insight on the poor knowledge regarding child TB and indicate that despite the
... 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 ...
Igari, Hidetoshi; Watanabe, Akira; Ichimura, Yasunori; Sakurai, Takayuki; Taniguchi, Toshibumi; Ishiwada, Naruhiko
QuantiFERON-TB gold in-tube has been used for screening latent tuberculosis infection in newly employed health care workers in Japan. There have been a few studies concerning quality control. We retrospectively analysed QuantiFERON-TB gold in-tube results in a hospital in Japan. Interferon-γ values in three blood collection tubes for QuantiFERON-TB gold in-tube were analysed in association with the positivity rate. The data set consisted of health care workers aged 20-29 years during the 7 years between 2010 and 2016. The yearly QuantiFERON-TB gold in-tube positivity rate was 0.9%, 16.4%, 3.0%, 39.3%, 2.8%, 0.9% and 1.5%, and was extremely high in 2011 and 2013. The interferon-γ values in the tuberculosis antigen tube were elevated in these two years, as indicated by higher median and wider interquartile range. The interferon-γ value in the negative control tube was also higher in 2011. The higher interferon-γ values in collection tubes (tuberculosis antigen tube and/or negative control tube) resulted in higher QuantiFERON-TB gold in-tube positivity rate. The distribution of interferon-γ in tuberculosis antigen tube and negative control tube, as evaluated by median and interquartile range, proved to be an effective index for the quality control of QuantiFERON-TB gold in-tube. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Flandrois, Jean-Pierre; Lina, Gérard; Dumitrescu, Oana
Tuberculosis is an infectious bacterial disease caused by Mycobacterium tuberculosis. It remains a major health threat, killing over one million people every year worldwide. An early antibiotic therapy is the basis of the treatment, and the emergence and spread of multidrug and extensively drug-resistant mutant strains raise significant challenges. As these bacteria grow very slowly, drug resistance mutations are currently detected using molecular biology techniques. Resistance mutations are identified by sequencing the resistance-linked genes followed by a comparison with the literature data. The only online database is the TB Drug Resistance Mutation database (TBDReaM database); however, it requires mutation detection before use, and its interrogation is complex due to its loose syntax and grammar. The MUBII-TB-DB database is a simple, highly structured text-based database that contains a set of Mycobacterium tuberculosis mutations (DNA and proteins) occurring at seven loci: rpoB, pncA, katG; mabA(fabG1)-inhA, gyrA, gyrB, and rrs. Resistance mutation data were extracted after the systematic review of MEDLINE referenced publications before March 2013. MUBII analyzes the query sequence obtained by PCR-sequencing using two parallel strategies: i) a BLAST search against a set of previously reconstructed mutated sequences and ii) the alignment of the query sequences (DNA and its protein translation) with the wild-type sequences. The post-treatment includes the extraction of the aligned sequences together with their descriptors (position and nature of mutations). The whole procedure is performed using the internet. The results are graphs (alignments) and text (description of the mutation, therapeutic significance). The system is quick and easy to use, even for technicians without bioinformatics training. MUBII-TB-DB is a structured database of the mutations occurring at seven loci of major therapeutic value in tuberculosis management. Moreover, the system provides
Atre, Sachin R; Mistry, Nerges F
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.
Van der Westhuizen, Helene-Mari; Dramowski, Angela
Medical students acquire latent tuberculosis (TB) infection at a rate of 23 cases/100 person-years. The frequency and impact of occupational TB disease in this population are unknown. A self-administered questionnaire was distributed via email and social media to current medical students and recently graduated doctors (2010 - 2015) at two medical schools in Cape Town. Individuals who had developed TB disease as undergraduate students were eligible to participate. Quantitative and qualitative data collected from the questionnaire and semi-structured interviews were analysed with descriptive statistics and a framework approach to identify emerging themes. Twelve individuals (10 female) reported a diagnosis of TB: pulmonary TB (n=6), pleural TB (n=3), TB lymphadenitis (n=2) and TB spine (n=1); 2/12 (17%) had drug-resistant disease (DR-TB). Mean diagnostic delay post consultation was 8.1 weeks, with only 42% of initial diagnoses being correct. Most consulted private healthcare providers (general practitioners (n=7); pulmonologists (n=4)), and nine underwent invasive procedures (bronchoscopy, pleural fluid aspiration and tissue biopsy). Substantial healthcare costs were incurred (mean ZAR25 000 for drug-sensitive TB, up to ZAR104 000 for DR-TB). Students struggled to obtain treatment, incurred high transport costs and missed academic time. Students with DR-TB interrupted their studies and experienced severe side-effects (hepatotoxicity, depression and permanent ototoxicity). Most participants cited poor TB infection-control practices at their training hospitals as a major risk factor for occupational TB. Undergraduate medical students in Cape Town are at high risk of occupationally acquired TB, with an unmet need for comprehensive occupational health services and support.
Bunyasi, Erick Wekesa; Schmidt, Bey-Marrie; Abdullahi, Leila Hussein; Mulenga, Humphrey; Tameris, Michele; Luabeya, Angelique; Shenje, Justin; Scriba, Thomas; Geldenhuys, Hennie; Wood, Robin; Hatherill, Mark
Almost a third of the world population has latent tuberculosis (TB) infection (LTBI), ∼10 million of whom develop TB disease annually, despite existence of effective, but lengthy, preventive and curative drug regimens. Although adolescents appear to have a very high force of LTBI, their reported incidence of TB disease is less than that of their corresponding general population. The few available studies on adolescent TB infection and disease prevalence are not sufficient to address the apparent discordance between rates of infection and disease in high TB burden countries in Africa. Therefore, we aim to perform a systematic review to examine the relationship between adolescent LTBI and TB disease, benchmarked against national TB disease burden data. A comprehensive literature search will be performed for cross-sectional studies and screening data in cohort studies to determine the prevalence of LTBI and TB disease among adolescents in high TB burden countries in Africa in the following databases: PubMed , Scopus , Cochrane library , Web of Science , Africa Wide , CINAHL and the Africa Index Medicus . This will be supplemented by a search of reference lists of selected articles for potentially relevant articles. We will restrict our search to articles published in the English language between 1990 and 2016 among adolescents in order to obtain estimates reflective of the mature HIV epidemic in most high TB burden countries in Africa that occurred over this critical period. Primary end points are: prevalence of LTBI and TB disease. We will use the random-effects or fixed-effects modelling for our meta-analysis based on heterogeneity estimates. No ethics approval is required given that this is a systematic review. Findings will be disseminated in a peer-reviewed journal in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). CRD42015023495. Published by the BMJ Publishing Group Limited. For permission to use (where not already
Hermans, Sabine M; Elbireer, Sawsan; Tibakabikoba, Harriet; Hoefman, Bas J; Manabe, Yukari C
Background Low tuberculosis (TB) treatment completion rates in sub-Saharan Africa are an important driver of multidrug resistance. Mobile technology-based interventions have been shown to improve adherence to antiretroviral therapy in sub-Saharan Africa. We aimed to test the effect of a short-message service (SMS) intervention on loss to follow-up (LFU). Materials and methods In this quasi-experimental study, all adult, literate, HIV-infected patients with mobile phone access diagnosed with TB between November 2010 and October 2011 in an urban clinic in Uganda were eligible to receive adherence and appointment reminders and educational quizzes during the first 8 weeks of TB treatment. Their risk of LFU in the first 8 weeks of treatment was compared with that of patients starting treatment between March 2009 and August 2010 using logistic regression. Results One of 183 (0.5%) enrolled patients was lost to FU during the intervention compared to six of 302 (2.0%) in the preintervention control group (RR 0.27, 95% CI 0.03–2.07; P=0.22). The SMS intervention was rated as very helpful by 96%. Barriers identified included interrupted phone access (26%, median 14 days) and difficulties responding by SMS. The response rate to educational quizzes was below 10%. There were no unintentional disclosures of TB or HIV status due to the intervention. Conclusion An SMS reminder service did not show a clear effect on short-term risk of LFU in this study, which was underpowered due to a lower baseline risk in the control group than expected. The SMS-reminder service was rated highly, and there were no breaches of confidentiality. Important technological barriers have implications for larger-scale implementation, not only for TB but also other disease modalities. PMID:28919720
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
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.
Sintayehu, Dejene W; Heitkönig, Ignas M A; Prins, Herbert H T; Tessema, Zewdu K; DE Boer, Willem F
Current theories on diversity-disease relationships describe host species diversity and species identity as important factors influencing disease risk, either diluting or amplifying disease prevalence in a community. Whereas the simple term 'diversity' embodies a set of animal community characteristics, it is not clear how different measures of species diversity are correlated with disease risk. We therefore tested the effects of species richness, Pielou's evenness and Shannon's diversity on bovine tuberculosis (bTB) risk in cattle in the Afar Region and Awash National Park between November 2013 and April 2015. We also analysed the identity effect of a particular species and the effect of host habitat use overlap on bTB risk. We used the comparative intradermal tuberculin test to assess the number of bTB-infected cattle. Our results suggested a dilution effect through species evenness. We found that the identity effect of greater kudu - a maintenance host - confounded the dilution effect of species diversity on bTB risk. bTB infection was positively correlated with habitat use overlap between greater kudu and cattle. Different diversity indices have to be considered together for assessing diversity-disease relationships, for understanding the underlying causal mechanisms. We posit that unpacking diversity metrics is also relevant for formulating disease control strategies to manage cattle in ecosystems characterized by seasonally limited resources and intense wildlife-livestock interactions.
Mc Laughlin, Anne Marie; O’Donnell, Rory A; Gibbons, Noel; Scully, Mary; O’Flangan, Darina; Keane, Joseph
We describe a case of a 25 year old female from Lithuania who presented with a productive cough. Chest radiograph demonstrated an infiltrate in the left upper lobe and a cavitating lesion in the right middle lobe. Sensitivity testing of her sputum led to a diagnosis of extensively drug-resistant tuberculosis (XDR-TB). This is the first case in Ireland and highlights the need for physicians to be aware of the possibility of XDR-TB. Moreover it underlines the need for improvement in service provision in terms of a TB reference laboratory and TB clinics. PMID:19340317
López-Gatell, H; Cole, SR; Margolick, JB; Witt, MD; Martinson, J; Phair, JP; Jacobson, LP
Evidence regarding the effect of tuberculosis disease (TB) on HIV disease progression at the population level remains inconclusive. We estimated the effect of incident TB on time to acquired immunodeficiency syndrome (AIDS)-related death, using a marginal structural Cox model. Between 1984 and 2005, 2,882 HIV-infected men in the Multicenter AIDS Cohort Study contributed 21,914 person-years while followed for a median of 5.4 years. At study entry, the median CD4 cell count and HIV-1 RNA viral load were 533 cells/mm3 (interquartile range [IQR], 365 – 737) and 12,953 copies/ml (IQR, 2,453 – 48,540), respectively. This study was performed in a setting with a modest exposure to HAART; 8,295 of 23,801 (35%) person-years were followed during the HAART era. Fifteen men incurred incident TB, yielding a TB incidence of 7 (95% confidence interval [CI]: 4, 14) per 10,000 person-years, and 1,072 died of AIDS-related causes. Accounting for potential confounders, including CD4 cell count and viral load, the hazard of AIDS-related death was 2.4 times larger for the person-time with TB, compared to the person-time without TB (95% CI: 1.2, 4.7). Results underscore the importance of avoiding TB by using preventive interventions, such as treatment of latent TB infection, particularly in populations with a large prevalence of HIV/TB co-infected individuals. PMID:18753866
Tuberculosis (TB) is commonly viewed as a pulmonary disease, in which infection, persistence, induction of pathology and bacterial expulsion all occur in the lungs. In this model, enlarged lymph nodes represent reactive adenitis and spread of organisms to extrapulmonary sites results in a non-transm...
Prevalence of post-traumatic stress symptoms and associated factors in tuberculosis (TB), TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa.
Peltzer, Karl; Naidoo, Pamela; Matseke, Gladys; Louw, Julia; McHunu, Gugu; Tutshana, Bomkazi
High rates of tuberculosis (TB) and TB/HIV co-infection is often linked with mental health issues such as post-traumatic stress disorder (PTSD) symptoms, which is further associated with poor health outcomes. In a country such as South Africa where rates of these infectious diseases are high, it is concerning that there is limited/no data on prevalence rates of mental disorders such as PTSD and its associated factors. Therefore, the aim of this study was to establish the prevalence of PTSD symptoms and associated factors in TB, TB retreatment and/or TB-HIV co-infected primary public health-care patients in three districts in South Africa. Brief screening self-report tools were used to measure: PTSD symptoms, psychological distress (anxiety and depression) and alcohol misuse. Other relevant measures, such as adherence to medication, stressful life events and sexual risk-taking behaviours, were obtained through structured questions. A total of 4900 public primary care adult patients from clinics in high TB burden districts from three provinces in South Africa participated. All the patients screened positive for TB (either new or retreatment cases). The prevalence of PTSD symptoms was 29.6%. Patients who screened positive for PTSD symptoms and psychological distress were more likely to be on antidepressant medication. Factors that predicted PTSD symptoms were poverty, residing in an urban area, psychological distress, suicide attempt, alcohol and/or drug use before sex, unprotected sex, TB-HIV co-infected and the number of other chronic conditions. Health-care systems should be strengthened to improve delivery of mental health care, by focusing on existing programmes and activities, such as those which address the prevention and treatment of TB and HIV.
Bai, Fengmin; Zhang, Shu; Jiang, Ting; Shen, Jie; Zhu, Qi; Yue, Tao; Shao, Lingyun; Gao, Yan; Feng, Yun; Weng, Xinhua; Zou, Hejian; Zhang, Ying
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
Differential cellular recognition pattern to M. tuberculosis targets defined by IFN-γ and IL-17 production in blood from TB + patients from Honduras as compared to health care workers: TB and immune responses in patients from Honduras.
Alvarez-Corrales, Nancy; Ahmed, Raija K; Rodriguez, Carol A; Balaji, Kithiganahalli N; Rivera, Rebeca; Sompallae, Ramakrishna; Vudattu, Nalini K; Hoffner, Sven E; Zumla, Alimuddin; Pineda-Garcia, Lelany; Maeurer, Markus
A better understanding of the quality of cellular immune responses directed against molecularly defined targets will guide the development of TB diagnostics and identification of molecularly defined, clinically relevant M.tb vaccine candidates. Recombinant proteins (n = 8) and peptide pools (n = 14) from M. tuberculosis (M.tb) targets were used to compare cellular immune responses defined by IFN-γ and IL-17 production using a Whole Blood Assay (WBA) in a cohort of 148 individuals, i.e. patients with TB + (n = 38), TB- individuals with other pulmonary diseases (n = 81) and individuals exposed to TB without evidence of clinical TB (health care workers, n = 29). M.tb antigens Rv2958c (glycosyltransferase), Rv2962c (mycolyltransferase), Rv1886c (Ag85B), Rv3804c (Ag85A), and the PPE family member Rv3347c were frequently recognized, defined by IFN-γ production, in blood from healthy individuals exposed to M.tb (health care workers). A different recognition pattern was found for IL-17 production in blood from M.tb exposed individuals responding to TB10.4 (Rv0288), Ag85B (Rv1886c) and the PPE family members Rv0978c and Rv1917c. The pattern of immune target recognition is different in regard to IFN-γ and IL-17 production to defined molecular M.tb targets in PBMCs from individuals frequently exposed to M.tb. The data represent the first mapping of cellular immune responses against M.tb targets in TB patients from Honduras.
Kerr, Joanne; Elwell, Jack
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)
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
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
N'guessan, K; Horo, K; Coulibaly, I; Adegbele, J; Kouame-Adjei, N; Seck-Angu, H; Guei, A; Kouakou, J; Dosso, M
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
... chest x-ray, or positive sputum smear or culture • • Has active TB bacteria in his/her body • • Usually feels sick and may have symptoms such as coughing, fever, and weight loss • • May spread TB bacteria to others • • Needs treatment ...
Welch, Ryan J.; Lawless, Kathleen M.
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
Matsumoto, Kenji; Komukai, Jun; Tsuda, Yuko; Furukawa, Kanae; Saito, Kazumi; Hirota, Satoshi; Koda, Shinichi; Kasai, Sachi; Shimouchi, Akira
QuantiFERON® TB-Gold In-Tube (3G) testing was performed on tuberculosis-positive index cases and their contacts. The purpose of this study was to evaluate the relationship between 3G test results and the subsequent development of tuberculosis, and to identify effective strategies to prevent the onset of tuberculosis. Index cases and their contacts were subjected to 3G testing in a contact investigation in Osaka City in 2011-2012. For index cases, sputum smears were tested, and the infecting organism was identified. For the contacts, the following information was collected: age, results of 3G testing, presence or absence of latent tuberculosis infection (LTBI) treatment, and onset of tuberculosis disease within 2 years of follow-up from the last contact with the index cases. (1) There were 830 index cases, including 774 subjects with pulmonary tuberculosis (93.3%) and 3 with laryngeal tuberculosis (0.4%). From sputum smear tests, 726 patients (87.5%) were determined to be 3G positive, and 83 (10.0%) were determined to be 3G negative. (2) In total, 2,644 contacts were subjected to 3G testing. Of these, 2,072 patients (78.4%) tested negative, 196 (7.4%) showed an equivocal result, and 375 (14.2%) tested positive. Their mean ages were 33.7, 38.0, and 38.8 years, respectively, showing significant differences in tuberculosis status according to age (P < 0.001). (3) Among the 2,072 3G-negative contacts, tuberculosis developed in 2 (0.1%) of 2063. None of these contacts was treated for LTBI. Among the 375 3G-positive contacts, tuberculosis developed in 36 (36.0%) of 100 subjects that were not LTBI treated, while tuberculosis developed in 3 (1.1 %) of 275 subjects that were LTBI treated. A significant difference in the incidence of tuberculosis between treated and untreated 3G-positive contacts was observed (P < 0.001). Tuberculosis developed in a high proportion of 3G-positive contacts that were not LTBI treated, suggesting the need for preventive management of 3G
Naidoo, Pamela; Peltzer, Karl; Louw, Julia; Matseke, Gladys; McHunu, Gugu; Tutshana, Bomkazi
Despite the downward trend in the absolute number of tuberculosis (TB) cases since 2006 and the fall in the incidence rates since 2001, the burden of disease caused by TB remains a global health challenge. The co-infection between TB and HIV adds to this disease burden. TB is completely curable through the intake of a strict anti-TB drug treatment regimen which requires an extremely high and consistent level of adherence.The aim of this study was to investigate factors associated with adherence to anti-TB and HIV treatment drugs. A cross-sectional survey method was used. Three study districts (14 primary health care facilities in each) were selected on the basis of the highest TB caseload per clinic. All new TB and new TB retreatment patients were consecutively screened within one month of anti-tuberculosis treatment. The sample comprised of 3107 TB patients who had been on treatment for at least three weeks and a sub-sample of the total sample were on both anti-TB treatment and anti-retro-viral therapy(ART) (N = 757). Data collection tools included: a Socio-Demographic Questionnaire; a Post-Traumatic-Stress-Disorder (PTSD) Screen; a Psychological Distress Scale; the Alcohol Use Disorder Identification Test (AUDIT); and self-report measures of tobacco use, perceived health status and adherence to anti-TB drugs and ART. The majority of the participants (N = 3107) were new TB cases with a 55.9% HIV co-infection rate in this adult male and female sample 18 years and older. Significant predictors of non-adherence common to both anti-TB drugs and to dual therapy (ART and anti-TB drugs) included poverty, having one or more co-morbid health condition, being a high risk for alcohol mis-use and a partner who is HIV positive. An additional predictor for non-adherence to anti-TB drugs was tobacco use. A comprehensive treatment programme addressing poverty, alcohol mis-use, tobacco use and psycho-social counseling is indicated for TB patients (with and without HIV
Hillemann, D; Rüsch-Gerdes, S; Richter, E
The usefulness of a low-tech rapid test for culture confirmation of Mycobacterium tuberculosis complex, Capilia TB, was tested on 172 mycobacteria-positive clinical samples. The overall sensitivity and specificity were 92.4% and 100%, respectively. In three of nine false-negative isolates a mutation in the mpb64 gene could be detected.
Takasaki, Jin; Manabe, Toshie; Morino, Eriko; Muto, Yoshikazu; Hashimoto, Masao; Iikura, Motoyasu; Izumi, Shinyu; Sugiyama, Haruhito; Kudo, Koichiro
The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination of its diagnostic accuracy is crucial before it is launched in Japan. We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared. The sensitivity of the QFT-Plus was 98.9% (95% confidence interval [CI], 0.934-0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929-0.998) and T-SPOT (96.9%; 95% CI, 0.914-0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934-0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs. The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Demile, Biresaw; Zenebu, Amare; Shewaye, Haile; Xia, Siqing; Guadie, Awoke
Ethiopia is one of the world health organization defined higher tuberculosis (TB) burden countries where the disease remains a massive public health threat. This study aimed to identify the prevalence and associated factors of multidrug-resistant tuberculosis (MDR-TB) using all armed force and civilian TB attendants in a tertiary level armed force hospital, where data for MDR-TB are previously unpublished. Cross-sectional study was conducted from September 2014 to August 2015 in a tertiary level Armed Force Referral and Teaching Hospital (AFRTH), Ethiopia. Armed force members (n = 251) and civilians (n = 130) which has been undergone TB diagnosis at AFRTH were included. All the specimens collected were subjected to microscopic smear observation, culture growth and drug susceptibility testing. Data were analyzed using statistical package for social sciences following binary logistic regression and Chi-square. P-values < 0.05 were considered statistically significant. Among 381 TB patients, 355 (93.2%) new and 26 (6.8%) retreatment cases were identified. Culture and smear positive TB cases were identified in 297 (77.9%) and 252 (66.1%) patients, respectively. The overall prevalence of MDR-TB in AFRTH was found 1.8% (1.3% for armed force members and 0.5% for civilian patients) all of which were previously TB treated cases. The entire treatment success rates were 92.6% achieved highest in the armed force (active and pension) than the civilian patients. The failure and dead cases were also found 2.5 and 4.6%, respectively. Using bivariate analysis, category of attendants and TB contact history were strong predictors of MDR-TB in armed force and civilian patients. Moreover, human immunodeficiency virus (HIV) infection also identified a significant (OR = 14.6; 95% CI = 2.3-92.1; p = 0.004) predicting factor for MDR-TB in armed force members. However, sex, age and body mass index were not associated factor for MDR-TB. In AFRTH, lower prevalence of
Shaik, Monisha; Danquah, Cynthia Amaning
ABSTRACT To say that tuberculosis (TB) has regained a strong foothold in the global human health and wellbeing scenario would be an understatement. Ranking alongside HIV/AIDS as the top reason for mortality due to a single infectious disease, the impact of TB extends far into socio-economic context worldwide. As global efforts led by experts and political bodies converge to mitigate the predicted outcome of growing antimicrobial resistance, the academic community of students, practitioners and researchers have mobilised to develop integrated, inter-disciplinary programmes to bring the plans of the former to fruition. Enabling this crucial requirement for unimpeded dissemination of scientific discovery was the TB Summit 2016, held in London, United Kingdom. This report critically discusses the recent breakthroughs made in diagnostics and treatment while bringing to light the major hurdles in the control of the disease as discussed in the course of the 3-day international event. Conferences and symposia such as these are the breeding grounds for successful local and global collaborations and therefore must be supported to expand the understanding and outreach of basic science research. PMID:27813702
Tanner, Lloyd; Denti, Paolo; Wiesner, Lubbe; Warner, Digby F
Anti-tuberculosis (TB) drugs possess diverse abilities to penetrate the different host tissues and cell types in which infecting Mycobacterium tuberculosis bacilli are located during active disease. This is important since there is increasing evidence that the respective "lesion-penetrating" properties of the front-line TB drugs appear to correlate well with their specific activity in standard combination therapy. In turn, these observations suggest that rational efforts to discover novel treatment-shortening drugs and drug combinations should incorporate knowledge about the comparative abilities of both existing and experimental anti-TB agents to access bacilli in defined physiological states at different sites of infection, as well as avoid elimination by efflux or inactivation by host or bacterial metabolism. However, while there is a fundamental requirement to understand the mode of action and pharmacological properties of any current or experimental anti-TB agent within the context of the obligate human host, this is complex and, until recently, has been severely limited by the available methodologies and models. Here, we discuss advances in analytical models and technologies which have enabled investigations of drug metabolism and pharmacokinetics (DMPK) for new TB drug development. In particular, we consider the potential to shift the focus of traditional pharmacokinetic-pharmacodynamic analyses away from plasma to a more specific "site of action" drug exposure as an essential criterion for drug development and the design of dosing strategies. Moreover, in summarising approaches to determine DMPK data for the "unit of infection" comprising host macrophage and intracellular bacillus, we evaluate the potential benefits of including these analyses at an early stage in the preclinical drug development algorithm. © 2018 IUBMB Life, 2018. © 2018 International Union of Biochemistry and Molecular Biology.
Adane, Kelemework; Spigt, Mark; Johanna, Laturnus; Noortje, Dorscheidt; Abera, Semaw Ferede; Dinant, Geert-Jan
Although awareness is an important component in tuberculosis (TB) control, we do not know how much Ethiopian prisoners know about TB. This study assessed the level of knowledge, attitudes, and practices (KAP) of prisoners about TB in eight northern Ethiopian prisons. Data were collected cross-sectionally from 615 prisoners using a standardized questionnaire between March and May 2016. The outcome variables were defined considering the basic elements about TB. Out of 615 prisoners, only 37.7% mentioned bacteria as a cause of TB while 21.7% related TB to exposure to cold wind. Eighty-eight per cent correctly mentioned the aerial route of TB transmission and 27.3% had perceived stigma towards TB. The majority (63.7%) was not aware of the possibility of getting multi-drug-resistant strains when they would not adhere to treatment. Overall, only 24% knew the basic elements about TB, 41% had favorable attitudes, and 55% had a good practice. Prisoners who were urban residents were generally more knowledgeable than rural residents (adjusted OR = 2.16; 95% CI = 1.15-4.06). Illiterates were found to be less knowledgeable (adjusted OR = 0.17; 95% CI = 0.06-0.46), less likely to have a favorable attitude (adjusted OR = 0.31; 95% CI = 0.15-0.64), and less good practice (adjusted OR = 0.35; 95% CI = 0.18-0.69). Significant differences were also observed between the different study prisons. Knowledge of prisoners regarding the cause of TB and consequences of non-adherence to TB treatment was low. Knowledge on the transmission, symptoms, and prevention was fairly high. Health education interventions, focused on the cause and the translation of the knowledge to appropriate practices, are needed in all the study prisons. Special attention should be given to less educated prisoners, and to prisons with a high number of prisoners and those in remote areas.
Shakoor, Sadia; Qamar, Farah Naz; Mir, Fatima; Zaidi, Anita; Hasan, Rumina
Paediatric tuberculosis (TB) has long been an evasive entity for public health practitioners striving to control the disease. Owing to difficulty in diagnosis of paediatric TB, incidence estimates based on current case detection fall short of actual rates. The four high-burden countries in South Asia (SA-HBC)-Afghanistan, Pakistan, India and Bangladesh-alone account for >75% of missed TB cases worldwide. It follows that these countries are also responsible for a large although unmeasured proportion of missed paediatric cases. In view of current Millennium Development Goals recommending a scale-up of paediatric TB detection and management globally, there is a dire need to improve paediatric TB programmes in these high-burden countries. Inherent problems with diagnosis of paediatric TB are compounded by programmatic and social barriers in SA-HBC. We have reviewed the current situation of TB control programmes in SA-HBC countries based on published statistics and performed a strengths, weaknesses, opportunities and threats situational analysis with a view towards identifying critical issues operant in the region posing barriers to improving paediatric TB control. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Koesoemadinata, Raspati C; McAllister, Susan M; Soetedjo, Nanny N M; Febni Ratnaningsih, Dwi; Ruslami, Rovina; Kerry, Sarah; Verrall, Ayesha J; Apriani, Lika; van Crevel, Reinout; Alisjahbana, Bachti; Hill, Philip C
Screening and treatment of latent TB infection (LTBI) and TB disease could reduce diabetes mellitus (DM)-associated TB. We aimed to describe the prevalence of LTBI and pulmonary TB among patients with DM in a TB-endemic setting. Patients with DM attending a hospital and community centres in Bandung, Indonesia, underwent LTBI screening using interferon gamma release assay (IGRA). TB was investigated by sputum smear, culture and x-ray. TB contacts from a parallel study were age- and sex-matched to patients with DM to compare LTBI and TB disease prevalence. Of 682 patients with DM screened, 651 (95.5%) were eligible. Among 'TB disease-free' patients, LTBI prevalence was 38.9% (206/530; 95% CI 34.7-43.2). Patients with DM were less likely to be IGRA positive than TB contacts (38.6%, 54/140; 95% CI 30.5-46.6 vs 68.6%, 96/140; 95% CI 60.9-72.3: p<0.001); but had a higher disease prevalence (4.9%, 8/164; 95% CI 1.6-8.2 vs 1.2%, 2/164; 95% CI -0.5 to 2.9: p=0.054). Patients with DM in crowded households had increased risk of LTBI (AOR 1.71; 95% CI 1.19-2.45). LTBI prevalence in patients with DM was lower than in household contacts, but patients with DM were more likely to have TB disease. Further studies should explore possible benefits of LTBI screening and preventive therapy in patients with DM in TB-endemic settings. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
McIvor, Amanda; Koornhof, Hendrik; Kana, Bavesh Davandra
Tuberculosis (TB) disease can be characterized by genotypic and phenotypic complexity in Mycobacterium tuberculosis bacilli within a single patient. This microbiological heterogeneity has become an area of intense study due its perceived importance in drug tolerance, drug resistance and as a surrogate measure of transmission rates. This review presents a descriptive analysis of research describing the prevalence of mixed-strain TB infections in geographically distinct locations. Despite significant variation in disease burden and a rampant human immunodeficiency virus (HIV)-TB co-epidemic, there was no difference in the prevalence range of mixed infections reported in African countries when compared to the rest of the world. The occurrence of recurrent TB was associated with a higher prevalence of mixed-strain infections, but this difference was not reported as statistically significant. These interpretations were limited by differences in the design and overall size of the studies assessed. Factors such as sputum quality, culture media, number of repeated culture steps, molecular typing methods and HIV-infection status can affect the detection of mixed-strain infection. It is recommended that future clinical studies should focus on settings with varying TB burdens, with a common sample processing protocol to gain further insight into these phenomena and develop novel transmission blocking strategies. © FEMS 2017. All rights reserved. For permissions, please e-mail: email@example.com.
Baquero-Artigao, F; Mellado Peña, M J; Del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L
Tuberculosis (TB) screening in pregnancy using tuberculin skin test (TST) is recommended in case of symptoms of TB disease, close contact with a patient with infectious TB, or high risk of developing active disease. The new interferon gamma release assay (IGRA) tests are recommended in BCG-vaccinated pregnant women with positive TST and no known risk factors for TB, and in those immunocompromised, with clinical suspicion of TB but negative TST. TB diagnosis is difficult due to the non-specific symptoms, the increased frequency of extrapulmonary disease, the delay in radiological examinations, and the high rate of tuberculin anergy. Neonatal TB can be acquired in utero (congenital TB), or through airborne transmission after delivery (postnatal TB). Congenital TB is extremely rare and does not cause fetal malformations. It may be evident at birth, although it usually presents after the second week of life. In newborns with no family history of TB, the disease should be considered in cases of miliary pneumonia, hepatosplenomegaly with focal lesions, or lymphocytic meningitis with hypoglycorrhachia, especially in those born to immigrants from high TB-burden countries. TST is usually negative, and IGRAs have lower sensitivity than in older children. However, the yield of acid-fast smear and culture is higher, mostly in congenital TB. Molecular diagnosis techniques enable early diagnosis and detection of drug resistance mutations. There is a substantial risk of disseminated disease and death. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.
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 ...
Diel, Roland; Vandeputte, Joris; de Vries, Gerard; Stillo, Jonathan; Wanlin, Maryse; Nienhaus, Albert
Without better vaccines it is unlikely that tuberculosis (TB) will ever be eliminated. An investment of ∼ €560 million is considered necessary to develop a new, effective vaccine in the European Union (EU). However, less is known about the costs of TB disease in the EU. We performed a systematic review of literature and institutional websites addressing the 27 EU members to summarise cost data. We searched MEDLINE, EMBASE and Cochrane bibliographies for relevant articles. Combining direct and indirect costs, we arrived at an average per-TB case costs in the original EU-15 states plus Cyprus, Malta and Slovenia of €10 282 for drug-susceptible TB, €57 213 for multidrug resistant (MDR)-TB and €170 744 for extensively drug resistant (XDR)-TB. In the remaining new EU states, costs amounted to €3427 for drug-susceptible TB and €24 166 for MDR-TB/XDR-TB. For the 70 340 susceptible TB cases, 1488 MDR-TB and 136 XDR-TB cases notified in 2011 costs of €536 890 315 accumulated in 2012. In the same year, the 103 104 disability-adjusted life years caused by these cases, when stated in monetary terms, amounted to a total of €5 361 408 000. Thus, the resulting economic burden of TB in the EU clearly outweighs the cost of investing in more efficient vaccines against TB.
Wlodarska, Marta; Johnston, James C.; Gardy, Jennifer L.
SUMMARY Tuberculosis (TB) is an ancient disease with an enormous global impact. Despite declining global incidence, the diagnosis, phenotyping, and epidemiological investigation of TB require significant clinical microbiology laboratory resources. Current methods for the detection and characterization of Mycobacterium tuberculosis consist of a series of laboratory tests varying in speed and performance, each of which yields incremental information about the disease. Since the sequencing of the first M. tuberculosis genome in 1998, genomic tools have aided in the diagnosis, treatment, and control of TB. Here we summarize genomics-based methods that are positioned to be introduced in the modern clinical TB laboratory, and we highlight how recent advances in genomics will improve the detection of antibiotic resistance-conferring mutations and the understanding of M. tuberculosis transmission dynamics and epidemiology. We imagine the future TB clinic as one that relies heavily on genomic interrogation of the M. tuberculosis isolate, allowing for more rapid diagnosis of TB and real-time monitoring of outbreak emergence. PMID:25810419
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. ...
Veeser, Peggy Ingram; Smith, Phillip Karl; Handy, Barry; Martin, Sharon R.
Detecting and managing "Mycobacterium tuberculosis" (TB) infection in a health-science center population is a clinical dilemma. Tuberculin skin tests are still the preferred method for detecting present or past infection of TB. The authors discuss the performance of whole blood interferon gamma release assay test commercially known as…
Horne, D J; Jones, B E; Kamada, A; Fukushima, K; Winthrop, K L; Siegel, S A R; Kovacs, A; Anthony, P; Meekin, K A; Bhat, S; Kerndt, P; Chang, A; Koelle, D M; Narita, M
QuantiFERON®-TB Gold Plus (QFT-Plus), recently approved for use in the United States, is a new-generation QuantiFERON assay that differs from its predecessors in that it uses an additional antigen tube containing peptides to elicit both CD8+ and CD4+ T-lymphocyte responses. To assess the sensitivity of QFT-Plus compared with QuantiFERON®-TB Gold In-Tube (QFT-GIT) in participants with active TB. Adult patients with active TB at three US and two Japanese sites were eligible for this study if they had culture-confirmed TB and were either untreated or had received 14 days of anti-tuberculosis treatment. We enrolled 164 participants, nine of whom had indeterminate results. Excluding indeterminate values, there were 150 QFT-GIT-positive results among 159 tests and 146 QFT-Plus-positive results among 157 tests, with sensitivities of respectively 94.3% (95%CI 89.5-97.4) and 93.02% (95%CI 87.8-96.5%). The estimated sensitivities for the two tests were not significantly different (P = 0.16). Overall test agreement was 98.7%, with a κ statistic of 0.89 (95%CI 0.75-1.00). In this multisite study, we found that QFT-Plus had similar sensitivity to QFT-GIT in adult patients with active TB.
Li, Hao; Wang, Xing-Xing; Wang, Bin; Fu, Lei; Liu, Guan; Lu, Yu; Cao, Min; Huang, Hairong; Javid, Babak
The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb. We tested antibodies isolated from 48 healthcare workers and compared these with 12 patients with active TB. We found that antibodies from 7 of 48 healthcare workers but none from active TB patients showed moderate protection against Mtb in an aerosol mouse challenge model. Intriguingly, three of seven healthcare workers who made protective antibody responses had no evidence of prior TB infection by IFN-γ release assay. There was also good correlation between protection observed in vivo and neutralization of Mtb in an in vitro human whole-blood assay. Antibodies mediating protection were directed against the surface of Mtb and depended on both immune complexes and CD4+ T cells for efficacy. Our results indicate that certain individuals make protective antibodies against Mtb and challenge paradigms about the nature of an effective immune response to TB.
Shamshirband, Shahaboddin; Hessam, Somayeh; Javidnia, Hossein; Amiribesheli, Mohsen; Vahdat, Shaghayegh; Petković, Dalibor; Gani, Abdullah; Kiah, Miss Laiha Mat
There is a high risk of tuberculosis (TB) disease diagnosis among conventional methods. This study is aimed at diagnosing TB using hybrid machine learning approaches. Patient epicrisis reports obtained from the Pasteur Laboratory in the north of Iran were used. All 175 samples have twenty features. The features are classified based on incorporating a fuzzy logic controller and artificial immune recognition system. The features are normalized through a fuzzy rule based on a labeling system. The labeled features are categorized into normal and tuberculosis classes using the Artificial Immune Recognition Algorithm. Overall, the highest classification accuracy reached was for the 0.8 learning rate (α) values. The artificial immune recognition system (AIRS) classification approaches using fuzzy logic also yielded better diagnosis results in terms of detection accuracy compared to other empirical methods. Classification accuracy was 99.14%, sensitivity 87.00%, and specificity 86.12%.
Devasundaram, Santhi; Raja, Alamelu
The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates. Multicolor flow cytometry analysis of whole-blood cultures showed higher Lpd-specific Th1 recall response (IFN-γ, TNF-α, and IL-2; P = 0.0006) and memory CD4 + and CD8 + T cells (CCR7 + CD45RA - and CCR7 - CD45RA - ) in healthy household contacts (HHC) of TB ( P < 0.0001), which is comparable with or higher than the standard antigens, ESAT-6 and CFP-10. The frequency of Lpd-specific multifunctional T cells was higher in HHC compared with PTB patients. However, there is no significant statistical correlation. Regulatory T cell (T reg ) analysis of HHCs and active TB patients demonstrated very low Lpd-specific CD4 + T regs relative to ESAT-6 and CFP-10. Our study demonstrates that the Lpd antigen induces a strong cellular immune response in healthy mycobacteria-infected individuals. In consideration of this population having demonstrated immunologic protection against active TB disease development, our data are encouraging about the possible use of Lpd as a target for further TB subunit vaccine development. © Society for Leukocyte Biology.
[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].
Fujiki, Akiko; Kato, Seiya
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
Sawyer, Kelly; Nizova, Nataliya
Ukraine has successfully implemented e-TB Manager nationwide as its mandatory national tuberculosis registry after first introducing it in 2009. Our objective was to perform an end-of-programme evaluation after formal handover of the registry administration to Ukraine's Centre for Disease Control in 2015. We conducted a nationwide, cross-sectional, anonymous, 18-point user experience survey, and stratified the registry's transaction statistics to demonstrate usability. Contrary to initial implementation experience, older users (aged >50 years), often with limited or no computer proficiency prior to using the registry, had significantly better user experience scores for at least six of the 12 measures compared to younger users (aged 18–29 years). Using the registry for >3 years was associated with significantly higher scores for having capacity, adequacy of training received and satisfaction with the registry. Of the 5.9 million transactions over a 4-year period, nine out of 24 oblasts (regions) and Kiev city accounted for 62.5% of all transactions, and corresponded to 59% of Ukraine's tuberculosis burden. There were 437 unique active users in 486 rayons (districts) of Ukraine, demonstrating extensive reach. Our key findings complement the World Health Organization and European Respiratory Society's agenda for action on digital health to help implement the End TB Strategy. PMID:28512634
Konduri, Niranjan; Sawyer, Kelly; Nizova, Nataliya
Ukraine has successfully implemented e-TB Manager nationwide as its mandatory national tuberculosis registry after first introducing it in 2009. Our objective was to perform an end-of-programme evaluation after formal handover of the registry administration to Ukraine's Centre for Disease Control in 2015. We conducted a nationwide, cross-sectional, anonymous, 18-point user experience survey, and stratified the registry's transaction statistics to demonstrate usability. Contrary to initial implementation experience, older users (aged >50 years), often with limited or no computer proficiency prior to using the registry, had significantly better user experience scores for at least six of the 12 measures compared to younger users (aged 18-29 years). Using the registry for >3 years was associated with significantly higher scores for having capacity, adequacy of training received and satisfaction with the registry. Of the 5.9 million transactions over a 4-year period, nine out of 24 oblasts (regions) and Kiev city accounted for 62.5% of all transactions, and corresponded to 59% of Ukraine's tuberculosis burden. There were 437 unique active users in 486 rayons (districts) of Ukraine, demonstrating extensive reach. Our key findings complement the World Health Organization and European Respiratory Society's agenda for action on digital health to help implement the End TB Strategy.
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
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.
Tsuyuguchi, Kazunari; Nagai, Hideaki; Ogawa, Kenji; Matsumoto, Tomoshige; Morimoto, Kozo; Takaki, Akiko; Mitarai, Satoshi
Xpert MTB/RIF is an automated nucleic acid amplification test (NAT) that can detect the presence of Mycobacterium tuberculosis complex (MTC) in clinical specimens as well as rifampicin (RIF) resistance resulting from rpoB mutation. Despite its high sensitivity and specificity for diagnosing tuberculosis (TB) with or without RIF resistance, the clinical performance of the test is variable. In this study, we evaluated the performance of Xpert MTB/RIF in a setting of moderate TB burden and high medical resources. A total of 427 sputum specimens were obtained from 237 suspected TB cases. Of these, 159 were identified as active TB, while the other 78 were non-TB diseases. The overall sensitivity and specificity of MTC detection by Xpert MTB/RIF using culture results as a reference were 86.8% [95% confidence interval (CI): 81.8%-90.6%] and 96.8% (95% CI: 93.1%-98.5%), respectively. Among MTC-positive culture specimens, Xpert MTB/RIF positivity was 95.2% (95% CI: 91.2%-97.5%) in smear-positive and 44.7% (95% CI 30.1-60.3) in smear-negative specimens. Xpert MTB/RIF was similar to other NATs (TaqMan MTB and TRCRapid M.TB) in terms of performance. Xpert MTB/RIF detected 25 RIF-resistant isolates as compared to 22 with the mycobacterial growth indicator tube antimicrobial susceptibility testing system, yielding a sensitivity of 100% (95% CI: 85.1%-100%) and specificity of 98.3% (95% CI: 95.1%-99.4%). These results indicate that although sensitivity in smear-negative/culture-positive specimens was relatively low, Xpert MTB/RIF is a useful diagnostic tool for detecting TB and RIF resistance even in settings of moderate TB burden. Copyright © 2016. Published by Elsevier Ltd.
Jalal, Tengku Mardhiah Tengku; Abdullah, Sarimah; Wahab, Farhanah Abd; Dir, Sharina; Naing, Nyi Nyi
One of the six strategies developed by WHO, in order to stop Tuberculosis (TB) is addressing TB/HIV high-risk groups. This study aimed to determine the prevalence of successful TB treatment and factors associated with TB treatment success among TB/HIV co-infection patients in North-East Malaysia. A cross-sectional study was carried out in the a-year period from 2003 to 2012 by reviewing TB/HIV records in all hospitals and health clinics. The outcome of interest was treatment success as defined by Ministry of Health (MOH) when the patients was cured or completed TB treatment. Out of 1510 total TB/HIV co-infection cases, 27.9% (95% CI: 25.2, 30.6) of the patients were having treatment success. A majority of TB/HIV co-infection cases were male (91.1%). Fifty-eight percent the patients were drug addicts and 6% were having positive tuberculin tests. The multiple logistic regression revealed that male (OR: 0.39, 95% CI: 0.22, 0.71) and positive tuberculin test result (OR: 2.61, 95% CI: 1.63, 4.19) were significantly associated with the treatment success of TB/HIV co-infection patients. Other factors such as age, comorbid, sputum smear and x-ray findings were not significantly factors in this study. Female patients and those with negative tuberculin test should be emphasised for successful tuberculosis treatment.
Dejene, Sintayehu W; Heitkönig, Ignas M A; Prins, Herbert H T; Lemma, Fitsum A; Mekonnen, Daniel A; Alemu, Zelalem E; Kelkay, Tessema Z; de Boer, Willem F
Bovine tuberculosis (bTB) infection is generally correlated with individual cattle's age, sex, body condition, and with husbandry practices such as herd composition, cattle movement, herd size, production system and proximity to wildlife-including bTB maintenance hosts. We tested the correlation between those factors and the prevalence of bTB, which is endemic in Ethiopia's highland cattle, in the Afar Region and Awash National Park between November 2013 and April 2015. A total of 2550 cattle from 102 herds were tested for bTB presence using the comparative intradermal tuberculin test (CITT). Data on herd structure, herd movement, management and production system, livestock transfer, and contact with wildlife were collected using semi-structured interviews with cattle herders and herd owners. The individual overall prevalence of cattle bTB was 5.5%, with a herd prevalence of 46%. Generalized Linear Mixed Models with a random herd-effect were used to analyse risk factors of cattle reactors within each herd. The older the age of the cattle and the lower the body condition the higher the chance of a positive bTB test result, but sex, lactation status and reproductive status were not correlated with bTB status. At herd level, General Linear Models showed that pastoral production systems with transhumant herds had a higher bTB prevalence than sedentary herds. A model averaging analysis identified herd size, contact with wildlife, and the interaction of herd size and contact with wildlife as significant risk factors for bTB prevalence in cattle. A subsequent Structural Equation Model showed that the probability of contact with wildlife was influenced by herd size, through herd movement. Larger herds moved more and grazed in larger areas, hence the probability of grazing in an area with wildlife and contact with either infected cattle or infected wildlife hosts increased, enhancing the chances for bTB infection. Therefore, future bTB control strategies in cattle in
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
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.
