Tuberculosis Facts - TB Can Be Treated

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

Tuberculosis Facts - You Can Prevent TB

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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 ...

Childhood multidrug-resistant tuberculosis in the European Union and European Economic Area: an analysis of tuberculosis surveillance data from 2007 to 2015.

PubMed

Ködmön, Csaba; van den Boom, Martin; Zucs, Phillip; van der Werf, Marieke Johanna

2017-11-01

BackgroundConfirming tuberculosis (TB) in children and obtaining information on drug susceptibility is essential to ensure adequate treatment. We assessed whether there are gaps in diagnosis and treatment of multidrug-resistant (MDR) TB in children in the European Union and European Economic Area (EU/EEA), quantified the burden of MDR TB in children and characterised cases. Methods : We analysed surveillance data from 2007 to 2015 for paediatric cases younger than 15 years. Results : In that period, 26 EU/EEA countries reported 18,826 paediatric TB cases of whom 4,129 (21.9%) were laboratory-confirmed. Drug susceptibility testing results were available for 3,378 (17.9%), representing 81.8% of the confirmed cases. The majority (n = 2,967; 87.8%) had drug-sensitive TB, 249 (7.4%) mono-resistant TB, 64 (1.9%) poly-resistant TB, 90 (2.7%) MDR TB and eight (0.2%) had extensively drug-resistant (XDR) TB. MDR TB was more frequently reported among paediatric cases with foreign background (adjusted odds ratio (aOR) = 1.73; 95% confidence interval (95% CI): 1.12-2.67) or previous TB treatment (aOR: 6.42; 95% CI: 3.24-12.75). Successful treatment outcome was reported for 58 of 74 paediatric MDR TB cases with outcome reported from 2007 to 2013; only the group of 5-9 years-olds was significantly associated with unsuccessful treatment outcome (crude odds ratio (cOR) = 11.45; 95% CI: 1.24-106.04). Conclusions : The burden of MDR TB in children in the EU/EEA appears low, but may be underestimated owing to challenges in laboratory confirmation. Diagnostic improvements are needed for early detection and adequate treatment of MDR TB. Children previously treated for TB or of foreign origin may warrant higher attention.

Tuberculosis Facts - Exposure to TB

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

Tuberculosis Facts - Testing for TB

MedlinePlus

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

Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into emergence and spread of multidrug resistance

PubMed Central

Manson, Abigail L.; Cohen, Keira A.; Abeel, Thomas; Desjardins, Christopher A.; Armstrong, Derek T.; Barry, Clifton E.; Brand, Jeannette; Chapman, Sinéad B.; Cho, Sang-Nae; Gabrielian, Andrei; Gomez, James; Jodals, Andreea M.; Joloba, Moses; Jureen, Pontus; Lee, Jong Seok; Malinga, Lesibana; Maiga, Mamoudou; Nordenberg, Dale; Noroc, Ecaterina; Romancenco, Elena; Salazar, Alex; Ssengooba, Willy; Velayati, A. A.; Winglee, Kathryn; Zalutskaya, Aksana; Via, Laura E.; Cassell, Gail H.; Dorman, Susan E.; Ellner, Jerrold; Farnia, Parissa; Galagan, James E.; Rosenthal, Alex; Crudu, Valeriu; Homorodean, Daniela; Hsueh, Po-Ren; Narayanan, Sujatha; Pym, Alexander S.; Skrahina, Alena; Swaminathan, Soumya; Van der Walt, Martie; Alland, David; Bishai, William R.; Cohen, Ted; Hoffner, Sven; Birren, Bruce W.; Earl, Ashlee M.

2017-01-01

Multidrug-resistant tuberculosis (MDR-TB), caused by drug resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. In this study, we examined a dataset of 5,310 M. tuberculosis whole genome sequences from five continents. Despite great diversity with respect to geographic point of isolation, genetic background and drug resistance, patterns of drug resistance emergence were conserved globally. We have identified harbinger mutations that often precede MDR. In particular, the katG S315T mutation, conferring resistance to isoniazid, overwhelmingly arose before rifampicin resistance across all lineages, geographic regions, and time periods. Molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of pre-MDR polymorphisms, particularly katG S315, into molecular diagnostics will enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB. PMID:28092681

Tuberculosis Facts - TB and HIV/AIDS

MedlinePlus

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

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

PubMed

Okimoto, Niro; Kurihara, Takeyuki; Miyashita, Naoyuki

2016-04-01

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

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

PubMed Central

2012-01-01

Background In Ethiopia where there is no strong surveillance system and state of the art diagnostic facilities are limited, the real burden of tuberculosis (TB) is not well known. We conducted a community based survey to estimate the prevalence of pulmonary TB and spoligotype pattern of the Mycobacterium tuberculosis isolates in Southwest Ethiopia. Methods A total of 30040 adults in 10882 households were screened for pulmonary TB in Gilgel Gibe field research centre in Southwest Ethiopia. A total of 482 TB suspects were identified and smear microscopy and culture was done for 428 TB suspects. Counseling and testing for HIV/AIDS was done for all TB suspects. Spoligotyping was done to characterize the Mycobacterium tuberculosis isolates. Results Majority of the TB suspects were females (60.7%) and non-literates (83.6%). Using smear microscopy, a total of 5 new and 4 old cases of pulmonary TB cases were identified making the prevalence of TB 30 per 100,000. However, using the culture method, we identified 17 new cases with a prevalence of 76.1 per 100,000. There were 4.3 undiagnosed pulmonary TB cases for every TB case who was diagnosed through the passive case detection mechanism in the health facility. Eleven isolates (64.7%) belonged to the six previously known spoligotypes: T, Haarlem and Central-Asian (CAS). Six new spoligotype patterns of Mycobacterium tuberculosis, not present in the international database (SpolDB4) were identified. None of the rural residents was HIV infected and only 5 (5.5%) of the urban TB suspects were positive for HIV. Conclusion The prevalence of TB in the rural community of Southwest Ethiopia is low. There are large numbers of undiagnosed TB cases in the community. However, the number of sputum smear-positive cases was very low and therefore the risk of transmitting the infection to others may be limited. Active case finding through health extension workers in the community can improve the low case detection rate in Ethiopia. A large scale study on the genotyping of Mycobacterium tuberculosis in Ethiopia is crucial to understand transmission dynamics, identification of drug resistant strains and design preventive strategies. PMID:22414165

Genitourinary Tuberculosis: A Rare Cause of Obstructive Uropathy in Pregnancy

PubMed Central

Duryea, Elaine L.; Sheffield, Jeanne S.

2014-01-01

Background. A rare but morbid form of extrapulmonary tuberculosis (TB), genitourinary TB is an important cause of obstructive uropathy and is likely underdiagnosed in pregnancy. Case. A 30-year-old primigravida undergoing treatment for active pulmonary TB presented with anuria at 13-14-weeks gestation. Bilateral ureteral strictures above the level of the ureterovesicular junctions were seen on imaging studies. Given her pulmonary disease, her obstructive uropathy was attributed to genitourinary TB. Bilateral percutaneous nephrostomy tubes were placed during pregnancy with successful ureteral reimplantation postpartum. Conclusion. Genitourinary TB should be considered as an etiology of urinary tract pathology during pregnancy, especially in foreign-born and immunocompromised persons. Early recognition resulting in prompt treatment can prevent further deterioration of maternal renal function and optimize pregnancy outcomes. PMID:25045558

Trends in prevalence of multi drug resistant tuberculosis in sub-Saharan Africa: A systematic review and meta-analysis

PubMed Central

Adamu, Aishatu L.; Galadanci, Najibah A.; Zubayr, Bashir; Odoh, Chisom N.; Aliyu, Muktar H.

2017-01-01

Background Multidrug resistant tuberculosis (MDR-TB), is an emerging public health problem in sub-Saharan Africa (SSA). This study aims to determine the trends in prevalence of MDR-TB among new TB cases in sub-Saharan Africa over two decades. Methods We searched electronic data bases and accessed all prevalence studies of MDR-TB within SSA between 2007 and 2017. We determined pooled prevalence estimates using random effects models and determined trends using meta-regression. Results Results: We identified 915 studies satisfying inclusion criteria. Cumulatively, studies reported on MDR-TB culture of 34,652 persons. The pooled prevalence of MDR-TB in new cases was 2.1% (95% CI; 1.7–2.5%). There was a non-significant decline in prevalence by 0.12% per year. Conclusion We found a low prevalence estimate of MDR-TB, and a slight temporal decline over the study period. There is a need for continuous MDR-TB surveillance among patients with TB. PMID:28945771

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

PubMed

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

2015-01-01

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

Alarming Levels of Drug-Resistant Tuberculosis in HIV-Infected Patients in Metropolitan Mumbai, India

PubMed Central

Isaakidis, Petros; Das, Mrinalini; Kumar, Ajay M V; Peskett, Christopher; Khetarpal, Minni; Bamne, Arun; Adsul, Balkrishna; Manglani, Mamta; Sachdeva, Kuldeep Singh; Parmar, Malik; Kanchar, Avinash; Rewari, B.B.; Deshpande, Alaka; Rodrigues, Camilla; Shetty, Anjali; Rebello, Lorraine; Saranchuk, Peter

2014-01-01

Background Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. Methods A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Results Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%–40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. Conclusion The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with ‘presumptive TB’ rather than ‘presumptive DR-TB’ and tailor the treatment regimen based on the resistance patterns. PMID:25333696

Direct Detection by the Xpert MTB/RIF Assay and Characterization of Multi and Poly Drug-Resistant Tuberculosis in Guinea-Bissau, West Africa

PubMed Central

Ponce, Gema; Sanca, Lilica; Mané, Morto; Armada, Ana; Machado, Diana; Vieira, Fina; Gomes, Victor F.; Martins, Elisabete; Colombatti, Raffaella; Riccardi, Fabio; Perdigão, João; Sotero, Joana; Portugal, Isabel; Couto, Isabel; Atouguia, Jorge; Rodrigues, Amabélia; Viveiros, Miguel

2015-01-01

Background This study aimed to evaluate the usefulness of the Xpert MTB/RIF assay for the rapid direct detection of M. tuberculosis complex (MTBC) strains and rifampicin resistance associated mutations in a resource-limited setting such as Guinea-Bissau and its implications in the management of tuberculosis (TB) and drug resistant tuberculosis, complementing the scarce information on resistance and genotypic diversity of MTBC strains in this West African country. Methods and Results This cross-sectional prospective study included 100 consecutive TB patients with positive acid-fast smears at two months of anti-tuberculosis treatment or in a re-treatment situation, between May and December 2012. Resistance to rifampicin was detected using the GeneXpert system and the Xpert MTB/RIF assay. MTBC isolates obtained with the BACTEC MGIT 960 system were tested for susceptibility to first- and second-line anti-tuberculosis drugs. Overall, the prevalence of multidrug-resistant tuberculosis (MDR-TB) was found to be 9 cases. Of these, 67% (6 patients) of confirmed MDR-TB cases had no past history of TB treatment and 33% (3 patients) were previously treated cases. Extensively drug-resistant TB was not found. Molecular typing of the MDR-TB strains revealed recent transmission patterns of imported MDR strains. Conclusions The Xpert MTB/RIF assay was reliable for the detection of rifampicin resistant MTBC strains directly from sputum samples of patients undergoing first-line treatment for two months, being more trustworthy than the simple presence of acid-fast bacilli in the smear. Its implementation is technically simple, does not require specialized laboratory infrastructures and is suitable for resource-limited settings when a regular source of electricity and maintenance is available as well as financial and operation sustainability is guaranteed by the health authorities. A high prevalence of MDR-TB among patients at risk of MDR-TB after two months of first-line treatment was found, in support of the WHO recommendations for its use in the management of this risk group. PMID:26017968

Old Disease, New Threat: TB Makes an Unwelcome Comeback.