Kirenga, Bruce J.; Kiragga, Agnes; Lukande, Robert; Nsereko, Maria; Ssengooba, Willy; Katamba, Achilles; Worodria, William; Joloba, Moses L.; Mayanja-Kizza, Harriet
Background Diagnosis of pleural tuberculosis (TB) using routinely available diagnostic methods is challenging due to the paucibacillary nature of the disease. Histopathology and pleural tissue TB culture involves an invasive procedure which requires expertise and appropriate equipment, both often unavailable in many health units. Xpert MTB/Rif test has been widely evaluated in sputum specimens but data on its performance in pleural TB is scarce. We evaluated the accuracy of Cepheid's Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural TB in Uganda. Methods Consenting adult patients with exudative pleural effusions underwent pleural biopsy and the tissue obtained subjected to Lowenstein-Jensen and mycobacterial growth indicator tube MTB cultures and histopathology. Pleural fluid for Xpert MTB/Rif testing was also collected. Data on socio-demographic characteristics, clinical symptoms, HIV status and CD4 count were also collected. Sensitivity, specificity, positive and negative predictive values of Xpert MTB/Rif test on pleural fluid in pleural TB diagnosis were calculated using pleural tissue MTB culture and/or histopathology as the reference standard. Results Of the 116 participants [female 50%, mean age 34 (SD ±13], 87/116 (75%) had pleural TB confirmed on pleural tissue culture and/or histopathology. The Xpert MTB/Rif test identified 25 (28.7%) of the 87 confirmed pleural TB cases. The sensitivity and specificity of Xpert MTB/Rif test were 28.7% and 96.6% respectively while the positive and negative predictive values were 96.1% and 31.1% respectively. Conclusion Xpert MTB/Rif test on pleural fluid does not accurately diagnose pleural TB and therefore cannot be used as an initial evaluation test in patients with suspected pleural TB. New, rapid and accurate tests for the diagnosis of pleural TB are still warranted. PMID:25051491
Lusiba, John K; Nakiyingi, Lydia; Kirenga, Bruce J; Kiragga, Agnes; Lukande, Robert; Nsereko, Maria; Ssengooba, Willy; Katamba, Achilles; Worodria, William; Joloba, Moses L; Mayanja-Kizza, Harriet
Diagnosis of pleural tuberculosis (TB) using routinely available diagnostic methods is challenging due to the paucibacillary nature of the disease. Histopathology and pleural tissue TB culture involves an invasive procedure which requires expertise and appropriate equipment, both often unavailable in many health units. Xpert MTB/Rif test has been widely evaluated in sputum specimens but data on its performance in pleural TB is scarce. We evaluated the accuracy of Cepheid's Xpert MTB/Rif test on pleural fluid in the diagnosis of pleural TB in Uganda. Consenting adult patients with exudative pleural effusions underwent pleural biopsy and the tissue obtained subjected to Lowenstein-Jensen and mycobacterial growth indicator tube MTB cultures and histopathology. Pleural fluid for Xpert MTB/Rif testing was also collected. Data on socio-demographic characteristics, clinical symptoms, HIV status and CD4 count were also collected. Sensitivity, specificity, positive and negative predictive values of Xpert MTB/Rif test on pleural fluid in pleural TB diagnosis were calculated using pleural tissue MTB culture and/or histopathology as the reference standard. Of the 116 participants [female 50%, mean age 34 (SD ±13], 87/116 (75%) had pleural TB confirmed on pleural tissue culture and/or histopathology. The Xpert MTB/Rif test identified 25 (28.7%) of the 87 confirmed pleural TB cases. The sensitivity and specificity of Xpert MTB/Rif test were 28.7% and 96.6% respectively while the positive and negative predictive values were 96.1% and 31.1% respectively. Xpert MTB/Rif test on pleural fluid does not accurately diagnose pleural TB and therefore cannot be used as an initial evaluation test in patients with suspected pleural TB. New, rapid and accurate tests for the diagnosis of pleural TB are still warranted.
Xu, Yuhui; Wu, Jianan; Liao, Sha; Sun, Zhaogang
Tuberculosis (TB) is considered as one of the most serious threats to public health in many parts of the world. The threat is even more severe in the developing countries where there is a lack of advanced medical amenities and contemporary anti-TB drugs. In such situations, dosage optimization of existing medication regimens seems to be the only viable option. Therapeutic drug monitoring study results suggest that high-dose treatment regimens can compensate the low serum concentration of anti-TB drugs and shorten the therapy duration. The article presents a critical review on the possible changes that occur in the host and the pathogen upon the administration of standard and high-dose regimens. Some of the most common factors that are responsible for low anti-TB drug concentrations in the serum are differences in hosts' body weight, metabolic processing of the drug, malabsorption and/or drug-drug interaction. Furthermore, failure to reach the cavitary pulmonary and extrapulmonary tissues also contributes to the therapeutic inefficiency of the drugs. In such conditions, administration of higher doses can help in compensating the pathogenic outcomes of enhancement of the pathogen's physical barriers, efflux pumps and genetic mutations. The present article also presents a summary of the recorded treatment outcomes of clinical trials that were conducted to test the efficacy of administration of high dose of anti-tuberculosis drugs. This review will help physicians across the globe to understand the underlying pathophysiological changes (including side effects) that dictate the clinical outcomes in patients administered with standard and/or high dose anti-TB drugs.
Wang, Linchuan; Tian, Xu-Dong; Yu, Yan; Chen, Wei
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.
Hadizadeh Tasbiti, Alireza; Yari, Shamsi; Siadat, Seyed Davar; Tabarsi, Payam; Saeedfar, Kayvan; Yari, Fatemeh
Tuberculosis (TB) is a crucial public health problem with prevalence of multidrug resistant (MDR) rising. An accurate TB biomarker is urgently needed to monitor the response to treatment in patients with MDR tuberculosis. To analyze interaction between selected MDR-TB purified protein and immune cells, dendritic cells from MDR-TB patients and healthy subjects were stimulated by 55KDa protein fractions (Rv0147). The purified proteins identified by proteomic techniques (two-dimensional gel electrophoresis, mass spectrometry) and peptide sequences are known to bind a MHC class I alleles which are extracted from the Immune Epitope Database and Analysis Resource database ( www.iedb.org ). T cells were isolated from PBMC by negative selection and cells were cultured in RPMI-1640 at 37 °C and 5% CO 2 . Cell culture was assayed for cytokine IL-10 and INF-γ by ELISA. We found that INF-γ production was significantly (335 ± 35.5 pg/ml, P ˂ 0.05) upregulated after protein candidate (Rv0147) stimulation by dendritic cells from MDR-TB patients, whereas IL-10 production was greatly reduced compared with production in healthy subjects (212 ± 9.94 pg/ml, P ˂ 0.05). In fact, the purified protein, Rv0147, stimulated dendritic cells from MDR-TB patients, failed to produce IL-10 and directly stimulates INF-γ production by T cells. These results suggest that the purified protein, Rv0147, may stimulate Th1 type protective cytokine response in MDR-TB patients but not in normal subjects. The production of INF-γ but not IL-10 in the presence of purified protein, Rv0147, may be shifted to Th1 responses in MDR-TB patients and supports its potential as protein vaccine candidates against TB.
Diop, ElHadji Assane; Queiroz, Emerson Ferreira; Kicka, Sébastien; Rudaz, Serge; Diop, Tahir; Soldati, Thierry; Wolfender, Jean-Luc
In West Africa, populations are used to taking traditional medicine as a first aid against common health problems. In this aspect, many plants are claimed to be effective in the treatment of Tuberculosis (TB), which according to the World Health Organization (WHO) remains one of the world's deadliest communicable diseases. The main aim of this study was to identify plants used to treat TB-symptoms by the population of Senegal and to evaluate their possible concomitant use with clinically approved TB-drugs. This approach allowed the selection of plants effectively used in traditional medicine. In order to verify if the usage of some of these plants can be rationalized, the activity of their traditional preparations was assessed with both an intracellular and extracellular antimycobacterial host-pathogen assays. An ethnopharmacological survey conducted on 117 TB-patients and 30 healers in Senegal from March to May 2014. The questionnaires were focused on the use of medicinal plants to treat common TB -symptoms (cough longer than 2 weeks, fever, night sweats, weight loss and bloody sputum). Local plant names, utilized organs (herbal drugs) and traditional formulations of the plants were recorded. Extracts were prepared by mimicking the traditional decoction in boiling water and screened for their antimycobacterial activity using Mycobacterium marinum, as a validated TB surrogate, and an Acanthamoeba castellanii - M. marinum whole-cell based host-pathogen assay, to detect anti-infective activities. By the end of the survey, nearly 30 plants were cited and the 12 most cited herbal drugs were collected and their usage documented by extensive literature search. Extracts of the chosen herbs were screened with the described assays; with a main focus on traditional formulas (mainly herbal decoctions). Two of the water extracts from Combretum aculeatum and Guiera senegalensis showed significant antimycobacterial activities when compared to the positive control drug (rifampin
MacDougall, D S
About 2 billion people worldwide are infected with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). TB is the leading cause of premature death in less industrialized countries, and 8 million more people become infected every year. The World Health Organization (WHO) declared TB a global emergency in 1993 and launched a series of prevention and vaccination programs. In spite of effective drug therapy and a vaccine, tuberculosis remains a major public health problem. The TB and HIV epidemics are closely intertwined, and the risk of TB disease progression is 100 times greater in HIV-positive individuals. TB is the leading cause of death among HIV-infected people worldwide, and virologic evidence suggests that the host immune response to TB may enhance HIV replication and accelerate the progression of HIV infection. The interaction between the two diseases was the subject of a conference called TB & HIV: Applying Advances to the Clinic, Public Health, and the World. Charts and tables show reported TB cases in the U.S., trends in TB cases among foreign-born persons in the U.S., and the country of origin for foreign-born persons with TB in the U.S. Several poster sessions from the conference are summarized. Strategies for dealing with the TB epidemic are outlined.
Paz-Soldan, Valerie A.; Alban, Rebecca E.; Dimos Jones, Christy; Powell, Amy R.; Oberhelman, Richard A.
Introduction: Tuberculosis (TB) remains a significant public health challenge worldwide, and particularly in Peru with one of the highest incidence rates in Latin America. TB patient behavior has a direct influence on whether a patient will receive timely diagnosis and successful treatment of their illness. Objectives: The objective was to understand the complex factors that can impact TB patient health seeking behavior. Methods: In-depth interviews were conducted with adult and parents of pediatric patients receiving TB treatment (n = 43), within that group a sub-group was also co-infected with HIV (n = 11). Results: Almost all of the study participants recognized delays in seeking either their child’s or their own diagnosis of their TB symptoms. The principal reasons for treatment-seeking delays were lack of knowledge and confusion of TB symptoms, fear and embarrassment of receiving a TB diagnosis, and a patient tendency to self-medicate prior to seeking formal medical attention. Conclusion: Health promotion activities that target patient delays have the potential to improve individual patient outcomes and mitigate the spread of TB at a community level. PMID:25566523
Luetkemeyer, Anne F; Kendall, Michelle A; Nyirenda, Mulinda; Wu, Xingye; Ive, Prudence; Benson, Constance A; Andersen, Janet W; Swindells, Susan; Sanne, Ian M; Havlir, Diane V; Kumwenda, Johnstone
Earlier initiation of antiretroviral therapy (ART) in HIV-tuberculosis (TB) is associated with increased immune reconstitution inflammatory syndrome (IRIS). The severity, frequency, and complications of TB IRIS were evaluated in A5221, a randomized trial of earlier ART (within 2 weeks after TB treatment initiation) vs. later ART (8-12 weeks after TB treatment) in HIV-infected patients starting TB treatment. In 806 participants, TB IRIS was defined using published clinical criteria. Cases were classified as severe (hospitalization/death), moderate (corticosteroid use/invasive procedure), or mild (no hospitalization/procedures/steroids). Fisher exact, Wilcoxon, and log-rank tests were used for comparisons. TB IRIS occurred in 61 (7.6%) patients: 10.4% in earlier vs. 4.7% in later ART, 11.5% with CD4 <50 vs. 5.4% with CD4 ≥50 cells per cubic millimeter. The CD4/ART arm interaction was significant, P = 0.014, with 44.3% of TB IRIS occurring with CD4 <50 and earlier ART. TB IRIS occurred sooner with earlier vs. later ART initiation, at a median of 29 vs. 82 days after TB treatment initiation (P < 0.001). IRIS manifestations included lymphadenopathy (59.0%), constitutional symptoms (54.1%), and radiographic changes (41.0%); central nervous system TB IRIS was uncommon (6.6%). TB IRIS was mild in 27.9%, moderate in 41.0%, and severe in 31.1%. No TB IRIS-associated deaths occurred. IRIS management required ≥1 invasive procedures in 34.4%, hospitalization in 31.1%, and corticosteroids in 54.1%. TB IRIS was more frequent with earlier ART initiation and CD4 <50 cells per cubic millimeter. As ART is implemented earlier in HIV-TB coinfection, programs will require the diagnostic capabilities, clinical resources, and training necessary to manage TB IRIS.
Domínguez, J; Boettger, E C; Cirillo, D; Cobelens, F; Eisenach, K D; Gagneux, S; Hillemann, D; Horsburgh, R; Molina-Moya, B; Niemann, S; Tortoli, E; Whitelaw, A; Lange, C
The emergence of drug-resistant strains of Mycobacterium tuberculosis is a challenge to global tuberculosis (TB) control. Although culture-based methods have been regarded as the gold standard for drug susceptibility testing (DST), molecular methods provide rapid information on mutations in the M. tuberculosis genome associated with resistance to anti-tuberculosis drugs. We ascertained consensus on the use of the results of molecular DST for clinical treatment decisions in TB patients. This document has been developed by TBNET and RESIST-TB groups to reach a consensus about reporting standards in the clinical use of molecular DST results. Review of the available literature and the search for evidence included hand-searching journals and searching electronic databases. The panel identified single nucleotide mutations in genomic regions of M. tuberculosis coding for katG, inhA, rpoB, embB, rrs, rpsL and gyrA that are likely related to drug resistance in vivo. Identification of any of these mutations in clinical isolates of M. tuberculosis has implications for the management of TB patients, pending the results of in vitro DST. However, false-positive and false-negative results in detecting resistance-associated mutations in drugs for which there is poor or unproven correlation between phenotypic and clinical drug resistance complicate the interpretation. Reports of molecular DST results should therefore include specific information on the mutations identified and provide guidance for clinicians on interpretation and on the choice of the appropriate initial drug regimen.
Guggino, Giuliana; Orlando, Valentina; Cutrera, Stella; La Manna, Marco P; Di Liberto, Diana; Vanini, Valentina; Petruccioli, Elisa; Dieli, Francesco; Goletti, Delia; Caccamo, Nadia
Cytotoxic molecules such as granulysin, perforin and granzymes produced by cytolytic T cells directly contribute to immune defense against tuberculosis (TB). In search for novel TB biomarkers, we have evaluated the levels of granzyme A in plasma obtained from QuantiFERON-TB Gold In tube (QFT-IT) assays from patients with active TB disease and subjects with latent TB infection (LTBI). Granzyme A serum levels in TB patients were significantly lower than values found in LTBI subjects even after subtraction of the unstimulated levels from the antigen-stimulated responses. The receiver operator characteristics (ROC) curve analysis comparing TB patients and LTBI groups, showed that at a cut-off value of granzyme A of <3.425pg/ml, the sensitivity and the specificity of the assay were 29.41% and 94.74%, respectively. Our results suggest that granzyme A could be considered another biomarker of TB, that can be used, other than IFN-γ, to discriminate between patients with active TB and LTBI subjects in a well characterized cohort of confirmed Mycobacterium tuberculosis-infected individuals. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
Tuberculosis (TB) is an ancient disease, but not a disease of the past. The increasing prevalence of drug-resistant strains of Mycobacterium tuberculosis, the causative agent of TB, demands new measures to combat the situation. Rapid and accurate detection of the pathogen, and its drug susceptibility pattern, is essential for timely initiation of treatment, and ultimately, control of the disease. Molecular-based methods offer a great chance to improve detection of drug-resistant TB; however, their development and usage should be accompanied with a profound understanding of drug resistance mechanisms and circulating M. tuberculosis strains in specific settings, as otherwise, the usefulness of such tests may be limited. This review gives an overview of the history of TB treatment and drug resistance, drug resistance mechanisms for the most commonly used drugs and molecular methods designed to detect drug-resistant strains.
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.
Sonika, Ujjwal; Kar, Premashis
Tuberculosis is one of the most common diseases in India and has attained epidemic proportions. Tuberculosis and liver are related in many ways. Liver disease can occur due to hepatic tuberculosis or the treatment with various anti-tubercular drugs may precipitate hepatic injury or patients with chronic liver disease may develop tuberculosis and pose special management problems. Tuberculosis per se can affect liver in three forms. The most common form is the diffuse hepatic involvement, seen along with pulmonary or miliary tuberculosis. The second is granulomatous hepatitis and the third, much rarer form presents as focal/local tuberculoma or abscess. Tubercular disease of liver occurring along with pulmonary involvement as in disseminated tuberculosis is treated with standard regimen for pulmonary tuberculosis. Granulomatous hepatitis and tubercular liver abscess are treated like any other extra-pulmonary tubercular lesions without any extra risk of hepatotoxicity by anti-tubercular drugs. Treatment of tuberculosis in patients who already have a chronic liver disease poses various clinical challenges. There is an increased risk of drug induced hepatitis in these patients and its implications are potentially more serious in these patients as their hepatic reserve is already depleted. However, hepatotoxic anti-tubercular drugs can be safely used in these patients if the number of drugs used is adjusted appropriately. Thus, the main principle is to closely monitor the patient for signs of worsening liver disease and to reduce the number of hepatotoxic drugs in the anti-tubercular regimen according to the severity of underlying liver disease.
Maertzdorf, Jeroen; Weiner, January; Mollenkopf, Hans-Joachim; Bauer, Torsten; Prasse, Antje; Müller-Quernheim, Joachim; Kaufmann, Stefan H E
In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, with a common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.
Leonard, Michael K; Blumberg, Henry M
Musculoskeletal tuberculosis (TB) accounts for approximately 10% of all extrapulmonary TB cases in the United States and is the third most common site of extrapulmonary TB after pleural and lymphatic disease. Vertebral involvement (tuberculous spondylitis, or Pott's disease) is the most common type of skeletal TB, accounting for about half of all cases of musculoskeletal TB. The presentation of musculoskeletal TB may be insidious over a long period and the diagnosis may be elusive and delayed, as TB may not be the initial consideration in the differential diagnosis. Concomitant pulmonary involvement may not be present, thus confusing the diagnosis even further. Early diagnosis of bone and joint disease is important to minimize the risk of deformity and enhance outcome. The introduction of newer imaging modalities, including MRI (imaging procedure of choice) and CT, has enhanced the diagnostic evaluation of patients with musculoskeletal TB and for directed biopsies of affected areas of the musculoskeletal system. Obtaining appropriate specimens for culture and other diagnostic tests is essential to establish a definitive diagnosis and recover M. tuberculosis for susceptibility testing. A total of 6 to 9 months of a rifampin-based regimen, like treatment of pulmonary TB, is recommended for the treatment of drug susceptible musculoskeletal disease. Randomized trials of tuberculous spondylitis have demonstrated that such regimens are efficacious. These data and those from the treatment of pulmonary TB have been extrapolated to form the basis of treatment regimen recommendations for other forms of musculoskeletal TB.
Pyszczynski, Dennis R.
Tuberculosis is on the rise in the United States. The article discusses its background, factors contributing to its increase, the likelihood of children and teens developing tuberculosis, how to prevent the disease from spreading, and what schools and states can do. (SM)
Séraphin, Marie Nancy; Doggett, Richard; Johnston, Lori; Zabala, Jose; Gerace, Alexandra M; Lauzardo, Michael
Mycobacterium tuberculosis is characterized into four global lineages with strong geographical restriction. To date one study in the United States has investigated M. tuberculosis lineage association with tuberculosis (TB) disease presentation (extra-pulmonary versus pulmonary). We update this analysis using recent (2009-2015) data from the State of Florida to measure lineage association with pulmonary TB, the infectious form of the disease. M. tuberculosis lineage was assigned based on the spacer oligonucleotide typing (spoligotyping) patterns. TB disease site was defined as exclusively pulmonary or extra-pulmonary. We used ORs to measure the association between M. tuberculosis lineages and pulmonary compared to extra-pulmonary TB. The final multivariable model was adjusted for patient socio-demographics, HIV and diabetes status. We analyzed 3061 cases, 83.4% were infected with a Euro-American lineage, 8.4% Indo-Oceanic and 8.2% East-Asian lineage. The majority of the cases (86.0%) were exclusively pulmonary. Compared to the Indo-Oceanic lineage, infection with a Euro-American (AOR=1.87, 95% CI: 1.21, 2.91) or an East-Asian (AOR=2.11, 95% CI: 1.27, 3.50) lineage favored pulmonary disease compared to extra-pulmonary. In a sub-analysis among pulmonary cases, strain lineage was not associated with sputum smear positive status, indicating that the observed association with pulmonary disease is independent of host contagiousness. As an obligate pathogen, M. tuberculosis' fitness is directly correlated to its transmission potential. In this analysis, we show that M. tuberculosis lineage is associated with pulmonary disease presentation. This association may explain the predominance in a region of certain lineages compared to others. Copyright © 2017 Elsevier B.V. All rights reserved.
Socio-demographic and AIDS-related factors associated with tuberculosis stigma in southern Thailand: a quantitative, cross-sectional study of stigma among patients with TB and healthy community members
Background Tuberculosis (TB) remains one of the most important infectious diseases worldwide. A comprehensive approach towards disease control that addresses social factors including stigma is now advocated. Patients with TB report fears of isolation and rejection that may lead to delays in seeking care and could affect treatment adherence. Qualitative studies have identified socio-demographic, TB knowledge, and clinical determinants of TB stigma, but only one prior study has quantified these associations using formally developed and validated stigma scales. The purpose of this study was to measure TB stigma and identify factors associated with TB stigma among patients and healthy community members. Methods A cross-sectional study was performed in southern Thailand among two different groups of participants: 480 patients with TB and 300 healthy community members. Data were collected on socio-demographic characteristics, TB knowledge, and clinical factors. Scales measuring perceived TB stigma, experienced/felt TB stigma, and perceived AIDS stigma were administered to patients with TB. Community members responded to a community TB stigma and community AIDS stigma scale, which contained the same items as the perceived stigma scales given to patients. Stigma scores could range from zero to 30, 33, or 36 depending on the scale. Three separate multivariable linear regressions were performed among patients with TB (perceived and experience/felt stigma) and community members (community stigma) to determine which factors were associated with higher mean TB stigma scores. Results Only low level of education, belief that TB increases the chance of getting AIDS, and AIDS stigma were associated with higher TB stigma scores in all three analyses. Co-infection with HIV was associated with higher TB stigma among patients. All differences in mean stigma scores between index and referent levels of each factor were less than two points, except for incorrectly believing that TB
Pan, Sheng-Wei; Yen, Yung-Feng; Feng, Jia-Yih; Su, Vincent Yi-Fong; Kou, Yu Ru; Su, Wei-Juin
Tuberculosis (TB) disease may be transmitted to close contacts of index cases, causing physical illness. No studies have investigated the risk of developing depressive disorder among TB contacts in a TB-endemic area.Adult participants with a new diagnosis of TB contact (ICD-9-CM codes V01.1 plus chest radiographic order) since January 1, 2008, were identified from the National Health Insurance Research Database in Taiwan. A control cohort matched for age (±5 y), sex, enrolled years, and income level was selected. These 2 cohorts were followed until December 31, 2012, and observed for the development of depressive disorder. The Kaplan-Meier method and the log-rank test were used to examine the difference in cumulative incidences of depressive disorder between groups. Cox proportional-hazard models were used to calculate adjusted hazard ratios (aHRs) for depressive disorder.The TB contact cohort consisted of 9046 patients and matched controls of 36,184 ones. The mean age of TB contacts was 44.7 years, and 56.0% of them were women. During a mean follow-up period of 2.5 years, 127 (1.40%) TB contacts and 521 (1.44%) matched controls developed depressive disorder. TB exposure was found to be an independent risk factor of depressive disorder in women (aHR 1.34, 95% confidence interval [CI] 1.07-1.68), but not in men (aHR 0.71, 95% CI 0.48-1.06) after adjusting for age, comorbidities, and income levels. The risk of depression was significantly higher for female TB contacts than for matched controls in the first and second years (aHR 1.49, 95% CI 1.03-2.14; and aHR 1.53, 95% CI 1.05-2.23, respectively), but not thereafter. Of note, 67 (0.74%) TB contacts and 88 (0.24%) matched controls developed active TB, but none of them had subsequent depressive disorder during follow-up periods.Female TB contacts had an increased risk of depression within the first 2 years after exposure. Clinicians should consider conducting depression evaluations in addition to routine TB contact
Sánchez-Soto, Eduardo; Ponce-Ramos, Rosa; Hernández-Gutiérrez, Rodolfo; Gutiérrez-Ortega, Abel; Álvarez, Angel H; Martínez-Velázquez, Moisés; Absalón, Angel E; Ortiz-Lazareno, Pablo; Limón-Flores, Alberto; Estrada-Chávez, Ciro; Herrera-Rodríguez, Sara E
Bovine colostrum contains compounds, which provide passive immune protection from mother to newborn calves. Little is known about cytokine levels and their role in bovine colostrum. Moreover, the capacity of bovine colostrum cells to mount specific immune responses after natural exposure to bovine tuberculosis (bTB) antigens in dairy herds has not been studied, thus far. The purpose of this study was to identify biomarkers for bTB infection measurable in bovine colostrum. The present study reveals that isolated-immune colostrum cells can mount a specific immune response against bTB antigens, by measuring the novo IFN-γ release in cell culture. We found that IFN-γ levels in the responders (Bov + ) to bTB antigen were higher than in non-responders (Bov - ). On the other hand, proinflammatory cytokines contained in colostrum's whey were tested in Tuberculin Skin Test (TST) reactor (TST + ) and non-reactor (TST - ) animals to assess their potential role as biomarker. We observed that IFN-γ levels were lower or undetectable, as opposed to IL4 levels were measurable, the TNF-α level was higher in TST - than TST + , while IL-6 levels showed the opposite reaction and with no statistical significance. Moreover, IL-1α mRNA expression levels were higher in colostrum mononuclear cells (CMC) in Bov + cattle. Collectively, these data suggest that the differential expression of pro and anti-inflammatory cytokines could have relevant value to diagnose bTB in cattle. Copyright © 2016 Elsevier Ltd. All rights reserved.
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
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.
Monin, Leticia; Griffiths, Kristin L.; Lam, Wing Y.; Gopal, Radha; Kang, Dongwan D.; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K.; Mitreva, Makedonka; Rosa, Bruce A.; Ramos-Payan, Rosalio; Morrison, Thomas E.; Murray, Peter J.; Rangel-Moreno, Javier; Pearce, Edward J.; Khader, Shabaana A.
Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1–expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1–expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB. PMID:26571397
Monin, Leticia; Griffiths, Kristin L; Lam, Wing Y; Gopal, Radha; Kang, Dongwan D; Ahmed, Mushtaq; Rajamanickam, Anuradha; Cruz-Lagunas, Alfredo; Zúñiga, Joaquín; Babu, Subash; Kolls, Jay K; Mitreva, Makedonka; Rosa, Bruce A; Ramos-Payan, Rosalio; Morrison, Thomas E; Murray, Peter J; Rangel-Moreno, Javier; Pearce, Edward J; Khader, Shabaana A
Parasitic helminth worms, such as Schistosoma mansoni, are endemic in regions with a high prevalence of tuberculosis (TB) among the population. Human studies suggest that helminth coinfections contribute to increased TB susceptibility and increased rates of TB reactivation. Prevailing models suggest that T helper type 2 (Th2) responses induced by helminth infection impair Th1 immune responses and thereby limit Mycobacterium tuberculosis (Mtb) control. Using a pulmonary mouse model of Mtb infection, we demonstrated that S. mansoni coinfection or immunization with S. mansoni egg antigens can reversibly impair Mtb-specific T cell responses without affecting macrophage-mediated Mtb control. Instead, S. mansoni infection resulted in accumulation of high arginase-1-expressing macrophages in the lung, which formed type 2 granulomas and exacerbated inflammation in Mtb-infected mice. Treatment of coinfected animals with an antihelminthic improved Mtb-specific Th1 responses and reduced disease severity. In a genetically diverse mouse population infected with Mtb, enhanced arginase-1 activity was associated with increased lung inflammation. Moreover, in patients with pulmonary TB, lung damage correlated with increased serum activity of arginase-1, which was elevated in TB patients coinfected with helminths. Together, our data indicate that helminth coinfection induces arginase-1-expressing type 2 granulomas, thereby increasing inflammation and TB disease severity. These results also provide insight into the mechanisms by which helminth coinfections drive increased susceptibility, disease progression, and severity in TB.
Jewett, Amy; Bell, Teal; Cohen, Nicole J.; Buckley, Kirsten; Leino, E. Victor; Even, Susan; Beavers, Suzanne; Brown, Clive; Marano, Nina
Objective: Colleges are at risk for communicable disease outbreaks because of the high degree of person-to-person interactions and relatively crowded dormitory settings. This report describes the US college student health screening requirements among US resident and international students for tuberculosis (TB) and vaccine-preventable diseases…
Evaluation of risk factors for false-negative results with an antigen-specific peripheral blood-based quantitative T cell assay (T-SPOT®. TB) in the diagnosis of active tuberculosis: A large-scale retrospective study in China.
Yang, Chi; Zhang, Shaojun; Yao, Lan; Fan, Lin
Objective To investigate the diagnostic efficacy of an interferon-γ release assay, T-SPOT ® . TB, for diagnosing active tuberculosis (TB) and to identify risk factors for false-negative results. Methods This retrospective study enrolled consecutive patients with active TB and with non-TB respiratory diseases to evaluate the risk factors for false-negative results when using the T-SPOT ® . TB assay for the diagnosis of active TB. Patients with active TB were categorized as having confirmed pulmonary TB, clinically diagnosed pulmonary TB or extrapulmonary TB (EPTB). Results This study analysed 4964 consecutive patients; 2425 with active TB and 2539 with non-TB respiratory diseases. Multivariate logistic regression analyses identified the following five factors that were all associated with an increased false-negative rate with the T-SPOT ® . TB assay: increased age (odds ratio [OR] 1.018; 95% confidence interval [CI] 1.013, 1.024); decreased CD8+ count (OR 0.307; 95% CI 0.117, 0.803); negative sputum acid-fast bacilli (AFB) smear staining (OR 1.821; 95% CI 1.338, 2.477); negative mycobacterial cultures (OR 1.379; 95% CI 1.043, 1.824); and absence of EPTB (OR 1.291; 95% CI 1.026, 1.623). Conclusions Increased age, decreased CD8+ count, negative sputum AFB smear results, negative sputum mycobacterial cultures and absence of EPTB might lead to an increased false-negative rate when using the T-SPOT ® . TB assay.
Sarkar, Malay; Srinivasa; Madabhavi, Irappa; Kumar, Kushal
Reviewed the epidemiology, clinical characteristics, mechanisms, and treatment of tuberculosis associated chronic obstructive pulmonary disease. We searched PubMed, EMBASE, and the CINAHL from inception to June 2016. We used the following search terms: Tuberculosis, COPD, Tuberculosis associated COPD, and so forth. All types of study were chosen. Chronic obstructive pulmonary disease (COPD) and tuberculosis are significant public health problems, particularly in developing countries. Although, smoking is the conventional risk factor for COPD, nonsmoking related risk factors such as biomass fuel exposure, childhood lower-respiratory tract infections, chronic asthma, outdoor air pollution, and prior history of pulmonary tuberculosis have become important risk factors of COPD, particularly in developing countries. Past history of tuberculosis as a risk factor of chronic airflow obstruction has been reported in several studies. It may develop during the course of tuberculosis or after completion of tuberculosis treatment. Developing countries with large burden of tuberculosis can contribute significantly to the burden of chronic airflow obstruction. Prompt diagnosis and treatment of tuberculosis should be emphasized to lessen the future burden of chronic airflow obstruction. © 2017 John Wiley & Sons Ltd.
Wu, Shiau-Jiun; Lu, Po-Liang; Chen, Yen-Hsu; Pan, Hui-Juan; Feng, Ming-Chu
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.
Burgos, J. L.; Kahn, J. G.; Strathdee, S. A.; Valencia-Mendoza, A.; Bautista-Arredondo, S.; Laniado-Laborin, R.; Castañeda, R.; Deiss, R.; Garfein, R. S.
SUMMARY OBJECTIVE To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. DESIGN We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON®-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. RESULTS Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. CONCLUSIONS In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective. PMID:19723375
Burgos, J L; Kahn, J G; Strathdee, S A; Valencia-Mendoza, A; Bautista-Arredondo, S; Laniado-Laborin, R; Castañeda, R; Deiss, R; Garfein, R S
To assess the cost-effectiveness of screening for latent tuberculosis infection (LTBI) using a commercially available detection test and treating individuals at high risk for human immunodeficiency virus (HIV) infection in a middle-income country. We developed a Markov model to evaluate the cost per LTBI case detected, TB case averted and quality-adjusted life year (QALY) gained for a cohort of 1000 individuals at high risk for HIV infection over 20 years. Baseline model inputs for LTBI prevalence were obtained from published literature and cross-sectional data from tuberculosis (TB) screening using QuantiFERON-TB Gold In-Tube (QFT-GIT) testing among sex workers and illicit drug users at high risk for HIV recruited through street outreach in Tijuana, Mexico. Costs are reported in 2007 US dollars. Future costs and QALYs were discounted at 3% per year. Sensitivity analyses were performed to evaluate model robustness. Over 20 years, we estimate the program would prevent 78 cases of active TB and 55 TB-related deaths. The incremental cost per case of LTBI detected was US$730, cost per active TB averted was US$529 and cost per QALY gained was US$108. In settings of endemic TB and escalating HIV incidence, targeting LTBI screening and treatment among high-risk groups may be highly cost-effective.
Interdisciplinary Public Health Intervention in a Multigenerational Tuberculosis (TB) Outbreak in Harris County, Texas: A Case Study with Implications for Disease Control Process Improvement and Transmission Cycle Interruption
Haynie, Aisha; Plasencia, Carlos; Fields, Kimberly; Nesbitt, Elna; Lovings-Clark, Audrey; Scott, Mary; Wiltz-Beckham, Dana; Reed, Brian; Shah, Umair A
Abstract Background Harris County Public Health (HCPH) is the health department for Harris County, Texas jurisdiction. Harris County as a whole is the nation’s third most populous county, with 4.3 million residents, and a TB case rate more than double that of the USA. (7.6 cases per 100,000 pop). A total, 327 individuals were diagnosed with TB in Harris County during 2015, over two-thirds occurring in foreign-born individuals. In 2016, HCPH treated an immigrant female with active TB. Initial contact investigation (CI) yielded five household contacts (HHC). Two tested positive, but refused subsequent clinical evaluation by HCPH. Two months later, HCPH was notified of a HHC hospitalized with TB. After hospital discharge, the sick HHC moved into a motel in attempts to self-isolate, but refused evaluation of additional HHC in the home, and banned home access, precluding adequate CI. After numerous phone calls, visits to motel and home, and multiple rescheduled appointments, legal action appeared inevitable. Days later, HCPH was notified of another HHC diagnosed with active TB. Methods With alarm regarding the family’s adherence to control orders, TB staff implemented an innovative multidisciplinary team-based intervention in hopes of avoiding legal action. A site visit was paid to the motel by a local health authority, two TB staff, a county public investigator, and a refugee clinic outreach worker fluent in the family’s language. Patients were presented with letters requesting immediate cooperation to avoid court filings. Questions were answered, misinformation corrected, and education provided. Results Intermediary on-site intervention using a compassionate, firm multidisciplinary team approach resulted in 16 additional family members tested, yielding an infant with active TB (Case 4) and 8 with TB Infection (TBI). Isolation breaches were also discovered. Most importantly, TB transmission cycle was interrupted. Cultural and economic barriers hindering
O'Brien, Amanda; Whelan, Clare; Clarke, John B.; Hayton, Alastair; Watt, Neil J.
ABSTRACT Tuberculosis in goats is usually diagnosed clinically, at postmortem, or by a positive skin test. However, none of these approaches detects all infected animals. Serology offers an additional tool to identify infected animals missed by current tests. We describe the use of the Enferplex Caprine TB serology test to aid the management of a large dairy goat herd undergoing a tuberculosis breakdown. Initial skin and serology testing showed that IgG antibodies were present in both serum and milk from 100% of skin test-positive animals and in serum and milk from 77.8 and 95.4% of skin test-negative animals, respectively. A good correlation was observed between serum and milk antibody levels. The herd had been vaccinated against Mycobacterium avium subsp. paratuberculosis, but no direct serological cross-reactions were found. Subsequent skin testing revealed 13.7% positive animals, 64.9% of which were antibody positive, while 42.1% of skin test-negative animals were seropositive. Antibody responses remained high 1 month later (57.1% positive), and the herd was slaughtered. Postmortem analysis of 20 skin test-negative goats revealed visible lesions in 6 animals, all of which had antibodies to six Mycobacterium bovis antigens. The results provide indirect evidence that serology testing with serum or milk could be a useful tool in the diagnosis and management of tuberculosis in goats. PMID:27974399
O'Brien, Amanda; Whelan, Clare; Clarke, John B; Hayton, Alastair; Watt, Neil J; Harkiss, Gordon D
Tuberculosis in goats is usually diagnosed clinically, at postmortem, or by a positive skin test. However, none of these approaches detects all infected animals. Serology offers an additional tool to identify infected animals missed by current tests. We describe the use of the Enferplex Caprine TB serology test to aid the management of a large dairy goat herd undergoing a tuberculosis breakdown. Initial skin and serology testing showed that IgG antibodies were present in both serum and milk from 100% of skin test-positive animals and in serum and milk from 77.8 and 95.4% of skin test-negative animals, respectively. A good correlation was observed between serum and milk antibody levels. The herd had been vaccinated against Mycobacterium avium subsp. paratuberculosis, but no direct serological cross-reactions were found. Subsequent skin testing revealed 13.7% positive animals, 64.9% of which were antibody positive, while 42.1% of skin test-negative animals were seropositive. Antibody responses remained high 1 month later (57.1% positive), and the herd was slaughtered. Postmortem analysis of 20 skin test-negative goats revealed visible lesions in 6 animals, all of which had antibodies to six Mycobacterium bovis antigens. The results provide indirect evidence that serology testing with serum or milk could be a useful tool in the diagnosis and management of tuberculosis in goats. Copyright © 2017 American Society for Microbiology.
Sharma, Surendra K; Vashishtha, Richa; Chauhan, L S; Sreenivas, V; Seth, Divya
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.
Nurwidya, Fariz; Handayani, Diah; Burhan, Erlina; Yunus, Faisal
Tuberculosis (TB) is one of the leading causes of adult death in the Asia-Pacific Region, including Indonesia. As an infectious disease caused by Mycobacterium tuberculosis (MTB), TB remains a major public health issue especially in developing nations due to the lack of adequate diagnostic testing facilities. Diagnosis of TB has entered an era of molecular detection that provides faster and more cost-effective methods to diagnose and confirm drug resistance in TB cases, meanwhile, diagnosis by conventional culture systems requires several weeks. New advances in the molecular detection of TB, including the faster and simpler nucleic acid amplification test (NAAT) and whole-genome sequencing (WGS), have resulted in a shorter time for diagnosis and, therefore, faster TB treatments. In this review, we explored the current findings on molecular diagnosis of TB and drug-resistant TB to see how this advancement could be integrated into public health systems in order to control TB.
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Bagchi, S; Sachdev, S S; Nalwa, A; Das, C J; Sinha, S; Suri, V; Mahajan, S; Bhowmik, D; Agarwal, S
Renal transplant recipients may present with intracranial space-occupying lesions (SOLs) due to infections as well as a post-transplant lymphoproliferative disorder (PTLD). Here, we discuss a renal transplant recipient who presented with neurologic symptoms and magnetic resonance imaging (MRI) of the brain showed multiple focal SOLs. Tuberculosis (TB), toxoplasmosis, nocardiosis, fungal infections, and PTLD were considered in the differential diagnosis. MRI spectroscopy was suggestive of an infectious cause, such as toxoplasmosis or TB. Serologic tests using Toxoplasma were negative. A brain biopsy followed by immunohistochemical staining using Toxoplasma antibody demonstrated multiple intravascular cysts of toxoplasma. This case highlights the diagnostic dilemma in an immunocompromised patient with multiple focal brain lesions, especially in areas where TB is endemic. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Schulz, S A; Draper, H R; Naidoo, P
Although health policy in South Africa calls for the integration of services, the effectiveness of different models of integration on patient outcomes has not been well demonstrated. To evaluate the outcomes of coinfected patients starting antiretroviral treatment (ART) in a tuberculosis (TB) hospital who received different models of ongoing care. This cohort study compared outcomes for 271 coinfected patients who started ART in a TB hospital in the Western Cape. After discharge, one group of patients received anti-tuberculosis treatment and ART from different providers, in the same or in different clinics (vertical care). The other group received anti-tuberculosis treatment and ART at the same visit from the same service provider (integrated care). Demographic and clinical data and TB and ART outcomes were compared. The vertical care model had more unfavourable outcomes for anti-tuberculosis treatment (28.7% vs. 5.9%, P < 0.001) and ART (30.1% vs. 7.4%, P < 0.001) than the integrated care model. The vertical care model showed no difference whether services were provided by two service providers in the same or in geographically separate primary health care clinics. Patient outcomes were better when TB and HIV care was received from the same service provider at the same visit.
Lempp, Jason M; Zajdowicz, Margan J; Hankinson, Arlene L; Toney, Sean R; Keep, Lisa W; Mancuso, James D; Mazurek, Gerald H
Immunologic tests such as the tuberculin skin test (TST) and QuantiFERON®-TB Gold In-Tube test (QFT-GIT) are designed to detect Mycobacterium tuberculosis infection, both latent M. tuberculosis infection (LTBI) and infection manifesting as active tuberculosis disease (TB). These tests need high specificity to minimize unnecessary treatment and high sensitivity to allow maximum detection and prevention of TB. Estimate QFT-GIT specificity, compare QFT-GIT and TST results, and assess factor associations with test discordance among U.S. Navy recruits. Among 792 subjects with completed TST and QFT-GIT, 42(5.3%) had TST indurations ≥10mm, 23(2.9%) had indurations ≥15mm, 14(1.8%) had positive QFT-GIT results, and 5(0.6%) had indeterminate QFT-GITs. Of 787 subjects with completed TST and determinate QFT-GIT, 510(64.8%) were at low-risk for infection, 277(35.2%) were at increased risk, and none had TB. Among 510 subjects at low-risk (presumed not infected), estimated TST specificity using a 15mm cutoff, 99.0% (95%CI: 98.2-99.9%), and QFT-GIT specificity, 98.8% (95%CI: 97.9-99.8%), were not significantly different (p>0.99). Most discordance was among recruits at increased risk of infection, and most was TST-positive but QFT-GIT-negative discordance. Of 18 recruits with TST ≥15mm but QFT-GIT negative discordance, 14(78%) were at increased risk. TB prevalence in country of birth was the strongest predictor of positive TST results, positive QFT-GIT results, and TST-positive but QFT-GIT-negative discordance. Reactivity to M. avium purified protein derivative (PPD) was associated with positive TST results and with TST-positive but QFT-GIT-negative discordance using a 10 mm cutoff, but not using a 15 mm cutoff or with QFT-GIT results. M. tuberculosis infection prevalence was low, with the vast majority of infection occurring in recruits with recognizable risks. QFT-GIT and TST specificities were high and not significantly different. Negative QFT-GIT results among subjects
Chang, Ping-Chin; Wang, Pin-Hui; Chen, Kow-Tong
The value of QuantiFERON in the diagnosis of tuberculosis disease and in the monitoring of the response to anti-tuberculosis treatment is unclear. The aims of this study were to evaluate the accuracy of the QuantiFERON-TB Gold In-Tube (QFT-GIT) test in the diagnosis of tuberculosis and in the monitoring of the response to anti-tuberculosis treatment in patients with active pulmonary tuberculosis (PTB). Between January 2013 and December 2015, 133 cases with active PTB and 133 controls with no mycobacterial infection, matched by age (within 3 years) and by the week that they visited Tainan Chest Hospital, were enrolled in the study. Serial testing by QFT-GIT at baseline and after 2 and 6 months of treatment was performed. At these time points, a comparison of the performance of QFT-GIT with that of sputum culture status among study subjects was conducted. Compared to baseline, 116 (87.2%) cases showed a decreased response, whereas 17 (12.8%) showed persistent or stronger interferon-gamma (IFN-γ) responses at 2 months. PTB patients IFN-γ responses declined significantly from baseline to 2 months (median, 6.32 vs. 4.12; p < 0.005). The sensitivity values of the QFT-GIT test for the detection of pulmonary tuberculosis at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 74.4%, 78.2%, and 80.5%, respectively. The specificity values at cut-off points of 0.35 IU/mL, 0.20 IU/mL, and 0.10 IU/mL were 66.2%, 63.9%, and 57.1%, respectively. Our results support the QFT-GIT assay as a potential tool for diagnosing tuberculosis and for monitoring the efficacy of anti-tuberculosis treatment.
Kuyinu, Y A; Mohammed, A S; Adeyeye, O O; Odugbemi, B A; Goodman, O O; Odusanya, O O
Tuberculosis infection among health care workers is capable of worsening the existing health human resource problems of low--and middle-income countries. Tuberculosis infection control is often weakly implemented in these parts of the world therefore, understanding the reasons for poor implementation of tuberculosis infection control guidelines are important. This study was aimed at assessing tuberculosis infection control practices and barriers to its implementation in Ikeja, Nigeria. A cross-sectional study in 20 tuberculosis care facilities (16 public and 4 private) in Ikeja, Lagos was conducted. The study included a facility survey to assess the availability of tuberculosis infection control guidelines, the adequacy of facilities to prevent transmission of tuberculosis and observations of practices to assess the implementation of tuberculosis infection control guidelines. Four focus group discussions were carried out to highlight HCWs' perceptions on tuberculosis infection control guidelines and barriers to its implementation. The observational study showed that none of the clinics had a tuberculosis infection control plan. No clinic was consistently screening patients for cough. Twelve facilities (60%) consistently provided masks to patients who were coughing. Ventilation in the waiting areas was assessed to be adequate in 60% of the clinics while four clinics (20%) possessed N-95 respirators. Findings from the focus group discussions showed weak managerial support, poor funding, under-staffing, lack of space and not wanting to be seen as stigmatizing against tuberculosis patients as barriers that hindered the implementation of TB infection control measures. Tuberculosis infection control measures were not adequately implemented in health facilities in Ikeja, Nigeria. A multi-pronged approach is required to address the identified barriers to the implementation of tuberculosis infection control guidelines.
Zhang, Lifan; Shi, Xiaochun; Zhang, Yueqiu; Zhang, Yao; Huo, Feifei; Zhou, Baotong; Deng, Guohua; Liu, Xiaoqing
T-SPOT.TB didn't perform a perfect diagnosis for active tuberculosis (ATB), and some factors may influence the results. We did this study to evaluate possible factors associated with the sensitivity and specificity of T-SPOT.TB, and the diagnostic parameters under varied conditions. Patients with suspected ATB were enrolled prospectively. Influencing factors of the sensitivity and specificity of T-SPOT.TB were evaluated using logistic regression models. Sensitivity, specificity, predictive values (PV), and likelihood ratios (LR) were calculated with consideration of relevant factors. Of the 865 participants, 205 (23.7%) had ATB, including 58 (28.3%) microbiologically confirmed TB and 147 (71.7%) clinically diagnosed TB. 615 (71.7%) were non-TB. 45 (5.2%) cases were clinically indeterminate and excluded from the final analysis. In multivariate analysis, serous effusion was the only independent risk factor related to lower sensitivity (OR = 0.39, 95% CI: 0.18-0.81) among patients with ATB. Among non-TB patients, age, TB history, immunosuppressive agents/glucocorticoid treatment and lymphocyte count were the independent risk factors related to specificity of T-SPOT.TB. Sensitivity, specificity, PV+, PV-, LR+ and LR- of T-SPOT.TB for diagnosis of ATB were 78.5%, 74.1%, 50.3%, 91.2%, 3.0 and 0.3, respectively. This study suggests that influencing factors of sensitivity and specificity of T-SPOT.TB should be considered for interpretation of T-SPOT.TB results.
Ludvigsson, J F; Sanders, D S; Maeurer, M; Jonsson, J; Grunewald, J; Wahlström, J
Research suggests a positive association between coeliac disease and tuberculosis (TB), but that research has often been limited to in-patients and small sample size. We examined the relationship between TB and coeliac disease. To examine the association of TB and coeliac disease. We collected biopsy data from all pathology departments in Sweden (n=28) to identify individuals who were diagnosed with coeliac disease between 1969 and 2007 (Marsh 3: villous atrophy; n=29,026 unique individuals). Population-based sex- and age-matched controls were selected from the Total Population Register. Using Cox regression, we calculated hazard ratios (HRs) for TB from data in the Swedish national health registers. Individuals with coeliac disease were at increased risk of TB (HR=2.0; 95% CI=1.3-3.0) (during follow-up, 31 individuals with coeliac disease and 74 reference individuals had a diagnosis of TB). The absolute risk of TB in patients with coeliac disease was 10/100,000 person-years with an excess risk of 5/100,000. Risk estimates were the highest in the first year. Restricting our outcome to a diagnosis of TB confirmed by (I) a record of TB medication (HR=2.9; 95% CI=1.0-8.3), (II) data in the National Surveillance System for Infectious Diseases in Sweden (HR=2.6; 95% CI=1.3-5.2) or (III) positive TB cultivation (HR=3.3; 95% CI=1.6-6.8) increased risk estimates. The positive association between coeliac disease and TB was also observed before the coeliac disease diagnosis (odds ratio=1.6; 95% CI=1.2-2.1). We found a moderately increased risk of tuberculosis in patients with coeliac disease. © 2011 Blackwell Publishing Ltd.
Jenum, Synne; Selvam, Sumithra; Mahelai, Diana; Jesuraj, Nelson; Cárdenas, Vicky; Kenneth, John; Hesseling, Anneke C.; Doherty, Timothy Mark; Vaz, Mario
Background: Reliable identification of Mycobacterium tuberculosis infection or tuberculosis (TB) disease in young children is vital to assure adequate preventive and curative treatment. The tuberculin skin test (TST) and IFNγ-release assays may supplement the diagnosis of pediatric TB as cases are typically bacteriologically unconfirmed. However, it is unclear to what extent the performance of TST and QuantiFERON-TB Gold In-Tube (QFT; Cellestis’ IFNγ-release assay test) depends on the demographic, clinical and nutritional characteristics of children in whom they are tested. Methods: During a 2-year prospective observational study of 4382 neonates in Southern India, children with suspected TB were investigated and classified by a standard TB diagnostic algorithm. Results: Clinical TB was diagnosed in 13 of 705 children referred for case verification with suspected TB. TST and QFT had a susceptibility for clinical TB of 31% and 23%, respectively, in this group. Children <2 years were more likely to test QFT indeterminate. A height-for-age Z score within the lowest quartile increased the odds ratio (OR) for a positive or indeterminate QFT result [OR 2.46 (1.19–5.06), OR 3.08 (1.10–8.58)], whereas the OR for a positive TST was reduced with a weight-for-height Z score within the lowest quartile [OR 0.17 (0.06–0.47)]. Conclusion: The sensitivities of the TST and QFT for clinical TB in children <3 years of age were equally poor in this population. Stunted children were more susceptible to Mycobacterium tuberculosis infection and more prone to indeterminate QFT results. TST was less reliable in children with wasting. PMID:24797993
Jenum, Synne; Selvam, Sumithra; Mahelai, Diana; Jesuraj, Nelson; Cárdenas, Vicky; Kenneth, John; Hesseling, Anneke C; Doherty, Timothy Mark; Vaz, Mario; Grewal, Harleen M S
Reliable identification of Mycobacterium tuberculosis infection or tuberculosis (TB) disease in young children is vital to assure adequate preventive and curative treatment. The tuberculin skin test (TST) and IFNγ-release assays may supplement the diagnosis of pediatric TB as cases are typically bacteriologically unconfirmed. However, it is unclear to what extent the performance of TST and QuantiFERON-TB Gold In-Tube (QFT; Cellestis' IFNγ-release assay test) depends on the demographic, clinical and nutritional characteristics of children in whom they are tested. During a 2-year prospective observational study of 4382 neonates in Southern India, children with suspected TB were investigated and classified by a standard TB diagnostic algorithm. Clinical TB was diagnosed in 13 of 705 children referred for case verification with suspected TB. TST and QFT had a susceptibility for clinical TB of 31% and 23%, respectively, in this group. Children <2 years were more likely to test QFT indeterminate. A height-for-age Z score within the lowest quartile increased the odds ratio (OR) for a positive or indeterminate QFT result [OR 2.46 (1.19-5.06), OR 3.08 (1.10-8.58)], whereas the OR for a positive TST was reduced with a weight-for-height Z score within the lowest quartile [OR 0.17 (0.06-0.47)]. The sensitivities of the TST and QFT for clinical TB in children <3 years of age were equally poor in this population. Stunted children were more susceptible to Mycobacterium tuberculosis infection and more prone to indeterminate QFT results. TST was less reliable in children with wasting.
Chakaya, J; Uplekar, M; Mansoer, J; Kutwa, A; Karanja, G; Ombeka, V; Muthama, D; Kimuu, P; Odhiambo, J; Njiru, H; Kibuga, D; Sitienei, J
Nairobi, the capital of Kenya. To promote standardised tuberculosis (TB) care by private health providers and links with the public sector. A description of the results of interventions aimed at engaging private health providers in TB care and control in Nairobi. Participating providers are supported to provide TB care that conforms to national guidelines. The standard surveillance tools are used for programme monitoring and evaluation. By the end of 2006, 26 of 46 (57%) private hospitals and nursing homes were engaged. TB cases reported by private providers increased from 469 in 2002 to 1740 in 2006. The treatment success rate for smear-positive pulmonary TB treated by private providers ranged from 76% to 85% between 2002 and 2005. Of the 1740 TB patients notified by the private sector in 2006, 732 (42%) were tested for human immunodeficiency virus (HIV), of whom 372 (51%) were positive. Of the 372 HIV-positive TB patients, 227 (61%) were provided with cotrimoxazole preventive treatment (CPT) and 136 (37%) with antiretroviral treatment (ART). Private providers can be engaged to provide TB-HIV care conforming to national norms. The challenges include providing diagnostics, CPT and ART and the capacity to train and supervise these providers.
Niguse, Selam; Desta, Kassu; Gebremichael, Gebremdihin; Gebrezgeaxier, Atsebeha; Getahun, Mulluwork; Kassa, Desta
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.
Hormi, Myriam; Guérin-El Khourouj, Valérie; Pommelet, Virginie; Jeljeli, Mohamed; Pédron, Béatrice; Diana, Jean-Sébastien; Faye, Albert; Sterkers, Ghislaine
Data regarding the use of QuantiFERON to assist the diagnosis of active tuberculosis (TB) in HIV-infected children are limited, especially in countries with low incidence of TB/HIV coinfection. QuantiFERON results were analyzed in 63 HIV-infected children who presented to our hospital in Paris, France. Seventeen HIV-uninfected children with active TB (4 culture-confirmed) were included for comparison. The 63 HIV-infected children (median age: 11 yr) had 113 QuantiFERON tests. Thirty-four (54%) were born in sub-Saharan Africa. Vertical HIV transmission was documented for 50 of 52 (96%) and stage III HIV-infection for 30 of 50 children (60%). Over the study period, active TB was diagnosed in 7 of 63 HIV-infected children (3 culture-confirmed). Additional ongoing or previous opportunistic infections were present in 4 of 7. QuantiFERON results were positive in 2 of 7 HIV-infected children with active TB (sensitivity: 29%) and 16 of 17 HIV-uninfected children with active TB (sensitivity: 94%). At initial QuantiFERON testing of the 63 HIV-infected children, 8 (13%) had positive results (1, active TB; 5, latent TB; 2, previous TB) and 51 (81%) had negative results. Of 33 children with repeat testing after an initially positive or negative result, the only change was one conversion from a negative to a positive result at the onset of active TB. The 4 children (6%) with indeterminate quantiFERON results had a concomitant opportunistic infection. Results of repeat testing after clinical stabilization were negative in all 4. QuantiFERON testing performed poorly for active TB diagnosis in this series of children with advanced HIV infection.
Kerkhoff, A D; Meintjes, G; Opie, J; Vogt, M; Jhilmeet, N; Wood, R; Lawn, S D
Anaemia commonly complicates both human immunodeficiency virus (HIV) infection and tuberculosis (TB), contributing substantially to morbidity and mortality. The mechanisms underlying anaemia and corresponding treatments in co-infected patients are poorly defined. To determine the relative contributions of anaemia of chronic disease (ACD) and iron deficiency to anaemia in patients with HIV-associated TB. Consecutively recruited hospitalised (n = 102) and matched ambulatory patients (n = 51) with microbiologically confirmed HIV-associated TB in Cape Town, South Africa, were included. Haemoglobin levels, iron status markers, hepcidin and pro-inflammatory cytokines in blood were measured. We determined the prevalence of ACD and iron-deficiency anaemia (IDA) using seven different published definitions of IDA. More than 80% of enrolled HIV-associated TB patients were anaemic, and anaemia was more severe among in-patients. Over 95% of anaemic HIV-associated TB patients had ACD, whereas the proportion with IDA using a range of seven different definitions was low overall (median <3%, range 0-32.6) in both patient groups. The proportion with IDA and hepcidin concentration ⩿ 20.0 ng/ml (predictive of responsiveness to oral iron supplementation) was also very low (median <3%, range 0-15.1). ACD was the predominant cause underlying anaemia in HIV-associated TB patients, and IDA was very uncommon in this setting. The majority of anaemic HIV-associated TB patients were unlikely to benefit from oral iron supplementation.
Kassa, Desta; Gebremichael, Gebremedhin; Alemayehu, Yodit; Wolday, Dawit; Messele, Tsehaynesh; van Baarle, Debbie
HIV/TB coinfection remains a major challenge even after the initiation of HAART. Little is known about Mycobacterium tuberculosis (Mtb) specific immune restoration in relation to immunologic and virologic outcomes after long-term HAART during co-infections with latent and active TB. A total of 232 adults, including 59 HIV patients with clinical TB (HIV + TB+), 125 HIV patients without clinical TB (HIV + TB-), 13 HIV negative active TB patients (HIV-TB+), and 10 HIV negative Tuberculin Skin TST positive (HIV-TST+), and 25 HIV-TST- individuals were recruited. HAART was initiated in 113 HIV + patients (28 TB + and 85 TB-), and anti-TB treatment for all TB cases. CD4+ T-cell count, HIV RNA load, and IFN-γ responses to ESAT-6/CFP-10 were measured at baseline, 6 months (M6), 18 months (M18) and 24 months (M24) after HAART initiation. The majority of HIV + TB- (70%, 81%, 84%) as well as HIV + TB + patients (60%, 77%, 80%) had virologic success (HIV RNA < 50 copies/ml) by M6, M18 and M24, respectively. HAART also significantly increased CD4+ T-cell counts at 2 years in HIV + TB + (from 110.3 to 289.9 cells/μl), HIV + TB- patients (197.8 to 332.3 cells/μl), HIV + TST- (199 to 347 cells/μl) and HIV + TST + individuals (195 to 319 cells/μl). Overall, there was no significant difference in the percentage of patients that achieved virologic success and in total CD4+ counts increased between HIV patients with and without TB or LTBI. The Mtb specific IFN-γ response at baseline was significantly lower in HIV + TB + (3.6 pg/ml) compared to HIV-TB + patients (34.4 pg/ml) and HIV + TST + (46.3 pg/ml) individuals; and in HIV-TB + patients compared to HIV-TST + individuals (491.2 pg/ml). By M18 on HAART, the IFN-γ response remained impaired in HIV + TB + patients (18.1 pg/ml) while it normalized in HIV + TST + individuals (from 46.3 to 414.2 pg/ml). Our data show that
Stennis, N L; Meissner, J S; Bhavnani, D; Kreiswirth, B; Ahuja, S Desai
Tuberculosis (TB) has decreased substantially in New York City (NYC), but progress has slowed in recent years. Continued declines will require novel approaches tailored to foreign-born populations. To describe TB epidemiology among the Mexico-born population of NYC to inform interventions in this community. The study included NYC patients with TB disease identified from 2001 to 2014. Incidence rates were compared by country of birth groupings. Demographic and patient characteristics were analyzed for all Mexico-born TB patients. Patients were compared by Mycobacterium bovis vs. non-M. bovis TB strain. Culture-confirmed patients were compared by genotype clustering status. From 2001 to 2014, 621 Mexico-born TB patients were identified in NYC. TB rates were significantly higher among Mexico-born vs. US-born persons every year. Mexico-born patients had lived in the United States for a median 7 years at diagnosis. The geographic distribution of Mexico-born TB patients was similar to that of the total Mexico-born population. Overall, 71% of patients reported previous employment; 52% of non-M. bovis patients were clustered based on genotyping results. Our results provide a foundation to inform future interventions in the Mexico-born population. Additional work is needed to explore possible local TB transmission and health care-seeking practices.
Lee, B; Oh, H J; Chon, B S
To examine the effectiveness of a television campaign for preventing tuberculosis (TB) executed in South Korea in 2015. We used a genetic matching method to accurately test the effect of the campaign on changing people's knowledge and behaviour in a nationwide sample of 1000 adults; information was collected using face-to-face interviews. After matching individuals in treatment and controlled conditions using 11 covariates, we found that the campaign significantly improved people's knowledge about TB, and enhanced people's intention to undertake a TB test when they recognised the signs of TB. These data highlight the potential usefulness of genetic matching for enhancing statistical rigour when evaluating the effectiveness of a health campaign using a cross-sectional observational study.
Lobo, Eunice; Shah, Shimoni; Rangan, Sheela; Dholakia, Yatin; Mistry, Nerges
Background: Mumbai is witnessing a rising incidence of all forms of drug resistant tuberculosis (DR-TB). Methods: A population-based, retrospective study was conducted between April and July 2014, in 15 high TB burden wards in Mumbai, to capture the patient pathways to TB care. A total of 23 DR-TB patients were identified and their pathways to access DR-TB care were recorded using semi-structured interviews. Results: The total DR-TB pathway time of new patients (who did not report any past episode of TB) (180 days; IQR 123,346) was found to be more than twice that of retreatment patients (who reported a past episode of TB) (69 days; IQR 42,128). Conclusions: The unacceptable delay for diagnosis and treatment of DR-TB in Mumbai advocates for consistent implementation of early screening of patients using rapid gene-based technologies. PMID:29863175
Lobo, Eunice; Shah, Shimoni; Rangan, Sheela; Dholakia, Yatin; Mistry, Nerges
Background: Mumbai is witnessing a rising incidence of all forms of drug resistant tuberculosis (DR-TB). Methods: A population-based, retrospective study was conducted between April and July 2014, in 15 high TB burden wards in Mumbai, to capture the patient pathways to TB care. A total of 23 DR-TB patients were identified and their pathways to access DR-TB care were recorded using semi-structured interviews. Results: The total DR-TB pathway time of new patients (who did not report any past episode of TB) (180 days; IQR 123,346) was found to be more than twice that of retreatment patients (who reported a past episode of TB) (69 days; IQR 42,128). Conclusions: The unacceptable delay for diagnosis and treatment of DR-TB in Mumbai advocates for consistent implementation of early screening of patients using rapid gene-based technologies.
Adjemian, Jennifer; Frankland, Timothy B; Daida, Yihe G; Honda, Jennifer R; Olivier, Kenneth N; Zelazny, Adrian; Honda, Stacey; Prevots, D Rebecca
Previous studies found Hawaiians and Asian-Americans/Pacific Islanders to be independently at increased risk for nontuberculous mycobacterial pulmonary disease (NTMPD) and tuberculosis (TB). To better understand NTM infection and TB risk patterns in Hawaii, USA, we evaluated data on a cohort of patients in Hawaii for 2005-2013. Period prevalence of NTMPD was highest among Japanese, Chinese, and Vietnamese patients (>300/100,000 persons) and lowest among Native Hawaiians and Other Pacific Islanders (50/100,000). Japanese patients were twice as likely as all other racial/ethnic groups to have Mycobacterium abscessus isolated (adjusted odds ratio 2.0, 95% CI 1.2-3.2) but were not at increased risk for infection with other mycobacteria species. In contrast, incidence of TB was stable and was lowest among Japanese patients (no cases) and highest among Filipino, Korean, and Vietnamese patients (>50/100,000). Substantial differences exist in the epidemiology of NTMPD by race/ethnicity, suggesting behavioral and biologic factors that affect disease susceptibility.
Frankland, Timothy B.; Daida, Yihe G.; Honda, Jennifer R.; Olivier, Kenneth N.; Zelazny, Adrian; Honda, Stacey; Prevots, D. Rebecca
Previous studies found Hawaiians and Asian-Americans/Pacific Islanders to be independently at increased risk for nontuberculous mycobacterial pulmonary disease (NTMPD) and tuberculosis (TB). To better understand NTM infection and TB risk patterns in Hawaii, USA, we evaluated data on a cohort of patients in Hawaii for 2005–2013. Period prevalence of NTMPD was highest among Japanese, Chinese, and Vietnamese patients (>300/100,000 persons) and lowest among Native Hawaiians and Other Pacific Islanders (50/100,000). Japanese patients were twice as likely as all other racial/ethnic groups to have Mycobacterium abscessus isolated (adjusted odds ratio 2.0, 95% CI 1.2–3.2) but were not at increased risk for infection with other mycobacteria species. In contrast, incidence of TB was stable and was lowest among Japanese patients (no cases) and highest among Filipino, Korean, and Vietnamese patients (>50/100,000). Substantial differences exist in the epidemiology of NTMPD by race/ethnicity, suggesting behavioral and biologic factors that affect disease susceptibility. PMID:28221128
Pan, Liping; Jia, Hongyan; Liu, Fei; Gao, Mengqiu; Sun, Huishan; Du, Boping; Sun, Qi; Xing, Aiying; Wei, Rongrong; Zhang, Zongde
To evaluate the value of T-SPOT.TB assay in the diagnosis of pulmonary tuberculosis within different age groups. We analyzed 1 518 suspected pulmonary tuberculosis (PTB) patients who were admitted to the Beijing Chest Hospital from November 2012 to February 2014 and had valid T-SPOT.TB tests before anti-tuberculosis therapy. The 599 microbiologically and/or histopathologically-confirmed PTB patients (16-89 years old, 388 males and 211 females) and 235 non-TB patients (14-85 years old, 144 males and 91 females) were enrolled for the analysis of diagnostic performance of T-SPOT.TB, while patients with uncertain diagnosis or diagnosis based on clinical impression (n=684) were excluded from the analysis. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the T-SPOT.TB were analyzed according to the final diagnosis. Furthermore, the diagnostic performance of T-SPOT.TB assay in the younger patients (14-59 years old) and elderly patients (60-89 years old) were also analyzed respectively. Categorical variables were compared by Pearson's Chi-square test, while continuous variables were compared by the Mann-Whitney U-test. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of the T-SPOT.TB in diagnosis of PTB were 90.1% (540/599), 65.5% (154/235), 86.9% (540/621), 72.3% (154/213), 2.61, and 0.15, respectively. The sensitivity and specificity of T-SPOT.TB assay were 92.6% (375/405) and 75.6% (99/131), respectively in the younger patients, and 85.0% (165/194), 52.9% (55/104) respectively in the elderly patients. The sensitivity and specificity of T-SPOT.TB assay in the younger patients were significantly higher than those in the elderly patients (P<0.01), and the spot forming cells in the younger PTB patients were significantly higher than in the elderly PTB patients [300 (126, 666)/10(6) PBMCs vs
Young, Bonnie N; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L
Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB
Young, Bonnie N.; Rendón, Adrian; Rosas-Taraco, Adrian; Baker, Jack; Healy, Meghan; Gross, Jessica M.; Long, Jeffrey; Burgos, Marcos; Hunley, Keith L.
Diverse socioeconomic and clinical factors influence susceptibility to tuberculosis (TB) disease in Mexico. The role of genetic factors, particularly those that differ between the parental groups that admixed in Mexico, is unclear. The objectives of this study are to identify the socioeconomic and clinical predictors of the transition from latent TB infection (LTBI) to pulmonary TB disease in an urban population in northeastern Mexico, and to examine whether genetic ancestry plays an independent role in this transition. We recruited 97 pulmonary TB disease patients and 97 LTBI individuals from a public hospital in Monterrey, Nuevo León. Socioeconomic and clinical variables were collected from interviews and medical records, and genetic ancestry was estimated for a subset of 142 study participants from 291,917 single nucleotide polymorphisms (SNPs). We examined crude associations between the variables and TB disease status. Significant predictors from crude association tests were analyzed using multivariable logistic regression. We also compared genetic ancestry between LTBI individuals and TB disease patients at 1,314 SNPs in 273 genes from the TB biosystem in the NCBI BioSystems database. In crude association tests, 12 socioeconomic and clinical variables were associated with TB disease. Multivariable logistic regression analyses indicated that marital status, diabetes, and smoking were independently associated with TB status. Genetic ancestry was not associated with TB disease in either crude or multivariable analyses. Separate analyses showed that LTBI individuals recruited from hospital staff had significantly higher European genetic ancestry than LTBI individuals recruited from the clinics and waiting rooms. Genetic ancestry differed between individuals with LTBI and TB disease at SNPs located in two genes in the TB biosystem. These results indicate that Monterrey may be structured with respect to genetic ancestry, and that genetic differences in TB
Muñoz, Laura; Santin, Miguel; Alcaide, Fernando; Ruíz-Serrano, Maria Jesús; Gijón, Paloma; Bermúdez, Elena; Domínguez-Castellano, Angel; Navarro, María Dolores; Ramírez, Encarnación; Pérez-Escolano, Elvira; López-Prieto, María Dolores; Gutiérrez-Rodriguez, José; Anibarro, Luis; Calviño, Laura; Trigo, Matilde; Cifuentes, Carmen; García-Gasalla, Mercedes; Payeras, Antoni; Gasch, Oriol; Espasa, Mateu; Agüero, Ramon; Ferrer, Diego; Casas, Xavier; González-Cuevas, Araceli; García-Zamalloa, Alberto; Bikuña, Edurne; Lecuona, María; Galindo, Rosa; Ramírez-Lapausa, Marta; Carrillo, Raquel
Screening strategies based on interferon-γ release assays in tuberculosis contact tracing may reduce the need for preventive therapy without increasing subsequent active disease. We conducted an open-label, randomized trial to test the noninferiority of a 2-step strategy with the tuberculin skin test (TST) followed by QuantiFERON-TB Gold In-Tube (QFT-GIT) as a confirmatory test (the TST/QFT arm) to the standard TST-alone strategy (TST arm) for targeting preventive therapy in household contacts of patients with tuberculosis. Participants were followed for 24 months after randomization. The primary endpoint was the development of tuberculosis, with a noninferiority margin of 1.5 percentage points. A total of 871 contacts were randomized. Four contacts in the TST arm and 2 in the TST/QFT arm developed tuberculosis. In the modified intention-to-treat analysis, this accounted for 0.99% in the TST arm and 0.51% in the TST/QFT arm (-0.48% difference; 97.5% confidence interval [CI], -1.86% to 0.90%); in the per-protocol analysis, the corresponding rates were 1.67% and 0.82% in the TST and TST/QFT arms, respectively (-0.85% difference; 97.5% CI, -3.14% to 1.43%). Of the 792 contacts analyzed, 65.3% in the TST arm and 42.2% in the TST/QFT arm were diagnosed with tuberculosis infection (23.1% difference; 95% CI, 16.4% to 30.0%). In low-incidence settings, screening household contacts with the TST and using QFT-GIT as a confirmatory test is not inferior to TST-alone for preventing active tuberculosis, allowing a safe reduction of preventive treatments. NCT01223534. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: firstname.lastname@example.org.
Kundu, Debashish; Sharma, Nandini; Chadha, Sarabjit; Laokri, Samia; Awungafac, George; Jiang, Lai; Asaria, Miqdad
There are significant financial barriers to access treatment for multi drug resistant tuberculosis (MDR-TB) in India. To address these challenges, Chhattisgarh state in India has established a MDR-TB financial protection policy by creating MDR-TB benefit packages as part of the universal health insurance scheme that the state has rolled out in their effort towards attaining Universal Health Coverage for all its residents. In these schemes the state purchases health insurance against set packages of services from third party health insurance agencies on behalf of all its residents. Provider payment reform by strategic purchasing through output based payments (lump sum fee is reimbursed as per the MDR-TB benefit package rates) to the providers - both public and private health facilities empanelled under the insurance scheme was the key intervention. To understand the implementation gap between policy and practice of the benefit packages with respect to equity in utilization of package claims by the poor patients in public and private sector. Data from primary health insurance claims from January 2013 to December 2015, were analysed using an extension of 'Kingdon's multiple streams for policy implementation framework' to explain the implementation gap between policy and practice of the MDR-TB benefit packages. The total number of claims for MDR-TB benefit packages increased over the study period mainly from poor patients treated in public facilities, particularly for the pre-treatment evaluation and hospital stay packages. Variations and inequities in utilizing the packages were observed between poor and non-poor beneficiaries in public and private sector. Private providers participation in the new MDR-TB financial protection mechanism through the universal health insurance scheme was observed to be much lower than might be expected given their share of healthcare provision overall in India. Our findings suggest that there may be an implementation gap due to weak
Rangel, Carlos Mario; Atencia, Cesar; Merayo-Lloves, Jesus; Fernandez-Vega Sanz, Alvaro
A 59-year-old Hispanic woman presented with a 3-year history of floaters associated with bilateral reduced visual acuity. Her best-corrected visual acuity (BCVA) was 20/40. Both anterior segments were without inflammation, but fundoscopy showed mild vitreous inflammation and multiple inflammatory choroidal lesions. Tests for inflammatory and infectious diseases were negative except for human leucocyte antigen A29. The patient was diagnosed with birdshot choroidoretinopathy, and treatment was initiated with cyclosporine A 2.5 mg/kg/day. One year after treatment, the patient reported systemic symptoms with no improvement in visual acuity. Fundus findings remained with vitreal inflammation. QuantiFERON-TB Gold In-Tube Test was positive, and a diagnosis of presumed latent ocular tuberculosis (TB) was made. We initiated anti-TB treatment for 9 months. At 6 months of anti-TB therapy, there was no active inflammation. The patient was followed for 2 years with no medications and no active inflammation. Her final BCVA was 20/25. 2015 BMJ Publishing Group Ltd.
Byrne, A L; Marais, B J; Mitnick, C D; Garden, F L; Lecca, L; Contreras, C; Yauri, Y; Garcia, F; Marks, G B
The increasing prevalence of non-communicable diseases (NCDs) poses a major challenge to low- and middle-income countries. Patients' engagement with health services for anti-tuberculosis treatment provides an opportunity for screening for NCDs and for linkage to care. We explored the feasibility and yield of screening for NCDs in patients treated for tuberculosis (TB) in Lima, Peru, as part of a study focused on chronic respiratory sequelae. A representative sample of community controls was recruited from the same geographical area. Screening entailed taking a medical history and performing ambulatory blood pressure measurement and urinalysis. A total of 177 participants with previous TB (33 with multidrug-resistant TB) and 161 community controls were evaluated. There was an almost four-fold increased prevalence of self-reported diabetes mellitus (DM) in the TB group (adjusted prevalence ratio 3.66, 95%CI 1.68-8.01). Among those without self-reported DM, 3.3% had glycosuria, with a number needed to screen (NNS) of 31. The NNS to find one (new) case of hypertension or proteinuria in the TB group was respectively 24 and 5. Patient-centred care that includes pragmatic NCD screening is feasible in TB patients, and the treatment period provides a good opportunity to link patients to ongoing care.
Cleveland, Jennifer L; Robison, Valerie A; Panlilio, Adelisa L
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.
Brode, S K; Daley, C L; Marras, T K
Tuberculosis (TB) rates are decreasing in many areas, while non-tuberculous mycobacteria (NTM) infection rates are increasing. The relationship between the epidemiology of TB and NTM infections is not well understood. To understand the epidemiologic relationship between TB and NTM disease worldwide. A systematic review of Medline (1946-2014) was conducted to identify studies that reported temporal trends in NTM disease incidence. TB rates for each geographic area included were then retrieved. Linear regression models were fitted to calculate slopes describing changes over time. There were 22 studies reporting trends in rates of NTM disease, representing 16 geographic areas over four continents: 75% of areas had climbing incidence rates, while 12.5% had stable rates and 12.5% had declining rates. Most studies (81%) showed declining TB incidence rates. The proportion of incident mycobacterial disease caused by NTM was shown to be rising in almost every geographic area (94%). We found an increase in the proportion of mycobacterial disease caused by NTM in many parts of the world due to a simultaneous reduction in TB and increase in NTM disease. Research into the interaction between mycobacterial infections may help explain this inverse relationship.
Mirlekar, B; Pathak, S; Pathade, G
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
Bapat, Prachi R.; Satav, Ashish R.; Husain, Aliabbas A.; Shekhawat, Seema D.; Kawle, Anuja P.; Chu, Justin J.; Purohit, Hemant J.; Daginawala, Hatim F.; Taori, Girdhar M.; Kashyap, Rajpal S.
Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis. PMID:26241963
Lu, M-C; Lai, C-L; Tsai, C-C; Koo, M; Lai, N-S
Impaired immunity in patients with rheumatic diseases can increase the risk of pulmonary tuberculosis (PTB). However, it is less clear whether rheumatic diseases affect the risk of extra-pulmonary tuberculosis (EPTB). To investigate the risk of PTB and EPTB in patients with rheumatic diseases using a population-based database. From Taiwan's National Health Insurance Research Database, 8536 patients with tuberculosis (TB) were frequency-matched with 42,680 controls for sex, 10-year age group and index year. Subjects were retrospectively traced back for their first diagnosis of rheumatic diseases. The association between TB and rheumatic diseases was assessed using multivariate logistic regression analyses. The risk of developing PTB was significantly higher in patients with systemic lupus erythematosus (adjusted odds ratio [aOR] 4.90, P < 0.001), rheumatoid arthritis (RA) (aOR 2.00, P < 0.001) and Sjögren's syndrome (aOR 6.11, P < 0.001). In addition, the risks of developing EPTB were significantly higher in RA patients (aOR 4.67, P < 0.001), those with Sjögren's syndrome (aOR 5.94, P < 0.001), and the group comprising progressive systemic sclerosis, polymyositis or dermatomyositis (aOR 8.31, P = 0.021). Elevated risks of PTB and EPTB were associated with various rheumatic diseases. Rheumatologists should be vigilant to the possibility of TB, and particularly EPTB, in their patients.
Li, Jun; Chung, Pui-Hong; Leung, Cyrus L K; Nishikiori, Nobuyuki; Chan, Emily Y Y; Yeoh, Eng-Kiong
With the rapid pace of population ageing, tuberculosis (TB) in the elderly increasingly becomes a public health challenge. Despite the increasing burden and high risks for TB in the elderly, targeted strategy has not been well understood and evaluated. We undertook a scoping review to identify current TB strategies, research and policy gaps in the elderly and summarized the results within a strategic framework towards End TB targets. Databases of Embase, MEDLINE, Global health and EBM reviews were searched for original studies, review articles, and policy papers published in English between January 1990 and December 2015. Articles examining TB strategy, program, guideline or intervention in the elderly from public health perspective were included.Nineteen articles met the inclusion criteria. Most of them were qualitative studies, issued in high- and middle-income countries and after 2000. To break the chain of TB transmission and reactivation in the elderly, infection control, interventions of avoiding delay in diagnosis and containment are essential for preventing transmission, especially in elderly institutions and aged immigrants; screening of latent TB infection and preventive therapy had effective impacts on reducing the risk of reactivation and should be used less reluctantly in older people; optimizing early case-finding with a high index of suspicion, systematic screening for prioritized high-risk groups, initial empirical and adequate follow-up treatment with close monitoring and evaluation, as well as enhanced programmatic management are fundamental pillars for active TB elimination. Evaluation of TB epidemiology, risk factors, impacts and cost-effectiveness of interventions, adopting accurate and rapid diagnostic tools, shorter and less toxic preventive therapy, are critical issues for developing strategy in the elderly towards End TB targets.TB control strategies in the elderly were comprehensively mapped in a causal link pathway. The framework and
Metin Timur, Özge; Tanir, Gönül; Öz, Fatma Nur; Bayhan, Gülsüm İclal; Aydin Teke, Türkan; Tuygun, Nilden
In this study, we aimed to compare QuantiFERON-TB gold in-tube test (QFT-GIT) and tuberculin skin test (TST) as a diagnosis of latent tuberculosis infection in the children with Bacille Calmette-Guerin (BCG) vaccine. We evaluated 81 children in the study who have positive TST result without a known history of tuberculosis contact from 2008 to 2011 prospectively. Patients were separated into groups according to their ages, the reason of TST application, number of BCG vaccination scars and diameter of TST induration. Posteroanterior, lateral chest radiographies and computerized tomography, if necessary, were performed. The study consists of 48 (59.3%) boys and 33 (40.7%) girls with a mean age of 94.8 ± 51.9 months (ranged from 6 to 193 months). Sixty nine (85.2%) children had one and 12 (14.8%) had two BCG vaccination scars. The TST induration diameters were 15-19 mm in 65 (80.2%) children and ≥ 20 mm in 16 (19.8%) children. QFT-GIT positivity was found in 12 (14.8%) of the evaluated patients. QFT-GIT positive patients were treated with triple anti-tuberculosis regime or isoniazid (INH). In three years period of study, there were no tuberculosis disease observed among the children who had not been treated with anti-tuberculosis drugs. As a result of the study it is suggested to confirm positive TST results with tests based on interferon-gamma (IFN-γ) because it can reduce false positive diagnosis and treatment of latent tuberculosis infection, thus adverse reactions of drugs, in countries where BCG vaccination is routinely recommended especially for low risk children.
Cohen, Ted; Jenkins, Helen E.; Lu, Chunling; McLaughlin, Megan; Floyd, Katherine; Zignol, Matteo
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
Use of the Xpert(®) MTB/RIF assay for diagnosing pulmonary tuberculosis comorbidity and multidrug-resistant TB in obstetrics and gynaecology inpatient wards at the University Teaching Hospital, Lusaka, Zambia.
Bates, Matthew; Ahmed, Yusuf; Chilukutu, Lophina; Tembo, John; Cheelo, Busiku; Sinyangwe, Sylvester; Kapata, Nathan; Maeurer, Markus; O'Grady, Justin; Mwaba, Peter; Zumla, Alimuddin
In high-tuberculosis (TB)-endemic countries, comorbidity of pulmonary TB in hospitalised patients with non-communicable diseases is well documented. In this study, we evaluated the use of the Xpert(®) MTB/RIF assay for the detection of concomitant pulmonary TB in patients admitted to the University Teaching Hospital, Lusaka, Zambia, with a primary obstetric or gynaecological condition. The Study population were inpatients admitted with a primary obstetric or gynaecological problem who had a concomitant cough and were able to expectorate a sputum sample. Sputum samples from 94 patients were analysed for the presence of Mycobacterium tuberculosis (M.tb) by standard smear microscopy, MGIT culture, MGIT drug-susceptibility testing (DST) and the Xpert(®) MTB/RIF assay. The sensitivity and specificity of the Xpert(®) MTB/RIF assay were evaluated against the culture gold standard. Twenty-six of 94 (27.7%) patients had culture-confirmed pulmonary TB. The Xpert(®) MTB/RIF assay had a sensitivity of 80.8% [95% CI: 60.0-92.7%]) compared against MGIT culture. The Xpert(®) MTB/RIF assay was more sensitive than sputum smear microscopy (21/26 (80.8%) vs. 13/26 (50.0%), P = 0.02) and detected an additional eight culture-confirmed cases. Culture DST analysis identified two monoresistant M.tb strains: one resistant to rifampicin (rifampicin sensitive by the Xpert(®) MTB/RIF assay) and one to ethambutol. HIV infection was linked with a 3-fold increase in risk of TB, accounting for 87.5% (21/24) of TB cases. 50% of cases presented as comorbidities with other communicable diseases (CDs) and non-communicable diseases (NCDs). As an alternative to sputum microscopy, the Xpert(®) MTB/RIF assay provides a sensitive, specific and rapid method for the diagnosis of pulmonary TB in obstetric or gynaecological inpatients. Pulmonary TB is an important cause of concomitant comorbidity to the obstetric or gynaecological condition necessitating admission. TB and HIV comorbidities with other
Baquero-Artigao, F; Mellado Peña, M J; del Rosal Rabes, T; Noguera Julián, A; Goncé Mellgren, A; de la Calle Fernández-Miranda, M; Navarro Gómez, M L
In pregnant women who have been exposed to tuberculosis (TB), primary isoniazid prophylaxis is only recommended in cases of immunosuppression, chronic medical conditions or obstetric risk factors, and close and sustained contact with a patient with infectious TB. Isoniazid prophylaxis for latent tuberculosis infection (LTBI) is recommended in women who have close contact with an infectious TB patient or have risk factors for progression to active disease. Otherwise, it should be delayed until at least three weeks after delivery. Treatment of TB disease during pregnancy is the same as for the general adult population. Infants born to mothers with disseminated or extrapulmonary TB in pregnancy, with active TB at delivery, or with postnatal exposure to TB, should undergo a complete diagnostic evaluation. Primary isoniazid prophylaxis for at least 12 weeks is recommended for those with negative diagnostic tests and no evidence of disease. Repeated negative diagnostic tests are mandatory before interrupting prophylaxis. Isoniazid for 9 months is recommended in LTBI. Treatment of neonatal TB disease is similar to that of older children, but should be maintained for at least 9 months. Respiratory isolation is recommended in congenital TB, and in postnatal TB with positive gastric or bronchial aspirate acid-fast smears. Separation of mother and infant is only necessary when the mother has received treatment for less than 2 weeks, is sputum smear-positive, or has drug-resistant TB. Breastfeeding is not contraindicated, and in case of mother-infant separation expressed breast milk feeding is recommended. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.
Hall, Leslie; Jude, Kurt P; Clark, Shirley L; Dionne, Kim; Merson, Ryan; Boyer, Ana; Parrish, Nicole M; Wengenack, Nancy L
The Sensititre MycoTB plate (TREK Diagnostic Systems, Cleveland, OH) uses a microtiter plate MIC format for susceptibility testing of Mycobacterium tuberculosis complex isolates against first- and second-line antituberculosis agents. Categorical agreement versus the agar proportion method for 122 M. tuberculosis complex isolates was 94% to 100%.
Bourgarit, A; Mallet, H-P; Keshtmand, H; De Castro, N; Rambeloarisoa, J; Fain, O; Antoun, F; Picard, C; Rocher, G; Che, D; Farge, D
The impact of the TB-info software was assessed on the care of patients treated with antituberculosis regimen (ATT). Cohort study of patients with tuberculosis who received an ATT in 2004 in two hospitals and five medical centres in Paris. Follow-up was implemented with the TB-info software. Data were compared to those of the 1999-2003 cohort. Two hundred and nine ATT were initiated in 2004, with a mean duration of 7.2 months. Demographic and clinical data reflected this population precariousness: 79% were foreign-born, 25% lived in institutions and half of them had no or unusual health insurance. Compared to the previous cohort, viral co-infections were tested in more than 80% cases and showed association with HIV, HBV or HCV in 11, 10 and 5% of the patients, respectively. Twenty-one patients were lost for follow-up (11%) and 76% of the smear-positive pulmonary tuberculosis therapies were declared successful but only 34% were declared cured with the WHO criteria. Analysis of the data obtained with TB-info software showed an improvement of tuberculosis patients care with more co-infection tested and less lost for follow-up. These results confirm the usefulness of this software for patients care and assessment of physicians practice in France.
Kapata, Nathan; Chanda-Kapata, Pascalina; Ngosa, William; Metitiri, Mine; Klinkenberg, Eveline; Kalisvaart, Nico; Sunkutu, Veronica; Shibemba, Aaron; Chabala, Chishala; Chongwe, Gershom; Tembo, Mathias; Mulenga, Lutinala; Mbulo, Grace; Katemangwe, Patrick; Sakala, Sandra; Chizema-Kawesha, Elizabeth; Masiye, Felix; Sinyangwe, George; Onozaki, Ikushi; Mwaba, Peter; Chikamata, Davy; Zumla, Alimuddin; Grobusch, Martin P
Tuberculosis in Zambia is a major public health problem, however the country does not have reliable baseline data on the TB prevalence for impact measurement; therefore it was among the priority countries identified by the World Health Organization to conduct a national TB prevalence survey. To estimate the prevalence of tuberculosis among the adult Zambian population aged 15 years and above, in 2013-2014. A cross-sectional population-based survey was conducted in 66 clusters across all the 10 provinces of Zambia. Eligible participants aged 15 years and above were screened for TB symptoms, had a chest x-ray (CXR) performed and were offered an HIV test. Participants with TB symptoms and/or CXR abnormality underwent an in-depth interview and submitted one spot- and one morning sputum sample for smear microscopy and liquid culture. Digital data collection methods were used throughout the process. Of the 98,458 individuals who were enumerated, 54,830 (55.7%) were eligible to participate, and 46,099 (84.1%) participated. Of those who participated, 45,633/46,099 (99%) were screened by both symptom assessment and chest x-ray, while 466/46,099 (1.01%) were screened by interview only. 6,708 (14.6%) were eligible to submit sputum and 6,154/6,708 (91.7%) of them submitted at least one specimen for examination. MTB cases identified were 265/6,123 (4.3%). The estimated national adult prevalence of smear, culture and bacteriologically confirmed TB was 319/100,000 (232-406/100,000); 568/100,000 (440-697/100,000); and 638/100,000 (502-774/100,000) population, respectively. The risk of having TB was five times higher in the HIV positive than HIV negative individuals. The TB prevalence for all forms was estimated to be 455 /100,000 population for all age groups. The prevalence of tuberculosis in Zambia was higher than previously estimated. Innovative approaches are required to accelerate the control of TB.