ERIC Educational Resources Information Center

Pyszczynski, Dennis R.

1992-01-01

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)

Molecular Epidemiology of Mycobacterium tuberculosis Isolates in 100 Patients With Tuberculosis Using Pulsed Field Gel Electrophoresis

PubMed Central

Pooideh, Mohammad; Jabbarzadeh, Ismail; Ranjbar, Reza; Saifi, Mahnaz

2015-01-01

Background: Tuberculosis (TB) is a widespread infectious disease. Today, TB has created a public health crisis in the world. Genotyping of Mycobacterium tuberculosis isolates is useful for surveying the dynamics of TB infection, identifying new outbreaks, and preventing the disease. Different molecular methods for clustering of M. tuberculosis isolates have been used. Objectives: During a one year study of genotyping, 100 M. tuberculosis isolates from patients referred to Pasteur Institute of Iran were collected and their genotyping was accomplished using pulsed field gel electrophoresis (PFGE) method. Materials and Methods: Identification of all M. tuberculosis isolates was accomplished using standard biochemical and species-specific polymerase chain reaction (PCR) methods. Antibiotic susceptibility tests were performed using proportional method. After preparing PFGE plaques for each isolate of M. tuberculosis, XbaI restriction enzyme was applied for genome digestion. Finally, the digested DNA fragments were separated on 1% agarose gel and analyzed with GelCompar II software. Results: Genotyping of the studied isolates in comparison with the molecular weight marker revealed two common types; pulsotype A with 71 isolates and one multidrug resistant mycobacterium (MDR) case, and pulsotype B including 29 isolates and three MDR cases. No correlation between the antibiotypes and pulsotypes was observed. Conclusions: Molecular epidemiology studies of infectious diseases have been useful when bacterial isolates have been clustered in a period of time and in different geographical regions with variable antibiotic resistance patterns. In spite of high geographical differences and different antibiotic resistant patterns, low genetic diversity among the studied TB isolates may refer to the low rate of mutations in XbaI restriction sites in the mycobacterial genome. We also identified three MDR isolates in low-incidence pulsotype B, which could be disseminated and is highly important to consider in TB surveillance programs to prevent the spread of MDR-TB isolates in the population. PMID:26396714

Effect of Active Case Finding on Prevalence and Transmission of Pulmonary Tuberculosis in Dhaka Central Jail, Bangladesh

PubMed Central

Banu, Sayera; Rahman, Md. Toufiq; Uddin, Mohammad Khaja Mafij; Khatun, Razia; Khan, Md. Siddiqur Rahman; Rahman, Md. Mojibur; Uddin, Syed Iftekhar; Ahmed, Tahmeed; Heffelfinger, James D.

2015-01-01

Background Understanding tuberculosis (TB) transmission dynamics is essential for establishing effective TB control strategies in settings where the burden and risk of transmission are high. The objectives of this study were to evaluate the effect of active screening on controlling TB transmission and also to characterize Mycobacterium tuberculosis strains for investigating transmission dynamics in a correctional setting. Methods The study was carried out in Dhaka Central Jail (DCJ), from October 2005 to February 2010. An active case finding strategy for pulmonary TB was established both at the entry point to the prison and inside the prison. Three sputum specimens were collected from all pulmonary TB suspects and subjected to smear microscopy, culture, and drug susceptibility testing as well as genotyping which included deletion analysis, spoligotyping and analysis of mycobacterial interspersed repetitive units (MIRU). Results A total of 60,585 inmates were screened during the study period. We found 466 inmates with pulmonary TB of whom 357 (77%) had positive smear microscopy results and 109 (23%) had negative smear microscopy results but had positive results on culture. The number of pulmonary TB cases declined significantly, from 49 cases during the first quarter to 8 cases in the final quarter of the study period (p=0.001). Deletion analysis identified all isolates as M. tuberculosis and further identified 229 (70%) strains as ‘modern’ and 100 (30%) strains as ‘ancestral’. Analysis of MIRU showed that 347 strains (85%) exhibited unique patterns, whereas 61 strains (15%) clustered into 22 groups. The largest cluster comprised eight strains of the Beijing M. tuberculosis type. The rate of recent transmission was estimated to be 9.6%. Conclusions Implementation of active screening for TB was associated with a decline in TB cases in DCJ. Implementation of active screening in prison settings might substantially reduce the national burden of TB in Bangladesh. PMID:25933377

Influence of Age and Nutritional Status on the Performance of the Tuberculin Skin Test and QuantiFERON-TB Gold In-Tube in Young Children Evaluated for Tuberculosis in Southern India

PubMed Central

Jenum, Synne; Selvam, Sumithra; Mahelai, Diana; Jesuraj, Nelson; Cárdenas, Vicky; Kenneth, John; Hesseling, Anneke C.; Doherty, Timothy Mark; Vaz, Mario

2014-01-01

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

Tuberculosis: General Information

MedlinePlus

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

Different Patterns of Cytokines and Chemokines Combined with IFN-γ Production Reflect Mycobacterium tuberculosis Infection and Disease

PubMed Central

Hu, Shizong; Jin, Dongdong; Chen, Xinchun; Jin, Qi; Liu, Haiying

2012-01-01

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 stimulation. In conclusion, our data imply that the specific secretion of soluble immunological factors, in addition to IFN-γ, may be used to evaluate M.tb infection and tuberculosis disease. PMID:23028695

Tuberculosis Reports - UDOH-EPI

Science.gov Websites

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

Discovery of susceptibility loci associated with tuberculosis in Han Chinese.

PubMed

Qi, Hui; Zhang, Yong-Biao; Sun, Lin; Chen, Cheng; Xu, Biao; Xu, Fang; Liu, Jia-Wen; Liu, Jin-Cheng; Chen, Chen; Jiao, Wei-Wei; Shen, Chen; Xiao, Jing; Li, Jie-Qiong; Guo, Ya-Jie; Wang, Yong-Hong; Li, Qin-Jing; Yin, Qing-Qin; Li, Ying-Jia; Wang, Ting; Wang, Xing-Yun; Gu, Ming-Liang; Yu, Jun; Shen, A-Dong

2017-12-01

Genome-wide association studies (GWASs) have revealed the worldwide heterogeneity of genetic factors in tuberculosis (TB) susceptibility. Despite having the third highest global TB burden, no TB-related GWAS has been performed in China. Here, we performed the first three-stage GWAS on TB in the Han Chinese population. In the stage 1 (discovery stage), after quality control, 691 388 SNPs present in 972 TB patients and 1537 controls were retained. After replication on an additional 3460 TB patients and 4862 controls (stages 2 and 3), we identified three significant loci associated with TB, the most significant of which was rs4240897 (logistic regression P = 1.41 × 10-11, odds ratio = 0.79). The aforementioned three SNPs were harbored by MFN2, RGS12 and human leukocyte antigen class II beta chain paralogue encoding genes, all of which are candidate immune genes associated with TB. Our findings provide new insight into the genetic background of TB in the Han Chinese population. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

PubMed Central

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

2010-01-01

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

Descriptive review of tuberculosis surveillance systems across the circumpolar regions

PubMed Central

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

2016-01-01

Background Tuberculosis is highly prevalent in many Arctic areas. Members of the International Circumpolar Surveillance Tuberculosis (ICS-TB) Working Group collaborate to increase knowledge about tuberculosis in Arctic regions. Objective To establish baseline knowledge of tuberculosis surveillance systems used by ICS-TB member jurisdictions. Design Three questionnaires were developed to reflect the different surveillance levels (local, regional and national); all 3 were forwarded to the official representative of each of the 15 ICS-TB member jurisdictions in 2013. Respondents self-identified the level of surveillance conducted in their region and completed the applicable questionnaire. Information collected included surveillance system objectives, case definitions, data collection methodology, storage and dissemination. Results Thirteen ICS-TB jurisdictions [Canada (Labrador, Northwest Territories, Nunavik, Nunavut, Yukon), Finland, Greenland, Norway, Sweden, Russian Federation (Arkhangelsk, Khanty-Mansiysk Autonomous Okrug, Yakutia (Sakha Republic), United States (Alaska)] voluntarily completed the survey – representing 2 local, 7 regional and 4 national levels. Tuberculosis reporting is mandatory in all jurisdictions, and case definitions are comparable across regions. The common objectives across systems are to detect outbreaks, and inform the evaluation/planning of public health programmes and policies. All jurisdictions collect data on confirmed active tuberculosis cases and treatment outcomes; 11 collect contact tracing results. Faxing of standardized case reporting forms is the most common reporting method. Similar core data elements are collected; 8 regions report genotyping results. Data are stored using customized programmes (n=7) and commercial software (n=6). Nine jurisdictions provide monthly, bi-annual or annual reports to principally government and/or scientific/medical audiences. Conclusion This review successfully establishes baseline knowledge on similarities and differences among circumpolar tuberculosis surveillance systems. The similarity in case definitions will allow for description of the epidemiology of TB based on surveillance data in circumpolar regions, further study of tuberculosis trends across regions, and recommendation of best practices to improve surveillance activities. PMID:27121178

Descriptive review of tuberculosis surveillance systems across the circumpolar regions.