Chiang, S S; Roche, S; Contreras, C; Del Castillo, H; Canales, P; Jimenez, J; Tintaya, K; Becerra, M C; Lecca, L
In 2012, Peru's National TB Program (NTP) reported approximately 2400 incident cases of tuberculosis (TB) disease in children aged <15 years. Peru's TB burden is concentrated in the Lima metropolitan area, particularly in poor districts such as El Agustino and La Victoria, where this study was conducted. To identify barriers to the treatment of childhood tuberculous infection and TB disease in Lima from the perspective of front-line providers and patients' families. We conducted 10 semi-structured focus groups with 53 purposefully sampled primary care providers, community health workers, and parents/guardians of pediatric TB patients. We also completed nine in-depth interviews with National TB Program administrators and pulmonologists specializing in TB. Two authors performed inductive thematic analysis and identified emerging themes. Four main treatment barriers emerged from the data: 1) dosing errors, 2) time- and labor-intensive preparation and administration of medications, 3) provider concern that isoniazid preventive therapy (IPT) generates isoniazid resistance, and 4) poor adherence to IPT. Our findings highlight the urgent need for child-friendly formulations, provider and parent/guardian education about IPT, and strategies to promote adherence to IPT, including support and supervision by health workers and/or regimens with fewer doses.
Maslow, J N; Mikota, S K
Tuberculosis (TB) in elephants has been described since ancient times. However, it was not until 1996 when infection with Mycobacterium tuberculosis was identified in a herd of circus elephants that significant research into this disease began. The epidemiology and natural history of TB were unknown in elephants since there had been no comprehensive screening programs, and diagnostic techniques developed for cervidae and bovidae were of unknown value. And, while precepts of test and slaughter were the norm for cattle and deer, this was considered untenable for an endangered species. With no precedent for the treatment of TB in animals, treatment regimens for elephants were extrapolated from human protocols, which guided changes to the Guidelines for the Control of Tuberculosis in Elephants. In the absence of diagnostic testing to confirm cure in elephants, the efficacy of these treatment regimens is only beginning to be understood as treated elephants die and are examined postmortem. However, because of pressures arising from public relations related to elephant husbandry and the added considerations of TB infection in animals (whether real or imagined), sharing of information to aid in research and treatment has been problematic. Here we review the challenges and successes of the diagnosis of tuberculosis in elephants and discuss the natural history of the disease to put the work of Landolfi et al on the immunological response to tuberculosis in elephants in perspective. © The Author(s) 2015.
Harries, Anthony D; Murray, Megan B; Jeon, Christie Y; Ottmani, Salah-Eddine; Lonnroth, Knut; Barreto, Mauricio L; Billo, Nils; Brostrom, Richard; Bygbjerg, Ib Christian; Fisher-Hoch, Susan; Mori, Toru; Ramaiya, Kaushik; Roglic, Gojka; Strandgaard, Hanne; Unwin, Nigel; Viswanathan, Vijay; Whiting, David; Kapur, Anil
The steadily growing epidemic of diabetes mellitus (DM) poses a threat for global tuberculosis (TB) control. Previous studies have identified an important association between DM and TB. However, these studies have limitations: very few were carried out in low-income countries, with none in Africa, raising uncertainty about the strength of the DM-TB association in these settings, and many critical questions remain unanswered. An expert meeting was held in November 2009 to discuss where there was sufficient evidence to make firm recommendations about joint management of both diseases, to address research gaps and to develop a research agenda. Ten key research questions were identified, of which 4 were selected as high priority: i) whether, when and how to screen for TB in patients with DM and vice versa; ii) the impact of DM and non-DM hyperglycaemia on TB treatment outcomes and deaths, and the development of strategies to improve outcomes; iii) implementation and evaluation of the tuberculosis “DOTS” model for DM management; and iv) the development and evaluation of better point-of-care diagnostic and monitoring tests, including measurements of blood glucose and glycated haemoglobin A1c (HbA1c) for patients with DM. Implementation of this research agenda will benefit the control of both diseases. PMID:20406430
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
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
Wandwalo, Eliud; Kapalata, Neema; Tarimo, Edith; Corrigan, C Brigid; Morkve, Odd
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.
Roffe, T.J.; Smith, B.
Tuberculosis! Just the name conjures up images of a devastating, chronic, debilitating disease. And so it is in both humans and animals. Tuberculosis (TB) is not known to be present to any significant degree in the free-ranging elk herds of North America. But increasing reports of TB in deer species-including elk-on game ranches prompt grave concern.
Unacceptable treatment outcomes and associated factors among India's initial cohorts of multidrug-resistant tuberculosis (MDR-TB) patients under the revised national TB control programme (2007-2011): Evidence leading to policy enhancement.
Parmar, Malik M; Sachdeva, Kuldeep Singh; Dewan, Puneet K; Rade, Kiran; Nair, Sreenivas A; Pant, Rashmi; Khaparde, Sunil D
Globally, India has the world's highest burden of multidrug-resistant tuberculosis (MDR-TB). Programmatic Management of Drug Resistant TB (PMDT) in India began in 2007 and nationwide coverage was achieved in early 2013. Poor initial microbiological outcomes under the Revised National Tuberculosis Control Programme (RNTCP) prompted detailed analysis. This is the first study on factors significantly associated with poor outcomes in MDR-TB patients treated under the RNTCP. To evaluate initial sputum culture conversion, culture reversion and final treatment outcomes among MDR-TB patients registered in India from 2007 to early 2011 who were treated with a standard 24-month regimen under daily-observed treatment. This is a retrospective cohort study. Clinical and microbiological data were abstracted from PMDT records. Initial sputum culture conversion, culture reversion and treatment outcomes were defined by country adaptation of the standard WHO definitions (2008). Cox proportional hazards modeling with logistic regression, multinomial logistic regression and adjusted odds ratio was used to evaluate factors associated with interim and final outcomes respectively, controlling for demographic and clinical characteristics. In the cohort of 3712 MDR-TB patients, 2735 (73.6%) had initial sputum culture conversion at 100 median days (IQR 92-125), of which 506 (18.5%) had culture reversion at 279 median days (IQR 202-381). Treatment outcomes were available for 2264 (60.9%) patients while 1448 (39.0%) patients were still on treatment or yet to have a definite outcome at the time of analysis. Of 2264 patients, 781 (34.5%) had treatment success, 644 (28.4%) died, 670 (29.6%) were lost to follow up, 169 (7.5%) experienced treatment failure or were changed to XDR-TB treatment. Factors significantly associated with either culture non-conversion, culture reversion and/or unfavorable treatment outcomes were baseline BMI < 18; ≥ seven missed doses in intensive phase (IP) and
Unacceptable treatment outcomes and associated factors among India's initial cohorts of multidrug-resistant tuberculosis (MDR-TB) patients under the revised national TB control programme (2007–2011): Evidence leading to policy enhancement
Sachdeva, Kuldeep Singh; Dewan, Puneet K.; Rade, Kiran; Nair, Sreenivas A.; Pant, Rashmi; Khaparde, Sunil D.
Background Globally, India has the world’s highest burden of multidrug-resistant tuberculosis (MDR-TB). Programmatic Management of Drug Resistant TB (PMDT) in India began in 2007 and nationwide coverage was achieved in early 2013. Poor initial microbiological outcomes under the Revised National Tuberculosis Control Programme (RNTCP) prompted detailed analysis. This is the first study on factors significantly associated with poor outcomes in MDR-TB patients treated under the RNTCP. Objective To evaluate initial sputum culture conversion, culture reversion and final treatment outcomes among MDR-TB patients registered in India from 2007 to early 2011 who were treated with a standard 24-month regimen under daily-observed treatment. Methods This is a retrospective cohort study. Clinical and microbiological data were abstracted from PMDT records. Initial sputum culture conversion, culture reversion and treatment outcomes were defined by country adaptation of the standard WHO definitions (2008). Cox proportional hazards modeling with logistic regression, multinomial logistic regression and adjusted odds ratio was used to evaluate factors associated with interim and final outcomes respectively, controlling for demographic and clinical characteristics. Results In the cohort of 3712 MDR-TB patients, 2735 (73.6%) had initial sputum culture conversion at 100 median days (IQR 92–125), of which 506 (18.5%) had culture reversion at 279 median days (IQR 202–381). Treatment outcomes were available for 2264 (60.9%) patients while 1448 (39.0%) patients were still on treatment or yet to have a definite outcome at the time of analysis. Of 2264 patients, 781 (34.5%) had treatment success, 644 (28.4%) died, 670 (29.6%) were lost to follow up, 169 (7.5%) experienced treatment failure or were changed to XDR-TB treatment. Factors significantly associated with either culture non-conversion, culture reversion and/or unfavorable treatment outcomes were baseline BMI < 18; ≥ seven missed
Alcaide, Fernando; Coll, Pere
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.
Schmid, Karen Barros; Scherer, Luciene; Barcellos, Regina Bones; Kuhleis, Daniele; Prestes, Isaías Valente; Steffen, Ricardo Ewbank; Dalla Costa, Elis Regina; Rossetti, Maria Lucia Rosa
Prison conditions can favor the spread of tuberculosis (TB). This study aimed to evaluate in a Brazilian prison: the performance and accuracy of smear, culture and Detect-TB; performance of smear plus culture and smear plus Detect-TB, according to different TB prevalence rates; and the cost-effectiveness of these procedures for pulmonary tuberculosis (PTB) diagnosis. This paper describes a cost-effectiveness study. A decision analytic model was developed to estimate the costs and cost-effectiveness of five routine diagnostic procedures for diagnosis of PTB using sputum specimens: a) Smear alone, b) Culture alone, c) Detect-TB alone, d) Smear plus culture and e) Smear plus Detect-TB. The cost-effectiveness ratio of costs were evaluated per correctly diagnosed TB case and all procedures costs were attributed based on the procedure costs adopted by the Brazilian Public Health System. A total of 294 spontaneous sputum specimens from patients suspected of having TB were analyzed. The sensibility and specificity were calculated to be 47% and 100% for smear; 93% and 100%, for culture; 74% and 95%, for Detect-TB; 96% and 100%, for smear plus culture; and 86% and 95%, for smear plus Detect-TB. The negative and positive predictive values for smear plus Detect-TB, according to different TB prevalence rates, ranged from 83 to 99% and 48 to 96%, respectively. In a cost-effectiveness analysis, smear was both less costly and less effective than the other strategies. Culture and smear plus culture were more effective but more costly than the other strategies. Smear plus Detect-TB was the most cost-effective method. The Detect-TB evinced to be sensitive and effective for the PTB diagnosis when applied with smear microscopy. Diagnostic methods should be improved to increase TB case detection. To support rational decisions about the implementation of such techniques, cost-effectiveness studies are essential, including in prisons, which are known for health care assessment problems.
Tweed, Conor Duncan; Wills, Genevieve Helen; Crook, Angela M; Dawson, Rodney; Diacon, Andreas H; Louw, Cheryl E; McHugh, Timothy D; Mendel, Carl; Meredith, Sarah; Mohapi, Lerato; Murphy, Michael E; Murray, Stephen; Murthy, Sara; Nunn, Andrew J; Phillips, Patrick P J; Singh, Kasha; Spigelman, M; Gillespie, S H
Drug-induced liver injury (DILI) is a common complication of tuberculosis treatment. We utilised data from the REMoxTB clinical trial to describe the incidence of predisposing factors and the natural history in patients with liver enzyme levels elevated in response to tuberculosis treatment. Patients received either standard tuberculosis treatment (2EHRZ/4HR), or a 4-month regimen in which moxifloxacin replaced either ethambutol (isoniazid arm, 2MHRZ/2MHR) or isoniazid (ethambutol arm, 2EMRZ/2MR). Hepatic enzymes were measured at 0, 2, 4, 8, 12 and 17 weeks and as clinically indicated during reported adverse events. Patients included were those receiving at least one dose of drug and with two or more hepatic enzyme measurements. A total of 1928 patients were included (639 2EHRZ/4HR, 654 2MHRZ/2MHR and 635 2EMRZ/2MR). DILI was defined as peak alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (5 × ULN) or ALT ≥ 3 × ULN with total bilirubin > 2 × ULN. DILI was identified in 58 of the 1928 (3.0%) patients at a median time of 28 days (interquartile range IQR 14-56). Of 639 (6.4%) patients taking standard tuberculosis therapy, 41 experienced clinically significant enzyme elevations (peak ALT ≥ 3 × ULN). On standard therapy, 21.1% of patients aged >55 years developed a peak ALT/aspartate aminotransferase (AST) ≥ 3 × ULN (p = 0.01) and 15% of HIV-positive patients experienced a peak ALT/AST ≥ 3 × ULN compared to 9% of HIV-negative patients (p = 0.160). The median peak ALT/AST was higher in isoniazid-containing regimens vs no-isoniazid regimens (p < 0.05), and lower in moxifloxacin-containing arms vs no-moxifloxacin arms (p < 0.05). Patients receiving isoniazid reached a peak ALT ≥ 3 × ULN 9.5 days earlier than those on the ethambutol arm (median time of 28 days vs 18.5 days). Of the 67 Asian patients with a peak ALT/AST ≥ 3 × ULN, 57 (85.1%) were on an isoniazid-containing regimen (p = 0.008). Our results provide evidence of the risk
Wayengera, Misaki; Kateete, David P; Asiimwe, Benon; Joloba, Moses L
Precise designation of high risk forms of latent Mycobacterium tuberculosis-M.tb infections (LTBI) is impossible. Delineation of high-risk LTBI can, however, allow for chemoprophylaxis and curtail majority cases of active tuberculosis (ATB). There is epidemiological evidence to support the view that LTBI in context of HIV-1 co-infection is high-risk for progression to ATB relative to LTBI among HIV-ve persons. We recently showed that assays of M.tb thymidylate kinase (TMKmt) antigen and host specific IgG can differentiate ATB from LTBI and or no TB (NTB, or healthy controls). In this study, we aimed to expose the differential levels of TMKmt Ag among HIV+ve co-infected LTBI relative to HIV-ve LTBI as a strategy to advance these assays for designating incipient LTBI. TMKmt host specific IgM and IgG detection Enzyme Immuno-Assays (EIA) were conducted on 40 TB exposed house-hold contacts (22 LTBI vs. 18 no TB (NTB) by QunatiFERON-TB GOLD®); and TMKmt Ag detection EIA done on 82 LTBI (46 HIV+ve vs 36 HIV-ve) and 9 NTB (American donors). Purified recombinant TMKmt protein was used as positive control for the Ag assays. IgM levels were found to be equally low across QuantiFERON-TB GOLD® prequalified NTB and TB exposed house-hold contacts. Higher TMKmt host specific IgG trends were found among TB house-hold contacts relative to NTB controls. TMKmt Ag levels among HIV+ve LTBI were 0.2676 ± 0.0197 (95% CI: 0.2279 to 0.3073) relative to 0.1069 ± 0.01628 (95% CI: 0.07385 to 0.14) for HIV-ve LTBI (supporting incipient nature of LTBI in context of HIV-1 co-infection). NTB had TMKmt Ag levels of 0.1013 ± 0.02505 (5% CI: 0.0421 to 0.1606) (intimating that some were indeed LTBI). TMKmt Ag levels represent a novel surrogate biomarker for high-risk LTBI, while host-specific IgG can be used to designate NTB from LTBI.
Obasanjo, Olugbenga Olufemi
Given the reemergence of Tuberculosis (TB) in the United States (U.S.) in the 1980s and 1990s, several strategies have emerged to combat the disease. A successful tool has been Directly Observed Therapy (DOT). Chaulk, et al. showed that DOT was responsible for the maintaining the decline in TB rates in Baltimore through the corresponding period of an upswing in rates nationally. In this study, we measure the impact of DOT on the geographic pattern of TB in Baltimore. We used Geographical Information System (GIS) methods to compare the geographic patterns of TB in Baltimore before and after the introduction of DOT in the city. We identified both predictors of TB, and differences in geographic units in Baltimore over time. We measured the impact of the introduction of DOT and Rifampin on various treatment outcomes for TB at about the same time. Despite the drop in numbers of TB cases, the spatial distribution of cases generally remained unchanged until 1995. This was confirmed by the fact that similar predictors were identified in all of the years that were analyzed. However, higher proportions of TB cases were found among blacks and females in more recent years. Death rates have increased significantly while corresponding relapse rates and the mean length of therapy have declined significantly. Rifampin was associated with a longer length of therapy before DOT, but with a shorter duration of therapy following the introduction of DOT. In all of the years analyzed, losses to follow-up (LTFU) do not differ from those completing therapy and are not spatially clustered relative to those completing therapy. DOT has been effective in reducing the numbers of TB cases in Baltimore city-wide without an emphasis on so-called "high-risk" patients for LTFU. Thus, any declines in TB case rates are not due to a decline in a particular group or geographic sector of the city. Universal DOT is effective and does not cause a geographic clustering of difficult-to-reach patients. This
Pioneer studies on infectious disease and immunology by Jenner, Pasteur, Koch, Von Behring, Nocard, Roux, and Ehrlich forged a path for the dual-purpose with dual benefit approach, demonstrating a profound relevance of veterinary studies for biomedical applications. Tuberculosis (TB), primarily due ...
Erkens, Connie G M; Slump, Erika; Verhagen, Maurits; Schimmel, Henrieke; Cobelens, Frank; van den Hof, Susan
Diagnosis and preventive treatment of latent tuberculosis infection (LTBI) among high-risk groups is recommended to achieve tuberculosis (TB) elimination in low-incidence countries.We studied TB incidence rates among those notified with LTBI in the Netherlands from 2005 to 2013 and analysed associated risk factors. We stratified analyses by target group for screening, and by initiation and completion of preventive treatment.The incidence for those completing, stopping and not receiving preventive treatment was 187, 436 and 355 per 100 000 person-years for contacts of TB patients, respectively, and 63, 96 and 110 per 100 000 person-years for other target groups. The rate ratio for TB development among contacts compared to other target groups was 3.1 (95% CI 2.0-4.9). In both groups, incidence was highest in the first year after diagnosis. Independent factors associated with progression to TB among contacts were age <5 years and stopping preventive treatment within 28 days compared to those not receiving preventive treatment. Among other target groups, being foreign born was the only risk factor associated with the risk of developing TB.We conclude that the epidemiological impact of preventive treatment is highest in contacts of TB patients and limited in other target groups for LTBI management in the Netherlands. Copyright ©ERS 2016.
Differences in IgG responses against infection phase related Mycobacterium tuberculosis (Mtb) specific antigens in individuals exposed or not to Mtb correlate with control of TB infection and progression.
Coppola, Mariateresa; Arroyo, Leonar; van Meijgaarden, Krista E; Franken, Kees Lmc; Geluk, Annemieke; Barrera, Luis F; Ottenhoff, Tom H M
Tuberculosis (TB) occurs in only 3-10% of Mycobacterium tuberculosis (Mtb) infected individuals, suggesting that natural immunity can contain Mtb infection, although this remains poorly understood. Next to T-cells, a potentially protective role for B-cells and antibodies has emerged recently. However, the Mtb antigens involved remain ill-defined. Here, we investigated in a TB-endemic setting IgG levels against 15 Mtb antigens, representing various phases of Mtb infection and known to be potent human T-cell antigens. IgG levels against ESAT6/CFP10, Rv0440, Rv0867c, Rv1737c, Rv2029c, Rv2215, Rv2389c, Rv3616c and Mtb purified protein derivative (PPD) were higher in TB patients than in endemic and non-endemic controls. The only exception was Rv1733c that was preferentially recognized by antibodies from endemic controls compared to TB patients and non-endemic controls, suggesting a potential correlation with control of TB infection and progression. In patients, IgG levels against Ag85B and Rv2029c correlated with Mtb loads, while immunoglobulins against Rv0440 differed between genders. Our results support the potential role of certain Mtb antigen-(Rv1733c) specific antibodies in the control of TB infection and progression, while other Mtb antigen-specific antibodies correlate with TB disease activity and bacillary loads. The findings for Rv1733c agree with previous T-cell results and have implications for including antibody-mediated immunity in designing new strategies to control TB. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Porter, Brian O.; Chandrasekhar, Chockalingam; Venkatesan, Perumal; Menon, Pradeep A.; Subramanian, Sudha; Anbalagan, Selvaraj; Bhavani, Kannabiran P.; Sekar, Sathiyavelu; Padmapriyadarshini, Chandrasekaran; Kumar, Satagopan; Ravichandran, Narayanan; Raja, Krishnaraj; Bhanu, Kesavamurthy; Mahilmaran, Ayyamperumal; Sekar, Lakshmanan; Sher, Alan; Sereti, Irini; Swaminathan, Soumya
Background The incidence, manifestations, outcome and clinical predictors of paradoxical TB-IRIS in patients with HIV and culture confirmed pulmonary tuberculosis (PTB) in India have not been studied prospectively. Methods HIV+ patients with culture confirmed PTB started on anti-tuberculosis therapy (ATT) were followed prospectively after anti-retroviral therapy (ART) initiation. Established criteria for IRIS diagnosis were used including decline in plasma HIV RNA at IRIS event. Pre-ART plasma levels of interleukin (IL)-6 and C-reactive protein (CRP) were measured. Univariate and multivariate logistic regression models were used to evaluate associations between baseline variables and IRIS. Results Of 57 patients enrolled, 48 had complete follow up data. Median ATT-ART interval was 28 days (interquartile range, IQR 14–47). IRIS events occurred in 26 patients (54.2%) at a median of 11 days (IQR: 7–16) after ART initiation. Corticosteroids were required for treatment of most IRIS events that resolved within a median of 13 days (IQR: 9–23). Two patients died due to CNS TB-IRIS. Lower CD4+ T-cell counts, higher plasma HIV RNA levels, lower CD4/CD8 ratio, lower hemoglobin, shorter ATT to ART interval, extra-pulmonary or miliary TB and higher plasma IL-6 and CRP levels at baseline were associated with paradoxical TB-IRIS in the univariate analysis. Shorter ATT to ART interval, lower hemoglobin and higher IL-6 and CRP levels remained significant in the multivariate analysis. Conclusion Paradoxical TB–IRIS frequently complicates HIV-TB therapy in India. IL-6 and CRP may assist in predicting IRIS events and serve as potential targets for immune interventions. PMID:23691062
Khan, Wasiq Mehmood; Smith, Helen; Qadeer, Ejaz; Hassounah, Sondus
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
Khan, Wasiq Mehmood; Smith, Helen; Qadeer, Ejaz
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
Targeting the human macrophage with combinations of drugs and inhibitors of Ca2+ and K+ transport to enhance the killing of intracellular multi-drug resistant Mycobacterium tuberculosis (MDR-TB)--a novel, patentable approach to limit the emergence of XDR-TB.
The emergence of resistance in tuberculosis has become a serious problem for the control of this disease. For that reason, new therapeutic strategies that can be implemented in the clinical setting are urgently needed. The design of new compounds active against mycobacteria must take into account that tuberculosis is mainly an intracellular infection of the alveolar macrophage and therefore must maintain activity within the host cells. An alternative therapeutic approach will be described in this review, focusing on the activation of the phagocytic cell and the subsequent killing of the internalized bacteria. This approach explores the combined use of antibiotics and phenothiazines, or Ca(2+) and K(+) flux inhibitors, in the infected macrophage. Targeting the infected macrophage and not the internalized bacteria could overcome the problem of bacterial multi-drug resistance. This will potentially eliminate the appearance of new multi-drug resistant tuberculosis (MDR-TB) cases and subsequently prevent the emergence of extensively-drug resistant tuberculosis (XDR-TB). Patents resulting from this novel and innovative approach could be extremely valuable if they can be implemented in the clinical setting. Other patents will also be discussed such as the treatment of TB using immunomodulator compounds (for example: betaglycans).
Migliori, G. B.; Ambrosetti, M.; Besozzi, G.; Farris, B.; Nutini, S.; Saini, L.; Casali, L.; Nardini, S.; Bugiani, M.; Neri, M.; Raviglione, M. C.
Although in developing countries the treatment of tuberculosis (TB) cases is among the most cost-effective health interventions, few studies have evaluated the cost-effectiveness of TB control in low-prevalence countries. The aim of the present study was to carry out an economic analysis in Italy that takes into account both the perspective of the resource-allocating authority (i.e. the Ministry of Health) and the broader social perspective, including a cost description based on current outcomes applied to a representative sample of TB patients nationwide (admission and directly observed treatment (DOT) during the initial intensive phase of treatment); a cost-comparison analysis of two alternative programmes: current policy based on available data (scenario 1) and an hypothetical policy oriented more towards outpatient care (scenario 2) (both scenarios included the option of including or not including DOT outside hospital admission, and incentives) were compared in terms of cost per case treated successfully. Indirect costs (such as loss of productivity) were included in considerations of the broader social perspective. The study was designed as a prospective monitoring activity based on the supervised collection of forms from a representative sample of Italian TB units. Individual data were collected and analysed to obtain a complete economic profile of the patients enrolled and to evaluate the effectiveness of the intervention. A separate analysis was done for each scenario to determine the end-point at different levels of cure rate (50-90%). The mean length of treatment was 6.6 months (i.e. patients hospitalized during the intensive phase; length of stay was significantly higher in smear-positive patients and in human immunodeficiency virus (HIV) seropositive patients). Roughly six direct smear and culture examinations were performed during hospital admission and three during ambulatory treatment. The cost of a single bed day was US$186.90, whereas that of a
Sekizuka, Tsuyoshi; Yamashita, Akifumi; Murase, Yoshiro; Iwamoto, Tomotada; Mitarai, Satoshi; Kato, Seiya; Kuroda, Makoto
Whole-genome sequencing (WGS) with next-generation DNA sequencing (NGS) is an increasingly accessible and affordable method for genotyping hundreds of Mycobacterium tuberculosis (Mtb) isolates, leading to more effective epidemiological studies involving single nucleotide variations (SNVs) in core genomic sequences based on molecular evolution. We developed an all-in-one web-based tool for genotyping Mtb, referred to as the Total Genotyping Solution for TB (TGS-TB), to facilitate multiple genotyping platforms using NGS for spoligotyping and the detection of phylogenies with core genomic SNVs, IS6110 insertion sites, and 43 customized loci for variable number tandem repeat (VNTR) through a user-friendly, simple click interface. This methodology is implemented with a KvarQ script to predict MTBC lineages/sublineages and potential antimicrobial resistance. Seven Mtb isolates (JP01 to JP07) in this study showing the same VNTR profile were accurately discriminated through median-joining network analysis using SNVs unique to those isolates. An additional IS6110 insertion was detected in one of those isolates as supportive genetic information in addition to core genomic SNVs. The results of in silico analyses using TGS-TB are consistent with those obtained using conventional molecular genotyping methods, suggesting that NGS short reads could provide multiple genotypes to discriminate multiple strains of Mtb, although longer NGS reads (≥300-mer) will be required for full genotyping on the TGS-TB web site. Most available short reads (~100-mer) can be utilized to discriminate the isolates based on the core genome phylogeny. TGS-TB provides a more accurate and discriminative strain typing for clinical and epidemiological investigations; NGS strain typing offers a total genotyping solution for Mtb outbreak and surveillance. TGS-TB web site: https://gph.niid.go.jp/tgs-tb/. PMID:26565975
Andrade, Bruno B.; Kumar, Nathella Pavan; Amaral, Eduardo P.; Riteau, Nicolas; Mayer-Barber, Katrin D.; Tosh, Kevin W.; Maier, Nolan; Conceição, Elisabete L.; Kubler, Andre; Sridhar, Rathinam; Banurekha, Vaithilingam V.; Jawahar, Mohideen S.; Barbosa, Theolis; Manganiello, Vincent C.; Moss, Joel; Fontana, Joseph R.; Marciano, Beatriz E.; Sampaio, Elizabeth P.; Olivier, Kenneth N.; Holland, Steven M.; Jackson, Sharon H.; Moayeri, Mahtab; Leppla, Stephen; Sereti, Irini; Barber, Daniel L.; Nutman, Thomas B.; Babu, Subash; Sher, Alan
Pulmonary tuberculosis (TB) is characterized by oxidative stress and lung tissue destruction by matrix metalloproteinases (MMP). The interplay between these distinct pathological processes and the implications for TB diagnosis and disease staging are poorly understood. Heme oxygenase-1 (HO-1) levels have been shown to distinguish active from latent as well as successfully treated Mycobacterium tuberculosis (Mtb) infection. MMP-1 expression is also associated with active TB. Here, we measured plasma levels of these two important biomarkers in distinct TB cohorts from India and Brazil. Patients with active TB expressed either very high levels of HO-1 and low levels of MMP-1 or the converse. Moreover, TB patients with either high HO-1 or MMP-1 levels displayed distinct clinical presentations as well as plasma inflammatory marker profiles. In contrast, in an exploratory North American study, inversely correlated expression of HO-1 and MMP-1 was not observed in patients with other non-tuberculous lung diseases. To assess possible regulatory interactions in the biosynthesis of these two enzymes at the cellular level, we studied expression of HO-1 and MMP-1 in Mtb-infected human and murine macrophages. We found that infection of macrophages with live virulent Mtb is required for robust induction of high levels of HO-1, but not MMP-1. In addition, we observed that carbon monoxide, a product of Mtb induced HO-1 activity, inhibits MMP-1 expression by suppressing c-Jun/AP-1 activation. These findings reveal a mechanistic link between oxidative stress and tissue remodeling that may find applicability in the clinical staging of TB patients. PMID:26268658
Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi
We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity. PMID:28717080
Namikawa, Hiroki; Takemoto, Yasuhiko; Kainuma, Shigeto; Umeda, Sakurako; Makuuchi, Ayako; Fukumoto, Kazuo; Kobayashi, Masanori; Kinuhata, Shigeki; Isaka, Yoshihiro; Toyoda, Hiromitsu; Kamata, Noriko; Tochino, Yoshihiro; Hiura, Yoshikazu; Morimura, Mina; Shuto, Taichi
We herein report a case of Addison's disease caused by tuberculosis characterized by atypical hyperpigmentation, noted as exacerbation of the pigmentation of freckles and the occurrence of new freckles, that was diagnosed in the presence of active pulmonary tuberculosis. The clinical condition of the patient was markedly ameliorated by the administration of hydrocortisone and anti-tuberculosis agents. When exacerbation of the pigmentation of the freckles and/or the occurrence of new freckles are noted, Addison's disease should be considered as part of the differential diagnosis. In addition, the presence of active tuberculosis needs to be assumed whenever we treat patients with Addison's disease caused by tuberculosis, despite its rarity.
Pande, Tripti; Saravu, Kavitha; Temesgen, Zelalem; Seyoum, Al; Rai, Shipra; Rao, Raghavendra; Mahadev, Deekshith; Pai, Madhukar; Gagnon, Marie-Pierre
Tuberculosis (TB) is the leading infectious killer, and India accounts for 2.8 of the 10.4 million TB cases that occur each year, making it the highest TB burden country worldwide. Poor quality of TB care is a major driver of the epidemic in India. India's large private, unregulated sector manages over 50% of the TB patients, with studies showing suboptimal diagnosis and treatment in the private sector. Better education of doctors using mobile applications (apps) is a possible solution. While India has seen an explosion of mobile phone services, and while the use of mobile health interventions has been gaining interest, little is known about mHealth around tuberculosis in India. Our study aimed to understand the user experience and acceptability of a smartphone application, LearnTB , amongst private sector academic clinicians in India. This study was conducted amongst 101 clinicians at Kasturba Hospital, Manipal, India. The user experience of participants (part 1) and acceptability (part 2) were evaluated with the use of two valid, English, paper-based questionnaires. The first questionnaire was based on the System Usability Scale (SUS); the second questionnaire was based on the Technology Acceptance Model (TAM). Data were collected during February and March 2017 and were analyzed using descriptive statistics, multiple linear regression as well as logistic regression analysis. A response rate of 99% was achieved; 100 participants responded to the second questionnaire and 100% of the participants responded to the first questionnaire. User experience was very high [mean SUS score =94.4 (92.07-96.76)]. Perceived usefulness (PU) was significantly correlated to intention to use (IU) (r=0.707, P<0.0001), and perceived ease of use (PEU) was significantly correlated to PU (r=0.466, P<0.0001). Path analysis confirmed the direct relationship between PU and IU (0.936, P<0.0001), and the indirect relationship between PEU and IU (0.5102, P<0.0001). Logistic regression analysis
Pande, Tripti; Saravu, Kavitha; Temesgen, Zelalem; Seyoum, Al; Rai, Shipra; Rao, Raghavendra; Mahadev, Deekshith; Pai, Madhukar
Background Tuberculosis (TB) is the leading infectious killer, and India accounts for 2.8 of the 10.4 million TB cases that occur each year, making it the highest TB burden country worldwide. Poor quality of TB care is a major driver of the epidemic in India. India’s large private, unregulated sector manages over 50% of the TB patients, with studies showing suboptimal diagnosis and treatment in the private sector. Better education of doctors using mobile applications (apps) is a possible solution. While India has seen an explosion of mobile phone services, and while the use of mobile health interventions has been gaining interest, little is known about mHealth around tuberculosis in India. Methods Our study aimed to understand the user experience and acceptability of a smartphone application, LearnTB, amongst private sector academic clinicians in India. This study was conducted amongst 101 clinicians at Kasturba Hospital, Manipal, India. The user experience of participants (part 1) and acceptability (part 2) were evaluated with the use of two valid, English, paper-based questionnaires. The first questionnaire was based on the System Usability Scale (SUS); the second questionnaire was based on the Technology Acceptance Model (TAM). Data were collected during February and March 2017 and were analyzed using descriptive statistics, multiple linear regression as well as logistic regression analysis. Results A response rate of 99% was achieved; 100 participants responded to the second questionnaire and 100% of the participants responded to the first questionnaire. User experience was very high [mean SUS score =94.4 (92.07–96.76)]. Perceived usefulness (PU) was significantly correlated to intention to use (IU) (r=0.707, P<0.0001), and perceived ease of use (PEU) was significantly correlated to PU (r=0.466, P<0.0001). Path analysis confirmed the direct relationship between PU and IU (0.936, P<0.0001), and the indirect relationship between PEU and IU (0.5102, P<0
Yang, Qianting; Cai, Yi; Zhao, Wei; Wu, Fan; Zhang, Mingxia; Luo, Kai; Zhang, Yan; Liu, Haiying; Zhou, Boping; Kornfeld, Hardy; Chen, Xinchun
The diagnosis of active tuberculosis (TB) disease remains a challenge, especially in high-burden settings. Cytokines and chemokines are important in the pathogenesis of TB. Here we investigate the usefulness of circulating and compartmentalized cytokines/chemokines for diagnosis of TB. The levels of multiple cytokines/chemokines in plasma, pleural fluid (PF), and cerebrospinal fluid (CSF) were determined by Luminex liquid array-based multiplexed immunoassays. Three of 26 cytokines/chemokines in plasma were significantly different between TB and latent tuberculosis infection (LTBI). Among them, IP-10 and MIG had the highest diagnostic values, with an area under the receiver operating characteristic curve (ROC AUC) of 0.92 for IP-10 and 0.86 for MIG for distinguishing TB from LTBI. However, IP-10 and MIG levels in plasma were not different between TB and non-TB lung disease. In contrast, compartmentalized IP-10 and MIG in the PF and CSF showed promising diagnostic values in discriminating TB and non-TB pleural effusion (AUC = 0.87 for IP-10 and 0.93 for MIG), as well as TB meningitis and non-TB meningitis (AUC = 0.9 for IP-10 and 0.95 for MIG). A longitudinal study showed that the plasma levels of IP-10, MIG, granulocyte colony-stimulating factor (G-CSF), and gamma interferon (IFN-γ) decreased, while the levels of MCP-1/CCL2 and eotaxin-1/CCL11 increased, after successful treatment of TB. Our findings provide a practical methodology for discriminating active TB from LTBI by sequential IFN-γ release assays (IGRAs) and plasma IP-10 testing, while increased IP-10 and MIG at the site of infection (PF or CSF) can be used as a marker for distinguishing pleural effusion and meningitis caused by TB from those of non-TB origins. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Chang, David; Webber, Bryant J; Hetrick, Steven M; Owen, Jerry B; Blasi, Audra A; Steele, Bernadette M; Yun, Heather C
Between 1 January 2010 and 31 December 2016, a total of 14 U.S. and international military personnel in training at Joint Base San Antonio-Lackland, TX, were hospitalized due to suspected pulmonary tuberculosis (TB); of these, five personnel were diagnosed with active TB disease. Only one TB case had pulmonary symptoms, but these symptoms were not suggestive of TB. The incidence rate in the training population was 1.89 per 100,000 population (95% CI: 0.81, 4.42), with a higher rate when restricted to international military students attending the Defense Language Institute English Language Center. No instances of TB transmission were identified. The variety of atypical presentations and their resulting diagnostic and public health challenges prompted this retrospective review of all hospitalized cases. This case series highlights both the importance of a high index of clinical suspicion when TB is being considered in close congregate settings as well as the risk of overreliance on acid-fast bacilli staining and nucleic acid amplification testing for ruling out active pulmonary disease in young, otherwise healthy trainees. Practical solutions are suggested.
Berkowitz, Natacha; Okorie, Adaeze; Goliath, Rene; Levitt, Naomi; Wilkinson, Robert J; Oni, Tolu
Studies addressing the association between diabetes mellitus (DM) and tuberculosis (TB) in sub-Saharan Africa are limited. We assessed the prevalence of active TB among DM patients at a primary care clinic, and identified risk factors for prevalent TB. A cross-sectional study was conducted in adult DM patients attending a clinic in Khayelitsha, Cape Town. Participants were screened for active TB (symptom screening and microbiological diagnosis) and HIV. Among 440 DM patients screened, the active TB prevalence was 3.0% (95% CI 1.72-5.03). Of the 13 prevalent TB cases, 53.9% (n = 7; 95% CI 27.20-78.50) had no TB symptoms, and 61.5% (n = 8; 95% CI 33.30-83.70) were HIV-1 co-infected. There were no significant differences in either fasting plasma glucose or HbA 1c levels between TB and non-TB participants. On multivariate analysis, HIV-1 infection (OR 11.3, 95% CI 3.26-39.42) and hemoptysis (OR 31.4, 95% CI 3.62-273.35) were strongly associated with prevalent active TB, with no differences in this association by age or gender. The prevalence of active TB among DM patients was 4-fold higher than the national prevalence; suggesting the need for active TB screening, particularly if hemoptysis is reported. Our results highlight the importance of HIV screening in this older population group. The high prevalence of sub-clinical TB among those diagnosed with TB highlights the need for further research to determine how best to screen for active TB in high-risk TB/HIV population groups and settings. Copyright © 2018. Published by Elsevier B.V.
Hand, Jonathan; Sigel, Keith; Huprikar, Shirish; Hamula, Camille; Rana, Meena
Pre-transplant screening for latent tuberculosis infection (LTBI) is a complex consideration that varies by institution. Inconsistent performance of interferon-gamma release assay (IGRA) further complicates screening. Data regarding LTBI screening outcomes and test characteristics in a large, foreign-born pre-transplant population within the United States are limited. In this retrospective study, patients who received QuantiFERON ® -TB Gold (QFT) prior to liver transplantation (LT) were included. Characteristics of patients were compared by QFT result, and predictors of indeterminate results were evaluated. Similar comparisons were performed between patients who developed active TB and those who did not. Of 148 patients screened, the rate of positive, indeterminate, and negative testing was 13.5% (20/148), 27% (40/148), and 59% (88/148), respectively. An indeterminate QFT result was more than 16 times more likely in patients with a Model for End-stage Liver Disease score >25 (odds ratio [OR] 16.7; 95% confidence interval [CI], 2.1-132.0; P = .008) and more than 4 times when performed in our institution's lab compared with commercial lab (OR 4.1; 95% CI, 1.34-12.44; P = .013). The overall TB incidence was 1102/100 000 transplant cases. No patient who developed active TB had a positive QFT. All were born outside of the United States (P = .06) and had pre-transplantation chest imaging demonstrating granulomatous disease (P = .006). Our experience further highlights the challenges of LTBI screening prior to LT and suggests that QFT may be a poor predictor of active TB in higher risk pre-transplant populations. Candidates should be screened as early as possible to optimize QFT performance, and local epidemiological data should be used to create institution-specific screening protocols in areas with large populations from TB-endemic regions. Management should consider TB risk factors, QFT, and imaging instead of reliance on QFT testing alone. © 2018 John Wiley
Maitra, Arundhati; Bhakta, Sanjib
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
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. ...
... 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 ...
Zhang, Ting; Hu, Siyu; Li, Guoli; Li, Hui; Liu, Xiaoli; Niu, Jianjun; Wang, Feng; Wen, Huixin; Xu, Ye; Li, Qingge
Rapid and comprehensive detection of drug-resistance is essential for the control of tuberculosis, which has facilitated the development of molecular assays for the detection of drug-resistant mutations in Mycobacterium tuberculosis. We hereby assessed the analytical and clinical performance of an assay for streptomycin-resistant mutations. MeltPro TB/STR is a closed-tube, dual-color, melting curve analysis-based, real-time PCR test designed to detect 15 streptomycin-resistant mutations in rpsL 43, rpsL 88, rrs 513, rrs 514, rrs 517, and rrs 905-908 of M. tuberculosis. Analytical studies showed that the accuracy was 100%, the limit of detection was 50-500 bacilli per reaction, the reproducibility in the form of Tm variation was within 1.0 °C, and we could detect 20% STR resistance in mixed bacterial samples. The cross-platform study demonstrated that the assay could be performed on six models of real-time PCR instruments. A multicenter clinical study was conducted using 1056 clinical isolates, which were collected from three geographically different healthcare units, including 709 STR-susceptible and 347 STR-resistant isolates characterized on Löwenstein-Jensen solid medium by traditional drug susceptibility testing. The results showed that the clinical sensitivity and specificity of the MeltPro TB/STR was 88.8% and 95.8%, respectively. Sequencing analysis confirmed the accuracy of the mutation types. Among all the 8 mutation types detected, rpsL K43R (AAG → AGG), rpsL K88R (AAG → AGG) and rrs 514 A → C accounted for more than 90%. We concluded that MeltPro TB/STR represents a rapid and reliable assay for the detection of STR resistance in clinical isolates. Copyright © 2014. Published by Elsevier Ltd.
Scriba, Thomas J; Penn-Nicholson, Adam; Shankar, Smitha; Hraha, Tom; Thompson, Ethan G; Sterling, David; Nemes, Elisa; Darboe, Fatoumatta; Suliman, Sara; Amon, Lynn M; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Johnson, John L; Boom, W Henry; Hatherill, Mark; Valvo, Joe; De Groote, Mary Ann; Ochsner, Urs A; Aderem, Alan; Hanekom, Willem A; Zak, Daniel E
Our understanding of mechanisms underlying progression from Mycobacterium tuberculosis infection to pulmonary tuberculosis disease in humans remains limited. To define such mechanisms, we followed M. tuberculosis-infected adolescents longitudinally. Blood samples from forty-four adolescents who ultimately developed tuberculosis disease (“progressors”) were compared with those from 106 matched controls, who remained healthy during two years of follow up. We performed longitudinal whole blood transcriptomic analyses by RNA sequencing and plasma proteome analyses using multiplexed slow off-rate modified DNA aptamers. Tuberculosis progression was associated with sequential modulation of immunological processes. Type I/II interferon signalling and complement cascade were elevated 18 months before tuberculosis disease diagnosis, while changes in myeloid inflammation, lymphoid, monocyte and neutrophil gene modules occurred more proximally to tuberculosis disease. Analysis of gene expression in purified T cells also revealed early suppression of Th17 responses in progressors, relative to M. tuberculosis-infected controls. This was confirmed in an independent adult cohort who received BCG re-vaccination; transcript expression of interferon response genes in blood prior to BCG administration was associated with suppression of IL-17 expression by BCG-specific CD4 T cells 3 weeks post-vaccination. Our findings provide a timeline to the different immunological stages of disease progression which comprise sequential inflammatory dynamics and immune alterations that precede disease manifestations and diagnosis of tuberculosis disease. These findings have important implications for developing diagnostics, vaccination and host-directed therapies for tuberculosis. Clincialtrials.gov, NCT01119521.