PubMed

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

2016-01-01

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

Socio-demographic determinants and prevalence of Tuberculosis knowledge in three slum populations of Uganda

PubMed Central

2012-01-01

Background Knowledge of tuberculosis has been shown to influence health seeking behaviour; and urban slum dwellers are at a higher risk of acquiring tuberculosis than the general population. The study aim was to assess knowledge of tuberculosis and identify the associated socio-demographic determinants, in order to inform tailored interventions for advocacy, communication and social mobilisation in three urban-slum communities of Uganda. Methods A cross-sectional survey of 1361 adults between April and October 2011. Data was analyzed by descriptive statistics. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) of potential determinants of tuberculosis (TB) knowledge were estimated by multivariable ordinal logistic regression using Stata 11.2 software. Results We found low knowledge of TB cause (26.7%); symptoms (46.8%), transmission (54.3%), prevention (34%) and free treatment (35%). Knowledge about TB treatment (69.4) and cure (85.1) was relatively high. Independent determinants of poor knowledge of TB in the multivariable analysis included (aOR, 95% CI) lack of formal education (0.56; 0.38 – 0.83, P = 0.004), unemployment (0.67; 0.49 – 0.90, P = 0.010) and never testing for HIV (0.69; 0.51 – 0.92, P < 0.012). Whilst, older age (1.73; 1.30 – 2.29, P < 0.001) and residing in Lira (2.02; 1.50 – 2.72, P < 0.001) were independent determinants of higher knowledge of TB. Conclusion This study revealed deficiencies in the public health knowledge about TB symptoms, diagnosis and treatment among urban-slum dwellers in Uganda. Tuberculosis control programmes in similar settings should consider innovative strategies for TB education, advocacy, communication and social mobilisation to reach the youth, unemployed and less-educated; as well as those who have never tested for HIV. PMID:22824498

Pulmonary tuberculosis

MedlinePlus

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

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

USDA-ARS?s Scientific Manuscript database

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

Map the gap: missing children with drug-resistant tuberculosis

PubMed Central

Yuen, C. M.; Rodriguez, C. A.; Keshavjee, S.

2015-01-01

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

"Genetic regulation of Mycobacterium tuberculosis in a lipid-rich environment".

PubMed

Aguilar-Ayala, Diana A; Palomino, Juan Carlos; Vandamme, Peter; Martin, Anandi; Gonzalez-Y-Merchand, Jorge A

2017-11-01

Tuberculosis (TB) remains as one of the leading causes of morbidity and mortality among infectious diseases worldwide. Although lipids (mainly fatty acids and cholesterol) have been reported to play an important role during active and latent infection of M. tuberculosis, there are other molecular aspects of bacterial response to those substrates that are not fully understood, involving gene regulation background. This review highlights recent insights on pathogen gene expression: regulation during its active growth, during survival in presence of lipids and under variable hostile host microenvironments. We also propose several application options of this knowledge that may contribute for improved TB control. Copyright © 2016 Elsevier B.V. All rights reserved.

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

PubMed Central

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

2011-01-01

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

The Burden of Drug-Resistant Tuberculosis in Papua New Guinea: Results of a Large Population-Based Survey

PubMed Central

Aia, Paul; Kal, Margaret; Lavu, Evelyn; John, Lucy N.; Johnson, Karen; Coulter, Chris; Ershova, Julia; Tosas, Olga; Zignol, Matteo; Ahmadova, Shalala; Islam, Tauhid

2016-01-01

Background Reliable estimates of the burden of multidrug-resistant tuberculosis (MDR-TB) are crucial for effective control and prevention of tuberculosis (TB). Papua New Guinea (PNG) is a high TB burden country with limited information on the magnitude of the MDR-TB problem. Methods A cross-sectional study was conducted in four PNG provinces: Madang, Morobe, National Capital District and Western Province. Patient sputum samples were tested for rifampicin resistance by the Xpert MTB/RIF assay and those showing the presence of resistance underwent phenotypic susceptibility testing to first- and second-line anti-TB drugs including streptomycin, isoniazid, rifampicin, ethambutol, pyrazinamide, ofloxacin, amikacin, kanamycin and capreomycin. Results Among 1,182 TB patients enrolled in the study, MDR-TB was detected in 20 new (2.7%; 95% confidence intervals [CI] 1.1–4.3%) and 24 previously treated (19.1%; 95%CI: 8.5–29.8%) TB cases. No case of extensively drug-resistant TB (XDR-TB) was detected. Thirty percent (6/20) of new and 33.3% (8/24) of previously treated cases with MDR-TB were detected in a single cluster in Western Province. Conclusion In PNG the proportion of MDR-TB in new cases is slightly lower than the regional average of 4.4% (95%CI: 2.6–6.3%). A large proportion of MDR-TB cases were identified from a single hospital in Western Province, suggesting that the prevalence of MDR-TB across the country is heterogeneous. Future surveys should further explore this finding. The survey also helped strengthening the use of smear microscopy and Xpert MTB/RIF testing as diagnostic tools for TB in the country. PMID:27003160

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

PubMed

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

2012-06-01

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

Tuberculosis

MedlinePlus

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

Automatic detection of mycobacterium tuberculosis using artificial intelligence

PubMed Central

Xiong, Yan; Ba, Xiaojun; Hou, Ao; Zhang, Kaiwen; Chen, Longsen

2018-01-01

Background Tuberculosis (TB) is a global issue that seriously endangers public health. Pathology is one of the most important means for diagnosing TB in clinical practice. To confirm TB as the diagnosis, finding specially stained TB bacilli under a microscope is critical. Because of the very small size and number of bacilli, it is a time-consuming and strenuous work even for experienced pathologists, and this strenuosity often leads to low detection rate and false diagnoses. We investigated the clinical efficacy of an artificial intelligence (AI)-assisted detection method for acid-fast stained TB bacillus. Methods We built a convolutional neural networks (CNN) model, named tuberculosis AI (TB-AI), specifically to recognize TB bacillus. The training set contains 45 samples, including 30 positive cases and 15 negative cases, where bacilli are labeled by human pathologists. Upon training the neural network model, 201 samples (108 positive cases and 93 negative cases) were collected as test set and used to examine TB-AI. We compared the diagnosis of TB-AI to the ground truth result provided by human pathologists, analyzed inconsistencies between AI and human, and adjusted the protocol accordingly. Trained TB-AI were run on the test data twice. Results Examined against the double confirmed diagnosis by pathologists both via microscopes and digital slides, TB-AI achieved 97.94% sensitivity and 83.65% specificity. Conclusions TB-AI can be a promising support system to detect stained TB bacilli and help make clinical decisions. It holds the potential to relieve the heavy workload of pathologists and decrease chances of missed diagnosis. Samples labeled as positive by TB-AI must be confirmed by pathologists, and those labeled as negative should be reviewed to make sure that the digital slides are qualified. PMID:29707349

Association of Pulmonary Tuberculosis and Diabetes in Mexico: Analysis of the National Tuberculosis Registry 2000–2012

PubMed Central

Delgado-Sánchez, Guadalupe; García-García, Lourdes; Castellanos-Joya, Martín; Cruz-Hervert, Pablo; Ferreyra-Reyes, Leticia; Ferreira-Guerrero, Elizabeth; Hernández, Andrés; Ortega-Baeza, Victor Manuel; Montero-Campos, Rogelio; Sulca, José Antonio; Martínez-Olivares, Ma. de Lourdes; Mongua-Rodríguez, Norma; Baez-Saldaña, Renata; González-Roldán, Jesús Felipe; López-Gatell, Hugo; Ponce-de-León, Alfredo; Sifuentes-Osornio, José; Jiménez-Corona, María Eugenia

2015-01-01

Background Tuberculosis (TB) remains a public health problem in Mexico while the incidence of diabetes mellitus type 2 (DM) has increased rapidly in recent years. Objective To describe the trends of incidence rates of pulmonary TB associated with DM and not associated with DM and to compare the results of treatment outcomes in patients with and without DM. Materials and Methods We analysed the National Tuberculosis Registry from 2000 to 2012 including patients with pulmonary TB among individuals older than 20 years of age. The association between DM and treatment failure was analysed using logistic regression, accounting for clustering due to regional distribution. Results In Mexico from 2000 to 2012, the incidence rates of pulmonary TB associated to DM increased by 82.64%, (p <0.001) in contrast to rates of pulmonary TB rate without DM, which decreased by 26.77%, (p <0.001). Patients with a prior diagnosis of DM had a greater likelihood of failing treatment (adjusted odds ratio, 1.34 (1.11–1.61) p <0.002) compared with patients who did not have DM. There was statistical evidence of interaction between DM and sex. The odds of treatment failure were increased in both sexes. Conclusion Our data suggest that the growing DM epidemic has an impact on the rates of pulmonary TB. In addition, patients who suffer from both diseases have a greater probability of treatment failure. PMID:26075393

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

PubMed Central

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

2017-01-01

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

Management of multidrug-resistant tuberculosis in human immunodeficiency virus patients

NASA Astrophysics Data System (ADS)

Jamil, K. F.

2018-03-01

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

Tuberculosis Treatment and Pregnancy

MedlinePlus

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

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

PubMed

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

2016-06-01

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

Drug-resistant tuberculosis: challenges and opportunities for diagnosis and treatment.

PubMed

Koch, Anastasia; Cox, Helen; Mizrahi, Valerie

2018-06-06

With an estimated incidence of 490000 cases in 2016, multidrug resistant tuberculosis (TB), against which key first-line anti-tuberculars are less efficacious, presents major challenges for global health. Poor treatment outcomes coupled with a yawning treatment gap between those in need of second-line therapy and those who receive it, underscore the urgent need for new approaches to tackle the scourge of drug-resistant TB. Against this background, significant progress has been made in understanding the complex biology of TB drug resistance and disease pathogenesis, and in establishing a pipeline for delivering new drugs and drug combinations. In this review, we highlight the challenges of drug-resistant TB and the ways in which new advances could be harnessed to improve treatment outcomes. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

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

PubMed Central

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

2012-01-01

Background Children with latent tuberculosis infection (LTBI) represent a huge reservoir for future disease. We wished to determine Mycobacterium tuberculosis (M.tb) infection prevalence among BCG-immunised five-year-old children in Entebbe, Uganda, but there are limited data on the performance of immunoassays for diagnosis of tuberculosis infection in children in endemic settings. We therefore evaluated agreement between a commercial interferon gamma release assay (T-SPOT.TB) and the tuberculin skin test (TST; 2 units RT-23 tuberculin; positive defined as diameter ≥10 mm), along with the reproducibility of T-SPOT.TB on short-term follow-up, in this population. Methodology/Principal Findings We recruited 907 children of which 56 were household contacts of TB patients. They were tested with T-SPOT.TB at age five years and then re-examined with T-SPOT.TB (n = 405) and TST (n = 319) approximately three weeks later. The principal outcome measures were T-SPOT.TB and TST positivity. At five years, 88 (9.7%) children tested positive by T-SPOT.TB. More than half of those that were T-SPOT.TB positive at five years were negative at follow-up, whereas 96% of baseline negatives were consistently negative. We observed somewhat better agreement between initial and follow-up T-SPOT.TB results among household TB contacts (κ = 0.77) than among non-contacts (κ = 0.39). Agreement between T-SPOT.TB and TST was weak (κ = 0.28 and κ = 0.40 for T-SPOT.TB at 5 years and follow-up, respectively). Of 28 children who were positive on both T-SPOT.TB tests, 14 (50%) had a negative TST. Analysis of spot counts showed high levels of instability in responses between baseline and follow-up, indicating variability in circulating numbers of T cells specific for certain M.tb antigens. Conclusions/Significance We found that T-SPOT.TB positives are unstable over a three-week follow-up interval, and that TST compares poorly with T-SPOT.TB, making the categorisation of children as TB-infected or TB-uninfected difficult. Existing tools for the diagnosis of TB infection are unsatisfactory in determining infection among children in this setting. PMID:23077594

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

USDA-ARS?s Scientific Manuscript database

Background The use of serological assays for diagnosis of bovine tuberculosis (TB) has been intensively studied and use of specific antigens have aided in improving the diagnostic accuracy of the assays. In the present study, we report an in-house enzyme linked immunosorbent assay (ELISA), developed...