Painter, John A.; Graviss, Edward A.; Hai, Hoang Hoa; Nhung, Duong Thi Cam; Nga, Tran Thi Thanh; Ha, Ngan P.; Wall, Kirsten; Loan, Le Thien Huong; Parker, Matt; Manangan, Lilia; O’Brien, Rick; Maloney, Susan A.; Hoekstra, R. M.; Reves, Randall
Rationale Each year 1 million persons acquire permanent U.S. residency visas after tuberculosis (TB) screening. Most applicants undergo a 2-stage screening with tuberculin skin test (TST) followed by CXR only if TST-positive at > 5 mm. Due to cross reaction with bacillus Calmette-Guérin (BCG), TST may yield false positive results in BCG-vaccinated persons. Interferon gamma release assays exclude antigens found in BCG. In Vietnam, like most high TB-prevalence countries, there is universal BCG vaccination at birth. Objectives 1. Compare the sensitivity of QuantiFERON ®-TB Gold In-Tube Assay (QFT) and TST for culture-positive pulmonary TB. 2. Compare the age-specific and overall prevalence of positive TST and QFT among applicants with normal and abnormal CXR. Methods We obtained TST and QFT results on 996 applicants with abnormal CXR, of whom 132 had TB, and 479 with normal CXR. Results The sensitivity for tuberculosis was 86.4% for QFT; 89.4%, 81.1%, and 52.3% for TST at 5, 10, and 15 mm. The estimated prevalence of positive results at age 15–19 years was 22% and 42% for QFT and TST at 10 mm, respectively. The prevalence increased thereafter by 0.7% year of age for TST and 2.1% for QFT, the latter being more consistent with the increase in TB among applicants. Conclusions During 2-stage screening, QFT is as sensitive as TST in detecting TB with fewer requiring CXR and being diagnosed with LTBI. These data support the use of QFT over TST in this population. PMID:24367546
Hu, Shizong; Jin, Dongdong; Chen, Xinchun; Jin, Qi; Liu, Haiying
Background IFN-γ is presently the only soluble immunological marker used to help diagnose latent Mycobacterium tuberculosis (M.tb) infection. However, IFN-γ is not available to distinguish latent from active TB infection. Moreover, extrapulmonary tuberculosis, such as tuberculous pleurisy, cannot be properly diagnosed by IFN-γ release assay. As a result, other disease- or infection-related immunological biomarkers that would be more effective need to be screened and identified. Methodology A panel of 41 soluble immunological molecules (17 cytokines and 24 chemokines) was tested using Luminex liquid array-based multiplexed immunoassays. Samples, including plasma and pleural effusions, from healthy donors (HD, n = 12) or patients with latent tuberculosis infection (LTBI, n = 20), pulmonary tuberculosis (TB, n = 12), tuberculous pleurisy (TP, n = 15) or lung cancer (LC, n = 15) were collected and screened for soluble markers. Peripheral blood mononuclear cells (PBMCs) and pleural fluid mononuclear cells (PFMCs) were also isolated to investigate antigen-specific immune factors. Principal Findings For the 41 examined factors, our results indicated that three patterns were closely associated with infection and disease. (1) Significantly elevated plasma levels of IL-2, IP-10, CXCL11 and CXCL12 were present in both patients with tuberculosis and in a sub-group participant with latent tuberculosis infection who showed a higher level of IFN-γ producing cells by ELISPOT assay compared with other latently infected individuals. (2) IL-6 and IL-9 were only significantly increased in plasma from active TB patients, and the two factors were consistently highly secreted after M.tb antigen stimulation. (3) When patients developed tuberculous pleurisy, CCL1, CCL21 and IL-6 were specifically increased in the pleural effusions. In particular, these three factors were consistently highly secreted by pleural fluid mononuclear cells following M.tb-specific antigen
AbuHassan, Kamal J; Bakhori, Noremylia M; Kusnin, Norzila; Azmi, Umi Z M; Tania, Marzia H; Evans, Benjamin A; Yusof, Nor A; Hossain, M A
Tuberculosis (TB) remains one of the most devastating infectious diseases and its treatment efficiency is majorly influenced by the stage at which infection with the TB bacterium is diagnosed. The available methods for TB diagnosis are either time consuming, costly or not efficient. This study employs a signal generation mechanism for biosensing, known as Plasmonic ELISA, and computational intelligence to facilitate automatic diagnosis of TB. Plasmonic ELISA enables the detection of a few molecules of analyte by the incorporation of smart nanomaterials for better sensitivity of the developed detection system. The computational system uses k-means clustering and thresholding for image segmentation. This paper presents the results of the classification performance of the Plasmonic ELISA imaging data by using various types of classifiers. The five-fold cross-validation results show high accuracy rate (>97%) in classifying TB images using the entire data set. Future work will focus on developing an intelligent mobile-enabled expert system to diagnose TB in real-time. The intelligent system will be clinically validated and tested in collaboration with healthcare providers in Malaysia.
Grant, Alison D; Coetzee, Leonie; Fielding, Katherine L; Lewis, James J; Ntshele, Smanga; Luttig, Mariëtha M; Mngadi, Kathryn T; Muller, Dorothy; Popane, Flora; Mdluli, John; Mngadi, Nkosinathi; Sefuthi, Clement; Clark, David A; Churchyard, Gavin
To describe a programme of community education and mobilization to promote uptake in a cluster-randomized trial of tuberculosis preventive therapy offered to all members of intervention clusters. Gold mines in South Africa, where tuberculosis incidence is extremely high, despite conventional control measures. All employees in intervention clusters (mine shaft and associated hostel) were invited to enrol. Cumulative enrolment in the study in intervention clusters. Key steps in communicating information relevant to the study included extensive consultation with key stakeholders; working with a communication company to develop a project 'brand'; developing a communication strategy tailored to each intervention site; and involving actors from a popular television comedy series to help inform communities about the study. One-to-one communications used peer educators along with study staff, and participant advisory groups facilitated two-way communication between study staff and participants. By contrast, treatment 'buddies' and text messaging to promote adherence proved less successful. Mean cumulative enrolment in the first four intervention clusters was 61.9%, increasing to 83.0% in the final four clusters. A tailored communication strategy can facilitate a high level of enrolment in a community health intervention.
Wang, Yun F.; Leonard, Michael K.; White, Nancy; McFarland, Deborah A.; Blumberg, Henry M.
Introduction The Centers for Disease Control and Prevention has recommended using a nucleic acid amplification test (NAAT) for diagnosing pulmonary tuberculosis (TB) but there is a lack of data on NAAT cost-effectiveness. Methods We conducted a prospective cohort study that included all patients with an AFB smear-positive respiratory specimen at Grady Memorial Hospital in Atlanta, GA, USA between January 2002 and June 2008. We determined the sensitivity, specificity, and positive and negative predictive value of a commercially available and FDA-approved NAAT (amplified MTD, Gen-Probe) compared to the gold standard of culture. A cost analysis was performed and included costs related to laboratory tests, hospital charges, anti-TB medications, and contact investigations. Average cost per patient was calculated under two conditions: (1) using a NAAT on all AFB smear-postive respiratory specimens and (2) not using a NAAT. One-way sensitivity analyses were conducted to determine sensitivity of cost difference to reasonable ranges of model inputs. Results During a 6 1/2 year study period, there were 1,009 patients with an AFB smear-positive respiratory specimen at our public urban hospital. We found the NAAT to be highly sensitive (99.6%) and specific (99.1%) on AFB smear-positive specimens compared to culture. Overall, the positive predictive value (PPV) of an AFB smear-positive respiratory specimen for culture-confirmed TB was 27%. The PPV of an AFB smear-positive respiratory specimen for culture-confirmed TB was significantly higher for HIV-uninfected persons compared to those who were HIV-seropositive (152/271 [56%] vs. 85/445 [19%]; RR = 2.94, 95% CI 2.36–3.65, p<0.001). The cost savings of using the NAAT was $2,003 per AFB smear-positive case. Conclusions Routine use of the NAAT on AFB smear-positive respiratory specimens was highly cost-saving in our setting at a U.S. urban public hospital with a high prevalence of TB and HIV because of the low PPV of an AFB
Bonnet, M; Gagnidze, L; Varaine, F; Ramsay, A; Githui, W; Guerin, P J
To evaluate the performance and feasibility of FASTPlaqueTB in smear-negative tuberculosis (TB) suspects in a peripheral clinic after laboratory upgrading. Patients with cough > or=2 weeks, two sputum smear-negative results, no response to 1 week of amoxicillin and abnormal chest X-ray were defined as smear-negative suspects. One sputum sample was collected, decontaminated and divided into two: half was tested with FASTPlaqueTB in the clinic laboratory and the other half was cultured on Löwenstein-Jensen medium in the Kenyan Medical Research Institute. Test sensitivity and specificity were evaluated in all patients and in human immunodeficiency virus (HIV) infected patients. Feasibility was assessed by the contamination rate and the resources required to upgrade the laboratory. Of 208 patients included in the study, 56.2% were HIV-infected. Of 203 FASTPlaqueTB tests, 95 (46.8%) were contaminated, which interfered with result interpretation and led to the interruption of the study. Sensitivity and specificity were respectively 31.2% (95%CI 12.1-58.5) and 94.9% (95%CI 86.8-98.4) in all patients and 33.3% (95%CI 9.9-65.1) and 93.9% (95%CI 83.1-98.7) in HIV-infected patients. Upgrading the laboratory cost euro 20,000. FASTPlaqueTB did not perform satisfactorily in this setting. If contamination can be reduced, in addition to laboratory upgrading, its introduction in peripheral clinics would require further assessment in smear-negative and HIV co-infected patients and test adaptation for friendlier use.
King, Angela G.
Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis, which usually attacks the lung and is spread through the air from one person to another. Researchers from Johnson & Johnson Pharmaceutical Research and Development, the Swedish Institute for Infectious Disease Control and The Pitie-Salpetriere School of Medicine began their…
Avian tuberculosis is usually caused by the bacterium Mycobacterium avium. At least 20 different types of M. avium have been identified, only three of which are known to cause disease in birds. Other types of Mycobacterium rarely cause tuberculosis in most avian species; however, parrots, macaws, and other large perching birds are susceptible to human and bovine types of tuberculosis bacilli. Avian tuberculosis generally is transmitted by direct contact with infected birds, ingestion of contaminated feed and water, or contact with a contaminated environment. Inhalation of the bacterium can cause respiratory tract infections. Wild bird studies in the Netherlands disclosed tuberculosis-infected puncture-type injuries in birds of prey that fight at the nest site (kestrels) or on the ground (buteo-type buzzards), but tuberculosisinfected injuries were not found in accipiters (falco
Gonzalo-Asensio, Jesus; Aguilo, Nacho; Marinova, Dessislava; Martin, Carlos
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.
Paris, Luisa; Magni, Ruben; Zaidi, Fatima; Araujo, Robyn; Saini, Neal; Harpole, Michael; Coronel, Jorge; Kirwan, Daniela E; Steinberg, Hannah; Gilman, Robert H; Petricoin, Emanuel F; Nisini, Roberto; Luchini, Alessandra; Liotta, Lance
An accurate urine test for pulmonary tuberculosis (TB), affecting 9.6 million patients worldwide, is critically needed for surveillance and treatment management. Past attempts failed to reliably detect the mycobacterial glycan antigen lipoarabinomannan (LAM), a marker of active TB, in HIV-negative, pulmonary TB-infected patients' urine (85% of 9.6 million patients). We apply a copper complex dye within a hydrogel nanocage that captures LAM with very high affinity, displacing interfering urine proteins. The technology was applied to study pretreatment urine from 48 Peruvian patients, all negative for HIV, with microbiologically confirmed active pulmonary TB. LAM was quantitatively measured in the urine with a sensitivity of >95% and a specificity of >80% ( n = 101) in a concentration range of 14 to 2000 picograms per milliliter, as compared to non-TB, healthy and diseased, age-matched controls (evaluated by receiver operating characteristic analysis; area under the curve, 0.95; 95% confidence interval, 0.9005 to 0.9957). Urinary LAM was elevated in patients with a higher mycobacterial burden ( n = 42), a higher proportion of weight loss ( n = 37), or cough ( n = 50). The technology can be configured in a variety of formats to detect a panel of previously undetectable very-low-abundance TB urinary analytes. Eight of nine patients who were smear-negative and culture-positive for TB tested positive for urinary LAM. This technology has broad implications for pulmonary TB screening, transmission control, and treatment management for HIV-negative patients. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Fielding, Katherine L; Grant, Alison D; Hayes, Richard J; Chaisson, Richard E; Corbett, Elizabeth L; Churchyard, Gavin J
South Africa has the third highest annual number of new tuberculosis (TB) cases globally. The resurgence of TB which has particularly affected gold miners in South Africa, is attributed to occupational risk factors for TB including silica dust exposure and high HIV prevalence. Isoniazid preventive therapy (IPT) is recommended for individuals at high risk to prevent both HIV-related TB and silicotuberculosis, but global uptake has been poor. We describe the design of a cluster randomised study, "Thibela TB", which compares routine IPT targeted to those identified as at higher risk of TB (due to HIV infection or silicosis) against a "community-wide" approach in which IPT is offered to all employees. The trial is registered with the Current Controlled Trials: Registration number ISRCTN63327174. We describe the rationale for the intervention of community-wide IPT, drawing on studies conducted in 1950-1960s in the pre-HIV era. The design of the study, including the definition of the cluster, is presented and advantages and limitations of such a design are discussed. If successful in reducing TB incidence and prevalence, this trial has potential to make a major contribution to TB control policy in high HIV settings, providing evidence concerning efficacy, and additionally safety and population-level effects on drug susceptibility patterns. Such rigorous evaluation is essential to provide policy makers with an evidence base to guide community-level TB prevention strategies. Copyright © 2010 Elsevier Inc. All rights reserved.
Multidrug-resistant tuberculosis (MDR-TB), the prevalence of which has increased across the globe in recent years, is a serious threat to public health. Timely diagnosis of MDR-TB, especially among new TB cases, is essential to facilitate appropriate treatment, which can prevent further emergence of drug resistance and its spread in the population. The present case report from India aims to address some operational challenges in diagnosing MDR-TB among new cases and potential measures to overcome them. It argues that even after seven years of implementing the DOTS-Plus program for controlling MDR-TB, India still lacks the technical capacity for rapid MDR-TB diagnosis. The case report underscores an urgent need to explore the use of WHO-endorsed techniques such as Xpert MTB/Rif and commercial assays such as Genotype MTBDR for rapid diagnosis of MDR-TB among new cases. Suitable applications may be found for other TB high-burden countries where MDR-TB is a major concern. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.
Gordaliza, P M; Muñoz-Barrutia, A; Via, L E; Sharpe, S; Desco, M; Vaquero, J J
Computed tomography (CT) images enable capturing specific manifestations of tuberculosis (TB) that are undetectable using common diagnostic tests, which suffer from limited specificity. In this study, we aimed to automatically quantify the burden of Mycobacterium tuberculosis (Mtb) using biomarkers extracted from x-ray CT images. Nine macaques were aerosol-infected with Mtb and treated with various antibiotic cocktails. Chest CT scans were acquired in all animals at specific times independently of disease progression. First, a fully automatic segmentation of the healthy lungs from the acquired chest CT volumes was performed and air-like structures were extracted. Next, unsegmented pulmonary regions corresponding to damaged parenchymal tissue and TB lesions were included. CT biomarkers were extracted by classification of the probability distribution of the intensity of the segmented images into three tissue types: (1) Healthy tissue, parenchyma free from infection; (2) soft diseased tissue, and (3) hard diseased tissue. The probability distribution of tissue intensities was assumed to follow a Gaussian mixture model. The thresholds identifying each region were automatically computed using an expectation-maximization algorithm. The estimated longitudinal course of TB infection shows that subjects that have followed the same antibiotic treatment present a similar response (relative change in the diseased volume) with respect to baseline. More interestingly, the correlation between the diseased volume (soft tissue + hard tissue), which was manually delineated by an expert, and the automatically extracted volume with the proposed method was very strong (R 2 ≈ 0.8). We present a methodology that is suitable for automatic extraction of a radiological biomarker from CT images for TB disease burden. The method could be used to describe the longitudinal evolution of Mtb infection in a clinical trial devoted to the design of new drugs.
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.
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
Oeltmann, John E; Varma, Jay K; Ortega, Luis; Liu, Yecai; O'Rourke, Thomas; Cano, Maria; Harrington, Theresa; Toney, Sean; Jones, Warren; Karuchit, Samart; Diem, Lois; Rienthong, Dhanida; Tappero, Jordan W; Ijaz, Kashef; Maloney, Susan A
In January 2005, tuberculosis (TB), including multidrug-resistant TB (MDR TB), was reported among Hmong refugees who were living in or had recently immigrated to the United States from a camp in Thailand. We investigated TB and drug resistance, enhanced TB screenings, and expanded treatment capacity in the camp. In February 2005, 272 patients with TB (24 MDR TB) remained in the camp. Among 17 MDR TB patients interviewed, 13 were found to be linked socially. Of 23 MDR TB isolates genotyped, 20 were similar according to 3 molecular typing methods. Before enhanced screening was implemented, 46 TB cases (6 MDR TB) were diagnosed in the United States among 9,455 resettled refugees. After enhanced screening had begun, only 4 TB cases (1 MDR TB), were found among 5,705 resettled refugees. An MDR TB outbreak among US-bound refugees led to importation of disease; enhanced pre-immigration TB screening and treatment decreased subsequent importation.
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Little is known about the prevalence of non-communicable disease (NCD) multimorbidity among tuberculosis (TB) patients in Africa.Aim and setting: The aim of this study was to assess the prevalence of NCD multimorbidity, its pattern and impact on adverse health outcomes among patients with TB in public primary care in three selected districts of South Africa. In a cross-sectional survey, new TB and TB retreatment patients were interviewed, and medical records assessed in consecutive sampling within 1 month of anti-TB treatment. The sample included 4207 (54.5% men and 45.5% women) TB patients from 42 primary care clinics in three districts. Multimorbidity was measured as the simultaneous presence of two or more of 10 chronic conditions, including myocardial infarction or angina pectoris, arthritis, asthma, chronic lung disease, diabetes mellitus, hypertension, dyslipidaemia, malignant neoplasms, tobacco and alcohol-use disorder. The prevalence of comorbidity (with one NCD) was 26.9% and multimorbidity (with two or more NCDs) was 25.3%. We identified three patterns of multimorbidity: (1) cardio-metabolic disorders; (2) respiratory disorders, arthritis and cancer; and (3) substance-use disorders. The likelihood of multimorbidity was higher in older age, among men, and was lower in those with higher education and socio-economic status. The prevalence of physical health decreased, and common mental disorders and post-traumatic stress disorder increased with an increase in the number of chronic conditions. High NCD comorbidity and multimorbidity were found among TB patients predicted by socio-economic disparity.
Talbot, Elizabeth A.; Harland, Dawn; Wieland-Alter, Wendy; Burrer, Sherry; Adams, Lisa V.
Objective: Interferon-[gamma] release assays (IGRAs) are an important tool for detecting latent "Mycobacterium tuberculosis" infection (LTBI). Insufficient data exist about IGRA specificity in college health centers, most of which screen students for LTBI using the tuberculin skin test (TST). Participants: Students at a low-TB incidence college…
Bosco, Munyemana Jean; Wei, Ming; Hou, Hongyan; Yu, Jing; Lin, Qun; Luo, Ying; Sun, Ziyong; Wang, Feng
The CD4 + CXCR5 + T cells have been previously established. However, their decreased frequency during tuberculosis (TB) disease is partially understood. The aim of this study was to explore the depletion of CD4 + CXCR5 + T cells in human TB. The frequency and function of CD4 + CXCR5 + T cells were evaluated in active TB (ATB) patients and healthy control (HC) individuals. The function of CD4 + CXCR5 + T cells was determined after blockade of inhibitory receptors. The frequency of CD4 + CXCR5 + T cells was decreased in ATB patients. The expression of activation markers (HLA-DR and ICOS) and inhibitory receptors (Tim-3 and PD-1) on CD4 + CXCR5 + T cells was increased in ATB group. TB-specific antigen stimulation induced higher expression of inhibitory receptors than phytohemagglutinin stimulation in ATB group. In contrast, TB antigen stimulation did not induce a significantly increased expression of IL-21 and Ki-67 on CD4 + CXCR5 + T cells. However, blockade of inhibitory receptors Tim-3 and PD-1 not only increased the frequency of CD4 + CXCR5 + T cells, but also restored their proliferation and cytokine secretion potential. An increased expression of inhibitory receptors involves the depletion of CD4 + CXCR5 + T cells, and blockade of inhibitory receptors can restore the function of CD4 + CXCR5 + T cells in ATB patients. Copyright © 2018. Published by Elsevier Ltd.
Jones-López, Edward C; Acuña-Villaorduña, Carlos; Ssebidandi, Martin; Gaeddert, Mary; Kubiak, Rachel W; Ayakaka, Irene; White, Laura F; Joloba, Moses; Okwera, Alphonse; Fennelly, Kevin P
Tuberculosis disease develops in only 5%-10% of humans infected with Mycobacterium tuberculosis The mechanisms underlying this variability remain poorly understood. We recently demonstrated that colony-forming units of M. tuberculosis in cough-generated aerosols are a better predictor of infection than the standard sputum acid-fast bacilli smear. We hypothesized that cough aerosol cultures may also predict progression to tuberculosis disease in contacts. We conducted a retrospective cohort study of 85 patients with smear-positive tuberculosis and their 369 household contacts in Kampala, Uganda. Index case patients underwent a standard evaluation, and we cultured M. tuberculosis from cough aerosols. Contacts underwent a standard evaluation at enrollment, and they were later traced to determine their tuberculosis status. During a median follow-up of 3.9 years, 8 (2%) of the contacts developed tuberculosis disease. In unadjusted and adjusted analyses, incident tuberculosis disease in contacts was associated with sputum Mycobacterial Growth Indicator Tube culture (odds ratio, 8.2; 95% confidence interval, 1.1-59.2; P = .04), exposure to a high-aerosol tuberculosis case patient (6.0, 1.4-25.2; P = .01), and marginally, human immunodeficiency virus in the contact (6.11; 0.89-41.7; P = .07). We present data demonstrating that sputum and aerosol specimens measure 2 related but different phenomena. We found an increased risk of tuberculosis progression among contacts of high-aerosol case patients. The hypothesis that a larger infectious inoculum, represented by high aerosol production, determines the risk of disease progression deserves evaluation in future prospective studies. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail email@example.com.
Song, Neng; Tan, Yang; Zhang, Lingyun; Luo, Wei; Guan, Qing; Yan, Ming-Zhe; Zuo, Ruiqi; Liu, Weixiang; Luo, Feng-Ling; Zhang, Xiao-Lian
Mycobacterium tuberculosis (M. tb) is emerging as a more serious pathogen due to the increased multidrug-resistant TB and co-infection of human immunodeficiency virus (HIV). The development of an effective and sensitive detection method is urgently needed for bacterial load evaluation in vaccine development, early TB diagnosis, and TB treatment. Droplet digital polymerase chain reaction (ddPCR) is a newly developed sensitive PCR method for the absolute quantification of nucleic acid concentrations. Here, we used ddPCR to quantify the circulating virulent M. tb-specific CFP10 (10-kDa culture filtrate protein, Rv3874) and Rv1768 DNA copy numbers in the blood samples from Bacille Calmette-Guerin (BCG)-vaccinated and/or virulent M. tb H37Rv-challenged rhesus monkeys. We found that ddPCR was more sensitive compared to real-time fluorescence quantitative PCR (qPCR), as the detection limits of CFP10 were 1.2 copies/μl for ddPCR, but 15.8 copies/μl for qPCR. We demonstrated that ddPCR could detect CFP10 and Rv1768 DNA after 3 weeks of infection and at least two weeks earlier than qPCR in M.tb H37Rv-challenged rhesus monkey models. DdPCR could also successfully quantify CFP10 and Rv1768 DNA copy numbers in clinical TB patients' blood samples (active pulmonary TB, extrapulmonary TB (EPTB), and infant TB). To our knowledge, this study is the first to demonstrate that ddPCR is an effective and sensitive method of measuring the circulating CFP10 and Rv1768 DNA for vaccine development, bacterial load evaluation in vivo, and early TB (including EPTB and infant TB) diagnosis as well.
Khatua, Sutapa; Geltemeyer, Abby M; Gourishankar, Anand
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.
Introduction Afghanistan has faced health consequences of war including those due to displacement of populations, breakdown of health and social services, and increased risks of disease transmission for over three decades. Yet it was able to restructure its National Tuberculosis Control Programme (NTP), integrate tuberculosis treatment into primary health care and achieve most of its targets by the year 2011. What were the processes that enabled the programme to achieve its targets? More importantly, what were the underpinning factors that made this success possible? We addressed these important questions through a case study. Case description We adopted a processes and outcomes framework for this study, which began with examining the change in key programme indicators, followed by backwards tracing of the processes and underlying factors, responsible for this change. Methods included review of the published and grey literature along with in-depth interviews of 15 key informants involved with the care of tuberculosis patients in Afghanistan. Discussion and evaluation TB incidence and mortality per 100,000 decreased from 325 and 92 to 189 and 39 respectively, while case notification and treatment success improved during the decade under study. Efficient programme structures were enabled through high political commitment from the Government, strong leadership from the programme, effective partnership and coordination among stakeholders, and adequate technical and financial support from the development partners. Conclusions The NTP Afghanistan is an example that public health programmes can be effectively implemented in fragile states. High political commitment and strong local leadership are essential factors for such programmes. To ensure long-term effectiveness of the NTP, the international support should be withdrawn in a phased manner, coupled with a sequential increase in resources allocated to the NTP by the Government of Afghanistan. PMID:24507446
Zager, Ellen M; McNerney, Ruth
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
Jones-López, Edward C.; Acuña-Villaorduña, Carlos; Ssebidandi, Martin; Gaeddert, Mary; Kubiak, Rachel W.; Ayakaka, Irene; White, Laura F.; Joloba, Moses; Okwera, Alphonse; Fennelly, Kevin P.
Background. Tuberculosis disease develops in only 5%–10% of humans infected with Mycobacterium tuberculosis . The mechanisms underlying this variability remain poorly understood. We recently demonstrated that colony-forming units of M. tuberculosis in cough-generated aerosols are a better predictor of infection than the standard sputum acid-fast bacilli smear. We hypothesized that cough aerosol cultures may also predict progression to tuberculosis disease in contacts. Methods. We conducted a retrospective cohort study of 85 patients with smear-positive tuberculosis and their 369 household contacts in Kampala, Uganda. Index case patients underwent a standard evaluation, and we cultured M. tuberculosis from cough aerosols. Contacts underwent a standard evaluation at enrollment, and they were later traced to determine their tuberculosis status. Results. During a median follow-up of 3.9 years, 8 (2%) of the contacts developed tuberculosis disease. In unadjusted and adjusted analyses, incident tuberculosis disease in contacts was associated with sputum Mycobacterial Growth Indicator Tube culture (odds ratio, 8.2; 95% confidence interval, 1.1–59.2; P = .04), exposure to a high-aerosol tuberculosis case patient (6.0, 1.4–25.2; P = .01), and marginally, human immunodeficiency virus in the contact (6.11; 0.89–41.7; P = .07). We present data demonstrating that sputum and aerosol specimens measure 2 related but different phenomena. Conclusions. We found an increased risk of tuberculosis progression among contacts of high-aerosol case patients. The hypothesis that a larger infectious inoculum, represented by high aerosol production, determines the risk of disease progression deserves evaluation in future prospective studies. PMID:27025837
Kienzl-Palma, D; Prosch, H
Tuberculosis (TB) is a granulomatous disease caused by Mycobacterium tuberculosis and transmission is via an airborne route by droplet infection. In the majority of cases patients have thoracic TB, which most frequently presents with hilar lymphadenopathy and pulmonary manifestation. Due to the rise in incidence of TB in central Europe to be expected over the coming years, it is essential to be acquainted with the radiological manifestations of pulmonary TB, particularly to be able to discriminate active from inactive TB. Due to the use of molecular techniques entailing DNA fingerprinting, the traditional classification of TB in primary and postprimary TB is being challenged. These genetic studies have revealed that variations in the clinical and radiographic appearance of TB are mainly affected by the immune status of the patients. Due to the low prevalence of TB in central Europe and the wide variation of radiological presentations, the diagnosis and therapy of TB is often delayed. In this article, the radiographic manifestations of thoracic TB are summarized and discussed. Together with the medical history and bacteriological tests, chest X‑ray imaging and computed tomography (CT) play a major role not only in the detection of TB but also in the follow-up during and after therapy. Chest X‑radiographs should be the primary diagnostic method in patients with suspected TB in screening as well as for diagnosis and therapy monitoring. The use of CT is more sensitive than chest radiographs and is frequently performed after chest radiographs to obtain detailed information about subtle parenchymal changes or lymph node manifestation. When active TB is suspected CT should be performed. Tree in bud, lobular consolidations, centrilobular nodules, cavities and ground-glass opacification are typical changes in active TB.
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
Wang, Jann-Yuan; Lee, Li-Na; Lai, Hsin-Chih; Hsu, Hsiao-Leng; Jan, I-Shiow; Yu, Chong-Jen; Hsueh, Po-Ren; Yang, Pan-Chyr
Because of the increasing numbers of nontuberculous mycobacterial isolates from clinical specimens, rapid and accurate methods for culture confirmation of Mycobacterium tuberculosis are urgently needed. The study evaluated the performance of the Capilia TB immunochromatographic assay (TAUNS, Numazu, Japan) for culture confirmation of M. tuberculosis using 242 culture-positive liquid media in 2 mycobacterial laboratories from November 2005 to February 2006. Among the 242 samples, 183 were also tested with the BD ProbeTec ET (CTB) assay (Becton Dickinson, Sparks, MD). The results of both assays were compared to the culture results and to each other. The overall sensitivity and specificity of the Capilia TB assay were 98.6% and 97.9%, respectively, and for the CTB assay were 97.3% and 97.1%, respectively. The positive and negative predictive values for the Capilia TB assay were 98.6% and 97.9%, respectively, and for the CTB assay were 98.2% and 95.8%, respectively. Among the 183 samples tested with both assays, 8 had discrepant results, including Capilia-TB-false-positive in 2, CTB-false-positive in another 2, CTB-false-negative in 2, Capilia TB-false-negative in 1, and both assays with false-negative results in the remaining one. This study demonstrated that the Capilia TB assay has a similar diagnostic value with the CTB assay. In addition, with the immunochromatographic method, it is less time-consuming and does not require other laboratory equipment.
Tait, Peter; Saunders, Caroline; Nugent, Graham; Rutherford, Paul
We assess the non-monetary environmental benefits that accrue incidentally in New Zealand (NZ) from pest management conducted primarily to control an animal disease, bovine tuberculosis (TB). TB is an infectious disease that is one of the world's most serious animal health problems and, in many parts of the developing world, still a major mortality risk for humans. The incidence of TB in New Zealand (NZ) farmed livestock has been reduced progressively over the last 20 years, largely due to extensive and sustained population control of the main wildlife reservoir of disease, the introduced brushtail possum. Possums are also major pests that threaten indigenous forest biodiversity, and so extensive possum control for TB mitigation also incidental benefits conservation, but the extent and public value of this benefit has yet to be quantified. We conducted a choice experiment survey of the NZ public in an effort to value the native forest biodiversity benefits of TB-related possum control. We find strong public support for conservation outcomes consequent to TB-possum control in public native forests. The public place substantial value on the most observable biodiversity benefits of TB possum control, such as improved forest canopies and presence of native birds. The benefits, costs and values of TB-possum control are discussed in relation to the future directives of NZ's TB control programme, which is headed toward first regional and then national level disease eradication. Copyright © 2016 Elsevier Ltd. All rights reserved.
Bouchikh, S; Stirnemann, J; Prendki, V; Porcher, R; Kesthmand, H; Morin, A-S; Cruaud, P; Rouaghe, S; Farge, D; Fain, O
The recommended duration of pulmonary tuberculosis therapy is 6 months. For extrapulmonary tuberculosis, treatment duration depends on tuberculosis involvement and HIV status. The objective of this study was to describe the main characteristics of a cohort of extrapulmonary tuberculosis patients, to compare patients with a 6-month treatment to those with more than a 6-month treatment, and to analyze the compliance of medical centres with recommended duration of treatment. A retrospective cohort study of 210 patients with extrapulmonary tuberculosis was carried from January 1999 to December 2006 in two hospitals in the north-east of Paris. These patients were treated with quadruple therapy during two months, followed by dual therapy during 4 months (n=77) or more (n=66). The characteristics of each group were compared by uni- and multivariate analysis. The primary endpoint was the rate of relapse or treatment failure at 24-month follow-up after treatment completion. No relapse was observed after 24 months of follow-up after the end of treatment in the two groups. In univariate analysis, patients with lymph node tuberculosis were more often treated for 6 months than at other sites of tuberculosis (respectively 61% versus 40.9%; P=0.02); the decision of treatment duration was related to medical practices (79.2% treated 6 months in one hospital versus 20.7% in the other, P<0.001); patients living in private residence were more often treated during 6 months than patients living in residence (24.2% versus 10.3%, P=0.042). In multivariate analysis, only hospital (P=0.046), sex (P=0.007) and private residence were significantly different in each group. A period of 6 months seems to be sufficient to treat extrapulmonary tuberculosis (except for neuromeningeal localization). Copyright © 2012. Published by Elsevier SAS.
Govindasamy, Darshini; Kranzer, Katharina; van Schaik, Nienke; Noubary, Farzad; Wood, Robin; Walensky, Rochelle P.; Freedberg, Kenneth A.; Bassett, Ingrid V.; Bekker, Linda-Gail
Background HIV counseling and testing may serve as an entry point for non-communicable disease screening. Objectives To determine the yield of newly-diagnosed HIV, tuberculosis (TB) symptoms, diabetes and hypertension, and to assess CD4 count testing, linkage to care as well as correlates of linkage and barriers to care from a mobile testing unit. Methods A mobile unit provided screening for HIV, TB symptoms, diabetes and hypertension in Cape Town, South Africa between March 2010 and September 2011. The yield of newly-diagnosed cases of these conditions was measured and clients were followed-up between January and November 2011 to assess linkage. Linkage to care was defined as accessing care within one, three or six months post-HIV diagnosis (dependent on CD4 count) and one month post-diagnosis for other conditions. Clinical and socio-demographic correlates of linkage to care were evaluated using Poisson regression and barriers to care were determined. Results Of 9,806 clients screened, the yield of new diagnoses was: HIV (5.5%), TB suspects (10.1%), diabetes (0.8%) and hypertension (58.1%). Linkage to care for HIV-infected clients, TB suspects, diabetics and hypertensives was: 51.3%, 56.7%, 74.1% and 50.0%. Only disclosure of HIV-positive status to family members or partners (RR=2.6, 95% CI: 1.04-6.3, p=0.04) was independently associated with linkage to HIV care. The main barrier to care reported by all groups was lack of time to access a clinic. Conclusion Screening for HIV, TB symptoms and hypertension at mobile units in South Africa has a high yield but inadequate linkage. After-hours and weekend clinics may overcome a major barrier to accessing care. PMID:24236170
He, Guang Xue; van denHof, Susan; van der Werf, Marieke J; Wang, Guo Jie; Ma, Shi Wen; Zhao, Dong Yang; Hu, Yuan Lian; Yu, Shi Cheng; Borgdorff, Martien W
Hospitals with inadequate infection control are risky environments for the emergence and transmission of tuberculosis (TB). We evaluated TB infection control practices, and the prevalence of latent TB infection (LTBI) and TB disease and risk factors in health care workers (HCW) in TB centers in Henan province in China. A cross-sectional survey was conducted in 2005. To assess TB infection control practices in TB centers, checklists were used. HCW were tuberculin skin tested (TST) to measure LTBI prevalence, and were asked for sputum smears and chest X-rays to detect TB disease, and questionnaires to assess risk factors. Differences between groups for categorical variables were analyzed by binary logistic regression. The clustered design of the study was taken into account by using a multilevel logistic model. The assessment of infection control practices showed that only in a minority of the centers the patient consultation areas and X-ray areas were separated from the waiting areas and administrative areas. Mechanical ventilation was not available in any of the TB centers. N95 respirators were not available for HCW and surgical masks were not available for TB patients and suspects. The LTBI prevalence of HCW with and without BCG scar was 55.6% (432/777) and 49.0% (674/1376), respectively (P = 0.003). Older HCW, HCW with longer duration of employment, and HCW who worked in departments with increased contact with TB patients had a higher prevalence of LTBI. HCW who work in TB centers at the prefecture level, or with an inpatient ward also had a higher prevalence of LTBI. Twenty cases of pulmonary TB were detected among 3746 HCW. The TB prevalence was 6.7/1000 among medical staff and 2.5/1000 among administrative/logistic staff. TB infection control in TB centers in Henan, China, appears to be inadequate and the prevalence of LTBI and TB disease among HCW was high. TB infection control practices in TB centers should be strengthened in China, including administrative
Talwar, Harvinder; Talreja, Jaya; Samavati, Lobelia
One-third of the world's population is infected with tuberculosis, only 10% will develop active disease and the remaining 90% is considered to have latent TB (LTB). While active TB is contagious and can be lethal, the LTB can evolve to active TB. The diagnosis of TB can be challenging, especially in the early stages, due to the variability in presentation and nonspecific signs and symptoms. Currently, we have limited tools available to diagnose active TB, predict treatment efficacy and cure of active tuberculosis, the reactivation of latent tuberculosis infection, and the induction of protective immune responses through vaccination. Therefore, the identification of robust and accurate tuberculosis-specific biomarkers is crucial for the successful eradication of TB. In this commentary, we summarized the available methods for diagnosis and differentiation of active TB from LTB and their limitations. Additionally, we present a novel peptide microarray platform as promising strategy to identify TB biomarkers.
Ghosh, Smita; Moonan, Patrick K; Cowan, Lauren; Grant, Juliana; Kammerer, Steve; Navin, Thomas R
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.
Background The prevalence and the patterns of ocular inflammatory disease and ocular tuberculosis (TB) are largely undocumented among Multidrug Resistant TB (MDR-TB) patients co-infected with Human Immunodeficiency Virus (HIV) and on antituberculosis and antiretroviral therapy (ART). Methods Lilavati Hospital and Research Center and Médecins Sans Frontières (MSF) organized a cross-sectional ophthalmological evaluation of HIV/MDR-TB co-infected patients followed in an MSF-run HIV-clinic in Mumbai, India, which included measuring visual acuity, and slit lamp and dilated fundus examinations. Results Between February and April 2012, 47 HIV/MDR-TB co-infected patients (including three patients with extensively drug-resistant TB) were evaluated. Sixty-four per cent were male, mean age was 39 years (standard deviation: 8.7) and their median (IQR) CD4 count at the time of evaluation was 264 cells/μL (158–361). Thirteen patients (27%) had detectable levels of HIV viremia (>20 copies/ml). Overall, examination of the anterior segments was normal in 45/47 patients (96%). A dilated fundus examination revealed active ocular inflammatory disease in seven eyes of seven patients (15.5%, 95% Confidence Intervals (CI); 5.1-25.8%). ‘These included five eyes of five patients (10%) with choroidal tubercles, one eye of one patient (2%) with presumed tubercular chorioretinitis and one eye of one patient (2%) with evidence of presumed active CMV retinitis. Presumed ocular tuberculosis was thus seen in a total of six patients (12.7%, 95% CI; 3.2-22.2%). Two patients who had completed anti-TB treatment had active ocular inflammatory disease, in the form of choroidal tubercles (two eyes of two patients). Inactive scars were seen in three eyes of three patients (6%). Patients with extrapulmonary TB and patients <39 years old were at significantly higher risk of having ocular TB [Risk Ratio: 13.65 (95% CI: 2.4-78.5) and 6.38 (95% CI: 1.05-38.8) respectively]. Conclusions Ocular
Cajuste-Sequeira, Fritz; Bueno-Wong, Juan Luis; Rosas-Carrasco, Óscar; González-Vergara, Carolina; Bieletto-Trejo, Olivia
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.
Ugarte-Gil, César; Caro, Godofredo; Aylas, Rula; Castro, César; Lema, Claudia
Abstract This article analyzes the factors associated with vulnerability of the Ashaninka, the most populous indigenous Peruvian Amazonian people, to tuberculosis (TB). By applying a human rights-based analytical framework that assesses public policy against human rights standards and principles, and by offering a step-by-step framework for a full assessment of compliance, it provides evidence of the relationship between the incidence of TB among the Ashaninka and Peru’s poor level of compliance with its human rights obligations. The article argues that one of the main reasons for the historical vulnerability of the Ashaninka to diseases such as TB is a lack of political will on the part of the national government to increase public health spending, ensure that resources reach the most vulnerable population, and adopt and invest in a culturally appropriate health system. PMID:27780999
The Occupational Safety and Health Administration (OSHA) has published a proposed standard to provide health care workers with more protection against tuberculosis (TB). With one-quarter of new TB cases occurring in HIV-infected people, 5.3 million workers treating AIDS patients and working with at-risk populations need to be aware of the proposed guidelines. OSHA estimates that the new standard could eliminate most work-related TB infections and save up to $116 million in medical costs and lost production. The OSHA standards vary from those of the Centers for Disease Control (CDC) in several ways. CDC guidelines are voluntary, whereas OSHA standards are enforceable and facilities can be fined for violations. Although OSHA standards have incorporated basic elements of the CDC recommendations, OSHA standards also would require employers to conduct exposure assessments, require six-month skin testing, and call for respirator use in more instances. OSHA officials expect broad participation at public hearings on the new standard, scheduled to begin in February 1998.
Alladin, Bibi; Mack, Steve; Singh, Aruna; Singh, Chaitra; Smith, Belinda; Cummings, Emmanuel; Hershfield, Earl; Mohanlall, Jeetendra; Ramotar, Karam; La Fleur, Curtis
This study was conducted to determine the prevalence of diabetes mellitus among tuberculosis (TB) patients attending three TB clinics in Guyana. A cross-sectional study was conducted among TB patients attending TB clinics in three regions in Guyana. A structured questionnaire was used to collect demographic, clinical, and risk factor data. Random blood sugar testing was done using the OneTouch UltraSmart glucometer (LifeScan, Inc., 2002). One hundred TB patients were recruited; 90 had pulmonary TB and 10 had extrapulmonary disease. Fourteen patients were classified as diabetic: 12 had been previously diagnosed as diabetic by a physician and two had abnormally high random blood sugar at the time of enrolment. Of the 12 known diabetics, seven had been diagnosed before TB was discovered, three were identified at the time TB was diagnosed, and two after TB was diagnosed. All 14 diabetic patients presented with pulmonary TB. Thirty-one patients were HIV-positive and 28 of these had pulmonary TB, whereas three had extrapulmonary TB. None of the diabetics were infected with HIV. TB-diabetic patients tended to be older than non-diabetics (median age 44 vs. 36.5 years), were more likely to have been incarcerated at the time of TB diagnosis than non-diabetics (p=0.06), and were more likely to have an elevated (random) blood sugar level (p=0.02). Clinically, diabetes did not influence the presentation of TB. This study clearly highlights that diabetes and HIV are frequent in Guyanese TB patients. Routine screening of TB patients for diabetes and diabetic patients for TB should be speedily implemented. The National TB Programme should work closely with the diabetes clinics so that TB patients who are diabetics are optimally managed. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
Knowledge of tuberculosis (TB) and human immunodeficiency virus (HIV) and perception about provider initiated HIV testing and counselling among TB patients attending health facilities in Harar town, Eastern Ethiopia.
Seyoum, Ayichew; Legesse, Mengistu
Tuberculosis (TB) and Human Immunodeficiency Virus (HIV) co-infection is one of the major health problems in Ethiopia. The national TB and HIV control guideline in Ethiopia recommends provider initiated HIV testing and counselling (PITC) as a routine care for TB patients. However, the impact of this approach on the treatment seeking of TB patients has not been well studied. In this study, we assessed knowledge of TB and HIV, and perception about PITC among TB patients attending health facilities in Harar town, Eastern Ethiopia. In a health facilities based cross-sectional study, a total of 415 study participants were interviewed about knowledge of TB and HIV as well as the impact of HIV testing on their treatment seeking behavior using a semi-structured questionnaires. Multivariable logistic regression analysis showed the association of distance > 10 km from health facility [adjusted odds ratio (AOR)=0.48, 95% CI: 0.24 - 0.97, P=0.042] with low knowledge of TB. Distance > 10 km from health facility (AOR= 0.12, 95% CI: 0.06 -0.23, P < 0.001) was also associated with low knowledge of HIV testing. Delay in treatment seeking was associated with female participants (AOR = 0.11, 95% CI: 0.05-0.25, <0.001), single marital status (AOR =0.001, 95% CI: 0.00 - 0.01, P< 0.001) and distance > 10 km from health facility (AOR =0.46, 95% CI: 0.28 - 0.75, P=0.002). Most of the study participants (70%) believed that there is no association between TB and HIV/AIDS. On the other hand, two thirds (66.5%) of the participants thought that HIV testing has importance for TB patients. However, the majority (81.6%) of the study participants in the age category less than 21 years believed that fear of PITC could cause delay in treatment seeking. The study showed the association of low knowledge of the study participants about TB and HIV testing with distance > 10 km from health facility. Study participants in the age category less than 21 years thought that fear of PITC could cause treatment
Williams, Ann; Hatch, Graham J; Clark, Simon O; Gooch, Karen E; Hatch, Kim A; Hall, Graham A; Huygen, Kris; Ottenhoff, Tom H M; Franken, Kees L M C; Andersen, Peter; Doherty, T Mark; Kaufmann, Stefan H E; Grode, Leander; Seiler, Peter; Martin, Carlos; Gicquel, Brigitte; Cole, Stewart T; Brodin, Priscille; Pym, Alexander S; Dalemans, Wilfried; Cohen, Joe; Lobet, Yves; Goonetilleke, Nilu; McShane, Helen; Hill, Adrian; Parish, Tanya; Smith, Debbie; Stoker, Neil G; Lowrie, Douglas B; Källenius, Gunilla; Svenson, Stefan; Pawlowski, Andrzej; Blake, Karen; Marsh, Philip D
The TB Vaccine Cluster project funded by the EU Fifth Framework programme aims to provide novel vaccines against tuberculosis that are suitable for evaluation in humans. This paper describes the studies of the protective efficacy of vaccines in a guinea pig aerosol-infection model of primary tuberculosis. The objective was to conduct comparative evaluations of vaccines that had previously demonstrated efficacy in other animal models. Groups of 6 guinea pigs were immunized with vaccines provided by the relevant EU Vaccine Cluster partners. Survival over 17 or 26 weeks was used as the principal measure of vaccine efficacy following aerosol challenge with H37Rv. Counts of mycobacteria in lungs and spleens, and histopathological changes in the lungs, were also used to provide evidence of protection. A total of 24 vaccines were evaluated in 4 experiments each of a different design. A heterologous prime-boost strategy of DNA and MVA, each expressing Ag85A and a fusion protein of ESAT-6 and Ag85B in adjuvant, protected the guinea pigs to the same extent as BCG. Genetically modified BCG vaccines and boosted BCG strategies also protected guinea pigs to the same extent as BCG but not statistically significantly better. A relatively high aerosol-challenge dose and evaluation over a protracted time post-challenge allowed superior protection over BCG to be demonstrated by BCG boosted with MVA and fowl pox vectors expressing Ag85A.
Singh, Binit Kumar; Sharma, Surendra K; Sharma, Rohini; Sreenivas, Vishnubhatla; Myneedu, Vithal P; Kohli, Mikashmi; Bhasin, Dinkar; Sarin, Sanjay
To evaluate the performance of Genotype MTBDRplus VER 2.0 in the diagnosis of Mycobacterium tuberculosis (MTB) in sputum smear-negative pulmonary TB cases. A total of 572 Ziehl-Neelsen sputum smear-negative samples were selected and subjected to line probe assay (Genotype MTBDRplus VER 2.0), and culture in mycobacterial growth indicator tube (MGIT-960). Immunochromatographic test was used to confirm the MTB-complex (MTBC) in culture-positive samples and phenotypic drug-susceptibility testing was done using MGIT-960. The line probe assay was able to diagnose MTBC in 38.2% (213/558) of specimens after excluding 14 nontuberculous mycobacteria. Sensitivity and specificity of the assay were 68.4% and 89.3% respectively, considering MGIT-960 culture as gold standard after excluding contaminated and invalid results. On comparing with composite reference standard, the assay had 71.5% sensitivity and 100% specificity in the diagnosis of tuberculosis. The sensitivity and specificity for detecting resistance to rifampicin (RMP) were 100% and 99.24% respectively and for resistance to isoniazid (INH) were 97.62% and 98.55%, respectively. Genotype MTBDRplus VER 2.0 is a rapid and precise diagnostic tool for detection of MTB in sputum smear-negative samples. It also facilitates accurate diagnosis of RMP and INH resistance within turn around-time.
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
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/.
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
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
Via, Laura E.; Weiner, Danielle M.; Schimel, Daniel; Lin, Philana Ling; Dayao, Emmanuel; Tankersley, Sarah L.; Cai, Ying; Coleman, M. Teresa; Tomko, Jaime; Paripati, Praveen; Orandle, Marlene; Kastenmayer, Robin J.; Tartakovsky, Michael; Rosenthal, Alexander; Portevin, Damien; Eum, Seok Yong; Lahouar, Saher; Gagneux, Sebastien; Young, Douglas B.; Flynn, JoAnne L.
Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades. PMID:23716617
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
Lin, Philana Ling; Flynn, JoAnne L.
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
Diah, Ijlal Mohd; Aziz, Nazrina; Kasim, Maznah Mat
This paper presents the results of relative risk estimation that applied to TB data in Kedah using the most common approach, Standardized Morbidity Ratio (SMR). Disease mapping has been recognized as one of the methods that can be used by government and public health in order to control diseases since it can give a clear picture of the risk areas. To get good disease mapping, relative risk estimation is an important issue that need to be considered. TB risk areas will be recognized through the map. From the result, Kulim shows the lowest risk areas of contracting TB while Kota Setar has the highest risk area.
Piergallini, Tucker J; Turner, Joanne
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.
Zak, Daniel E.; Penn-Nicholson, Adam; Scriba, Thomas J.; Thompson, Ethan; Suliman, Sara; Amon, Lynn M.; Mahomed, Hassan; Erasmus, Mzwandile; Whatney, Wendy; Hussey, Gregory D.; Abrahams, Deborah; Kafaar, Fazlin; Hawkridge, Tony; Verver, Suzanne; Hughes, E. Jane; Ota, Martin; Sutherland, Jayne; Howe, Rawleigh; Dockrell, Hazel M.; Boom, W. Henry; Thiel, Bonnie; Ottenhoff, Tom H.M.; Mayanja-Kizza, Harriet; Crampin, Amelia C; Downing, Katrina; Hatherill, Mark; Valvo, Joe; Shankar, Smitha; Parida, Shreemanta K; Kaufmann, Stefan H.E.; Walzl, Gerhard; Aderem, Alan; Hanekom, Willem A.
Background Identification of blood biomarkers that prospectively predict progression of Mycobacterium tuberculosis infection to tuberculosis disease may lead to interventions that impact the epidemic. Methods Healthy, M. tuberculosis infected South African adolescents were followed for 2 years; blood was collected every 6 months. A prospective signature of risk was derived from whole blood RNA-Sequencing data by comparing participants who ultimately developed active tuberculosis disease (progressors) with those who remained healthy (matched controls). After adaptation to multiplex qRT-PCR, the signature was used to predict tuberculosis disease in untouched adolescent samples and in samples from independent cohorts of South African and Gambian adult progressors and controls. The latter participants were household contacts of adults with active pulmonary tuberculosis disease. Findings Of 6,363 adolescents screened, 46 progressors and 107 matched controls were identified. A 16 gene signature of risk was identified. The signature predicted tuberculosis progression with a sensitivity of 66·1% (95% confidence interval, 63·2–68·9) and a specificity of 80·6% (79·2–82·0) in the 12 months preceding tuberculosis diagnosis. The risk signature was validated in an untouched group of adolescents (p=0·018 for RNA-Seq and p=0·0095 for qRT-PCR) and in the independent South African and Gambian cohorts (p values <0·0001 by qRT-PCR) with a sensitivity of 53·7% (42·6–64·3) and a specificity of 82·8% (76·7–86) in 12 months preceding tuberculosis. Interpretation The whole blood tuberculosis risk signature prospectively identified persons at risk of developing active tuberculosis, opening the possibility for targeted intervention to prevent the disease. Funding Bill and Melinda Gates Foundation, the National Institutes of Health, Aeras, the European Union and the South African Medical Research Council (detail at end of text). PMID:27017310
Li, Jun; Yip, Benjamin H K; Leung, Chichiu; Chung, Wankyo; Kwok, Kin On; Chan, Emily Y Y; Yeoh, Engkiong; Chung, Puihong
Tuberculosis (TB) in the elderly remains a challenge in intermediate disease burden areas like Hong Kong. Given a higher TB burden in the elderly and limited impact of current case-finding strategy by patient-initiated pathway, proactive screening approaches for the high-risk group could be optimal and increasingly need targeted economic evaluations. In this study, we examined whether and under what circumstance the screening strategies are cost-effective compared with no screening strategy for the elderly at admission to residential care homes. A decision analytic process based on Markov model was adopted to evaluate the cost-effectiveness of four strategies: (i) no screening, (ii) TB screening (CXR) and (iii) TB screening (Xpert) represent screening for TB in symptomatic elderly by chest X-ray and Xpert® MTB/RIF respectively, and (iv) LTBI/TB screening represents screening for latent and active TB infection by QuantiFERON®-TB Gold In-Tube and chest X-ray. The target population was a hypothetical cohort of 65-year-old people, using a health service provider perspective and a time horizon of 20 years. The outcomes were direct medical costs, life-years and quality-adjusted life-years (QALYs) measured by incremental cost-effectiveness ratio (ICER). In the base-case analysis, no screening was the most cost-saving; TB screening (CXR) was dominated by TB screening (Xpert); LTBI/TB screening resulted in more life-years and QALYs accrued. The ICERs of LTBI/TB screening were US$19,712 and US$29,951 per QALY gained compared with no screening and TB screening (Xpert), respectively. At the willingness-to-pay threshold of US$50,000 per QALY gained, LTBI/TB screening was the most cost-effective when the probability of annual LTBI reactivation was greater than 0.155% and acceptability of LTBI/TB screening was greater than 38%. In 1,000 iterations of Monte Carlo simulation, the probabilities of no screening, TB screening (CXR), TB screening (Xpert), and LTBI/TB screening to be
Vashakidze, L; Salakaia, A.; Shubladze, N.; Cynamon, M.; Barbakadze, K.; Kikvidze, M.; Papitashvili, L.; Nonikashvili, M.; Solomonia, N.; Bejanishvili, N.; Khurtsilava, I.
SUMMARY Background Tuberculosis control in Georgia follows the WHO recommended DOTS strategy and has reached Global TB Control targets in treatment of sensitive TB, but the management of drug resistant forms of TB still represents a serious problem. A country-wide Drug Resistance Survey (DRS) found that the prevalence of MDR-TB was 6.8% in new and 27.4% in previously treated TB cases. Objective To determine prevalence and risk factors for drug resistance among TB patients in order to improve DR-TB case management and control. Methods Extensive social, clinical and bacteriological data were collected from hospitalized patients (National Centre for Tuberculosis and Lung Diseases, Georgia, 2005–2007). Results Out of 605 patients DR-TB was found in 491 (81.2%) cases, MDR-TB was observed in 261(43.1%) [51 (23%) out of 222 New cases and 210 (55%) out of 383 Previously treated cases], mono-DR-TB in 130 (21.5%), poly-DR-TB in 67 (11.1%) and XDR-TB in 33 (5.5%) cases. Study showed that female gender, living in densely populated capital, family TB contact and previous TB treatment are associated with risk for having MDR-TB. Conclusions Findings confirm the necessity of improvement of infection control measures and availability of standardized treatment for DR-TB patients. PMID:19723406
OBJECTIVES: The tuberculin skin test (TST) and the QuantiFERON-TB Gold test (QFT) are used to identify latent tuberculosis infections (LTBIs). The aim of this study was to determine the agreement between these two tests among health care workers in Iran. METHODS: This cross-sectional study included 177 tuberculosis (TB) laboratory staff and 67 non-TB staff. TST indurations of 10 mm or more were considered positive. The Student’s t-test and the chi-square test were used to compare the mean score and proportion of variables between the TB laboratory staff and the non-TB laboratory staff. Kappa statistics were used to evaluate the agreement between these tests, and logistic regression was used to assess the risk factors associated with positive results for each test. RESULTS: The prevalence of LTBIs according to both the QFT and the TST was 17% (95% confidence interval [CI], 12% to 21%) and 16% (95% CI, 11% to 21%), respectively. The agreement between the QFT and the TST was 77.46%, with a kappa of 0.19 (95% CI, 0.04 to 0.34). CONCLUSIONS: Although the prevalence of LTBI based on the QFT and the TST was not significantly different, the kappa statistic was low between these two tests for the detection of LTBIs. PMID:27457062
Vortia, Eugene; Uko, Victor E; Yen-Lieberman, Belinda; Frawley, Jill; Worley, Sarah E; Danziger-Isakov, Lara; Kaplan, Barbara; Mahajan, Lori
Tumor necrosis factor alpha (TNF-α) inhibitors are linked with increased risk of reactivation of active tuberculosis. The QuantiFERON-TB Gold In-Tube test is approved for screening latent tuberculosis infection in children and adults. There are limited data on the test performance in children on long-term treatment with TNF-α inhibitors. The objective of this study was to assess the proportion of indeterminate results for the QuantiFERON-TB Gold In-Tube in children with inflammatory bowel disease (IBD) on long-term infliximab treatment and to evaluate the range of interferon-γ responses to mitogen. A single-center prospective study of children 5 to 19 years of age with IBD on long-term infliximab treatment (>3 months). Each child was assessed for tuberculosis exposure risk and had blood drawn for the QuantiFERON-TB Gold In-Tube. Data on the range of interferon-γ responses and final QuantiFERON-TB Gold In-Tube test results were collected. Ninety-three children were included, with a median age of 16 years. The median total duration of infliximab therapy was 34 months (range, 3-119 months). The QuantiFERON-TB Gold In-Tube was indeterminate in 1 patient (1.1%), positive in 2 patients, and negative in 90 patients. The maximum interferon-γ response to mitogen (10 IU/mL) was observed in 82 patients (88%), with only 1 patient having an inadequate response. The proportion of indeterminate results was significantly lower than the prospectively hypothesized rate of 8%, based on prior studies in nonimmunosuppressed patients (P = 0.004). Pediatric patients with IBD on long-term treatment with infliximab had an adequate interferon-γ response to mitogen and a low indeterminate rate when assessed with the QuantiFERON-TB Gold In-Tube test. This study demonstrates a robust interferon gamma response to phytohemagglutinin stimulation in a pediatric population on long-term therapy with infliximab. The QuantiFERON-TB Gold In-Tube test may therefore be useful as a periodic
Jamil, K. F.
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.
Zalewska-Schönthaler, N; Schönthaler-Humiecka, J; Podlasin, R; Cholewińska, G; Rzeszkowicz, T; Mikuła, T; Horban, A
The aim of the search was investigation of tuberculosis in AIDS patients. Each year 8-9 mln people fall ill of tuberculosis and one third of them die. To the infection of tuberculosis and fast development into active state are especially exposed people with AIDS. 696 people were examined on tuberculosis most of which were AIDS patients hospitalized and cured in Hospital of Infection Diseases and Prison Hospital. 159 patients were women and 537 were men. The average age was between 25 and 45 (70%). The investigated population was characterized according to age, social and living conditions, using drugs and former contact with tuberculosis. All patients suspected of tuberculosis had chest X-rayed, sputum, BAL and pleural liquor were taken to bacteriological examination when extrapulmonary tuberculosis was suspected. The material was taken adequately to the disease process: CSF, urine, lymph nodes, peritoneal fluids, blood, stool, swabs and other. Bacteriological investigations have been carried out by fast cultivating method since 1998 and rapid genetic method since 1999. Apart from modern, fast diagnostic methods, routine bacteriological procedures were applied in tuberculosis diagnosis. More than 30% of the examined population were from bad social-living conditions, 78% had risk factors, 65% were drug users. The analysis of the tuberculosis illness from 1997 to July 2001 shows growing tendency. Nowadays it is 20% cases proved by bacteriological diagnosis. The structure of falling ill with tuberculosis has changed. Considerable increase of extrapulmonary tuberculosis was observed, 20 patients died due to tuberculosis and 8 patients due to mycobacteriosis. Resistance of M.tub.complex occurred within the range of 10% cases.
Carpio, D; Jauregui-Amezaga, A; de Francisco, R; de Castro, L; Barreiro-de Acosta, M; Mendoza, J L; Mañosa, M; Ollero, V; Castro, B; González-Conde, B; Hervías, D; Sierra Ausin, M; Sancho Del Val, L; Botella-Mateu, B; Martínez-Cadilla, J; Calvo, M; Chaparro, M; Ginard, D; Guerra, I; Maroto, N; Calvet, X; Fernández-Salgado, E; Gordillo, J; Rojas Feria, M
Despite having adopted preventive measures, tuberculosis (TB) may still occur in patients with inflammatory bowel disease (IBD) treated with anti-tumour necrosis factor (anti-TNF). Data on the causes and characteristics of TB cases in this scenario are lacking. Our aim was to describe the characteristics of TB in anti-TNF-treated IBD patients after the publication of the Spanish TB prevention guidelines in IBD patients and to evaluate the safety of restarting anti-TNF after a TB diagnosis. In this multicentre, retrospective, descriptive study, TB cases from Spanish hospitals were collected. Continuous variables were reported as mean and standard deviation or median and interquartile range. Categorical variables were described as absolute and relative frequencies and their confidence intervals when necessary. We collected 50 TB cases in anti-TNF-treated IBD patients, 60% male, median age 37.3 years (interquartile range [IQR] 30.4-47). Median latency between anti-TNF initiation and first TB symptoms was 155.5 days (IQR 88-301); 34% of TB cases were disseminated and 26% extrapulmonary. In 30 patients (60%), TB cases developed despite compliance with recommended preventive measures; *not performing 2-step TST (tuberculin skin test) was the main failure in compliance with recommendations. In 17 patients (34%) anti-TNF was restarted after a median of 13 months (IQR 7.1-17.3) and there were no cases of TB reactivation. Tuberculosis could still occur in anti-TNF-treated IBD patients despite compliance with recommended preventive measures. A significant number of cases developed when these recommendations were not followed. Restarting anti-TNF treatment in these patients seems to be safe. Copyright © 2016 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: firstname.lastname@example.org.
Mallick, G.; Agrawal, T. K.; Kumar, A. M. V.; Chadha, S. S.
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
Mourik, Bas C; Leenen, Pieter J M; de Knegt, Gerjo J; Huizinga, Ruth; van der Eerden, Bram C J; Wang, Jinshan; Krois, Charles R; Napoli, Joseph L; Bakker-Woudenberg, Irma A J M; de Steenwinkel, Jurriaan E M
Immune-modulating drugs that target myeloid-derived suppressor cells or stimulate natural killer T cells have been shown to reduce mycobacterial loads in tuberculosis (TB). We aimed to determine if a combination of these drugs as adjunct immunotherapy to conventional antibiotic treatment could also increase therapeutic efficacy against TB. In our model of pulmonary TB in mice, we applied treatment with isoniazid, rifampicin, and pyrazinamide for 13 weeks alone or combined with immunotherapy consisting of all-trans retinoic acid, 1,25(OH) 2 -vitamin D3, and α-galactosylceramide. Outcome parameters were mycobacterial load during treatment (therapeutic activity) and 13 weeks after termination of treatment (therapeutic efficacy). Moreover, cellular changes were analyzed using flow cytometry and cytokine expression was assessed at the mRNA and protein levels. Addition of immunotherapy was associated with lower mycobacterial loads after 5 weeks of treatment and significantly reduced relapse of disease after a shortened 13-week treatment course compared with antibiotic treatment alone. This was accompanied by reduced accumulation of immature myeloid cells in the lungs at the end of treatment and increased TNF-α protein levels throughout the treatment period. We demonstrate, in a mouse model of pulmonary TB, that immunotherapy consisting of three clinically approved drugs can improve the therapeutic efficacy of standard antibiotic treatment.
... 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 ...
Bojang, Adama L; Mendy, Francis S; Tientcheu, Leopold D; Otu, Jacob; Antonio, Martin; Kampmann, Beate; Agbla, Schadrac; Sutherland, Jayne S
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.
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.
Bothamley, Graham H; Lange, Christoph
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.
Fan, Yahui; Zhang, Shaoru; Li, Yan; Li, Yuelu; Zhang, Tianhua; Liu, Weiping; Jiang, Hualin
TB outbreaking in schools is extremely complex, and presents a major challenge for public health. Understanding the knowledge, attitudes and practices among student TB patients in such settings is fundamental when it comes to decreasing future TB cases. The objective of this study was to develop a Knowledge, Attitudes and Practices Questionnaire among Student Tuberculosis Patients (STBP-KAPQ), and evaluate its psychometric properties. This study was conducted in three stages: item construction, pilot testing in 10 student TB patients and psychometric testing, including reliability and validity. The item pool for the questionnaire was compiled from literature review and early individual interviews. The questionnaire items were evaluated by the Delphi method based on 12 experts. Reliability and validity were assessed using student TB patients (n = 416) and healthy students (n = 208). Reliability was examined with internal consistency reliability and test-retest reliability. Content validity was calculated by content validity index (CVI); Construct validity was examined using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA); The Public Tuberculosis Knowledge, Attitudes and Practices Questionnaire (PTB-KAPQ) was applied to evaluate criterion validity; As concerning discriminant validity, T-test was performed. The final STBP-KAPQ consisted of three dimensions and 25 items. Cronbach's α coefficient and intraclass correlation coefficient (ICC) was 0.817 and 0.765, respectively. Content validity index (CVI) was 0.962. Seven common factors were extracted by principal factor analysis and varimax rotation, with a cumulative contribution of 66.253%. The resulting CFA model of the STBP-KAPQ exhibited an appropriate model fit (χ2/df = 1.74, RMSEA = 0.082, CFI = 0.923, NNFI = 0.962). STBP-KAPQ and PTB-KAPQ had a strong correlation in the knowledge part, and the correlation coefficient was 0.606 (p < 0.05). Discriminant
Sharma, Surendra K.; Mohan, Alladi
Globally, tuberculosis (TB) still remains a major public health problem. India is a high TB burden country contributing to 26 per cent of global TB burden. During 1944-1980, TB became treatable and short-course chemotherapy emerged as the standard of care. When TB elimination seemed possible in the early 1980s, global human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) pandemic resulted in a resurgence of TB. Widespread occurrence of multidrug-resistant and extensively drug-resistant TB (M/XDR-TB) is threatening to destabilize TB control globally. Atypical clinical presentation still poses a challenge. Disseminated, miliary and cryptic TB are being increasingly recognized. Availability of newer imaging modalities has allowed more efficient localization of lesions and use of image guided procedures has facilitated definitive diagnosis of extrapulmonary TB. Introduction of liquid culture, rapid drug-susceptibility testing (DST), molecular diagnostic methods has helped in rapid detection, speciation and DST profiling of Mycobacterium tuberculosis isolates. While treatment of TB and HIV-TB co-infection has become simpler, efforts are on to shorten the treatment duration. However, drug toxicities and drug-drug interactions still constitute a significant challenge. Recently, there has been better understanding of anti-TB drug-induced hepatotoxicity and its frequent confounding by viral hepatitis, especially, in resource-constrained settings; and immune reconstitution inflammatory syndrome (IRIS) in HIV-TB. Quest for newer biomarkers for predicting a durable cure, relapse, discovery/repurposing of newer anti-TB drugs, development of newer vaccines continues to achieve the goal of eliminating TB altogether by 2050. PMID:23640554
A case of pulmonary tuberculosis caused by Mycobacterium tuberculosis was diagnosed in a horse. Clinical evaluation performed prior to euthanasia did not suggest tuberculosis, but postmortem examination provided pathological and bacteriological evidence of disease. In the lungs, multiple tuberculoid...
Gabriele, Francesca; Trachana, Maria; Simitsopoulou, Maria; Pratsidou-Gertsi, Polixeni; Iosifidis, Elias; Pana, Zoi Dorothea; Roilides, Emmanuel
To evaluate the performance of the Quantiferon ® -TB Gold In-Tube (QFT-IT) interferon (IFN)-γ assay for the detection of latent tuberculosis infection (LTBI) in children receiving anti-rheumatic treatment in a tertiary referral hospital of Northern Greece. A total of 79 consecutive children receiving anti-rheumatic treatment [of which 18 screened prior to antitumor necrosis factor (TNF)-α treatment] were tested using Mantoux tuberculin skin test (TST) and QFT-IT. Association of both tests with risk factors for latent tuberculosis and Bacillus Calmette-Guerin immunization was determined. Influence of age, TNF-α inhibitors, systemic corticosteroids, conventional disease modifying anti-rheumatic drugs (DMARDs) and total duration of therapy on the QFT-IT mitogen-induced response was evaluated. Agreement between TST and QFT-IT results was moderate (k=0.38). Frequency of QFT-IT indeterminate results was low (2.5%). In patients with risk factors for LTBI, the odds of a positive IFN-γ assay was increased by a factor of 27.6 (P=0.002), whereas there was no positive TST. There was a significant difference in the mitogen-induced IFN-γ secretion among various treatments (P=0.038). TNF-α inhibitors were associated with increased mitogen-induced IFN-γ secretion compared to monotherapy with conventional DMARDs (P=0.008). All children screened prior to anti-TNF-α treatment exhibited a negative QFT-IT and no active TB disease was detected during a 2-year follow-up. QFT-IT may be a more reliable test than TST for detection of LTBI in children with rheumatic diseases receiving anti-rheumatic treatment. Drug regimen might influence the mitogen-induced IFN-γ secretion and the effect of TNF-α inhibitors might vary according to the specific agent administered.
Cáceres, Neus; Pinto, Sergio; Díaz, Jorge; Cardona, Pere-Joan
The prophylactic capacity of the RUTI® vaccine, based on fragmented cells of Mycobacterium tuberculosis, has been evaluated in respect to aerosol challenge with virulent bacilli. Subcutaneous vaccination significantly reduced viable bacterial counts in both lungs and spleens of C57Bl mice, when challenged 4 weeks after vaccination. RUTI® protected the spleen less than BCG. Following a 9 month vaccination-challenge interval, protection was observed for the lungs, but not for the spleen. Survival of infected guinea pigs was prolonged by vaccination given 5 weeks before challenge. Inoculations of RUTI® shortly after infection significantly reduced the viable bacterial counts in the lungs, when compared with infected control mice. Thus, vaccination by RUTI® has potential for both the prophylaxis and immunotherapy of tuberculosis. PMID:21647222
Vilaplana, Cristina; Gil, Olga; Cáceres, Neus; Pinto, Sergio; Díaz, Jorge; Cardona, Pere-Joan
The prophylactic capacity of the RUTI® vaccine, based on fragmented cells of Mycobacterium tuberculosis, has been evaluated in respect to aerosol challenge with virulent bacilli. Subcutaneous vaccination significantly reduced viable bacterial counts in both lungs and spleens of C57Bl mice, when challenged 4 weeks after vaccination. RUTI® protected the spleen less than BCG. Following a 9 month vaccination-challenge interval, protection was observed for the lungs, but not for the spleen. Survival of infected guinea pigs was prolonged by vaccination given 5 weeks before challenge. Inoculations of RUTI® shortly after infection significantly reduced the viable bacterial counts in the lungs, when compared with infected control mice. Thus, vaccination by RUTI® has potential for both the prophylaxis and immunotherapy of tuberculosis.
Kwan, Candice K.; Ernst, Joel D.
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
Kwan, Candice K; Ernst, Joel D
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.
Chandra, Pallavi; Rajmani, R S; Verma, Garima; Bhavesh, Neel Sarovar; Kumar, Dhiraj
In view of emerging drug resistance among bacterial pathogens, including Mycobacterium tuberculosis, the development of novel therapeutic strategies is increasingly being sought. A recent paradigm in antituberculosis (anti-TB) drug development is to target the host molecules that are crucial for intracellular survival of the pathogen. We previously showed the importance of Src tyrosine kinases in mycobacterial pathogenesis. Here, we report that inhibition of Src significantly reduced survival of H37Rv as well as multidrug-resistant (MDR) and extremely drug-resistant (XDR) strains of M. tuberculosis in THP-1 macrophages. Src inhibition was also effective in controlling M. tuberculosis infection in guinea pigs. In guinea pigs, reduced M. tuberculosis burden due to Src inhibition also led to a marked decline in the disease pathology. In agreement with the theoretical framework of host-directed approaches against the pathogen, Src inhibition was equally effective against an XDR strain in controlling infection in guinea pigs. We propose that Src inhibitors could be developed into effective host-directed anti-TB drugs, which could be indiscriminately used against both drug-sensitive and drug-resistant strains of M. tuberculosis. IMPORTANCE The existing treatment regimen for tuberculosis (TB) suffers from deficiencies like high doses of antibiotics, long treatment duration, and inability to kill persistent populations in an efficient manner. Together, these contribute to the emergence of drug-resistant tuberculosis. Recently, several host factors were identified which help intracellular survival of Mycobacterium tuberculosis within the macrophage. These factors serve as attractive targets for developing alternate therapeutic strategies against M. tuberculosis. This strategy promises to be effective against drug-resistant strains. The approach also has potential to considerably lower the risk of emergence of new drug-resistant strains. We explored tyrosine kinase Src as a
van der Have, Mike; Oldenburg, Bas; Fidder, Herma H; Belderbos, Tim D G; Siersema, Peter D; van Oijen, Martijn G H
Treatment with tumor necrosis factor-α (TNF-α) inhibitors in patients with Crohn's disease (CD) is associated with potentially serious infections, including tuberculosis (TB) and hepatitis B virus (HBV). We assessed the cost-effectiveness of extensive TB screening and HBV screening prior to initiating TNF-α inhibitors in CD. We constructed two Markov models: (1) comparing tuberculin skin test (TST) combined with chest X-ray (conventional TB screening) versus TST and chest X-ray followed by the interferon-gamma release assay (extensive TB screening) in diagnosing TB; and (2) HBV screening versus no HBV screening. Our base-case included an adult CD patient starting with infliximab treatment. Input parameters were extracted from the literature. Direct medical costs were assessed and discounted following a third-party payer perspective. The main outcome was the incremental cost-effectiveness ratio (ICER). Sensitivity and Monte Carlo analyses were performed over wide ranges of probability and cost estimates. At base-case, the ICERs of extensive screening and HBV screening were €64,340 and €75,760 respectively to gain one quality-adjusted life year. Sensitivity analyses concluded that extensive TB screening was a cost-effective strategy if the latent TB prevalence is more than 12 % or if the false positivity rate of TST is more than 20 %. HBV screening became cost-effective if HBV reactivation or HBV-related mortality is higher than 37 and 62 %, respectively. Extensive TB screening and HBV screening are not cost-effective compared with conventional TB screening and no HBV screening, respectively. However, when targeted at high-risk patient groups, these screening strategies are likely to become cost-effective.
Farley, Jason E.; Kelly, Ana M.; Reiser, Katrina; Brown, Maria; Kub, Joan; Davis, Jeane G.; Walshe, Louise; Van der Walt, Martie
Setting Multidrug-resistant tuberculosis (MDR-TB) unit in KwaZulu-Natal, South Africa. Objective To develop and evaluate a nurse case management model and intervention using the tenets of the Chronic Care Model to manage treatment for MDR-TB patients with a high prevalence of human immunodeficiency virus (HIV) co-infection. Design A quasi-experimental pilot programme utilizing a nurse case manager to manage care for 40 hospitalized MDR-TB patients, 70% HIV co-infected, during the intensive phase of MDR-TB treatment. Patients were followed for six months to compare proximal outcomes identified in the model between the pre- and post-intervention period. Results The greatest percent differences between baseline and six-month MDR-TB proximal outcomes were seen in the following three areas: baseline symptom evaluation on treatment initiation (95% improvement), baseline and monthly laboratory evaluations completed per guidelines (75% improvement), and adverse drug reactions acted upon by medical and/or nursing intervention (75% improvement). Conclusion Improvements were identified in guideline-based treatment and monitoring of adverse drug reactions following implementation of the nurse case management intervention. Further study is required to determine if the intervention introduced in this model will ultimately result in improvements in final MDR-TB treatment outcomes. PMID:25405988
Cassidy, J P; Martineau, A R
Tuberculosis (TB) does not always develop in people or cattle exposed to the disease and some exposed individuals may not exhibit evidence of infection. Such variability in susceptibility may be mediated through host innate immunity, non-specific inflammatory responses that may successfully eliminate infection or at least reduce the infectious load, thus modulating and easing the burden on the subsequent acquired immune response. Assessing evidence from research in man, cattle and laboratory animal models, this review appraises the role of innate immunity in TB including the role of particular leucocytes (i.e. macrophages, neutrophils, γδ-T lymphocytes and natural killer cells), endogenous host defence compounds (i.e. cathelicidin, human neutrophil peptide, lipocalin and natural resistance-associated membrane protein-1) and, in particular, vitamin D. Innate responses may be particularly important in neonatal animals and people where adaptive responses have not yet established and their success in preventing the establishment of infection may be predicated on dose and/or route of infection as well as on characteristics of the infecting isolate. Innate defences could potentially be exploited in novel vaccination and immunotherapeutic approaches to disease control, modulating their effectiveness through the use of defined mycobacterial peptides as adjuvants or therapeutics. Such novel immunomodulatory compounds may be particularly relevant in countering emerging multi- and extremely drug-resistant strains of Mycobacterium tuberculosis (Mtb). Copyright © 2014 Elsevier Ltd. All rights reserved.
Ginsberg, Ann M.
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
Bielecka, Teresa; Komorowska-Piotrowska, Anna; Krenke, Katarzyna; Feleszko, Wojciech; Kulus, Marek
To assess whether children ≤5 years of age, produce sufficient amounts of interferon gamma (IFN-ɣ) in response to phytohaemagglutinin (mitogen), and Mycobacterium tuberculosis antigens (TB antigens) in the QuantiFERON-TB Gold in-Tube test (QFT-GIT), (Cellestis Ltd., Australia). Is TB-antigen-induced IFN-ɣ response in children ≤5 years sufficient to consider QFT-GIT a possible tool for TB diagnostics? Study design, patient-subject selection, and methods: We recruited children 0-17 years old suspected of TB infection to this cross-sectional study, in whom QFT-GIT and TST were performed. We analyzed the median IFN-ɣ levels in mitogen and TB antigen tubes in children ≤5 years and >5 years, and the correlation between IFN-ɣ level in both tubes and age. A total of 153 children were enrolled, age median was 7.8 (IQR:8), 45 (29.4%) aged ≤5 years (median 3.4, IQR:1.7), 108 > 5 years (median 10.55, IQR:5.93). In the mitogen tubes, the median IFN-ɣ level was higher in children >5 years (median 17.87, IQR:2.1 vs 16.77, IQR:7.6), but surprisingly in the TB antigen tubes it was higher in the younger group (median 0.12, IQR:0.21vs 0.06, IQR:0.09, P = 0.04). We proved a positive correlation between IFN-ɣ level and age in mitogen tubes (r = 0.18, P = 0.03) and a negative correlation in TB antigen tubes (r = -0.17, P = 0.04). In latent tuberculosis infection patients, the latter correlation was found to be even stronger (r = -0.39, P = 0.01). The youngest children release sufficient amount of IFN-ɣ in response to TB antigens thus QFT-GIT might be a useful tool for TB diagnostics in this age group. © 2017 Wiley Periodicals, Inc.
Elf, Jessica L; Eke, Onyinyechi; Rakgokong, Modiehi; Variava, Ebrahim; Baliram, Yudesh; Motlhaoleng, Katlego; Lebina, Limakatso; Shapiro, Adrienne E; Breysse, Patrick N; Golub, Jonathan E; Martinson, Neil
Secondhand tobacco smoke (SHS), use of solid fuels, and kerosene may play an important role in perpetuating the tuberculosis (TB) epidemic. The purpose of this study was to explore the prevalence of household air pollution (HAP) from these sources in homes of someone with TB in a high HIV-prevalence setting. A convenience sample of homes and household members participating in an ongoing active case-finding study in Matlosana district townships surrounding Klerksdorp, South Africa were included. We found a high prevalence of air pollution from SHS, solid fuels, and kerosene among individuals in homes with a case of prevalent active TB disease in Klerksdorp, South Africa. Adults in 40% of homes reported a daily smoker in the home, and 70% of homes had detectable air nicotine. In homes with a history of previous TB (prior to but not including the index case) as compared to those without previous TB, both SHS (83% vs. 65%, respectively) and solid/kerosene fuel use for more than 1 h/day (27% vs. 21%, respectively) were more prevalent. Larger studies are needed to estimate the risk of TB from these types of air pollution in HIV infected individuals and settings with high HIV prevalence.
Tang, Patrick; Johnston, James
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.
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
Awoniyi, Dolapo O; Teuchert, Andrea; Sutherland, Jayne S; Mayanja-Kizza, Harriet; Howe, Rawleigh; Mihret, Adane; Loxton, Andre G; Sheehama, Jacob; Kassa, Desta; Crampin, Amelia C; Dockrell, Hazel M; Kidd, Martin; Rosenkrands, Ida; Geluk, Annemieke; Ottenhoff, Tom H M; Corstjens, P L A M; Chegou, Novel N; Walzl, Gerhard
We investigated the accuracy of host markers detected in Mtb antigen-stimulated whole blood culture supernatant in the diagnosis of TB. Prospectively, blood from 322 individuals with presumed TB disease from six African sites was stimulated with four different Mtb antigens (Rv0081, Rv1284, ESAT-6/CFP-10, and Rv2034) in a 24 h whole blood stimulation assay (WBA). The concentrations of 42 host markers in the supernatants were measured using the Luminex multiplex platform. Diagnostic biosignatures were investigated through the use of multivariate analysis techniques. 17% of the participants were HIV infected, 106 had active TB disease and in 216 TB was excluded. Unstimulated concentrations of CRP, SAA, ferritin and IP-10 had better discriminating ability than markers from stimulated samples. Accuracy of marker combinations by general discriminant analysis (GDA) identified a six analyte model with 77% accuracy for TB cases and 84% for non TB cases, with a better performance in HIV uninfected patients. A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
an der Heiden, Maria; Hauer, Barbara; Fiebig, Lena; Glaser-Paschke, Gisela; Stemmler, Markus; Simon, Claudia; Rüsch-Gerdes, Sabine; Gilsdorf, Andreas; Haas, Walter
In July 2013, a passenger died of infectious extensively drug-resistant tuberculosis (XDR-TB) on board of an aircraft after a 3-hour flight from Turkey to Germany. Initial information indicated the patient had moved about the aircraft coughing blood. We thus aimed to contact and inform all persons exposed within the aircraft and to test them for newly acquired TB infection. Two-stage testing within 8 weeks from exposure and at least 8 weeks after exposure was suggested, using either interferon gamma release assays (IGRAs) or tuberculin skin test (TST). The TST cut-off was defined at a diameter > 10 mm; for differentiation between conversion and boosting, conversion was defined as increase of skin induration > 5 mm. Overall, 155 passengers and seven crew members were included in the investigation: the questionnaire response rate was 83%; 112 (69%) persons were tested at least once for TB infection. In one passenger, who sat next to the area where the patient died, a test conversion was registered. As of March 2017, no secondary active TB cases have been reported. We describe an unusual situation in which we applied contact tracing beyond existing European guidelines; we found one latent tuberculosis infection in a passenger, which we consider probably newly acquired. PMID:28367796
An der Heiden, Maria; Hauer, Barbara; Fiebig, Lena; Glaser-Paschke, Gisela; Stemmler, Markus; Simon, Claudia; Rüsch-Gerdes, Sabine; Gilsdorf, Andreas; Haas, Walter
In July 2013, a passenger died of infectious extensively drug-resistant tuberculosis (XDR-TB) on board of an aircraft after a 3-hour flight from Turkey to Germany. Initial information indicated the patient had moved about the aircraft coughing blood. We thus aimed to contact and inform all persons exposed within the aircraft and to test them for newly acquired TB infection. Two-stage testing within 8 weeks from exposure and at least 8 weeks after exposure was suggested, using either interferon gamma release assays (IGRAs) or tuberculin skin test (TST). The TST cut-off was defined at a diameter > 10 mm; for differentiation between conversion and boosting, conversion was defined as increase of skin induration > 5 mm. Overall, 155 passengers and seven crew members were included in the investigation: the questionnaire response rate was 83%; 112 (69%) persons were tested at least once for TB infection. In one passenger, who sat next to the area where the patient died, a test conversion was registered. As of March 2017, no secondary active TB cases have been reported. We describe an unusual situation in which we applied contact tracing beyond existing European guidelines; we found one latent tuberculosis infection in a passenger, which we consider probably newly acquired. This article is copyright of The Authors, 2017.
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
Mycobacterium tuberculosis and M. bovis are closely related (>99% genetic identity), inducing similar host responses and disease expression upon infection. There is a rich history of co-discovery in the development of control measures applicable to both human and bovine tuberculosis (TB) including s...
Merle, Corinne S C; Sismanidis, Charalambos; Sow, Oumou Bah; Gninafon, Martin; Horton, John; Lapujade, Olivier; Lo, Mame Bocar; Mitchinson, Denis A; Perronne, Christian; Portaels, Francoise; Odhiambo, Joseph; Olliaro, Piero; Rustomjee, Roxana; Lienhardt, Christian; Fielding, Katherine
There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize endpoint unavailability; and (2) distinguish
Background There have been no major advances in tuberculosis (TB) drug development since the first East African/British Medical Research Council short course chemotherapy trial 35 years ago. Since then, the landscape for conducting TB clinical trials has profoundly changed with the emergence of HIV infection, the spread of resistant TB bacilli strains, recent advances in mycobacteriological capacity, and drug discovery. As a consequence questions have arisen on the most appropriate approach to design and conduct current TB trials. To highlight key issues discussed: Is a superiority, equivalence, or non-inferiority design most appropriate? What should be the primary efficacy outcome? How to consider re-infections in the definition of the outcome? What is the optimal length of patient follow-up? Is blinding appropriate when treatment duration in test arm is shorter? What are the appropriate assumptions for sample size calculation? Methods Various drugs are currently in the development pipeline. We are presenting in this paper the design of the most recently completed phase III TB trial, the OFLOTUB project, which is the pivotal trial of a registration portfolio for a gatifloxacin-containing TB regimen. It is a randomized, open-label, multicenter, controlled trial aiming to evaluate the efficacy and safety of a gatifloxacin-containing 4-month regimen (trial registration: ClinicalTrial.gov database: NCT00216385). Results In the light of the recent scientific and regulatory discussions, we discuss some of the design issues in TB clinical trials and more specifically the reasons that guided our choices, in order to best answer the trial objectives, while at the same time satisfying regulatory authority requirements. Conclusion When shortening TB treatment, we are advocating for a non-inferiority, non-blinded design, with a composite unfavorable endpoint assessed 12 months post treatment completion, and added trial procedures specifically aiming to: (1) minimize
Kundu, Debashish; Chopra, Kamal; Khanna, Ashwani; Babbar, Neeti; Padmini, T J
In India, almost half of all patients with tuberculosis (TB) seek care in the private sector as the first point of care. The national programme is unable to support such TB patients and facilitate effective treatment, as there is no information on TB and Multi or Extensively Drug Resistant TB (M/XDR-TB) diagnosis and treatment in private sector. To improve this situation, Government of India declared TB a notifiable disease for establishing TB surveillance system, to extend supportive mechanism for TB treatment adherence and standardised practices in the private sector. But TB notification from the private sector is a challenge and still a lot needs to be done to accelerate TB notification. Delhi State TB Control Programme had taken initiatives for improving notification of TB cases from the private sector in 2014. Key steps taken were to constitute a state level TB notification committee to oversee the progress of TB notification efforts in the state and direct 'one to one' sensitisation of private practitioners (PPs) (in single PP's clinic, corporate hospitals and laboratories) by the state notification teams with the help of available tools for sensitising the PP on TB notification - TB Notification Government Order, Guidance Tool for TB Notification and Standards of TB Care in India. As a result of focussed state level interventions, without much external support, there was an accelerated notification of TB cases from the private sector. TB notification cases from the private sector rose from 341 (in 2013) to 4049 (by the end of March 2015). Active state level initiatives have led to increase in TB case notification. Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.
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.
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
Price, Patricia; Haddow, Lewis J; Affandi, Jacquita; Agarwal, Upasna; Easterbrook, Philippa J; Elliott, Julian; French, Martyn; Kumar, Manoj; Moosa, Mahomed-Yunus S; Oliver, Benjamin; Singh, Sarman; Sola, Marcelo; Saphonn, Vonthanak; Vun, Mean Chhi
Immune restoration disease associated with Mycobacterium tuberculosis (TB IRD) is clinically important among HIV patients commencing antiretroviral therapy in countries where tuberculosis is endemic. Vitamin D affects dendritic cell and T cell function and the antimicrobial activity of monocytes. Plasma levels of vitamin D and polymorphisms in the vitamin D receptor may affect tuberculosis, and HIV infection associates with vitamin D deficiency. Here we assess whether plasma vitamin D levels may predict TB IRD. Samples were available from prospective studies of TB IRD in Cambodia (26 cases), India (19 cases), and South Africa (29 cases). IRD cases and controls from each site were similar in age and baseline CD4(+) T cell count. Plasma samples were assessed using 25(OH) vitamin D immunoassay plates. DNA samples were available from a subset of patients and were genotyped for the VDR FokI (F/f) [C/T, rs10735810] SNP. When data from each cohort were pooled to assess ethnic/geographic differences, 25(OH)D levels were higher in Cambodian than Indian or South African patients (p<0.0001) and higher in South African than Indian patients (p<0.0001). TB IRD was not associated with differences in levels of 25(OH)D in any cohort (p=0.36-0.82), irrespective of the patients' prior TB diagnoses/treatment. Carriage of the minor allele of VDR FokI (F/f) was marginally associated with TB IRD in Indian patients (p=0.06) with no association in Cambodians. Neither plasma levels of vitamin D nor the vitamin D allele will usefully predict TB IRD in diverse populations from TB endemic regions.
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
Marlow, Mariel A; Maciel, Ethel Leonor Noia; Sales, Carolina Maia Martins; Gomes, Teresa; Snyder, Robert E; Daumas, Regina Paiva; Riley, Lee W
To quantitatively assess disease burden due to tuberculosis between populations residing in and outside of urban informal settlements in Rio de Janeiro, Brazil, we compared disability-adjusted life years (DALYs), or "DALY-gap." Using the 2010 Brazilian census definition of informal settlements as aglomerados subnormais (AGSN), we allocated tuberculosis (TB) DALYs to AGSN vs non-AGSN census tracts based on geocoded addresses of TB cases reported to the Brazilian Information System for Notifiable Diseases in 2005 and 2010. DALYs were calculated based on the 2010 Global Burden of Disease methodology. DALY-gap was calculated as the difference between age-adjusted DALYs/100,000 population between AGSN and non-AGSN. Total TB DALY in Rio in 2010 was 16,731 (266 DALYs/100,000). DALYs were higher in AGSN census tracts (306 vs 236 DALYs/100,000), yielding a DALY-gap of 70 DALYs/100,000. Attributable DALY fraction for living in an AGSN was 25.4%. DALY-gap was highest for males 40-59 years of age (501 DALYs/100,000) and in census tracts with <60% electricity (12,327 DALYs/100,000). DALY-gap comparison revealed spatial and quantitative differences in TB burden between slum vs non-slum census tracts that were not apparent using traditional measures of incidence and mortality. This metric could be applied to compare TB burden or burden for other diseases in mega-cities with large informal settlements for more targeted resource allocation and evaluation of intervention programs.