Granulysin-Expressing CD4+ T Cells as Candidate Immune Marker for Tuberculosis during Childhood and Adolescence

PubMed Central

Mueller, Henrik; Faé, Kellen C.; Magdorf, Klaus; Ganoza, Christian A.; Wahn, Ulrich; Guhlich, Ute; Feiterna-Sperling, Cornelia; Kaufmann, Stefan H. E.

2011-01-01

Background Granulysin produced by cytolytic T cells directly contributes to immune defense against tuberculosis (TB). We investigated granulysin as a candidate immune marker for childhood and adolescent TB. Methods Peripheral blood mononuclear cells (PBMC) from children and adolescents (1–17 years) with active TB, latent TB infection (LTBI), nontuberculous mycobacteria (NTM) infection and from uninfected controls were isolated and restimulated in a 7-day restimulation assay. Intracellular staining was then performed to analyze antigen-specific induction of activation markers and cytotoxic proteins, notably, granulysin in CD4+ CD45RO+ memory T cells. Results CD4+ CD45RO+ T cells co-expressing granulysin with specificity for Mycobacterium tuberculosis (Mtb) were present in high frequency in TB-experienced children and adolescents. Proliferating memory T cells (CFSElowCD4+CD45RO+) were identified as main source of granulysin and these cells expressed both central and effector memory phenotype. PBMC from study participants after TB drug therapy revealed that granulysin-expressing CD4+ T cells are long-lived, and express several activation and cytotoxicity markers with a proportion of cells being interferon-gamma-positive. In addition, granulysin-expressing T cell lines showed cytolytic activity against Mtb-infected target cells. Conclusions Our data suggest granulysin expression by CD4+ memory T cells as candidate immune marker for TB infection, notably, in childhood and adolescence. PMID:22216262

Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance.

PubMed

Manson, Abigail L; Cohen, Keira A; Abeel, Thomas; Desjardins, Christopher A; Armstrong, Derek T; Barry, Clifton E; Brand, Jeannette; Chapman, Sinéad B; Cho, Sang-Nae; Gabrielian, Andrei; Gomez, James; Jodals, Andreea M; Joloba, Moses; Jureen, Pontus; Lee, Jong Seok; Malinga, Lesibana; Maiga, Mamoudou; Nordenberg, Dale; Noroc, Ecaterina; Romancenco, Elena; Salazar, Alex; Ssengooba, Willy; Velayati, A A; Winglee, Kathryn; Zalutskaya, Aksana; Via, Laura E; Cassell, Gail H; Dorman, Susan E; Ellner, Jerrold; Farnia, Parissa; Galagan, James E; Rosenthal, Alex; Crudu, Valeriu; Homorodean, Daniela; Hsueh, Po-Ren; Narayanan, Sujatha; Pym, Alexander S; Skrahina, Alena; Swaminathan, Soumya; Van der Walt, Martie; Alland, David; Bishai, William R; Cohen, Ted; Hoffner, Sven; Birren, Bruce W; Earl, Ashlee M

2017-03-01

Multidrug-resistant tuberculosis (MDR-TB), caused by drug-resistant strains of Mycobacterium tuberculosis, is an increasingly serious problem worldwide. Here we examined a data set of whole-genome sequences from 5,310 M. tuberculosis isolates from five continents. Despite the great diversity of these isolates with respect to geographical point of isolation, genetic background and drug resistance, the patterns for the emergence of drug resistance were conserved globally. We have identified harbinger mutations that often precede multidrug resistance. In particular, the katG mutation encoding p.Ser315Thr, which confers resistance to isoniazid, overwhelmingly arose before mutations that conferred rifampicin resistance across all of the lineages, geographical regions and time periods. Therefore, molecular diagnostics that include markers for rifampicin resistance alone will be insufficient to identify pre-MDR strains. Incorporating knowledge of polymorphisms that occur before the emergence of multidrug resistance, particularly katG p.Ser315Thr, into molecular diagnostics should enable targeted treatment of patients with pre-MDR-TB to prevent further development of MDR-TB.

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

PubMed

Zhu, Feng; Ou, Qinfang; Zheng, Jian

2018-01-01

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

Evaluation of the 2007 WHO Guideline to Improve the Diagnosis of Tuberculosis in Ambulatory HIV-Positive Adults

PubMed Central

Koole, Olivier; Thai, Sopheak; Khun, Kim Eam; Pe, Reaksmey; van Griensven, Johan; Apers, Ludwig; Van den Ende, Jef; Mao, Tan Eang; Lynen, Lutgarde

2011-01-01

Background In 2007 WHO issued a guideline to improve the diagnosis of smear-negative and extrapulmonary tuberculosis (EPTB) in HIV-positive patients. This guideline relies heavily on the acceptance of HIV-testing and availability of chest X-rays. Methods and Findings Cohort study of TB suspects in four tuberculosis (TB) clinics in Phnom Penh, Cambodia. We assessed the operational performance of the guideline, the incremental yield of investigations, and the diagnostic accuracy for smear-negative tuberculosis in HIV-positive patients using culture positivity as reference standard. 1,147 (68.9%) of 1,665 TB suspects presented with unknown HIV status, 1,124 (98.0%) agreed to be tested, 79 (7.0%) were HIV-positive. Compliance with the guideline for chest X-rays and sputum culture requests was 97.1% and 98.3% respectively. Only 35 of 79 HIV-positive patients (44.3%) with a chest X-ray suggestive of TB started TB treatment within 10 days. 105 of 442 HIV-positive TB suspects started TB treatment (56.2% smear-negative pulmonary TB (PTB), 28.6% smear-positive PTB, 15.2% EPTB). The median time to TB treatment initiation was 5 days (IQR: 2–13 days), ranging from 2 days (IQR: 1–11.5 days) for EPTB, over 2.5 days (IQR: 1–4 days) for smear-positive PTB to 9 days (IQR: 3–17 days) for smear-negative PTB. Among the 34 smear-negative TB patients with a confirmed diagnosis, the incremental yield of chest X-ray, clinical suspicion or abdominal ultrasound, and culture was 41.2%, 17.6% and 41.2% respectively. The sensitivity and specificity of the algorithm to diagnose smear-negative TB in HIV-positive TB suspects was 58.8% (95%CI: 42.2%–73.6%) and 79.4% (95%CI: 74.8%–82.4%) respectively. Conclusions Pending point-of-care rapid diagnostic tests for TB disease, diagnostic algorithms are needed. The diagnostic accuracy of the 2007 WHO guideline to diagnose smear-negative TB is acceptable. There is, however, reluctance to comply with the guideline in terms of immediate treatment initiation. PMID:21494694

Active Tuberculosis in HIV-Exposed Tanzanian Children up to 2 years of Age: Early-Life Nutrition, Multivitamin Supplementation and Other Potential Risk Factors

PubMed Central

Liu, Enju; Manji, Karim P.; Danaei, Goodarz; Duggan, Christopher; Aboud, Said; Spiegelman, Donna; Fawzi, Wafaie W.

2016-01-01

Background: Over half a million children worldwide develop active tuberculosis (TB) each year. Early-life nutritional exposures have rarely been examined in relation to pediatric TB among HIV-exposed children. We therefore investigated independent associations of early-life nutritional exposures with active TB among HIV-exposed children up to 2 years of age. Methods: Participants were children from a randomized controlled multivitamin supplementation trial conducted in Dar es Salaam, Tanzania, from August 2004 to May 2008, who received daily multivitamin supplements or placebo for 24 months. Results: Lower mean corpuscular volumes [relative risks (RR): 0.48, 95% confidence interval (CI): 0.27, 0.87] and higher birth weights (RR: 0.61, 95% CI: 0.37, 0.99) were protective against active TB, whereas multivitamin supplementation was not associated with TB risk (RR: 0.87, 95% CI: 0.65, 1.16). Conclusions: Knowledge of nutrition-related risk and protective factors for TB in HIV-exposed children could enhance preventive and case-finding activities in this population, contributing to efforts to reduce the global TB burden. PMID:26494727

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

PubMed Central

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

2017-01-01

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

The Forest behind the Tree: Phylogenetic Exploration of a Dominant Mycobacterium tuberculosis Strain Lineage from a High Tuberculosis Burden Country

PubMed Central

Cardoso Oelemann, Maranibia; Gomes, Harrison M.; Willery, Eve; Possuelo, Lia; Batista Lima, Karla Valéria; Allix-Béguec, Caroline; Locht, Camille; Goguet de la Salmonière, Yves-Olivier L.; Gutierrez, Maria Cristina; Suffys, Philip; Supply, Philip

2011-01-01

Background Genotyping of Mycobacterium tuberculosis isolates is a powerful tool for epidemiological control of tuberculosis (TB) and phylogenetic exploration of the pathogen. Standardized PCR-based typing, based on 15 to 24 mycobacterial interspersed repetitive unit-variable number of tandem repeat (MIRU-VNTR) loci combined with spoligotyping, has been shown to have adequate resolution power for tracing TB transmission and to be useful for predicting diverse strain lineages in European settings. Its informative value needs to be tested in high TB-burden countries, where the use of genotyping is often complicated by dominance of geographically specific, genetically homogeneous strain lineages. Methodology/Principal Findings We tested this genotyping system for molecular epidemiological analysis of 369 M. tuberculosis isolates from 3 regions of Brazil, a high TB-burden country. Deligotyping, targeting 43 large sequence polymorphisms (LSPs), and the MIRU-VNTRplus identification database were used to assess phylogenetic predictions. High congruence between the different typing results consistently revealed the countrywide supremacy of the Latin-American-Mediterranean (LAM) lineage, comprised of three main branches. In addition to an already known RDRio branch, at least one other branch characterized by a phylogenetically informative LAM3 spoligo-signature seems to be globally distributed beyond Brazil. Nevertheless, by distinguishing 321 genotypes in this strain population, combined MIRU-VNTR typing and spoligotyping demonstrated the presence of multiple distinct clones. The use of 15 to 24 loci discriminated 21 to 25% more strains within the LAM lineage, compared to a restricted lineage-specific locus set suggested to be used after SNP analysis. Noteworthy, 23 of the 28 molecular clusters identified were exclusively composed of patient isolates from a same region, consistent with expected patterns of mostly local TB transmission. Conclusions/Significance Standard MIRU-VNTR typing combined with spoligotyping can reveal epidemiologically meaningful clonal diversity behind a dominant M. tuberculosis strain lineage in a high TB-burden country and is useful to explore international phylogenetical ramifications. PMID:21464915

Identification of mycobacterium tuberculosis in sputum smear slide using automatic scanning microscope

NASA Astrophysics Data System (ADS)

Rulaningtyas, Riries; Suksmono, Andriyan B.; Mengko, Tati L. R.; Saptawati, Putri

2015-04-01

Sputum smear observation has an important role in tuberculosis (TB) disease diagnosis, because it needs accurate identification to avoid high errors diagnosis. In development countries, sputum smear slide observation is commonly done with conventional light microscope from Ziehl-Neelsen stained tissue and it doesn't need high cost to maintain the microscope. The clinicians do manual screening process for sputum smear slide which is time consuming and needs highly training to detect the presence of TB bacilli (mycobacterium tuberculosis) accurately, especially for negative slide and slide with less number of TB bacilli. For helping the clinicians, we propose automatic scanning microscope with automatic identification of TB bacilli. The designed system modified the field movement of light microscope with stepper motor which was controlled by microcontroller. Every sputum smear field was captured by camera. After that some image processing techniques were done for the sputum smear images. The color threshold was used for background subtraction with hue canal in HSV color space. Sobel edge detection algorithm was used for TB bacilli image segmentation. We used feature extraction based on shape for bacilli analyzing and then neural network classified TB bacilli or not. The results indicated identification of TB bacilli that we have done worked well and detected TB bacilli accurately in sputum smear slide with normal staining, but not worked well in over staining and less staining tissue slide. However, overall the designed system can help the clinicians in sputum smear observation becomes more easily.

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

PubMed Central

2013-01-01

Background The prevalence and the patterns of ocular inflammatory disease and ocular tuberculosis (TB) are largely undocumented among Multidrug Resistant TB (MDR-TB) patients co-infected with Human Immunodeficiency Virus (HIV) and on antituberculosis and antiretroviral therapy (ART). Methods Lilavati Hospital and Research Center and Médecins Sans Frontières (MSF) organized a cross-sectional ophthalmological evaluation of HIV/MDR-TB co-infected patients followed in an MSF-run HIV-clinic in Mumbai, India, which included measuring visual acuity, and slit lamp and dilated fundus examinations. Results Between February and April 2012, 47 HIV/MDR-TB co-infected patients (including three patients with extensively drug-resistant TB) were evaluated. Sixty-four per cent were male, mean age was 39 years (standard deviation: 8.7) and their median (IQR) CD4 count at the time of evaluation was 264 cells/μL (158–361). Thirteen patients (27%) had detectable levels of HIV viremia (>20 copies/ml). Overall, examination of the anterior segments was normal in 45/47 patients (96%). A dilated fundus examination revealed active ocular inflammatory disease in seven eyes of seven patients (15.5%, 95% Confidence Intervals (CI); 5.1-25.8%). ‘These included five eyes of five patients (10%) with choroidal tubercles, one eye of one patient (2%) with presumed tubercular chorioretinitis and one eye of one patient (2%) with evidence of presumed active CMV retinitis. Presumed ocular tuberculosis was thus seen in a total of six patients (12.7%, 95% CI; 3.2-22.2%). Two patients who had completed anti-TB treatment had active ocular inflammatory disease, in the form of choroidal tubercles (two eyes of two patients). Inactive scars were seen in three eyes of three patients (6%). Patients with extrapulmonary TB and patients <39 years old were at significantly higher risk of having ocular TB [Risk Ratio: 13.65 (95% CI: 2.4-78.5) and 6.38 (95% CI: 1.05-38.8) respectively]. Conclusions Ocular inflammatory disease, mainly ocular tuberculosis, was common in a cohort of HIV/MDR-TB co-infected patients in Mumbai, India. Ophthalmological examination should be routinely considered in HIV patients diagnosed with or suspected to have MDR-TB, especially in those with extrapulmonary TB. PMID:23687908

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

PubMed Central

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

2011-01-01

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

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

PubMed Central

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

1992-01-01

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

A comparative examination of tuberculosis immigration medical screening programs from selected countries with high immigration and low tuberculosis incidence rates

PubMed Central

2011-01-01

Background Tuberculosis (TB) in migrants is an ongoing challenge in several low TB incidence countries since a large proportion of TB in these countries occurs in migrants from high incidence countries. To meet these challenges, several countries utilize TB screening programs. The programs attempt to identify and treat those with active and/or infectious stages of the disease. In addition, screening is used to identify and manage those with latent or inactive disease after arrival. Between nations, considerable variation exists in the methods used in migration-associated TB screening. The present study aimed to compare the TB immigration medical examination requirements in selected countries of high immigration and low TB incidence rates. Methods Descriptive study of immigration TB screening programs Results 16 out of 18 eligible countries responded to the written standardized survey and phone interview. Comparisons in specific areas of TB immigration screening programs included authorities responsible for TB screening, the primary objectives of the TB screening program, the yield of detection of active TB disease, screening details and aspects of follow up for inactive pulmonary TB. No two countries had the same approach to TB screening among migrants. Important differences, common practices, common problems, evidence or lack of evidence for program specifics were noted. Conclusions In spite of common goals, there is great diversity in the processes and practices designed to mitigate the impact of migration-associated TB among nations that screen migrants for the disease. The long-term goal in decreasing migration-related introduction of TB from high to low incidence countries remains diminishing the prevalence of the disease in those high incidence locations. In the meantime, existing or planned migration screening programs for TB can be made more efficient and evidenced based. Cooperation among countries doing research in the areas outlined in this study should facilitate the development of improved screening programs. PMID:21205318

Evaluation of the hyplex® TBC PCR test for detection of Mycobacterium tuberculosis complex in clinical samples

PubMed Central

2010-01-01

Background Tuberculosis (TB) is one of the major public health concerns worldwide. The detection of the pathogen Mycobacterium tuberculosis complex (MTBC) as early as possible has a great impact on the effective control of the spread of the disease. In our study, we evaluated the hyplex® TBC PCR test (BAG Health Care GmbH), a novel assay using a nucleic acid amplification technique (NAAT) with reverse hybridisation and ELISA read out for the rapid detection of M. tuberculosis directly in clinical samples. Results A total of 581 respiratory and non-respiratory specimens from our pneumological hospital and the National TB Institute of Uzbekistan were used for the evaluation of the PCR assay. Of these, 292 were classified as TB samples and 289 as non-TB samples based on the results of the TB cultures as reference method. The PCR results were initially used to optimise the cut-off value of the hyplex® TBC test system by means of a ROC analysis. The overall sensitivity of the assay was determined to be 83.1%. In smear-positive TB samples, the sensitivity of the hyplex® TBC PCR test was estimated to 93.4% versus 45.1% in smear-negative samples. The specificity of the test was 99.25%. Of the two specimens (0.75%) with false-positive PCR results, one yielded a culture positive for non-tuberculous mycobacteria. Based on the assumption of a prevalence of 8% TB positives among the samples in our diagnostic TB laboratory, the positive and negative predictive values were estimated to 90.4% and 98.5%, respectively. Conclusions The hyplex® TBC PCR test is an accurate NAAT assay for a rapid and reliable detection of M. tuberculosis in various respiratory and non-respiratory specimens. Compared to many other conventional NAAT assays, the hyplex® TBC PCR test is in a low price segment which makes it an attractive option for developing and emerging countries with high TB burdens. PMID:20356361

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

PubMed Central

2013-01-01

Background Tuberculosis (TB) is a major cause of mortality and suffering worldwide, with over 95% of TB deaths occurring in low- and middle-income countries. In recent years, molecular typing methods have been widely used in epidemiological studies to aid the control of TB, but this usage has not been the case with many African countries, including Cameroon. The aims of the present investigation were to identify and evaluate the diversity of the Mycobacterium tuberculosis complex (MTBC) isolates circulating in two ecological zones of Cameroon, seven years after the last studies in the West Region, and after the re-organization of the National TB Control Program (NTBCP). These were expected to shed light also on the transmission of TB in the country. The study was conducted from February to July 2009. During this period, 169 patients with symptomatic disease and with sputum cultures that were positive for MTBC were randomly selected for the study from amongst 964 suspected patients in the savannah mosaic zone (West and North West regions) and the tropical rainforest zone (Central region). After culture and diagnosis, DNA was extracted from each of the MTBC isolates and transported to the BecA-ILRI Hub in Nairobi, Kenya for molecular analysis. Methods Genetic characterization was done by mycobacterial interspersed repetitive unit–variable number tandem repeat typing (MIRU-VNTR) and Spoligotyping. Results Molecular analysis showed that all TB cases reported in this study were caused by infections with Mycobacterium tuberculosis (98.8%) and Mycobacterium africanum (M. africanum) (1.2%) respectively. We did not detect any M. bovis. Comparative analyses using spoligotyping revealed that the majority of isolates belong to major clades of M. tuberculosis: Haarlem (7.6%), Latin American-Mediterranean (34.4%) and T clade (26.7%); the remaining isolates (31.3%) where distributed among the minor clades. The predominant group of isolates (34.4%) corresponded to spoligotype 61, previously described as the “Cameroon family. Further analysis based on MIRU-VNTR profiles had greater resolving power than spoligotyping and defined additional genotypes in the same spoligotype cluster. Conclusion The molecular characterization of MTBC strains from humans in two ecological regions of Cameroon has shown that M. tuberculosis sensu stricto is the predominant agent of TB cases in the zones. Three decades ago, TB was reported to be caused by M. africanum in 56.0% of cases. The present findings are consistent with a major shift in the prevalence of M. tuberculosis in Cameroon. PMID:24028382

Tuberculosis (TB): Treatment

MedlinePlus

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

Demographic predictors of active tuberculosis in people migrating to British Columbia, Canada: a retrospective cohort study

PubMed Central

Ronald, Lisa A.; Campbell, Jonathon R.; Balshaw, Robert F.; Romanowski, Kamila; Roth, David Z.; Marra, Fawziah; Cook, Victoria J.; Johnston, James C.