Floridia, Marco; Ciccacci, Fausto; Andreotti, Mauro; Hassane, Archa; Sidumo, Zita; Magid, Nurja A; Sotomane, Horacio; David, Muhlavasse; Mutemba, Elsa; Cebola, Junia; Mugunhe, Remigio Josè; Riccardi, Fabio; Marazzi, Maria Cristina; Giuliano, Marina; Palombi, Leonardo; Mancinelli, Sandro
Tuberculosis is a major health concern in several countries, and effective diagnostic algorithms for use in human immunodeficiency virus (HIV)-positive patients are urgently needed. At prescription of antiretroviral therapy, all patients in 3 Mozambican health centers were screened for tuberculosis, with a combined approach: World Health Organization (WHO) 4-symptom screening (fever, cough, night sweats, and weight loss), a rapid test detecting mycobacterial lipoarabinomannan in urine (Determine TB LAM), and a molecular assay performed on a sputum sample (Xpert MTB/RIF; repeated if first result was negative). Patients with positive LAM or Xpert MTB/RIF results were referred for tuberculosis treatment. Among 972 patients with a complete diagnostic algorithm (58.5% female; median CD4 cell count, 278/μL; WHO HIV stage I, 66.8%), 98 (10.1%) tested positive with Xpert (90, 9.3%) or LAM (34, 3.5%) assays. Compared with a single-test Xpert strategy, dual Xpert tests improved case finding by 21.6%, LAM testing alone improved it by 13.5%, and dual Xpert tests plus LAM testing improved it by 32.4%. Rifampicin resistance in Xpert-positive patients was infrequent (2.5%). Among patients with positive results, 22 of 98 (22.4%) had no symptoms at WHO 4-symptom screening. Patients with tuberculosis diagnosed had significantly lower CD4 cell counts and hemoglobin levels, more advanced WHO stage, and higher HIV RNA levels. Fifteen (15.3%) did not start tuberculosis treatment, mostly owing to rapidly deteriorating clinical conditions or logistical constraints. The median interval between start of the diagnostic algorithm and start of tuberculosis treatment was 7 days. The prevalence of tuberculosis among Mozambican HIV-positive patients starting antiretroviral therapy was 10%, with limited rifampicin resistance. Use of combined point-of-care tests increased case finding, with a short time to treatment. Interventions are needed to remove logistical barriers and prevent presentation
Kassa, Desta; de Jager, Wilco; Gebremichael, Gebremedhin; Alemayehu, Yodit; Ran, Leonie; Fransen, Justin; Wolday, Dawit; Messele, Tsehaynesh; Tegbaru, Belete; Ottenhoff, Tom H M; van Baarle, Debbie
Identification of Mtb specific induced cytokine/chemokine host biomarkers could assist in developing novel diagnostic, prognostic and therapeutic tools for TB. Levels of IFN-γ, IL-2, IL-17, IL-10, IP-10 and MIP-1α were measured in supernatants of whole blood stimulated with Mtb specific fusion protein ESAT-6/CFP-10 using xMAP technology. The study groups were HIV positive TB patients (HIV(+)TB(+)), HIV negative TB patients (HIV(-)TB(+)), HIV positive tuberculin skin test positive (TST+) (HIV(+)TST(+)), HIV negative TST+ (HIV(-)TST(+)), and HIV(-)TST(-) individuals. Compared to HIV(-)TST(-), latent TB infection led to increased levels of IP-10, IFN-γ and IL-17, while levels of IL-2 and IP-10 were increased with active TB. Levels of IFN-γ, IL-17, MIP-1α, and IL-10 were increased in HIV(-)TST(+) individuals compared to HIV(-)TB(+) patients. HIV coinfection decreased the level of IFN-γ, IL-17, IP-10 and IL-2. After six months (M6) of anti-TB treatment (ATT) in HIV(-)TB(+) patients, IFN-γ, IL-10, and MIP-1α levels normalized. After M6 and M18 of ATT plus HAART in HIV(+)TB(+) patients, levels of MIP-1α and IL-10 normalized, while this was not the case for IFN-γ, IL-2, IL-17, and IP-10 levels. In HIV(+)TST(+) patients on HAART, levels of IFN-γ, IL-17, IL-10 and MIP-1α normalized, while no change in the levels of IL-2 and IP-10 were observed. In conclusion, the simultaneous measurement of IFN-γ, IL-17 and IP-10 may assist in diagnosing LTBI; IL-2 and IP-10 may assist in diagnosing active TB; while IFN-γ, IL-17, MIP-1α, and IL-10 levels could help to discriminate LTBI and active TB. In addition, IL-10 and MIP-1α levels could help to monitor responses to TB treatment and HAART. Copyright © 2015 Elsevier Ltd. All rights reserved.
Rajasekaran, S; Khandelwal, Gaurav
Although the discovery of effective anti-tuberculosis drugs has made uncomplicated spinal tuberculosis a medical disease, the advent of multi-drug-resistant Mycobacterium tuberculosis and the co-infection of HIV with tuberculosis have led to a resurgence of the disease recently. The principles of drug treatment of spinal tuberculosis are derived from our experience in treating pulmonary tuberculosis. Spinal tuberculosis is classified to be a severe form of extrapulmonary tuberculosis and hence is included in Category I of the WHO classification. The tuberculosis bacilli isolated from patients are of four different types with different growth kinetics and metabolic characteristics. Hence multiple drugs, which act on the different groups of the mycobacteria, are included in each anti-tuberculosis drug regimen. Prolonged and uninterrupted chemotherapy (which may be 'short course' and 'intermittent' but preferably 'directly observed') is effective in controlling the infection. Spinal Multi-drug-resistant TB and spinal TB in HIV-positive patients present unique problems in management and have much poorer prognosis. Failure of chemotherapy and emergence of drug resistance are frequent due to the failure of compliance hence all efforts must be made to improve patient compliance to the prescribed drug regimen.
Schnippel, Kathryn; Sharp, Alana
Objective Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. Methods We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. Findings Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low
McLaren, Zoë M; Schnippel, Kathryn; Sharp, Alana
Identifying those infected with tuberculosis (TB) is an important component of any strategy for reducing TB transmission and population prevalence. The Stop TB Global Partnership recently launched an initiative with a focus on key populations at greater risk for TB infection or poor clinical outcomes, due to housing and working conditions, incarceration, low household income, malnutrition, co-morbidities, exposure to tobacco and silica dust, or barriers to accessing medical care. To achieve operational targets, the global health community needs effective, low cost, and large-scale strategies for identifying key populations. Using South Africa as a test case, we assess the feasibility and effectiveness of targeting active case finding to populations with TB risk factors identified from regularly collected sources of data. Our approach is applicable to all countries with TB testing and census data. It allows countries to tailor their outreach activities to the particular risk factors of greatest significance in their national context. We use a national database of TB test results to estimate municipality-level TB infection prevalence, and link it to Census data to measure population risk factors for TB including rates of urban households, informal settlements, household income, unemployment, and mobile phone ownership. To examine the relationship between TB prevalence and risk factors, we perform linear regression analysis and plot the set of population characteristics against TB prevalence and TB testing rate by municipality. We overlay lines of best fit and smoothed curves of best fit from locally weighted scatter plot smoothing. Higher TB prevalence is statistically significantly associated with more urban municipalities (slope coefficient β1 = 0.129, p < 0.0001, R2 = 0.133), lower mobile phone access (β1 = -0.053, p < 0.001, R2 = 0.089), lower unemployment rates (β1 = -0.020, p = 0.003, R2 = 0.048), and a lower proportion of low-income households (β1 = -0
Vijayan, Tara; Klausner, Jeffrey D.
The success of antiretroviral therapy (ART) programs in the developing world is limited by the lack of adequate diagnostic tests to screen for life-threatening opportunistic infections such as tuberculosis (TB) and cryptococcal disease. Furthermore, there is an increasing need for implementation research in measuring the effectiveness of currently available rapid diagnostic tests. The recently developed lateral flow assays for both cryptococcal disease and TB have the potential to improve care and greatly reduce the time to initiation of ART among individuals who need it the most. However, we caution that the data on feasibility and effectiveness of these assays are limited and such research agendas must be prioritized. PMID:24065780
Governmental neglect of tuberculosis (TB), inadequately managed and inaccurately designed TB control programs, population growth, and the HIV epidemic account for the resurgence of TB in sub-Saharan Africa. The World Health Organization and the International Union against TB and Lung Disease have developed a TB control strategy that aims to reduce mortality, morbidity, and transmission of TB. It aims for an 85% cure rate among detected new cases of smear-positive TB and a 70% rate of detecting existing smear-positive TB cases. The strategy involves the provision of short-course chemotherapy (SCC) to all identified smear-positive TB cases through directly observed treatment (DOTS). SCC treatment regimens for smear-positive pulmonary TB recommended for sub-Saharan African countries are: initial phase = daily administration over 2 months of streptomycin, rifampicin, isoniazid, and pyrazinamide; continuation phase = 3 doses over 4 months of isoniazid and rifampicin or daily administration of thiacetazone and isoniazid or of ethambutol and isoniazid. A TB control policy must be implemented to bring about effective TB control. The essential elements of this policy include political commitment, case detection through passive case-finding, SCC, a regular supply of essential drugs, and a monitoring and evaluation system. Political commitment involves establishing a National TB Control Program to be integrated into the existing health structure. Increased awareness of TB in the community and among health workers and a reference laboratory are needed to make case finding successful. A distribution and logistics system is needed to ensure uninterrupted intake of drugs throughout treatment. These regimens have been very successful and cost-effective but pose several disadvantages (e.g., heavy workload of recommended 3 sputum smear tests). A simplified approach involves 1 initial sputum smear for 6 months; 6-months, intermittent rifampicin-based therapy, 100% DOTS throughout
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
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
Fahmi, M. R. G.; Khumaidah, L.; Ilmiah, T. K.; Fadlan, A.; Santoso, M.
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.
Vajravelu, Ravy K; Osterman, Mark T; Aberra, Faten N; Roy, Jason A; Lichtenstein, Gary R; Mamtani, Ronac; Goldberg, David S; Lewis, James D; Scott, Frank I
QuantiFERON-TB Gold (QFTG) is a blood test used to diagnose latent tuberculosis infection (LTBI) prior to TNF-α inhibitor (anti-TNF) initiation. We sought to determine factors associated with indeterminate QFTG results in inflammatory bowel disease (IBD) patients and whether indeterminate results are associated with IBD-related morbidity. This nested case-control study included IBD patients who underwent QFTG testing. Cases were patients with indeterminate QFTG and controls were those with negative QFTG. The association of demographic and clinical data with indeterminate QFTG result was assessed using logistic regression. We examined the clinical impact of indeterminate QFTG results on risk of hospitalization and delay in anti-TNF initiation using inverse probability-of-treatment weighting (IPTW) regression. We identified 411 patients with QFTG testing (320 negative, 80 indeterminate, and 11 positive results). No patient with an indeterminate result subsequently had LTBI. Systemic corticosteroid use (OR, 4.4; 95% CI, 2.0-9.6) and hospitalization at the time of QFTG (OR, 3.8; 95% CI, 1.9-7.7) were associated with indeterminate QFTG, while immunomodulator use was nearly statistically significant (OR, 3.1; 95% CI, 0.9-9.8) and anti-TNF use was not (OR, 0.9; 95% CI, 0.2-4.6). After IPTW adjustment, indeterminate QFTG was associated with a 23.1% (95% CI, 8.2%-37.9%) greater probability of delay in anti-TNF initiation beyond 30 days and an 11.9% (95% CI, 0.6%-23.1%) greater probability of hospitalization within 60 days. Systemic corticosteroid use and hospitalization were associated with an indeterminate QFTG result. Indeterminate QFTG results were associated with delayed anti-TNF initiation and subsequent hospitalization. © 2017 Crohn’s & Colitis Foundation of America. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: email@example.com
Grace, G. Angeline; Devaleenal, D. Bella; Natrajan, Mohan
The morbidity and mortality due to tuberculosis (TB) is high worldwide, and the burden of disease among women is significant, especially in developing countries. Mycobacterium tuberculosis bacilli reach the genital tract primarily by haematogenous spread and dissemination from foci outside the genitalia with lungs as the common primary focus. Genital TB in females is a chronic disease with low-grade symptoms. The fallopian tubes are affected in almost all cases of genital TB, and along with endometrial involvement, it causes infertility in patients. Many women present with atypical symptoms which mimic other gynaecological conditions. A combination of investigations is needed to establish the diagnosis of female genital TB (FGTB). Multidrug anti-TB treatment is the mainstay of management and surgery may be required in advanced cases. Conception rates are low among infertile women with genital TB even after multidrug therapy for TB, and the risk of complications such as ectopic pregnancy and miscarriage is high. More research is needed on the changing trends in the prevalence and on the appropriate methods for diagnosis of FGTB. PMID:28862174
Yang, Chongguang; Gao, Qian
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.
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
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.
Martin, Laura; Coronel, Jorge; Faulx, Dunia; Valdez, Melissa; Metzler, Mutsumi; Crudder, Chris; Castillo, Edith; Caviedes, Luz; Grandjean, Louis; Rodriguez, Mitzi; Friedland, Jon S.; Gilman, Robert H.; Moore, David A. J.
Background Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory. Methods & Findings 2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ), conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct) DST and proportion method (indirect) DST. 778 samples (31.8%) were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals) of the MODS Kit were 99.3% (98.3–99.8%), 98.3% (97.5–98.8%), 95.8% (94.0–97.1%), and 99.7% (99.3–99.9%). Median (interquartile ranges) time to culture-positivity (and rifampicin and isoniazid DST) was 10 (9–13) days for conventional MODS and 8.5 (7–11) for MODS Kit (p<0.01). Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples) and reference indirect DST (97.9% agreement, 687/702 evaluable samples). Conclusions MODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked), readily repurposed for second-line DST in the near future
Martin, Laura; Coronel, Jorge; Faulx, Dunia; Valdez, Melissa; Metzler, Mutsumi; Crudder, Chris; Castillo, Edith; Caviedes, Luz; Grandjean, Louis; Rodriguez, Mitzi; Friedland, Jon S; Gilman, Robert H; Moore, David A J
Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory. 2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ), conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct) DST and proportion method (indirect) DST. 778 samples (31.8%) were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals) of the MODS Kit were 99.3% (98.3-99.8%), 98.3% (97.5-98.8%), 95.8% (94.0-97.1%), and 99.7% (99.3-99.9%). Median (interquartile ranges) time to culture-positivity (and rifampicin and isoniazid DST) was 10 (9-13) days for conventional MODS and 8.5 (7-11) for MODS Kit (p<0.01). Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples) and reference indirect DST (97.9% agreement, 687/702 evaluable samples). MODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked), readily repurposed for second-line DST in the near future, provides a fresh opportunity for improving equity of
Sens, Patrícia Maria; Almeida, Clemente I R; Valle, Lupércio O do; Costa, Luís H C; Angeli, Miguel L S
Tuberculosis is a rare cause of chronic suppurative otitis media and mastoiditis; the predisposing factors of this association, however, are not commonly described. There has been an alarming increase in the incidence of tuberculosis in Brazil, including tuberculous otitis media. These patients typically present multiple perforations of the tympanic membrane, an ear discharge, and progressive hearing loss. This diagnosis should be taken into account in patients that do not respond to routine therapy for fungal external otitis or bacterial otitis media. In this retrospective study, the authors describe four cases of patients with tuberculous otitis media. This sample consisted of two physicians, a chemical engineer and an underage child in whose family there were cases of active tuberculosis. Predisposing factors for tuberculous otitis were contact with family members that had tuberculosis, professional contact with patients and exposure to pathogenic microorganisms in airways.
Min, Joo-Won; Lee, Ha-Youn; Lee, Ji Sun; Lee, Jinwoo; Chung, Jae Ho; Han, Sung Koo; Yim, Jae-Joon
Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results.
Min, Joo-Won; Lee, Ha-Youn; Lee, Ji Sun; Lee, Jinwoo; Chung, Jae Ho; Han, Sung Koo
Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results. PMID:23825190
Jenkins, Helen E
In 2015, the World Health Organization (WHO) declared tuberculosis (TB) to be responsible for more deaths than any other single infectious disease. The burden of TB among children has frequently been dismissed as relatively low with resulting deaths contributing very little to global under-five all-cause mortality, although without rigorous estimates of these statistics, the burden of childhood TB was, in reality, unknown. Recent work in the area has resulted in a WHO estimate of 1 million new cases of childhood TB in 2014 resulting in 136,000 deaths. Around 3% of these cases likely have multidrug-resistant TB and at least 40,000 are in HIV-infected children. TB is now thought to be a major or contributory cause of many deaths in children under five years old, despite not being recorded as such, and is likely in the top ten causes of global mortality in this age group. In particular, recent work has shown that TB is an under-lying cause of a substantial proportion of pneumonia deaths in TB-endemic countries. Childhood TB should be given higher priority: we need to identify children at greatest risk of TB disease and death and make more use of tools such as active case-finding and preventive therapy. TB is a preventable and treatable disease from which no child should die.
Childhood TB is an indication of failing TB control in the community. It allows disease persistence in the population. Mortality and morbidity due to TB is high in children. Moreover, HIV co-infection and multidrug-resistant diseases are as frequent in children as in adults. Infection is more frequent in younger children. Disease risk after primary infection is greatest in infants younger than 2 years. In case of exposure, evidence of infection can be obtained using the tuberculin skin test (TST) or an interferon-gamma assay (IGRA). There is no evidence to support the use of IGRA over TST in young children. TB suspicion should be confirmed whenever possible, using new available tools, particularly in case of pulmonary and lymph node TB. Induced sputum, nasopharyngeal aspiration and fine needle aspiration biopsy provide a rapid and definitive diagnosis of mycobacterial infection in a large proportion of patients. Analysis of paediatric samples revealed higher sensitivity and specificity values of molecular techniques in comparison with the ones originated from adults. Children require higher drugs dosages than adults. Short courses of steroids are associated with TB treatment in case of respiratory distress, bronchoscopic desobstruction is proposed for severe airways involvement and antiretroviral therapy is mandatory in case of HIV infection. Post-exposure prophylaxis in children is a highly effective strategy to reduce the risk of TB disease. The optimal therapy for treatment of latent infection with a presumably multidrug-resistant Mycobacterium tuberculosis strain is currently not known. Copyright © 2014 Elsevier Masson SAS. All rights reserved.
Sutherland, Jayne S.; Lalor, Maeve K.; Black, Gillian F.; Ambrose, Lyn R.; Loxton, Andre G.; Chegou, Novel N.; Kassa, Desta; Mihret, Adane; Howe, Rawleigh; Mayanja-Kizza, Harriet; Gomez, Marie P.; Donkor, Simon; Franken, Kees; Hanekom, Willem; Klein, Michel R.; Parida, Shreemanta K.; Boom, W. Henry; Thiel, Bonnie A.; Crampin, Amelia C.; Ota, Martin; Walzl, Gerhard; Ottenhoff, Tom H. M.; Dockrell, Hazel M.; Kaufmann, Stefan H. E.
Background Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. Methods We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. Results There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST- and TST+ contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST+ contacts (LTBI) compared to TB and TST- contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. Conclusions Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may
Sutherland, Jayne S; Lalor, Maeve K; Black, Gillian F; Ambrose, Lyn R; Loxton, Andre G; Chegou, Novel N; Kassa, Desta; Mihret, Adane; Howe, Rawleigh; Mayanja-Kizza, Harriet; Gomez, Marie P; Donkor, Simon; Franken, Kees; Hanekom, Willem; Klein, Michel R; Parida, Shreemanta K; Boom, W Henry; Thiel, Bonnie A; Crampin, Amelia C; Ota, Martin; Walzl, Gerhard; Ottenhoff, Tom H M; Dockrell, Hazel M; Kaufmann, Stefan H E
Tuberculosis (TB) remains a global health threat with 9 million new cases and 1.4 million deaths per year. In order to develop a protective vaccine, we need to define the antigens expressed by Mycobacterium tuberculosis (Mtb), which are relevant to protective immunity in high-endemic areas. We analysed responses to 23 Mtb antigens in a total of 1247 subjects with different HIV and TB status across 5 geographically diverse sites in Africa (South Africa, The Gambia, Ethiopia, Malawi and Uganda). We used a 7-day whole blood assay followed by IFN-γ ELISA on the supernatants. Antigens included PPD, ESAT-6 and Ag85B (dominant antigens) together with novel resuscitation-promoting factors (rpf), reactivation proteins, latency (Mtb DosR regulon-encoded) antigens, starvation-induced antigens and secreted antigens. There was variation between sites in responses to the antigens, presumably due to underlying genetic and environmental differences. When results from all sites were combined, HIV- subjects with active TB showed significantly lower responses compared to both TST(-) and TST(+) contacts to latency antigens (Rv0569, Rv1733, Rv1735, Rv1737) and the rpf Rv0867; whilst responses to ESAT-6/CFP-10 fusion protein (EC), PPD, Rv2029, TB10.3, and TB10.4 were significantly higher in TST(+) contacts (LTBI) compared to TB and TST(-) contacts fewer differences were seen in subjects with HIV co-infection, with responses to the mitogen PHA significantly lower in subjects with active TB compared to those with LTBI and no difference with any antigen. Our multi-site study design for testing novel Mtb antigens revealed promising antigens for future vaccine development. The IFN-γ ELISA is a cheap and useful tool for screening potential antigenicity in subjects with different ethnic backgrounds and across a spectrum of TB and HIV infection states. Analysis of cytokines other than IFN-γ is currently on-going to determine correlates of protection, which may be useful for vaccine efficacy
Yuan, Li; Zhang, Hui; Zhou, Changming; Jiang, Weili; Zhao, Qi; Biao, Xu
The primary unit of tuberculosis (TB) medical care in China is the county TB dispensary or county designated hospital (CTD), where patients can receive free diagnosis and treatment. However, a substantial number of patients seek their anti-TB treatment from general health facilities (Non-CTDs). This study aimed to investigate the first anti-TB treatment experience and choice of health facilities of retreated TB patients and their determinants. A cross-sectional study was conducted in Jiangsu, Shandong and Sichuan provinces. All registered re-treated TB patients were investigated using a structured questionnaire covering information on demographics, socio-economic characteristics, and previous anti-TB treatment experiences. Totally, 75.3% of 544 patients visited CTD directly for initial treatment. Patients who were female (OR:1.71, 95% CI: 1.01-2.87), over 40 years of age (OR:2.80, 95% CI: 1.24-6.33), from Jiangsu (OR:3.07, 95% CI: 1.57-6.01) and Sichuan (OR:4.47, 95% CI: 2.29-8.73) and those diagnosed before 2005 (OR:6.87, 95% CI: 4.24-11.13) had a significant higher risk receiving their initial treatment at a non-CTD. Patients were more likely to have standardized diagnosis and treatment regimens in CTD (89.8%) than in non-CTDs (65.9%). Patients treated in non-CTDs versus in CTD had a lower possibility to complete their treatment course during first TB episode (χ 2 = 3.926, P = 0.048), but there was no significant difference in the cure rate between different facilities (CTD 60.8%, Non-CTDs 59.1%). Patients in non-CTDs incurred higher costs (1,360 CNY) than those treated in CTD (920CNY). CTD play a key role in the National Tuberculosis Control Program. Patients should be guided to seek health care in county designated hospital, where they are more likely to receive appropriate examinations, treatment regimens and rigorous supervision, and to bear a lighter economic burden.
Saito, Reiko; Takao, Yoshiko; Fukazawa, Keiji; Ohmori, Masako; Nagamine, Michiko; Shima, Fumiko; Kaguraoka, Sumi; Fukuuchi, Keiko; Ishikawa, Nobukatsu
A homeless patient with tuberculosis (TB), who had often quit his TB treatment in mid-course and then gone homeless again, succeeded in completing his treatment for over 10 months through on-the-street DOTS ("Bluesky DOTS" is another expression). Based on the analysis of this case, we have discussed how to provide effective countermeasures to non-compliant TB patients. An episode of a successful on-the-street DOTS for a 70-year-old homeless man with sputum smear positive pulmonary TB was qualitatively analyzed, with a view toward patient's empowerment. The patient had had human-relations problems in his life, and trouble with medical and welfare service staff. During his hospital admissions, he repeatedly self-discharged or was forced to discharge due to violent behavior against staff. Public health nurses at Shinjuku public health center visited the patient frequently at the hospital, and tried to build a good relationship with the patient from the beginning of the treatment. Following a two and half month interruption of the TB treatment after he disappeared from the hospital, he was discovered staying outside at a canal side in the area, and on-the-street TB treatment was carried out, with good cooperation with the hospital and social welfare office. Directly observed TB medication was given to him by a public health nurse and another health center staff member for 293 days, at the park near his living place. The patient often rejected the medication, particularly when he was hungry, but offering lunch to him was a very effective incentive. Through comprehensive supports to the patient, he gradually changed his attitude, and on his own came to consider his health and his future. We have analyzed a successfully treated case of a homeless TB patient who had difficulties in maintaining a social life and had not been cooperative in complying with the medication. The level of independence improved during the course of on-the-street DOTS with incentive and other
Harries, Anthony D.; Kumar, Ajay M.V.; Satyanarayana, Srinath; Lin, Yan; Zachariah, Rony; Lönnroth, Knut; Kapur, Anil
As we enter the new era of Sustainable Development Goals, the international community has committed to ending the TB epidemic by 2030 through implementation of an ambitious strategy to reduce TB-incidence and TB-related mortality and avoiding catastrophic costs for TB-affected families. Diabetes mellitus (DM) triples the risk of TB and increases the probability of adverse TB treatment outcomes such as failure, death and recurrent TB. The rapidly escalating global epidemic of DM means that DM needs to be addressed if TB-related milestones and targets are to be achieved. WHO and the International Union Against Tuberculosis and Lung Disease's Collaborative Framework for Care and Control of Tuberculosis and Diabetes, launched in 2011, provides a template to guide policy makers and implementers to combat the epidemics of both diseases. However, more evidence is required to answer important questions about bi-directional screening, optimal ways of delivering treatment, integration of DM and TB services, and infection control. This should in turn contribute to better and earlier TB case detection, and improved TB treatment outcomes and prevention. DM and TB collaborative care can also help guide the development of a more effective and integrated public health approach for managing non-communicable diseases. PMID:26884497
Ordway, Diane J; Pinto, Luisa; Costa, Leonor; Martins, Marta; Leandro, Clara; Viveiros, Miguel; Amaral, Leonard; Arroz, Maria J; Ventura, Fernando A; Dockrell, Hazel M
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.
Kim, Cherry; Park, So Hee; Oh, Sang Young; Kim, Sung-Soo; Jo, Kyung-Wook; Shim, Tae Sun; Kim, Mi Young
This article focuses on the differences between CT findings of HIV-negative patients who have cavities with nontuberculous mycobacteria (NTM) disease and those with Mycobacterium tuberculosis infections (TB). We retrospectively reviewed 128 NTM disease patients (79 males and 49 females) with cavities in chest CT, matched for age and gender with 128 TB patients in the same period. Sputum cultures of all patients were positive for pathogens. Two independent chest radiologists evaluated the characteristics of the largest cavity and related factors. Interobserver agreement was excellent (κ value, 0.853-0.938). Cavity walls in NTM disease were significantly thinner (6.9±4 mm vs 10.9±6 mm, P<0.001) and more even (the ratio of thickness, 2.6±1 vs 3.7±2, P<0.001) than those in TB. The thickening of adjacent pleura next to the cavity was also significantly thicker in NTM than TB (P<0.001). However, in the multivariate analysis, thickening of adjacent pleura was the only significant factor among the representative cavity findings (Odds ratio [OR], 6.49; P<0.001). In addition, ill-defined tree-in-bud nodules (OR, 8.82; P<0.001), number of non-cavitary nodules (≥10mm) (OR, 0.72; P = 0.003), and bronchiectasis in the RUL (OR, 5.3; P = 0.002) were significantly associated ancillary findings with NTM disease in the multivariate analysis. The major cavities in NTM disease generally have thinner and more even walls than those in TB. When cavities are associated with adjacent pleural thickening, ill-defined satellite tree-in-bud nodules, or fewer non-cavitary nodules ≥10 mm, these CT findings are highly suggestive of NTM disease rather than TB.
Zazueta-Beltran, Jorge; León-Sicairos, Claudia; Canizalez-Roman, Adrián
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.
Spalgais, Sonam; Agarwal, Upasna; Sarin, Rohit; Chauhan, Devesh; Yadav, Anita; Jaiswal, Anand
High proportion of TB in people living with HIV (PLHIV) is undiagnosed. Due to this active TB case finding is recommended for HIV clinics in high TB burden countries. Presently sputum examination and chest radiography are frontline tests recommended for HIV infected TB presumptives. Abdominal TB which occurs frequently in PLHIV may be missed even by existing programmatic intensified case finding protocols. This study evaluated the routine use of ultrasonography (USG) for active case finding of abdominal TB in HIV clinics. Retrospective analysis of eight years' data from an HIV Clinic in a TB hospital in India. Patients underwent chest x-ray, sputum examination, USG abdomen and routine blood tests at entry to HIV care. Case forms were scrutinized for diagnosis of TB, USG findings and CD4 cell counts. Abdominal TB was classified as probable or possible TB. Probable TB was based on presence of two major USG (abdomen) findings suggestive of active TB, or one major USG finding with at least two minor USG findings or at least two symptoms, or any USG finding with microbiologically confirmed active TB at another site. Possible TB was based on the presence of one major USG finding, or the presence of two minor USG findings with at least two symptoms. Bacteriological confirmation was not obtained. Eight hundred and eighty-nine people PLHIV underwent a baseline USG abdomen. One hundred and thirteen of 340 cases already diagnosed with TB and 87 of the 91 newly diagnosed with TB at time of HIV clinic registration had abdominal TB. Non-abdominal symptoms like weight loss, fever and cough were seen in 53% and 22% cases had no symptoms at all. Enlarged abdominal lymph nodes with central caseation, ascitis, splenic microabsesses, bowel thickening and hepatosplenomegaly were the USG findings in these cases. Abdominal TB is a frequent TB site in PLHIV presenting with non-abdominal symptoms. It can be easily detected on basis of features seen on a simple abdominal ultrasound
Eggerth, Donald E; Keller, Brenna M; Flynn, Michael A
Persons born outside the United States are more likely to be diagnosed with tuberculosis disease (TB) than native-born individuals. Foreign-born Latinos at risk of TB may be difficult to reach with public health interventions due to cultural and institutional barriers. Workplaces employing large concentrations of foreign-born Latinos may be useful locations for TB interventions targeting this high-risk population. This study used a two-phase approach to investigate the feasibility of workplace TB interventions. The first phase investigated employer knowledge of TB and receptiveness to allowing TB interventions in their businesses through 5 structured interviews. The second phase investigated foreign-born workers' knowledge of TB and their receptiveness to receiving TB interventions in their places of employment through 12 focus groups stratified by gender and education. Phase 1: Only 1 of the 5 employers interviewed had a high level of knowledge about TB, and three had no knowledge other than that TB was a disease that involved coughing. They were receptive to workplace TB interventions, but were concerned about lost productivity and customers finding out if an employee had TB. Phase 2: There was no observed differences in responses between gender and between the bottom two education groups, so the final analysis took place between a gender-combined lower education group and higher education group. The higher education group tended to have knowledge that was more accurate and to view TB as a disease associated with poverty. The lower education group tended to have more misconceptions about TB and more often expressed concern that their employers would not support worksite interventions. The results from both phases indicate that more TB education is needed among both foreign-born Latino workers and their employers. Obstacles to implementing workplace TB interventions include knowledge, potential productivity loss, employer liability, and perceived customer response
Tuberculosis (TB) in animals and humans may result from exposure to bacilli within the Mycobacterium tuberculosis complex (i.e., M. tuberculosis, M. bovis, M. africanum, M. pinnipedii, M. microti, M. caprae, or M. canetti). Mycobacterium bovis is the species most often isolated from tuberculous catt...
Tuberculosis (TB) in animals and humans may result from exposure to bacilli within the Mycobacterium tuberculosis complex (i.e., M. tuberculosis, M. bovis, M. africanum, M. pinnipedii, M. microti, M. caprae, or M. canetti) . Mycobacterium bovis is the species most often isolated from tuberculous cat...
Whittaker, Elizabeth; Kampmann, Beate
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.
Kwon, Hyuk-Sang; Kim, Sang-Il; Yoo, Soon-Jib; Yoon, Kun-Ho; Lee, Kwang-Woo; Kang, Moon-Won; Son, Ho-Young; Kang, Sung-Koo; Cha, Bong-Yun
Cushing's disease is a disorder of hypercortisolism caused by a pituitary micro- or macro-adenoma. Most patients with Cushing's disease have a bilateral adrenal enlargement, which depends on the duration of the disease, as a result of the long standing ACTH stimulation of both adrenal glands. However, in macronodular adrenocortical hyperplasia (MNH) that is caused by Cushing's disease, if the MNH gains autonomy, a bilateral adrenalectomy, as well as the removal of pituitary adenoma, is often essential. We encountered a patient diagnosed with Cushing's disease with bilateral adrenal tuberculosis simulating MNH. She had taken anti-tuberculosis medications one year prior to admission due to spinal tuberculosis. Sellar MRI revealed a pituitary macroadenoma, but adrenal CT showed enlargement in both adrenal glands that appeared to be MNH. A hormonal study and bilateral inferior petrosal sinus sampling revealed Cushing's disease. Therefore, she underwent trans-sphenoidal surgery of the pituitary mass. The pituitary surgery was successful and the serum cortisol returned to normal range. However, the adrenal mass rapidly enlarged after removing the pituitary tumor without showing evidence of a recurrence or adrenal autonomy of hypercortisolism. Accordingly, a laparoscopic left adrenalectomy was performed to examine the nature of the mass. The resected left adrenal gland was pathologically determined to have a lesion of tuberculosis with some part of the intact cortex. So we assumed that the cause of rapid adrenal enlargement might be due to adrenal tuberculosis. In summary, to the best of our knowledge, this is the first case of Cushing's disease coexisting with both adrenal tuberculosis simulating a bilateral MNH.
Nemoto, Kenji; Oh-ishi, Shuji; Taguchi, Masato; Hyodo, Kentaro; Kanazawa, Jun; Miura, Yukiko; Takaku, Takio; Usui, Shingo; Hayashihara, Kenji; Saito, Takefumi
T-SPOT.TB (T-SPOT), an interferon-gamma release assay, has shown promise as a diagnostic tool for active tuberculosis (TB), and its use is expanding. Addition of the T-Cell Xtend (TCX) reagent may allow delayed processing, and this characteristic is important for using this test in the field. However, limited data is available on the usefulness of T-SPOT with TCX as a field test for diagnosing active TB. To investigate the clinical utility of T-SPOT with TCX and the risk factors for a false-negative result in patients with active TB. A total of 57 patients with active TB who underwent the T-SPOT test with TCX prior to treatment were enrolled between May 2013 and May 2015. One patient with an indeterminate result for T-SPOT was excluded; therefore, the data of 56 patients were eventually included in the final analysis. The basic characteristics and clinical findings were compared between the true-positive and false-negative T-SPOT groups. Of the 56 patients, 40 (71.4%), 13 (23.2%), 3 (5.4%) had true-positive, false-negative, and borderline T-SPOT results, respectively. This study did not reveal any significant risk factors for a false-negative T-SPOT result. In this clinical study, the proportion of patients with a false-negative result for T-SPOT with TCX for active TB was higher than that reported previously. Therefore, careful interpretation of a negative result for T-SPOT with TCX is necessary, regardless of the patient's background.
Muniyandi, Malaisamy; Ramachandran, Rajeswari
India accounts for 25% of the global burden of MDR-TB. In 2016, the India's Revised National TB Control Programme reported a success rate of 46% among 19,298 MDR-TB patients treated under the programme. This suboptimal treatment outcome warrants an urgent need for newer drugs and newer regimens in the treatment of MDR-TB. India requires new shorter, cheap, safe and effective anti-TB regimen to treat MDR-TB. Areas covered: We used different search strategies to obtain relevant literature from PubMed, on Indian experiences of developing therapies for the treatment of MDR-TB. Further information from the Central TB Division Government of India on programmatic management of resistant TB was collected. Expert opinion: In 2016 WHO recommended a shorter MDR-TB regimen of 9-12 months (4-6 Km-Mfx-Pto-Cfz-Z-Hhigh-dose-E /5 Mfx-Cfz-Z-E) may be used instead of longer regimens. Currently, conducting trials involving newer drugs such as bedaquiline, have been proposed. The regimen will be of a shorter duration containing isoniazid, prothionamide, bedaquiline, levofloxacin, ciprofloxacin, ethambutol and pyrazinamide (STREAM regimen). To successfully treat MDR-TB one requires new classes of antibiotic and newer diagnostic tests. This represents an enormous financial and technical challenge to the programme managers and policy makers.
Sinanovic, Edina; Kumaranayake, Lilani
To explore the economic costs and sources of financing for different public-private partnership (PPP) arrangements to tuberculosis (TB) provision involving both workplace and non-profit private providers in South Africa. The financing required for the different models from the perspective of the provincial TB programme, provider, and the patient are considered. Two models of TB provider partnerships were evaluated, relative to sole public provision: public-private workplace (PWP) and public-private non-government (PNP). The cost analysis was undertaken from a societal perspective. Costs were collected retrospectively to consider both the financial and economic costs. Patient costs were estimated using a retrospective structured patient interview. Expansion of PPPs could potentially lead to reduced government sector financing requirements for new patients: government financing would require $609-690 per new patient treated in the purely public model, in contrast to PNP sites which would only need to $130-139 per patient and $36-46 with the PWP model. Moreover, there are no patient costs associated with the treatment in the employer-based facilities and the cost to the patient supervised in the community is, on average, three times lower than in public sector facilities. The results suggest that there is a strong economic case for expanding PPP involvement in TB treatment in the process of scaling up. The cost to the government per new patient treated could be reduced by enhanced partnership between the private and public sectors.
Lee, Jung Nam; Ryu, Dong Yup; Park, Sung Han; You, Hyun Seok; Lee, Bong Eun; Kim, Dong Uk; Kim, Tae Oh; Heo, Jeong; Kim, Gwang Ha; Song, Geun Am; Kim, Suk; Park, Do Youn
It is difficult to clinically and endoscopically differentiate intestinal tuberculosis (ITB) and Crohns disease (CD). The aim of this study was to evaluate the usefulness of in vitro interferon-gamma (INF-gamma) assay for differential diagnosis between ITB and CD. Sixty patients for whom differential diagnosis between ITB and CD was difficult were enrolled between January 2007 and January 2009. The INF-gamma-producing T-cell response to early secreted antigenic target 6 and culture filtrate protein 10 were measured by T-SPOT.TB blood test in vitro. We evaluated the usefulness of T-SPOT.TB blood test by comparing its results with the final diagnosis. Twenty and forty patients were revealed to be positive and negative in T-SPOT.TB blood test, respectively. Of the 20 patients found to be positive, 12 patients (60%) were finally diagnosed as ITB, 6 patients as CD, and 2 patients as Behcets enterocolitis. Of the 40 patients with negative results, 38 patients (95%) were diagnosed as CD; one as Behcets enterocolitis; one as nonspecific colitis; none as ITB. The sensitivity and specificity of T-SPOT.TB blood test for ITB were 100% and 83.3%, respectively. Positive and negative predictive values of T-SPOT.TB blood test for ITB were 60.0% and 100%, respectively. When differential diagnosis between ITB and CD is difficult, T-SPOT.TB blood test may be a helpful and rapid diagnostic tool to exclude ITB. Prospective large-scaled studies are required for further evaluation of the usefulness of T-SPOT.TB blood test for differential diagnosis between ITB and CD.
Gong, Wenping; Liang, Yan; Wu, Xueqiong
Mycobacterium tuberculosis complex causes tuberculosis (TB), one of the top 10 causes of death worldwide. TB results in more fatalities than multi-drug resistant (MDR) HIV strain related coinfection. Vaccines play a key role in the prevention and control of infectious diseases. Unfortunately, the only licensed preventive vaccine against TB, bacilli Calmette-Guérin (BCG), is ineffective for prevention of pulmonary TB in adults. Therefore, it is very important to develop novel vaccines for TB prevention and control. This literature review provides an overview of the innate and adaptive immune response during M. tuberculosis infection, and presents current developments and challenges to novel TB vaccines. A comprehensive understanding of vaccines in preclinical and clinical studies provides extensive insight for the development of safer and more efficient vaccines, and may inspire new ideas for TB prevention and treatment.
Thakur, Harshad P
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.
Safety and efficacy of the C-Tb skin test to diagnose Mycobacterium tuberculosis infection, compared with an interferon γ release assay and the tuberculin skin test: a phase 3, double-blind, randomised, controlled trial.
Ruhwald, Morten; Aggerbeck, Henrik; Gallardo, Rafael Vázquez; Hoff, Søren T; Villate, José I; Borregaard, Bettine; Martinez, José A; Kromann, Ingrid; Penas, Antón; Anibarro, Luis L; de Souza-Galvão, Maria Luiza; Sánchez, Francisca; Rodrigo-Pendás, Jose Ángel; Noguera-Julian, Antoni; Martínez-Lacasa, Xavier; Tuñez, Maria Victoria; Fernández, Virginia Leiro; Millet, Joan P; Moreno, Antonio; Cobos, Nazaret; Miró, José M; Roldan, Llanos; Orcau, Angels; Andersen, Peter; Caylá, Joan A
Targeted screening and treatment of Mycobacterium tuberculosis infection substantially reduces the risk of developing active tuberculosis. C-Tb (Statens Serum Institute, Copenhagen, Denmark) is a novel specific skin test based on ESAT-6 and CFP10 antigens. We investigated the safety and diagnostic potential of C-Tb compared with established tests in the contact-tracing setting. Negative controls, close contacts, occasional contacts, and patients with active pulmonary tuberculosis were enrolled at 13 centres in Spain. We compared C-Tb with the QuantiFERON-TB Gold In-Tube ([QFT] Qiagen, Hilden, Germany) interferon γ release assay (IGRA) and the purified protein derivative (PPD) RT 23 tuberculin skin test ([TST] Statens Serum Institute). All participants older than 5 years were tested with QFT. Some participants in the negative control group received C-Tb without the TST to test for potential interactions between C-Tb and PPD RT 23. The rest were randomly assigned in blocks of ten and tested with both C-Tb and TST, with five in each block receiving injection of C-Tb in the right arm and the TST in the left arm and five vice versa. The primary and safety analyses were done in all participants randomly assigned to a group who received any test. This trial is registered with ClinicalTrials.gov, number NCT01631266, and with EudraCT, number 2011-005617-36. From July 24, 2012, to Oct 2, 2014, 979 participants were enrolled, of whom 263 were negative controls, 299 were occasional contacts, 316 were close contacts, and 101 were patients with tuberculosis. 970 (99%) participants completed the trial. Induration sizes were similar for C-Tb and TST, but TST positivity was affected by BCG vaccination status. We found a strong positive trend towards C-Tb test positivity with increasing risk of infection, from 3% in negative controls to 16% in occasional contacts, to 43% in close contacts. C-Tb and QFT results were concordant in 785 (94%) of 834 participants aged 5 years and older
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
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
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
Reichler, Mary R; Khan, Awal; Sterling, Timothy R; Zhao, Hui; Moran, Joyce; McAuley, James; Bessler, Patricia; Mangura, Bonita
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.
Natale, Jo Anna
The reemergence of tuberculosis, particularly of new drug-resistant strains, points up the need for well-coordinated school health programs. Immigration effects, growing populations of HIV-infected persons, and relaxed screening procedures are partly responsible for TB's reemergence. Two sidebars offer advice on coping with TB at school and…
Bunyasi, Erick Wekesa; Tameris, Michele; Geldenhuys, Hennie; Schmidt, Bey-Marrie; Luabeya, Angelique Kany Kany; Mulenga, Humphrey; Scriba, Thomas J; Hanekom, Willem A; Mahomed, Hassan; McShane, Helen; Hatherill, Mark
Diagnosis of childhood tuberculosis is limited by the paucibacillary respiratory samples obtained from young children with pulmonary disease. We aimed to compare accuracy of the Xpert® MTB/RIF assay, an automated nucleic acid amplification test, between induced sputum and gastric lavage samples from young children in a tuberculosis endemic setting. We analyzed standardized diagnostic data from HIV negative children younger than four years of age who were investigated for tuberculosis disease near Cape Town, South Africa [2009-2012]. Two paired, consecutive induced sputa and early morning gastric lavage samples were obtained from children with suspected tuberculosis. Samples underwent Mycobacterial Growth Indicator Tube [MGIT] culture and Xpert MTB/RIF assay. We compared diagnostic yield across samples using the two-sample test of proportions and McNemar's χ2 test; and Wilson's score method to calculate sensitivity and specificity. 1,020 children were evaluated for tuberculosis during 1,214 admission episodes. Not all children had 4 samples collected. 57 of 4,463[1.3%] and 26 of 4,606[0.6%] samples tested positive for Mycobacterium tuberculosis on MGIT culture and Xpert MTB/RIF assay respectively. 27 of 2,198[1.2%] and 40 of 2,183[1.8%] samples tested positive [on either Xpert MTB/RIF assay or MGIT culture] on induced sputum and gastric lavage samples, respectively. 19/1,028[1.8%] and 33/1,017[3.2%] admission episodes yielded a positive MGIT culture or Xpert MTB/RIF assay from induced sputum and gastric lavage, respectively. Sensitivity of Xpert MTB/RIF assay was 8/30[26.7%; 95% CI: 14.2-44.4] for two induced sputum samples and 7/31[22.6%; 11.4-39.8] [p = 0.711] for two gastric lavage samples. Corresponding specificity was 893/893[100%;99.6-100] and 885/890[99.4%;98.7-99.8] respectively [p = 0.025]. Sensitivity of Xpert MTB/RIF assay was low, compared to MGIT culture, but diagnostic performance of Xpert MTB/RIF did not differ sufficiently between induced sputum
Mitrzyk, Beatriz Manzor
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.
Early and rapid detection of bovine tuberculosis (bTB) is critical to controlling the spread of this disease in cattle and other animals. In this study, we demonstrate the development of an immunoassay for the direct detection of the bovine bTB biomarker, lipomannan (LM) in serum using a waveguide-...