2018-01-01

BACKGROUND: Canadian tuberculosis (TB) guidelines recommend targeting postlanding screening for and treatment of latent tuberculosis infection (LTBI) in people migrating to Canada who are at increased risk for TB reactivation. Our objectives were to calculate robust longitudinal estimates of TB incidence in a cohort of people migrating to British Columbia, Canada, over a 29-year period, and to identify groups at highest risk of developing TB based on demographic characteristics at time of landing. METHODS: We included all individuals (n = 1 080 908) who became permanent residents of Canada between Jan. 1, 1985, and Dec. 31, 2012, and were resident in BC at any time between 1985 and 2013. Multiple administrative databases were linked to the provincial TB registry. We used recursive partitioning models to identify populations with high TB yield. RESULTS: Active TB was diagnosed in 2814 individuals (incidence rate 24.2/100 000 person-years). Demographic factors (live-in caregiver, family, refugee immigration classes; higher TB incidence in country of birth; and older age) were strong predictors of TB incidence in BC, with elevated rates continuing many years after entry into the cohort. Recursive partitioning identified refugees 18–64 years of age from countries with a TB incidence greater than 224/100 000 population as a high-yield group, with 1% developing TB within the first 10 years. INTERPRETATION: These findings support recommendations in Canadian guidelines to target postlanding screening for and treatment of LTBI in adult refugees from high-incidence countries. Because high-yield populations can be identified at entry via demographic data, screening at this point may be practical and high-impact, particularly if the LTBI care cascade can be optimized. PMID:29483329

Breaking Transmission with Vaccines: The Case of Tuberculosis.

PubMed

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

2017-07-01

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

A 3'UTR polymorphism of IL-6R is associated with Chinese pediatric tuberculosis.

PubMed

Shen, Chen; Qi, Hui; Sun, Lin; Xiao, Jing; Yin, Qing-qin; Jiao, Wei-wei; Wu, Xi-rong; Tian, Jian-ling; Han, Rui; Shen, A-dong

2014-01-01

IL-6 is a proinflammatory cytokine that plays a critical role in host defense against tuberculosis (TB). Genetic polymorphisms of IL-6 and its receptor IL-6R had been discussed in adult TB recently. However, their role in pediatric TB is still unclear. Due to the obvious differences in TB pathophysiology in children, which may also reflect differences in genetic background, further association studies in pediatric populations are needed. A case-control study was carried out in a Chinese pediatric population including 353 TB patients and 400 healthy controls. Tag-SNPs of IL-6 and IL-6R genes were selected by Haploview software, genotyped using MassArray, and analyzed statistically. One polymorphism, rs2229238, in the 3'UTR region of IL-6R was observed to be associated with increased resistance to TB (adjusted P = 0.03). The rs2229238 T allele contributed to a reduced risk to TB in recessive heritable model (OR, 0.53; 95% CI, 0.35-0.78). By tag-SNP genotyping based case-control study, we identified a genetic polymorphism in the IL-6R 3'UTR that regulates host resistance to pediatric TB in a Chinese population.

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

PubMed

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

2015-02-01

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

Assess drug resistance pattern and genetic profile of Mycobacterium tuberculosis clinical isolates by molecular typing methods using direct repeats and IS6110 in pulmonary tuberculosis cases

PubMed Central

Kalo, Deepika; Kant, Surya; Srivastava, Kanchan; Sharma, Ajay K

2017-01-01

Background: Tuberculosis (TB), a highly contagious disease that sees no gender, age, or race is mainly a disease of lungs. According to World Health Organization, a TB patient can be completely cured with 6–9 months of anti-TB treatment under directly observed treatment short course. Objectives: The aim of this study was to check the mono, multi- and triple-drug resistance to first line drugs (FLDs) among TB patients and to access their genetic profile using DR 3074, DR 0270, DR 0642, DR 2068, and DR 4110 using molecular techniques. Material and Methods: To gain a better understanding of drug resistant TB, we characterized 121 clinical isolates recovered from 159 drug resistant pulmonary tuberculosis patients by IS6110 genotyping. MTB isolates recovered from HIV- negative, and smear positive cases of both genders, age varied from 18 to 70 years with drug resistant-TB that was refractory to chemotherapy given for > 12 months. Of a total of 159 sputum smear positive patients sum number of male and female patients was 121 (76.10%) and 38 (23.89%), respectively. Among these patients, number of literate and illiterate patients were 123 (77.3%) and 36 (22.6%). 25 (15.7%) patients had farming as their occupation, 80 (50.3%) had nonagricultural occupation and 54 (33.9%) women were housewives. Results: Mono drug resistant, multi-drug resistant, and totally drug resistant (TDR) cases of TB were calculated as 113.83%, 125.1%, and 67.9%. Isoniazid showed the highest percentage of resistance among the patients. Conclusion: Any noncompliance to TB medications, lack of knowledge, and poor management in health centers, etc., results in the emergence of deadly direct repeat forms of TB, which are further complicated and complex to treat. PMID:28360464

Helminth Coinfection Does Not Affect Therapeutic Effect of a DNA Vaccine in Mice Harboring Tuberculosis

PubMed Central

Frantz, Fabiani G.; Rosada, Rogério S.; Peres-Buzalaf, Camila; Perusso, Franciele R. T.; Rodrigues, Vanderlei; Ramos, Simone G.; Kunkel, Steven L.; Silva, Célio L.; Faccioli, Lúcia H.

2010-01-01

Background Helminthiasis and tuberculosis (TB) coincide geographically and there is much interest in exploring how concurrent worm infections might alter immune responses against bacilli and might necessitate altered therapeutic approaches. A DNA vaccine that codifies heat shock protein Hsp65 from M. leprae (DNAhsp65) has been used in therapy during experimental tuberculosis. This study focused on the impact of the co-existence of worms and TB on the therapeutic effects of DNAhsp65. Methodology/Principal Findings Mice were infected with Toxocara canis or with Schistosoma mansoni, followed by coinfection with M. tuberculosis and treatment with DNAhsp65. While T. canis infection did not increase vulnerability to pulmonary TB, S. mansoni enhanced susceptibility to TB as shown by higher numbers of bacteria in the lungs and spleen, which was associated with an increase in Th2 and regulatory cytokines. However, in coinfected mice, the therapeutic effect of DNAhsp65 was not abrogated, as indicated by colony forming units and analysis of histopathological changes. In vitro studies indicated that Hsp65-specific IFN-γ production was correlated with vaccine-induced protection in coinfected mice. Moreover, in S. mansoni-coinfected mice, DNA treatment inhibited in vivo TGF-β and IL-10 production, which could be associated with long-term protection. Conclusions/Significance We have demonstrated that the therapeutic effects of DNAhsp65 in experimental TB infection are persistent in the presence of an unrelated Th2 immune response induced by helminth infections. PMID:20544012

Estimating Fitness by Competition Assays between Drug Susceptible and Resistant Mycobacterium tuberculosis of Predominant Lineages in Mumbai, India

PubMed Central

Bhatter, Purva; Chatterjee, Anirvan; D'souza, Desiree; Tolani, Monica; Mistry, Nerges

2012-01-01

Background Multi Drug Resistant Tuberculosis (MDR TB) is a threat to global tuberculosis control. A significant fitness cost has been associated with DR strains from specific lineages. Evaluation of the influence of the competing drug susceptible strains on fitness of drug resistant strains may have an important bearing on understanding the spread of MDR TB. The aim of this study was to evaluate the fitness of MDR TB strains, from a TB endemic region of western India: Mumbai, belonging to 3 predominant lineages namely CAS, Beijing and MANU in the presence of drug susceptible strains from the same lineages. Methodology Drug susceptible strains from a single lineage were mixed with drug resistant strain, bearing particular non synonymous mutation (rpoB D516V; inhA, A16G; katG, S315T1/T2) from the same or different lineages. Fitness of M.tuberculosis (M.tb) strains was evaluated using the difference in growth rates obtained by using the CFU assay system. Conclusion/Significance While MANU were most fit amongst the drug susceptible strains of the 3 lineages, only Beijing MDR strains were found to grow in the presence of any of the competing drug susceptible strains. A disproportionate increase in Beijing MDR could be an alarm for an impending epidemic in this locale. In addition to particular non synonymous substitutions, the competing strains in an environment may impact the fitness of circulating drug resistant strains. PMID:22479407

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

PubMed

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

2017-01-01

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

Predictors of change in nutritional and hemoglobin status among adults treated for tuberculosis in Tanzania

PubMed Central

Kawai, Kosuke; Villamor, Eduardo; Mugusi, Ferdinand M; Saathoff, Elmar; Urassa, Willy; Bosch, Ronald J; Spiegelman, Donna; Fawzi, Wafaie W

2012-01-01

BACKGROUND Patients with tuberculosis (TB) often suffer from profound malnutrition. OBJECTIVE To examine the patterns and predictors of change in nutritional and hemoglobin status during and after TB treatment. METHODS A total of 471 HIV-positive and 416 HIV-negative adults with pulmonary TB were prospectively followed in Dar es Salaam, Tanzania. All patients received 8 months TB treatment following enrollment. RESULTS About 40% of HIV-positive and 47% of HIV-negative TB patients had BMI <18.5 kg/m2 at baseline. About 94% of HIV-positive and 84% of HIV-negative participants were anemic at baseline. Both HIV-positive and HIV-negative patients experienced increases in BMI and hemoglobin concentrations over the course of TB treatment. Among HIV-positive patients, older age, low CD4 cell counts, and high viral load were independently associated with a smaller increase in BMI from baseline to 8 months. Female sex, older age, low CD4 cell counts, previous TB infection, and less money spent on food were independently associated with a smaller improvement in hemoglobin among HIV-positive patients during treatment. CONCLUSION HIV- positive TB patients, especially those with low CD4 cell counts, showed poor nutritional recovery during TB treatment. Adequate nutritional support should be considered during TB treatment. PMID:22283899

Treatment: Latent TB Infection (LTBI) and TB Disease

MedlinePlus

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

TB Terms

MedlinePlus

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

Cost-effectiveness of bedaquiline in MDR and XDR tuberculosis in Italy

PubMed Central

Codecasa, Luigi R.; Toumi, Mondher; D’Ausilio, Anna; Aiello, Andrea; Damele, Francesco; Termini, Roberta; Uglietti, Alessia; Hettle, Robert; Graziano, Giorgio; De Lorenzo, Saverio

2017-01-01

ABSTRACT Objective: To evaluate the cost-effectiveness of bedaquiline plus background drug regimens (BR) for multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in Italy. Methods: A Markov model was adapted to the Italian setting to estimate the incremental cost-effectiveness ratio (ICER) of bedaquiline plus BR (BBR) versus BR in the treatment of MDR-TB and XDR-TB over 10 years, from both the National Health Service (NHS) and societal perspective. Cost-effectiveness was evaluated in terms of life-years gained (LYG). Clinical data were sourced from trials; resource consumption for compared treatments was modelled according to advice from an expert clinicians panel. NHS tariffs for inpatient and outpatient resource consumption were retrieved from published Italian sources. Drug costs were provided by reference centres for disease treatment in Italy. A 3% annual discount was applied to both cost and effectiveness. Deterministic and probabilistic sensitivity analyses were conducted. Results: Over 10 years, BBR vs. BR alone is cost-effective, with ICERs of €16,639/LYG and €4081/LYG for the NHS and society, respectively. The sensitivity analyses confirmed the robustness of the results from both considered perspectives. Conclusion: In Italy, BBR vs. BR alone has proven to be cost-effective in the treatment of MDR-TB and XDR-TB under a range of scenarios. PMID:28265350

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

PubMed Central

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

2014-01-01

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

Diabetes Is Associated with Worse Clinical Presentation in Tuberculosis Patients from Brazil: A Retrospective Cohort Study

PubMed Central

Hickson, Lucas S.; Daltro, Carla; Castro, Simone; Kornfeld, Hardy; Netto, Eduardo M.; Andrade, Bruno B.

2016-01-01

Background The rising prevalence of diabetes mellitus (DM) worldwide, especially in developing countries, and the persistence of tuberculosis (TB) as a major public health issue in these same regions, emphasize the importance of investigating this association. Here, we compared the clinical profile and disease outcomes of TB patients with or without coincident DM in a TB reference center in Brazil. Methods We performed a retrospective analysis of a TB patient cohort (treatment naïve) of 408 individuals recruited at a TB primary care center in Brazil between 2004 and 2010. Data on diagnosis of TB and DM were used to define the groups. The study groups were compared with regard to TB disease presentation at diagnosis as well as to clinical outcomes such as cure and mortality rates upon anti-tuberculosis therapy (ATT) initiation. A composite score utilizing clinical, radiological and microbiological parameters was used to compare TB severity between the groups. Results DM patients were older than non-diabetic TB patients. In addition, diabetic individuals more frequently presented with cough, night sweats, hemoptysis and malaise than those without DM. The overall pattern of lung lesions assessed by chest radiographic examination was similar between the groups. Compared to non-diabetic patients, those with TB-diabetes exhibited positive acid-fast bacilli in sputum samples more frequently at diagnosis and at 30 days after ATT initiation. Notably, higher values of the TB severity score were significantly associated with TB-diabetes comorbidity after adjustment for confounding factors. Moreover, during ATT, diabetic patients required more frequent transfers to TB reference hospitals for complex clinical management. Nevertheless, overall mortality and cure rates were indistinguishable between the study groups. Conclusions These findings reinforce the idea that diabetes negatively impacts pulmonary TB severity. Our study argues for the systematic screening for DM in TB reference centers in endemic areas. PMID:26752596

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

PubMed Central

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

2012-01-01

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

From Multidrug- to Extensively Drug-Resistant Tuberculosis: Upward Trends as Seen from a 15-Year Nationwide Study

PubMed Central

Stoffels, Karolien; Allix-Béguec, Caroline; Groenen, Guido; Wanlin, Maryse; Berkvens, Dirk; Mathys, Vanessa; Supply, Philip; Fauville-Dufaux, Maryse

2013-01-01

Background Emergence of extensively drug-resistant tuberculosis (XDR-TB) represents an enormous challenge to Public Health globally. Methods Progression towards XDR-TB was investigated in Belgium, a country with a typically low TB incidence, by analyzing the magnitude, characteristics, and treatment success of multidrug-resistant tuberculosis (MDR-TB) through a population-based study from 1994 to 2008. Results Among the 174 MDR-TB patients, 81% were foreign-born, 48% of these being asylum seekers. Although the number of MDR-TB patients remained stable through the study period at around 15 new cases annually, frequencies of resistance of the patients’ first MDR-TB isolate to second-line drugs increased, as well as the total number of antibiotics it was resistant to (p<0.001). XDR-TB cases were detected from 2002 onwards. For 24 patients, additional resistance to several second-line drugs was acquired during treatment. Molecular-guided investigations indicated little to no contribution of in-country clonal spread or exogenous re-infection. The increase of pre-XDR and XDR cases could be attributed to rising proportions of patients from Asia and Central and Eastern Europe (p<0.001) and an increase in the isolation of Beijing strains in these groups (p<0.001). Despite augmented resistance, the treatment success rate improved from 63.0% to 75.8% (p = 0.080) after implementation in 2005 of improved surveillance measures and therapeutic access. Conclusions Increasing severity in drug resistance patterns leading to more XDR- and “panresistant” TB cases in a country with a low TB incidence like Belgium represents a strong alert on worsening situations in other world regions and requires intense public health measures. PMID:23671662

Testing for TB Infection

MedlinePlus

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

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

PubMed

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

2017-11-01

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

Tuberculosis and Diabetes

MedlinePlus

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

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

PubMed

Talwar, Harvinder; Talreja, Jaya; Samavati, Lobelia

2016-06-01

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

Questions and Answers about TB

MedlinePlus

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Isoniazid Mono-Resistant Tuberculosis: Impact on Treatment Outcome and Survival of Pulmonary Tuberculosis Patients in Southern Mexico 1995-2010

PubMed Central

Báez-Saldaña, Renata; Delgado-Sánchez, Guadalupe; García-García, Lourdes; Cruz-Hervert, Luis Pablo; Montesinos-Castillo, Marlene; Ferreyra-Reyes, Leticia; Bobadilla-del-Valle, Miriam; Canizales-Quintero, Sergio; Ferreira-Guerrero, Elizabeth; Téllez-Vázquez, Norma; Montero-Campos, Rogelio; Yanes-Lane, Mercedes; Mongua-Rodriguez, Norma; Martínez-Gamboa, Rosa Areli; Sifuentes-Osornio, José; Ponce-de-León, Alfredo

2016-01-01

Background Isoniazid mono-resistance (IMR) is the most common form of mono-resistance; its world prevalence is estimated to range between 0.0 to 9.5% globally. There is no consensus on how these patients should be treated. Objective To describe the impact of IMR tuberculosis (TB) on treatment outcome and survival among pulmonary TB patients treated under programmatic conditions in Orizaba, Veracruz, Mexico. Materials and Methods We conducted a prospective cohort study of pulmonary TB patients in Southern Mexico. From 1995 to 2010 patients with acid-fast bacilli or culture proven Mycobacterium tuberculosis in sputum samples underwent epidemiological, clinical and microbiological evaluation. We included patients who harbored isoniazid mono-resistant (IMR) strains and patients with strains susceptible to isoniazid, rifampicin, ethambutol and streptomycin. All patients were treated following Mexican TB Program guidelines. We performed annual follow-up to ascertain treatment outcome, recurrence, relapse and mortality. Results Between 1995 and 2010 1,243 patients with pulmonary TB were recruited; 902/1,243 (72.57%) had drug susceptibility testing; 716 (79.38%) harbored pan-susceptible and 88 (9.75%) IMR strains. Having any contact with a person with TB (adjusted odds ratio (aOR)) 1.85, 95% Confidence interval (CI) 1.15–2.96) and homelessness (adjusted odds ratio (aOR) 2.76, 95% CI 1.08–6.99) were associated with IMR. IMR patients had a higher probability of failure (adjusted hazard ratio (HR) 12.35, 95% CI 3.38–45.15) and death due to TB among HIV negative patients (aHR 3.30. 95% CI 1.00–10.84). All the models were adjusted for socio-demographic and clinical variables. Conclusions The results from our study provide evidence that the standardized treatment schedule with first line drugs in new and previously treated cases with pulmonary TB and IMR produces a high frequency of treatment failure and death due to tuberculosis. We recommend re-evaluating the optimal schedule for patients harboring IMR. It is necessary to strengthen scientific research for the evaluation of alternative treatment schedules in similar settings. PMID:28030600

Prevalence of Anti-Tuberculosis Drug Resistance in Foreign-Born Tuberculosis Cases in the U.S. and in Their Countries of Origin

PubMed Central

Taylor, Allison B.; Kurbatova, Ekaterina V.; Cegielski, J. Peter

2012-01-01

Background Foreign-born individuals comprise >50% of tuberculosis (TB) cases in the U.S. Since anti-TB drug resistance is more common in most other countries, when evaluating a foreign-born individual for TB, one must consider the risk of drug resistance. Naturally, clinicians query The Global Project on Anti-tuberculosis Drug Resistance Surveillance (Global DRS) which provides population-based data on the prevalence of anti-TB drug resistance in 127 countries starting in 1994. However, foreign-born persons in the U.S. are a biased sample of the population of their countries of origin, and Global DRS data may not accurately predict their risk of drug resistance. Since implementing drug resistance surveillance in 1993, the U.S. National TB Surveillance System (NTSS) has accumulated systematic data on over 130,000 foreign-born TB cases from more than 200 countries and territories. Our objective was to determine whether the prevalence of drug resistance among foreign-born TB cases correlates better with data from the Global DRS or with data on foreign-born TB cases in the NTSS. Methods and Findings We compared the prevalence of resistance to isoniazid and rifampin among foreign-born TB cases in the U.S., 2007–2009, with US NTSS data from 1993 to 2006 and with Global DRS data from 1994–2007 visually with scatterplots and statistically with correlation and linear regression analyses. Among foreign-born TB cases in the U.S., 2007–2009, the prevalence of isoniazid resistance and multidrug resistance (MDR, i.e. resistance to isoniazid and rifampin), correlated much better with 1993–2006 US surveillance data (isoniazid: r = 0.95, P<.001, MDR: r = 0.75, P<.001) than with Global DRS data, 1994–2007 (isoniazid: r = 0.55, P = .001; MDR: r = 0.50, P<.001). Conclusion Since 1993, the US NTSS has accumulated sufficient data on foreign-born TB cases to estimate the risk of drug resistance among such individuals better than data from the Global DRS. PMID:23145161

TB in Children in the United States

MedlinePlus

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Analysis of Host Responses to Mycobacterium tuberculosis Antigens in a Multi-Site Study of Subjects with Different TB and HIV Infection States in Sub-Saharan Africa

PubMed Central

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.