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
Background In Ethiopia, where HIV and tuberculosis (TB) are very common, little is known about the prejudice and misconceptions of rural communities towards People living with HIV/AIDS (PLHA) and TB. Methods We conducted a cross sectional study in Gilgel Gibe Field Research area (GGFRA) in southwest Ethiopia to assess the prejudice and misconceptions of rural and urban communities towards PLHA and TB. The study population consisted of 862 randomly selected adults in GGFRA. Data were collected by trained personnel using a pretested structured questionnaire. To triangulate the findings, 8 focus group discussions among women and men were done. Results Of the 862 selected study participants, 750(87%) accepted to be interviewed. The mean age of the respondents was 31.2 (SD ± 11.0). Of the total interviewed individuals, 58% of them were females. More than half of the respondents did not know the possibility of transmission of HIV from a mother to a child or by breast feeding. For fear of contagion of HIV, most people do not want to eat, drink, and share utensils or clothes with a person living with HIV/AIDS. A higher proportion of females [OR = 1.5, (95% CI: 1.0, 2.2)], non-literate individuals [OR = 2.3, (95%CI: 1.4, 3.6)], rural residents [OR = 3.8, (95%CI: 2.2, 6.6)], and individuals who had poor knowledge of HIV/AIDS [OR = 2.8, (95%CI: 1.8, 2.2)] were more likely to have high prejudice towards PLHA than respectively males, literates, urban residents and individuals with good knowledge. Exposure to cold air was implicated as a major cause of TB. Literates had a much better knowledge about the cause and methods of transmission and prevention of TB than non-literates. More than half of the individuals (56%) had high prejudice towards a patient with TB. A larger proportion of females [OR = 1.3, (95% CI: 1.0, 1.9)] and non-literate individuals [OR = 1.4, (95% CI: 1.1, 2.0)] had high prejudice towards patients with TB than males and literate individuals. Conclusion TB
Ndzi, Elvis Ndukong; Nkenfou, Celine Nguefeu; Gwom, Luc Christian; Fainguem, Nadine; Fokam, Joseph; Pefura, Yone
Tuberculosis (TB) is a re-emerging disease with the advent of human immunodeficiency virus/AIDS infections. Discovered in 1959, diagnosed by various approaches and treated with antibiotics, the treatment of TB infection still poses public health concerns. Many cases of resistance and cross-resistance are observed. Diagnosis by culture, which is considered as the standard method, takes too long (20-30days) and is not suitable for extrapulmonary TB. QuantiFERON test, which is an indirect immunoassay based on blood, was developed. Much hope was placed in this new approach because it is based on blood, and many research teams have used it. We discuss the results of these different research groups who have used QuantiFERON for diagnosis, prediction of disease progression, or monitoring patients during the treatment of TB. Articles published in PubMed and documents published on Google were searched with the keywords: diagnosis and TB and QuantiFERON; TB and QuantiFERON and therapeutic monitoring; interferon-γ release assay; disease progression. These articles were read and analyzed. The results were controversial with regards to using the QuantiFERON test for the diagnosis of TB according to the study population (ethnic group, bacillus Calmette-Guérin vaccine use) and according to the state of the immune system of the people studied (human immunodeficiency virus immunosuppression in cancer medication, hypertension). Also, research findings were controversial with regards to using QuantiFERON for monitoring TB patients on anti-TB medications. Also, the predictive positive value for the progression to TB among immigrant close contacts of both interferon-γ release assays was not better than that of the tuberculin skin test. The QuantiFERON has advantages and limitations depending on the type of population studied. Recommendations are made to improve the sensitivity and specificity and to differentiate between latent and active TB by adding other specific proteins in the
Lange, Christoph; Chesov, Dumitru; Heyckendorf, Jan; Leung, Chi C; Udwadia, Zarir; Dheda, Keertan
The emergence of antimicrobial resistance against Mycobacterium tuberculosis, the leading cause of mortality due to a single microbial pathogen worldwide, represents a growing threat to public health and economic growth. The global burden of multidrug-resistant tuberculosis (MDR-TB) has recently increased by an annual rate of more than 20%. According to the World Health Organization approximately only half of all patients treated for MDR-TB achieved a successful outcome. For many years, patients with drug-resistant tuberculosis (TB) have received standardized treatment regimens, thereby accelerating the development of MDR-TB through drug-specific resistance amplification. Comprehensive drug susceptibility testing (phenotypic and/or genotypic) is necessary to inform physicians about the best drugs to treat individual patients with tailor-made treatment regimens. Phenotypic drug resistance can now often, but with variable sensitivity, be predicted by molecular drug susceptibility testing based on whole genome sequencing, which in the future could become an affordable method for the guidance of treatment decisions, especially in high-burden/resource-limited settings. More recently, MDR-TB treatment outcomes have dramatically improved with the use of bedaquiline-based regimens. Ongoing clinical trials with novel and repurposed drugs will potentially further improve cure-rates, and may substantially decrease the duration of MDR-TB treatment necessary to achieve relapse-free cure. © 2018 Asian Pacific Society of Respirology.
Ji, Lei; Lou, Yong-Liang; Wu, Zhong-Xiu; Jiang, Jin-Qin; Fan, Xing-Li; Wang, Li-Fang; Liu, Xiao-Xiang; Du, Peng; Yan, Jie; Sun, Ai-Hua
Quick diagnosis of smear-negative pulmonary tuberculosis (TB) and extra-pulmonary TB are urgently needed in clinical diagnosis. Our research aims to investigate the usefulness of the interferon-γ release assay (IGRA) for the diagnosis of smear-negative pulmonary and extra-pulmonary TB. We performed TB antibody and TB-IGRA tests on 389 pulmonary TB patients (including 120 smear-positive pulmonary TB patients and 269 smear-negative pulmonary TB patients), 113 extra-pulmonary TB patients, 81 patients with other pulmonary diseases and 100 healthy controls. Blood samples for the TB-Ab test and the TB-IGRA were collected, processed, and interpreted according to the manufacturer's protocol. The detection ratio of smear-positive pulmonary TB patients and smear-negative pulmonary TB patients were 90.8% (109 of 120) and 89.6% (241 of 269), respectively. There was no statistically significant difference of its performance between these two sample sets (P > 0.05). The detection ratio of positive TB patients and extra-pulmonary TB patients were 90.0% (350 of 389) and 87.6% (99 of 113), respectively, which was not significantly different (P > 0.05). In this work, the total detection ratio using TB-IGRA was 89.4%, therefore TB-IGRA has diagnostic values in smear-negative pulmonary TB and extra-pulmonary TB diagnosis.
Yuen, C. M.; Rodriguez, C. A.; Keshavjee, S.
Background: The lack of published information about children with multidrug-resistant tuberculosis (MDR-TB) is an obstacle to efforts to advocate for better diagnostics and treatment. Objective: To describe the lack of recognition in the published literature of MDR-TB and extensively drug-resistant TB (XDR-TB) in children. Design: We conducted a systematic search of the literature published in countries that reported any MDR- or XDR-TB case by 2012 to identify MDR- or XDR-TB cases in adults and in children. Results: Of 184 countries and territories that reported any case of MDR-TB during 2005–2012, we identified adult MDR-TB cases in the published literature in 143 (78%) countries and pediatric MDR-TB cases in 78 (42%) countries. Of the 92 countries that reported any case of XDR-TB, we identified adult XDR-TB cases in the published literature in 55 (60%) countries and pediatric XDR-TB cases for 9 (10%) countries. Conclusion: The absence of publications documenting child MDR- and XDR-TB cases in settings where MDR- and XDR-TB in adults have been reported indicates both exclusion of childhood disease from the public discourse on drug-resistant TB and likely underdetection of sick children. Our results highlight a large-scale lack of awareness about children with MDR- and XDR-TB. PMID:26400601
Droz, Nina; De Lauzanne, Agathe; Holvoet, Laurent; Missud, Florence; Benkerrou, Malika; Brousse, Valentine; Odièvre, Marie-Hélène; Faye, Albert; Koehl, Berengere
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.
Kirenga, Bruce J; Ssengooba, Willy; Muwonge, Catherine; Nakiyingi, Lydia; Kyaligonza, Stephen; Kasozi, Samuel; Mugabe, Frank; Boeree, Martin; Joloba, Moses; Okwera, Alphonse
Slow decline in the incidence of tuberculosis (TB) has been observed in most high TB burden countries. Knowledge of the prevalence of different TB risk factors can help expand TB control strategies. However with the exception of Human Immunodeficiency Virus (HIV) the prevalence of the other TB risk factors are poorly studied in Uganda. We aimed to determine the prevalence of different TB risk factors and TB disease presentation among TB patients in Kampala Uganda. We assessed 365 adult TB patients and used descriptive statistics to summarize their socio-demographic, clinical, radiological, sputum mycobacteriology and TB risk factors (HIV, diabetes, TB contact, alcohol use, tobacco smoking, poverty and overcrowding) data. A total of 158 (43.3%) patients were male and the median age was 29 (IQR 28-30). Majority of the patients (89.2%) had pulmonary TB, 86.9% were new and 13.2% were retreatment. Wasting (i.e. body mass index of <18.5 kg/m(2)) was found in 38.5% of the patients and 63% presented with cough. Constitutional symptoms (fever, anorexia, night sweats and weight loss) were reported by 32.1%. Most patients (78.6%) presented with non-cavity lung parenchyma disease (infiltrates, nodules, masses) but 35.2% had cavity disease. Pleural disease was detected in 19.3% of patients. Positive smear microscopy and culture (irrespective of month of treatment) was found in 52.7% and 36.5% of patients respectively. Any drug resistance was detected in 21.1% of patients while multidrug resistance (MDR) TB defined as resistance to rifampicin and isoniazid was detected in 6.3% of patients. All MDR patients were new patients. The prevalence of TB risk factors were as follows: HIV 41.4%, diabetes 5.4%, close contact 11.5%, family history 17.5%, smoking 26.37%, poverty 39.5%, overcrowding 57.3% and alcohol use 50.7%. Overcrowding increased smear positive rate, prevalence ratio 1.22, p = 0.09 but all the other studied risk factors did not affect clinical, radiological and
Gallegos Morales, Elia Noemi; Knierer, Johannes; Schablon, Anja; Nienhaus, Albert; Kersten, Jan Felix
The tuberculosis (TB) incidence rate in foreign-born individuals has been increasing in Germany in recent years. Foreign students may be an important source of latent tuberculosis infection (LTBI) in low-incidence countries. In Germany, there are no guidelines for LTBI screening of foreign students. The aim of the study was to estimate LTBI prevalence and evaluate associated risk factors among foreign students in Germany. The second purpose of our study was to compare the results of the new generation of QuantiFERON-TB Gold Plus (QFT-Plus) to those of its predecessor QuantiFERON-TB Gold In-Tube (QFT-GIT). This cross - sectional study was conducted between February 2016 and March 2016. Foreign students and young professionals attending the university and higher education institutes in Lübeck, Germany were tested with QFT-Plus and QFT-GIT. Participants filled out a questionnaire for the purpose of LTBI risk assessment and analysis. Variables associated with a positive test result were analyzed using logistic regression. One hundred thirty four students participated in the study. The overall prevalence as regards positive results from both tests, QFT-Plus and QFT-GIT, was 9.7%, and the prevalence of positive QFT-Plus results was 8.2%. The main independent variables associated with a positive QFT-Plus result were a) being born in a high-incidence country (OR = 6.7, 95% CI: 1.3-34.3) and b) previous contact with a person with active TB (OR = 4.5, 95% CI: 1.1-18.3). Higher age (OR = 2.8, 95% CI: 0.7-11.3) and male gender (OR = 1.6, 95% CI: 0.4-6.7) showed a tendency toward positive QFT-Plus results but this was not statistically significant. Agreement between QFT-Plus and QFT-GIT results was κ = 0.85, p < 0.001. The LTBI prevalence among foreign students was about 10%. We recommend implementing a policy whereby all foreign students are screened by means of a questionnaire about LTBI risk factors, so that only students with present risk factors are tested
Yari, Shamsi; Hadizadeh Tasbiti, Alireza; Ghanei, Mostafa; Shokrgozar, Mohammad Ali; Fateh, Abolfazl; Mahdian, Reza; Yari, Fatemeh; Bahrmand, Ahmadreza
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.
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
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.
Pitabut, Nada; Sakurada, Shinsaku; Tanaka, Takahiro; Ridruechai, Chutharut; Tanuma, Junko; Aoki, Takahiro; Kantipong, Pacharee; Piyaworawong, Surachai; Kobayashi, Nobuyuki; Dhepakson, Panadda; Yanai, Hideki; Yamada, Norio; Oka, Shinichi; Okada, Masaji; Khusmith, Srisin; Keicho, Naoto
Background: Host effector mechanism against Mycobacterium tuberculosis (Mtb) infection is dependent on innate immune response by macrophages and neutrophils and the alterations in balanced adaptive immunity. Coordinated release of cytolytic effector molecules from NK cells and effector T cells and the subsequent granule-associated killing of infected cells have been documented; however, their role in clinical tuberculosis (TB) is still controversy. Objective: To investigate whether circulating granulysin and other effector molecules are associated with the number of NK cells, iNKT cells, Vγ9+Vδ2+ T cells, CD4+ T cells and CD8+ T cells, and such association influences the clinical outcome of the disease in patients with pulmonary TB and HIV/TB coinfection. Methods: Circulating granulysin, perforin, granzyme-B and IFN-γ levels were determined by ELISA. The isoforms of granulysin were analyzed by Western blot analysis. The effector cells were analyzed by flow cytometry. Results: Circulating granulysin and perforin levels in TB patients were lower than healthy controls, whereas the granulysin levels in HIV/TB coinfection were much higher than in any other groups, TB and HIV with or without receiving HAART, which corresponded to the number of CD8+ T cells which kept high, but not with NK cells and other possible cellular sources of granulysin. In addition, the 17kDa, 15kDa and 9kDa isoforms of granulysin were recognized in plasma of HIV/TB coinfection. Increased granulysin and decreased IFN-γ levels in HIV/TB coinfection and TB after completion of anti-TB therapy were observed. Conclusion: The results suggested that the alteration of circulating granulysin has potential function in host immune response against TB and HIV/TB coinfection. This is the first demonstration so far of granulysin in HIV/TB coinfection. PMID:23801887
Nainggolan, Jonner; Suparwati, Titik; Kawuwung, Westy B.
A tuberculosis model which incorporates treatment interruptions of infectives is established. Optimal control of individuals infected with active TB is given in the model. It is obtained that the control reproduction numbers is smaller than the reproduction number, this means treatment controls could optimize the decrease in the spread of active TB. For this model, controls on treatment of infection individuals to reduce the actively infected individual populations, by application the Pontryagins Maximum Principle for optimal control. The result further emphasized the importance of controlling disease relapse in reducing the number of actively infected and treatment interruptions individuals with tuberculosis.
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.
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
Kwedi Nolna, S; Kammogne, I D; Ndzinga, R; Afanda, B; Ntonè, R; Boum, Y; Nolna, D
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.
Lírio, Monique; dos Santos, Normeide Pedreira; Passos, Louran Andrade Reis; Kritski, Afrânio; Galvão-Castro, Bernardo; Grassi, Maria Fernanda Rios
The control of HIV / Tuberculosis (TB) co -infection remains a challenge for public health. Notification is mandatory for both diseases and the National Case Registry Database (Sinan) is responsible for the collection and processing of individual forms of reporting and monitoring. The adequate fulfillment of these fields chips (completeness) is essential to follow the dynamics of the disease and set priorities for intervention. The aim of this study was to evaluate the completeness of the notification forms of tuberculosis in the priority municipalities of Bahia (Camaçari , Feira de Santana , Ilhéus , Itabuna, Jequié, Lauro de Freitas , Porto Seguro , Teixeira de Freitas , Paulo Afonso, Barreiras and Salvador) to control the disease in individuals with HIV/AIDS using tabulations obtained from the Sinan in the period from 2001 to 2010. The results showed that despite the completeness of the field HIV be above 50 %, more than half the cases were met as "undone" or "being processed" in all municipalities assessed in the period. The low completeness of reporting forms may compromise the quality of surveillance of TB cases. The results suggest the need for greater availability of HIV testing in these individuals.
This is a qualitative study of the politics of public health surrounding a resurgent tuberculosis epidemic in Lima, Peru during the 1990s. The paper traces the role of debt and neoliberal economics in creating conditions for the epidemic, and the reforms that turned Peru's TB program into a model for treating drug-susceptible disease by 1996. Despite this success, public health officials were blind-sided by the appearance of drug-resistant TB in the late 1990s when their "good" program turned out to be not good enough. The study follows the conflict, and eventual collaboration, that ensued between the Ministry of Health and a local NGO affiliated with Boston-based Partners in Health, which undertook a radical program of community-based directly-observed therapy (DOTS-Plus) to treat drug-resistant patients who otherwise would have died. Lessons from this case are relevant to many international settings where "hot-spots" of drug-resistant TB currently exist and go untreated, posing a threat to the success of national TB control programs.
Baussano, Iacopo; Williams, Brian G; Nunn, Paul; Beggiato, Marta; Fedeli, Ugo; Scano, Fabio
Transmission of tuberculosis (TB) in prisons has been reported worldwide to be much higher than that reported for the corresponding general population. A systematic review has been performed to assess the risk of incident latent tuberculosis infection (LTBI) and TB disease in prisons, as compared to the incidence in the corresponding local general population, and to estimate the fraction of TB in the general population attributable (PAF%) to transmission within prisons. Primary peer-reviewed studies have been searched to assess the incidence of LTBI and/or TB within prisons published until June 2010; both inmates and prison staff were considered. Studies, which were independently screened by two reviewers, were eligible for inclusion if they reported the incidence of LTBI and TB disease in prisons. Available data were collected from 23 studies out of 582 potentially relevant unique citations. Five studies from the US and one from Brazil were available to assess the incidence of LTBI in prisons, while 19 studies were available to assess the incidence of TB. The median estimated annual incidence rate ratio (IRR) for LTBI and TB were 26.4 (interquartile range [IQR]: 13.0-61.8) and 23.0 (IQR: 11.7-36.1), respectively. The median estimated fraction (PAF%) of tuberculosis in the general population attributable to the exposure in prisons for TB was 8.5% (IQR: 1.9%-17.9%) and 6.3% (IQR: 2.7%-17.2%) in high- and middle/low-income countries, respectively. The very high IRR and the substantial population attributable fraction show that much better TB control in prisons could potentially protect prisoners and staff from within-prison spread of TB and would significantly reduce the national burden of TB. Future studies should measure the impact of the conditions in prisons on TB transmission and assess the population attributable risk of prison-to-community spread. Please see later in the article for the Editors' Summary.
Wingfield, Tom; Tovar, Marco A; Huff, Doug; Boccia, Delia; Saunders, Matthew J; Datta, Sumona; Montoya, Rosario; Ramos, Eric; Lewis, James J; Gilman, Robert H; Evans, Carlton
Poverty drives tuberculosis (TB) rates but the approach to TB control has been disproportionately biomedical. In 2015, the World Health Organization's End TB Strategy explicitly identified the need to address the social determinants of TB through socio-economic interventions. However, evidence concerning poverty reduction and cost mitigation strategies is limited. The research described in this article, based on the 2016 Royal College of Physicians Linacre Lecture, aimed to address this knowledge gap. The research was divided into two phases: the first phase was an analysis of a cohort study identifying TB-related costs of TB-affected households and creating a clinically relevant threshold above which those costs became catastrophic; the second was the design, implementation and evaluation of a household randomised controlled evaluation of socio-economic support to improve access to preventive therapy, increase TB cure, and mitigate the effects of catastrophic costs. The first phase showed TB remains a disease of people living in poverty - 'free' TB care was unaffordable for impoverished TB-affected households and incurring catastrophic costs was associated with as many adverse TB treatment outcomes (including death, failure of treatment, lost to follow-up and TB recurrence) as multidrug resistant (MDR) TB. The second phase showed that, in TB-affected households receiving socio-economic support, household contacts were more likely to start and adhere to TB preventive therapy, TB patients were more likely to be cured and households were less likely to incur catastrophic costs. In impoverished Peruvian shantytowns, poverty remains inextricably linked with TB and incurring catastrophic costs predicted adverse TB treatment outcome. A novel socio-economic support intervention increased TB preventive therapy uptake, improved TB treatment success and reduced catastrophic costs. The impact of the intervention on TB control is currently being evaluated by the Community
Orikiriza, Patrick; Nansumba, Margaret; Nyehangane, Dan; Bastard, Mathieu; Mugisha, Ivan Taremwa; Nansera, Denis; Mwanga-Amumpaire, Juliet; Boum, Yap; Kumbakumba, Elias; Bonnet, Maryline
The Xpert MTB/RIF assay is a major advance for diagnosis of tuberculosis (TB) in high-burden countries but is limited in children by their difficulty to produce sputum. We investigated TB in sputum and stool from children with the aim of improving paediatric TB diagnosis. A prospective cohort of children with presumptive TB, provided two sputum or induced sputum at enrolment in a regional referral hospital in Uganda. Stool was collected from those started on TB treatment. All specimen were tested for Xpert MTB/RIF, mycobacteria growth indicator tube (MGIT), Lowenstein Jensen cultures and microscopy (except stool). We compared TB detection between age categories and assessed the performance of Xpert MTB/RIF in sputum and stool. Of the 392 children enrolled, 357 (91.1%) produced at least one sputum sample. Sputum culture yield was 13/357 (3.6%): 3/109 (2.6%), 3/89 (3.2%), 3/101 (2.6%) and 4/44 (8.2%) among children of < 2, 2-5, ≥ 5-10 and > 10 years, respectively (p = 0.599). Xpert MTB/RIF yield was 14/350 (4.0%): 3/104 (2.9%), 4/92 (4.3%), 3/88 (2.9%) and 4/50 (.0%), respectively (p = 0.283). Sensitivity and specificity of Xpert MTB/RIF in sputum against sputum culture were 90.9% (95% CI 58.7-99.8) and 99.1% (99.1-99.8). In stool, it was 55.6% (21.2-86.3) and 98.2% (98.2-100) against Xpert MTB/RIF and culture in sputum. Only a minority of children had microbiologically confirmed TB with a higher proportion in children above 10 years. Although sensitivity of Xpert MTB/RIF in stool was low, with good optimization, it might be a good alternative to sputum in children.
The dormant cells of Mycobacterium tuberculosis may be resuscitated by targeting-expression system of recombinant mycobacteriophage-Rpf: implication of shorter course of TB chemotherapy in the future.
Gan, Yiling; Yao, Yiyong; Guo, Shuliang
Here we hypothesized that dormant cells of Mycobacterium tuberculosis (M. tuberculosis) may be resuscitated by a new expression system of recombinant mycobacteriophage-resuscitation-promoting factor (Rpf). In this system, gene of targeted Rpf was cloned into mycobacteriophage genome, since mycobacteriophages possess several characteristics, including automatic identification and specific infection of M. tuberculosis. Thus the targeted delivery and endogenous expression of Rpf to the infected area of M. tuberculosis can be realized, followed by resuscitating the dormant cells of M. tuberculosis. Finally, these resuscitated M. tuberculosis can be thoroughly killed by a strong short-term subsequent chemotherapy, which makes the course of TB chemotherapy much shorter in the future compared to simple chemotherapy. Early studies have confirmed that dormant cells of M. tuberculosis can be resuscitated by Rpf in vitro, but so far, there is no report that Rpf can succeed in resuscitating dormant cells of M. tuberculosis in vivo, the reason may be that it is difficult for purified Rpf to remain active in vivo, especially to achieve targeted delivery of exogenous Rpf to the infected area of dormant cells of M. tuberculosis. Mycobacteriophage is a virus, capable of specifically identifying and infecting mycobacterium, such as M. tuberculosis. Several studies show that motif 3-containing proteins have peptidoglycan-hydrolysing activity and that while this activity is not required for mycobacteriophage viability, it facilitates efficient infection and DNA injection of mycobacteriophage (including motif 3 protein) into stationary phase cells. Thus this expression system can achieve targeted delivery and endogenous expression of Rpf to infected area of dormant cells of M. tuberculosis. Finally, we discuss the implication of this recombinant expression system for shortening the course of TB chemotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.
Khan, Mishal S; Schwanke-Khilji, Sara; Yoong, Joanne; Tun, Zaw Myo; Watson, Samantha; Coker, Richard James
There are numerous challenges in planning and implementing effective disease control programmes in Myanmar, which is undergoing internal political and economic transformations whilst experiencing massive inflows of external funding. The objective of our study-involving key informant discussions, participant observations and linked literature reviews-was to analyse how tuberculosis (TB) control strategies in Myanmar are influenced by the broader political, economic, epidemiological and health systems context using the Systemic Rapid Assessment conceptual and analytical framework. Our findings indicate that the substantial influx of donor funding, in the order of one billion dollars over a 5-year period, may be too rapid for the country's infrastructure to effectively utilize. TB control strategies thus far have tended to favour medical or technological approaches rather than infrastructure development, and appear to be driven more by perceived urgency to 'do something' rather informed by evidence of cost-effectiveness and sustainable long-term impact. Progress has been made towards ambitious targets for scaling up treatment of drug-resistant TB, although there are concerns about ensuring quality of care. We also find substantial disparities in health and funding allocation between regions and ethnic groups, which are related to the political context and health system infrastructure. Our situational assessment of emerging TB control strategies in this transitioning health system indicates that large investments by international donors may be pushing Myanmar to scale up TB and drug-resistant TB services too quickly, without due consideration given to the health system (service delivery infrastructure, human resource capacity, quality of care, equity) and epidemiological (evidence of effectiveness of interventions, prevention of new cases) context. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical
Kang, Wanli; Wu, Meiying; Yang, Kunyun; Ertai, A; Wu, Shucai; Geng, Shujun; Li, Zhihui; Li, Mingwu; Pang, Yu; Tang, Shenjie
We compared the positive rates of T-SPOT.TB and bacterial culture in the smear-negative PTB, and analyzed the factors affecting the results of negative T-SPOT.TB and bacterial culture. Retrospective evaluation of data from smear-negative PTB patients who underwent T-SPOT.TB and bacterial culture were done. The agreement and concordance were analyzed between T-SPOT.TB and bacterial culture. Multivariable logistic regression analysis was used to explore the factors associated with positive results of T-SPOT.TB and bacterial culture in smear-negative PTB. 858 eligible smear-negative PTB patients were included in the study. The agreement rate was 25.6% (22.7~28.5%) between T-SPOT.TB and bacterial culture in smear- negative PTB patients. The positive rate of T-SPOT.TB was higher than that of bacterial culture in smear-negative PTB patients (p < 0.001). There were nearly no concordance between T-SPOT.TB and bacterial culture (p > 0.05). Using multivariable logistic regression analysis we found that older age ≥ 60 years (OR = 0.469, 95% CI: 0.287-0.768) and decreased albumin (OR = 0.614, 95% CI: 0.380-0.992) were associated with negative diagnostic results of T-SPOT.TB in smear-negative PTB patients. Female (OR = 0.654, 95% CI: 0.431-0.992) were associated with negative diagnostic results of bacteria culture in smear-negative PTB patients. Our results indicated that the older age and decreased albumin were independently associated with negative T-SPOT.TB responses.
Vallada, Marcelo Genofre; Okay, Thelma Suely; Del Negro, Gilda Maria B.; Antonio, Claudio Amaral; Yamamoto, Lidia; Ramos, Sonia Regina T. S.
Objective: To evaluate the accuracy of an interferongamma release assay (QuantiFERON-TB Gold in Tube) for diagnosing Mycobacterium tuberculosis infection in a young pediatric population. Methods: 195 children previously vaccinated with BCG were evaluated, being 184 healthy individuals with no clinical or epidemiological evidence of mycobacterial infection, and 11 with Mycobacterium tuberculosis infection, according to clinical, radiological, and laboratory parameters. A blood sample was obtained from each child and processed according to the manufacturer's instructions. The assay performance was evaluated by a Receiver Operating Characteristic (ROC) curve. Results: In the group of 184 non-infected children, 130 (70.6%) were under the age of four years (mean age of 35 months). In this group, 177 children (96.2%) had negative test results, six (3.2%) had indeterminate results, and one (0.5%) had a positive result. In the group of 11 infected children, the mean age was 58.5 months, and two of them (18%) had negative results. The ROC curve had an area under the curve of 0.88 (95%CI 0.82-0.92; p<0.001), disclosing a predictive positive value of 81.8% for the test (95%CI 46.3-97.4). The assay sensitivity was 81.8% (95%CI 48.2-97.2) and the specificity was 98.8% (95%CI 96-99.8). Conclusions: In the present study, the QuantiFERON-TB Gold in Tube performance for diagnosing M. tuberculosis infection was appropriate in a young pediatric population. PMID:24676183
Traoré, F A; Sako, F B; Sylla, D; Bangoura, M; Kpamy, D O; Traoré, M; Doumbouya, M; Sangare, I
Despite many efforts of prevention and the availability of free treatment, TB/HIV co-infection is still rampant in Guinea. The objective of this study was to describe the epidemiology of smear positive pulmonary tuberculosis according to HIV status among patients hospitalized in the infectious diseases department of Conakry University Hospital. This was a descriptive and analytical retrospective study of patient records admitted for pulmonary tuberculosis from January 2003 to December 2012. During this period, 1953 cases of tuberculosis were collected of which 346 (17.7%) were smear positive. There was a marked male predominance (59.7%). The average age was 38 ± 11 years. The majority of patients originated from the suburbs of Conakry and its surrounding prefectures (76.7%). People without profession were most represented (40.7%). A level of primary education was the most frequently reported (39.7%). Out of 325 patients tested for HIV, the serology was positive in 185 patients (56.9%). A contact with a TB patient was reported in 21.4% of HIV negative patients, and in 6.5% of the HIV-positive group (p = 0.0006). There was no difference between the two groups regarding clinical signs and symptoms. The mean CD4 count was comparable in both groups (p = 0.05). Lethality was higher among co-infected patients (30.4% against 15.56%; p = 0.00037). Strengthening the prevention of TB among PLWHA by the administration of isoniazide seems necessary and warrants further study on this subject in Guinea.
Hu, Yi; Mathema, Barun; Zhao, Qi; Zheng, Xubin; Li, Dange; Jiang, Weili; Wang, Weibing; Xu, Biao
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
Ozsoy, Sait; Demirel, Birol; Albay, Ali; Kisa, Ozgul; Dinc, Ahmet H; Safali, Mukerrem
According to the 2008 World Health Organization report, in 2006, 9.2 million new cases were determined, and 1.7 million people have lost their life due to tuberculosis (TB) in all around the world. In our country (Turkey), it is estimated that 35,000 to 40,000 people have TB disease annually. The Ministry of Health could just determine 18,500 of these cases, and only 6500 patient could be treated effectively. According to the Tuberculosis Dispensary records, the incidence for TB in Turkey is 28/100,000. It is aimed to determine the infection with Mycobacterium tuberculosis using acidoresistant bacilli microscopy, TB culture, and histopathological methods in tissue samples that were obtained from lungs of forensic cases whose autopsies had been performed in Council of Forensic Medicine Ankara Department Morgue Specialized Committee. A total of 3 tissue samples that were obtained from lungs of randomized 302 cases, were positive for TB in Löwenstein-Jensen medium. Granuloma with caseating necrosis was found in histopathological examination and acidoresistant (+) bacilli (1+, 2+, and 2+, respectively) in microscopically analysis were also demonstrated in this 3 tissue samples. For this reason, we think that autopsy workers have to be careful about tuberculosis during their autopsy working.
William, Timothy; Parameswaran, Uma; Lee, Wai Khew; Yeo, Tsin Wen; Anstey, Nicholas M; Ralph, Anna P
Tuberculosis (TB) is generally well controlled in Malaysia, but remains an important problem in the nation's eastern states. In order to better understand factors contributing to high TB rates in the eastern state of Sabah, our aims were to describe characteristics of patients with TB at a large outpatient clinic, and determine the prevalence of HIV co-infection. Additionally, we sought to test sensitivity and specificity of the locally-available point-of-care HIV test kits. We enrolled consenting adults with smear-positive pulmonary TB for a 2-year period at Luyang Clinic, Kota Kinabalu, Malaysia. Participants were questioned about ethnicity, smoking, prior TB, disease duration, symptoms and comorbidities. Chest radiographs were scored using a previously devised tool. HIV was tested after counselling using 2 point-of-care tests for each patient: the test routinely in use at the TB clinic (either Advanced Quality™ Rapid Anti-HIV 1&2, FACTS anti-HIV 1/2 RAPID or HIV (1 + 2) Antibody Colloidal Gold), and a comparator test (Abbott Determine™ HIV-1/2, Inverness Medical). Positive tests were confirmed by enzyme immunoassay (EIA), particle agglutination and line immunoassay. 176 participants were enrolled; 59 (33.5%) were non-Malaysians and 104 (59.1%) were male. Smoking rates were high (81/104 males, 77.9%), most had cavitary disease (51/145, 64.8%), and 81/176 (46.0%) had haemoptysis. The median period of symptoms prior to treatment onset was 8 weeks. Diabetes was present in 12. People with diabetes or other comorbidities had less severe TB, suggesting different healthcare seeking behaviours in this group. All participants consented to HIV testing: three (1.7%) were positive according to Determine™ and EIA, but one of these tested negative on the point-of-care test available at the clinic (Advanced Quality™ Rapid Anti-HIV 1&2). The low number of positive tests and changes in locally-available test type meant that accurate estimates of sensitivity and
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
Bahi, Gnogbo Alexis; Boyvin, Lydie; Méité, Souleymane; M'Boh, Gervais Melaine; Yeo, Kadjowely; N'Guessan, Kouassi Raymond; Bidié, Alain Dit Philippe; Djaman, Allico Joseph
In Côte d'Ivoire, multidrug-resistant tuberculosis (MDR-TB) is a serious public health problem with a prevalence estimated at 2.5% in 2006. Zinc and copper are essential Trace element needed to strengthen the immune system and also useful in the fight against tuberculosis. The Cu / Zn ratio is a good indicator of oxidative stress. The principal aim of this study was to evaluate the serum concentration of some trace element and determine the Cu / Zn ratio in patients with multidrug resistant pulmonary tuberculosis (MDR-TB) before and after second line treatment of TB. Blood samples were obtained from 100 MDR-TB patients after confirmation of their status through the microscopic and molecular diagnosis of resistance to Isoniazid and Rifampicin by GeneXpert. The concentration level of zinc and copper were determined using flame air / acetylene atomic absorption spectrometer (AAS) Type Varian Spectr AA-20 Victoria, Australlia. A significant decrease in zinc levels (P < 0.05) and an increased Cu / Zn ratio (P < 0.05) was observed in MDR-TB patients compared to controls TB free. During treatment a significant reduction in Cu / Zn ratio (P < 0.05) was observed compared to the initial result. The decrease in serum zinc level and the high Cu / Zn ratio could explain the immune system dysfunction and the high level of oxidative stress in patients with MDR-TB. Therefore the evaluation of the zinc and copper status could represent essential parameters in monitoring of TB second line treatment for better treatment management.
Tian, Yuan; Osgood, Nathaniel D.; Al-Azem, Assaad; Hoeppner, Vernon H.
Tuberculosis (TB) is a potentially fatal disease spread by an airborne pathogen infecting approximately one third of the globe. For decades, contact tracing (CT) has served a key role in the control of TB and many other notifiable communicable diseases. Unfortunately, CT is a labor-intensive and time-consuming process and is often conducted by a…
Hlavsa, Michele C; Moonan, Patrick K; Cowan, Lauren S; Navin, Thomas R; Kammerer, J Steve; Morlock, Glenn P; Crawford, Jack T; Lobue, Philip A
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
van Rensburg, Ilana C; Loxton, Andre G
Regulatory B cells (Bregs) have been shown to be present during several disease states. The phenotype of the cells is not completely defined and the function of these cells differ between disease. The presence of FASL expressing (killer) B cells during latent and successfully treated TB disease have been shown but whether these cells are similar to regulatory B cells remain unclear. We assessed the receptor expression of FASL/IL5 (killer B cells), CD24/CD38 (regulatory B cells) on whole peripheral blood of participants with untreated active TB and healthy controls. We then isolated B cells from a second cohort of M.tb exposed (Quantiferon (QFN) positive) and unexposed (Quantiferon negative) HIV negative participants, and evaluated the frequency of killer B cells induced following stimulation with BCG and/or CD40 and IL5. Our data reveal no difference in the expression on CD24 and CD38 between participants with active TB and the controls. There was also no difference in the frequency of regulatory B cells measured in the peripheral blood mononuclear cells (PBMC) fraction between latent TB and uninfected controls. We did however notice that regulatory B cells (CD24hiCD38hi) population express the FASL receptor. The expression of killer B cell phenotype (CD178+IL5RA+) was significantly higher in controls compared to those with active TB disease (1,06% vs 0,455%). Furthermore, we found that BCG restimulation significantly induced the FASL/IL5RA B cells but this was only evident in the QFN positive group. Our data suggest that both regulatory and killer B cells are present during latent and active TB disease but that the frequency of these populations are increased during latent disease. We also show that the FASL+IL5RA+ B killer B cells are induced in latent TB infection following BCG restimulation but whether these cells are indicative of protection remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.
Rahevar, Kalpeshsinh; Fujiwara, Paula I; Ahmadova, Shalala; Morishita, Fukushi; Reichman, Lee B
The End TB Strategy aims to end the global tuberculosis (TB) epidemic by 2035 in line with the sustainable development goals targets and has been implemented in the World Health Organization (WHO) Western Pacific Region since 2015. Significant progress has been made in implementing this strategy. However, several challenges still remain. In 2016, an estimated 1.8 million people developed TB in the region, and of these about 20% were missed by national TB programmes. The gap in diagnosis and enrolment as well as treatment completion is greater with drug-resistant TB. Many TB-affected families face catastrophic costs due to the disease. Sustaining financing for TB care is a long-term challenge in many countries. This article emphasizes targeted interventions in high-risk populations, including systematic screening and patient-centred TB care. Several other approaches including improving TB diagnostic tools and algorithm, and engaging all care providers are suggested to find missing TB patients. Drug-resistant TB requires additional resourcing for laboratories, enrolment and patient support. Specific measures are required at different levels to mitigate financial burden due to TB including linking TB to overall social protection schemes. The Moscow Ministerial conference in 2017 and upcoming United Nations (UN) 2018 high-level meeting provide an opportunity to raise TB higher on the global agenda, forge partnerships and move towards universal health coverage. © 2018 Asian Pacific Society of Respirology.
Simon, G G
The neglected tropical diseases (NTDs) are the most common infections of humans in Sub-Saharan Africa. Virtually all of the population living below the World Bank poverty figure is affected by one or more NTDs. New evidence indicates a high degree of geographic overlap between the highest-prevalence NTDs (soil-transmitted helminths, schistosomiasis, onchocerciasis, lymphatic filariasis, and trachoma) and malaria and HIV, exhibiting a high degree of co-infection. Recent research suggests that NTDs can affect HIV and AIDS, tuberculosis (TB), and malaria disease progression. A combination of immunological, epidemiological, and clinical factors can contribute to these interactions and add to a worsening prognosis for people affected by HIV/AIDS, TB, and malaria. Together these results point to the impacts of the highest-prevalence NTDs on the health outcomes of malaria, HIV/AIDS, and TB and present new opportunities to design innovative public health interventions and strategies for these 'big three' diseases. This analysis describes the current findings of research and what research is still needed to strengthen the knowledge base of the impacts NTDs have on the big three. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.
Carstensen, Michelle; DonCarlos, Michael W.
Bovine tuberculosis (bTB) has been found in 12 cattle operations and 27 free-ranging white-tailed deer (Odocoileus virginianus) in northwestern Minnesota, following the state's most recent outbreak of the disease in 2005 in the northwest part of the state. Both deer and cattle have the same strain of bTB. The Minnesota Board of Animal Health has been leading efforts to eradicate the disease in Minnesota's cattle, which have included the depopulation of all infected herds, a cattle buy-out program, and mandatory fencing of stored feeds. The Minnesota Department of Natural Resources began surveillance efforts in free-ranging white-tailed deer in fall 2005. All bTB-infected deer have been found within a 16 km2 area in direct association with infected cattle farms. Aggressive efforts to reduce deer densities through liberalized hunting and sharpshooting have resulted in a 55% decline in deer densities. Also, recreational feeding of wild deer has been banned. Disease prevalence in deer has decreased from 1.2% in 2005 to an undetectable level in 2010. PMID:21647335
Huang, Jing-Yang; Jian, Zhi-Hong; Ndi Nfor, Oswald; Jhang, Kai-Ming; Ku, Wen-Yuan; Ko, Pei-Chieh; Jan, Shiou-Rung; Ho, Chien-Chang; Lung, Chia-Chi; Pan, Hui-Hsien; Liang, Yu-Chiu; Liaw, Yung-Po
Pulmonary diseases [asthma, chronic obstructive pulmonary disease (COPD), and tuberculosis (TB)] are associated with lung cancer mortality. However, the relationship between coexisting pulmonary diseases and survival in patients with lung squamous cell carcinoma (SqCC) has not been well defined. Patients newly diagnosed with SqCC between 2003 and 2008 were identified by linking the National Health Insurance Research Database and Taiwan Cancer Registry Database. Cases with SqCC were followed up until death, loss to follow-up, or study end in 2010. Information on health status, date of death and the main causes of death was ascertained from the National Death Registry Database. Cox proportional hazard regression was used to calculate the hazard ratio (HR) of coexisting asthma, COPD and/or TB. During the study period, a total of 5406 cases with SqCC were enrolled. For all cause-mortality, HRs were 1.08 [95% confidence interval (CI), 0.99-1.18], 1.04 (95% CI, 0.97-1.12), and 1.14 (95% CI, 1.00-1.31) for individuals with asthma, COPD, and TB, respectively. Specifically, among men with coexisting pulmonary diseases, the HRs were 1.56 (95% CI, 1.23-1.97) and 1.11 (95% CI, 1.00-1.24) for individuals with asthma+COPD+TB and asthma+COPD, respectively. Among male patients with stage III SqCC, HRs were 3.41 (95%CI, 1.27-9.17) and 1.65 (95%CI, 1.10-2.47) for individuals with asthma+TB and asthma+COPD+TB, respectively. Among male patients with stage IV SqCC, HRs were 1.40 (95%CI, 1.00-1.97) and 1.25 (95%CI, 1.03-1.52) for individuals with asthma+ COPD+TB and asthma. Among female patients with stage I and II, HR was 0.19 (95%CI, 005-0.77) for individuals with asthma. Coexisting pulmonary diseases increased the risk of mortality from SqCC in male patients. For female patients with early stage SqCC, pre-existing asthma decreased mortality. These patients deserve greater attention while undergoing cancer treatment.
Richter, Linda M; Lönnroth, Knut; Desmond, Chris; Jackson, Robin; Jaramillo, Ernesto; Weil, Diana
People with TB and/or HIV frequently experience severe economic barriers to health care, including out-of-pocket expenses related to diagnosis and treatment, as well as indirect costs due to loss of income. These barriers can both aggravate economic hardship and prevent or delay diagnosis, treatment and successful outcome, leading to increased transmission, morbidity and mortality. WHO, UNAIDS and the ILO argue that economic support of various kinds is essential to enable vulnerable people to protect themselves from infection, avoid delayed diagnosis and treatment, overcome barriers to adherence, and avert destitution. This paper analyses successful country proposals to the Global Fund to Fight AIDS, Tuberculosis and Malaria that include economic support in Rounds 7 and 10; 36 and 20 HIV and TB grants in Round 7 and 32 and 26, respectively, in Round 10. Of these, up to 84 percent included direct or indirect economic support for beneficiaries, although the amount constituted a very small proportion of the total grant. In TB grants, the objectives of economic support were generally clearly stated, and focused on mechanisms to improve treatment uptake and adherence, and the case was most clearly made for MDR-TB patients. In HIV grants, the objectives were much broader in scope, including mitigation of adverse economic and social effects of HIV and its treatment on both patients and families. The analysis shows that economic support is on the radar for countries developing Global Fund proposals, and a wide range of economic support activities are in place. In order to move forward in this area, the wealth of country experience that exists needs to be collated, assessed and disseminated. In addition to trials, operational research and programme evaluations, more precise guidance to countries is needed to inform evidence-based decision about activities that are cost-effective, affordable and feasible.
Richter, Linda M.; Lönnroth, Knut; Desmond, Chris; Jackson, Robin; Jaramillo, Ernesto; Weil, Diana
People with TB and/or HIV frequently experience severe economic barriers to health care, including out-of-pocket expenses related to diagnosis and treatment, as well as indirect costs due to loss of income. These barriers can both aggravate economic hardship and prevent or delay diagnosis, treatment and successful outcome, leading to increased transmission, morbidity and mortality. WHO, UNAIDS and the ILO argue that economic support of various kinds is essential to enable vulnerable people to protect themselves from infection, avoid delayed diagnosis and treatment, overcome barriers to adherence, and avert destitution. This paper analyses successful country proposals to the Global Fund to Fight AIDS, Tuberculosis and Malaria that include economic support in Rounds 7 and 10; 36 and 20 HIV and TB grants in Round 7 and 32 and 26, respectively, in Round 10. Of these, up to 84 percent included direct or indirect economic support for beneficiaries, although the amount constituted a very small proportion of the total grant. In TB grants, the objectives of economic support were generally clearly stated, and focused on mechanisms to improve treatment uptake and adherence, and the case was most clearly made for MDR-TB patients. In HIV grants, the objectives were much broader in scope, including mitigation of adverse economic and social effects of HIV and its treatment on both patients and families. The analysis shows that economic support is on the radar for countries developing Global Fund proposals, and a wide range of economic support activities are in place. In order to move forward in this area, the wealth of country experience that exists needs to be collated, assessed and disseminated. In addition to trials, operational research and programme evaluations, more precise guidance to countries is needed to inform evidence-based decision about activities that are cost-effective, affordable and feasible. PMID:24489702
Huang, Fei; Cheng, ShiMing; Du, Xin; Chen, Wei; Scano, Fabio; Falzon, Dennis; Wang, Lixia
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
Zhao, Z; Leow, W Q
Infection and graft-versus-host disease (GVHD) are among the most common complications after hematopoietic stem cell transplantation (HSCT). With well-known risk factors including allogeneic HSCT and GVHD, tuberculosis (TB) has a higher incidence and shorter