2013-01-01

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 be useful for vaccine efficacy trials. PMID:24040170

Female genital tuberculosis cases with distinct clinical symptoms: Four case reports

PubMed Central

Aslan, Gonul; Ulger, Mahmut; Ulger, Seda Tezcan; Durukan, Huseyin; Yazici, Faik Gurkan; Emekdas, Gurol

2018-01-01

Background: Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis. Genital TB (GTB) is a form of extrapulmonary TB that occurs more frequently in women, in whom it classically presents in association with menstrual irregularity, pregnancy loss and short and long-term sequelae especially infertility in infected women. Patients with GTB are usually young women diagnosed during workup for infertility. GTB is rare in postmenopausal women and responsible for only approximately 1% of postmenopausal bleeding. In this study, we aimed to evaluate the laboratory, clinical and demographic characteristics of female GTB cases. Case: We presented four female GTB cases with distinct clinical symptoms. All patients have no history of TB, and no acid-fast bacilli were seen in smears prepared from the clinical materials of the patients. Histopathological examinations revealed granulomatous inflammation in all patients. Conclusion: In the light of the clinical features of these cases we aimed to emphasize that, female GTB must be taken into account in the patients with different clinical symptoms like postmenopausal bleeding, menometrorrhagia, infertility, and menstrual irregularities. We believe that these symptoms will be helpful for the diagnosis and treatment of female GTB. PMID:29675489

Is Universal Screening Necessary? Incidence of Tuberculosis among Tibetan Refugees Arriving in Calgary, Alberta.

PubMed

Lim, Rachel; Jarand, Julie; Field, Stephen K; Fisher, Dina

2016-01-01

Background . Canadian policy requires refugees with a history of tuberculosis (TB) or abnormal chest radiograph to be screened after arrival for TB. However, Tibetan refugees are indiscriminately screened, regardless of preimmigration assessment. We sought to determine the incidence of latent (LTBI) and active TB, as well as treatment-related outcomes and associations between preimmigration factors and TB infection among Tibetan refugees arriving in Calgary, Alberta. Design . Retrospective cohort study including Tibetan refugees arriving between 2014 and 2016. Associations between preimmigration factors and incidence of latent and active TB were determined using Chi-square tests. Results . Out of 180 subjects, 49 percent had LTBI. LTBI was more common in migrants 30 years of age or older ( P = 0.009). Treatment initiation and completion rates were high at 90 percent and 76 percent, respectively. No associations between preimmigration factors and treatment completion were found. A case of active TB was detected and treated. Conclusion . Within this cohort, the case of active TB would have been detected through the usual postsurveillance process due to a history of TB and abnormal chest radiograph. Forty-nine percent had LTBI, compared to previously quoted rates of 97 percent. Tibetan refugees should be screened for TB in a similar manner to other refugees resettling in Canada.

Tuberculosis patients’ knowledge and beliefs about tuberculosis: a mixed methods study from the Pacific Island nation of Vanuatu

PubMed Central

2014-01-01

Background The setting for this study was the Pacific island nation of Vanuatu, an archipelago of 82 islands, located in the South Pacific Ocean. Our objective was to assess the knowledge, attitudes and practices of tuberculosis (TB) patients towards TB. Methods This was a descriptive study using qualitative and quantitative methods. Quantitative analysis was based on the responses provided to closed questions, and we present frequencies to describe the TB patients’ knowledge, attitudes and practice relating to TB. Qualitative analysis was based on open questions permitting fuller explanations. We used thematic analysis and developed a posteriori inductive categories to draw conclusions. Results Thirty five TB patients were interviewed; 22 (63%) were male. They attributed TB to cigarettes, kava, alcohol, contaminated food, sharing eating utensils and “kastom” (the local term for the traditional way of life, but also for sorcery). Most (94%) did not attribute TB to a bacterial cause. However, almost all TB patients (89%) thought that TB was best treated at a hospital with antibiotics. Three quarters (74%) experienced stigma after their TB diagnosis. Seeking health care from a traditional healer was common; 54% of TB patients stated that they would first consult a traditional healer for any illness. When seeking a diagnosis for signs and symptoms of TB, 34% first consulted a traditional healer. Patients cited cost, distance and beliefs about TB causation as reasons for first consulting a traditional healer or going to the hospital. Of the TB patients who consulted a traditional healer first, there was an average of two weeks delay before they consulted the health service. In some cases, however, the delay was up to six years. Conclusion The majority of the TB patients interviewed did not attribute TB to a bacterial cause. Consulting a traditional healer for health care, including while seeking a diagnosis for TB symptoms, was common and may have delayed diagnosis. People require better information about TB to correct commonly held misperceptions about the disease. Traditional healers could also be engaged with the national TB programme, in order to refer people with signs and symptoms of TB to the nearest health service. PMID:24885057

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

PubMed

Thakur, Harshad P

2013-01-01

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

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

PubMed

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

2014-03-01

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

Tuberculosis in Poland in 2012.

PubMed

Korzeniewska-Koseła, Maria

2014-01-01

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

Direct detection of Mycobacterium tuberculosis and drug resistance in respiratory specimen using Abbott Realtime MTB detection and RIF/INH resistance assay.

PubMed

Tam, Kingsley King-Gee; Leung, Kenneth Siu-Sing; To, Sabrina Wai-Chi; Siu, Gilman Kit-Hang; Lau, Terrence Chi-Kong; Shek, Victor Chi-Man; Tse, Cindy Wing-Sze; Wong, Samson Sai-Yin; Ho, Pak-Leung; Yam, Wing-Cheong

2017-10-01

Abbott RealTime MTB (Abbott-RT) in conjunction with Abbott RealTime MTB RIF/INH Resistance (Abbott-RIF/INH) is a new, high-throughput automated nucleic acid amplification platform (Abbott-MDR) for detection of Mycobacterium tuberculosis complex (MTBC) and the genotypic markers for rifampicin (RIF) and isoniazid (INH) resistance directly from respiratory specimens. This prospective study evaluated the diagnostic performance of this new platform for MTBC and multidrug-resistant tuberculosis (MDR-TB) using 610 sputum specimens in a tuberculosis high-burden setting. Using conventional culture results and clinical background as reference standards, Abbott-RT exhibited an overall sensitivity and specificity of 95.2% and 99.8%, respectively. Genotypic RIF/INH resistance of 178 "MTB detected" specimens was subsequently analyzed by Abbott-RIF/INH. Compared to phenotypic drug susceptibility test results, Abbott-RIF/INH detected resistance genotypic markers in 84.6% MDR-TB, 80% mono-RIF-resistant and 66.7% mono-INH-resistant specimens. Two of the RIF-resistant specimens carried a novel single, nonsense mutation at rpoB Q513 and in silico simulation demonstrated that the truncated RpoB protein failed to bind with other subunits for transcription. Overall, Abbott-MDR platform provided high throughput and reliable diagnosis of MDR-TB within a TB high-burden region. Copyright © 2017 Elsevier Inc. All rights reserved.

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

ERIC Educational Resources Information Center

Amaro, Rodolfo

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

Factors Associated with Anti-Tuberculosis Medication Adverse Effects: A Case-Control Study in Lima, Peru

PubMed Central

Chung-Delgado, Kocfa; Revilla-Montag, Alejandro; Guillen-Bravo, Sonia; Velez-Segovia, Eduardo; Soria-Montoya, Andrea; Nuñez-Garbin, Alexandra; Silva-Caso, Wilmer; Bernabe-Ortiz, Antonio

2011-01-01

Background Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use. Methodology and Results A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005–2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65–9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17–3.89), anemia (OR = 2.10; IC95%: 1.13–3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29–19.6), and smoking (OR = 2.00; 95%CI: 1.03–3.87) were independently associated with adverse drug reactions. Conclusions Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients. PMID:22110689

Paradoxical Tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) in HIV Patients with Culture Confirmed Pulmonary Tuberculosis in India and the Potential Role of IL-6 in Prediction

PubMed Central

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

2013-01-01

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

Rights and Responsibilities of Tuberculosis Patients, and the Global Fund: A Qualitative Study

PubMed Central

Atif, Muhammad; Javaid, Sareema; Farooqui, Maryam; Sarwar, Muhammad Rehan

2016-01-01

Background Implementation of the Charter to protect patients’ rights is an important criterion to achieve patient-centered approach and receive financial support from the Global Fund. Our study aims to explore the knowledge of tuberculosis (TB) patients about their rights and responsibilities at the Chest Disease Unit of the Bahawal Victoria Hospital, Bahawalpur, Pakistan. Methods This was a qualitative study. The data from purposefully selected TB patients was collected by in-depth interviews. Eligibility criteria included confirmed diagnosis of TB and enrollment in the TB program. A pilot tested interview protocol was based upon the objectives of the study, and was used uniformly in each interview to maintain the consistency. The sample size was limited by applying the saturation criteria. All interviews were audiotaped and transcribed verbatim. Inductive thematic content analysis was applied to analyze the data and draw conclusions. Results Out of the total 16 patients, four were female, and seven were illiterate. Eight patients were known cases of multi-drug resistant TB. Analysis of the data yielded seven themes; tuberculosis care services, moral support and stigmatization, dignity and privacy, complaints, fear of losing job, information sharing and compliance to the treatment plan, and contribution to eradicate TB. First five represented the rights section while latter two were related to the responsibilities section of the Charter. Conclusion Discriminatory access to TB care services and the right to privacy were two major concerns identified in this study. However, the respondents recognized their responsibilities as a TB patient. To ensure uninterrupted investment from the Global Fund, there is a need to implement fair TB care policies which support human rights-based approach. PMID:26998830

Childhood Tuberculosis in Northern Viet Nam: A Review of 103 Cases

PubMed Central

Blount, Robert J.; Tran, Bao; Jarlsberg, Leah G.; Phan, Ha; Thanh Hoang, Van; Nguyen, Nhung Viet; Lewinsohn, Deborah A.; Nahid, Payam

2014-01-01

Background Childhood tuberculosis causes significant morbidity and mortality in Southeast Asia, yet little is known about the epidemiology and clinical characteristics of this disease in Viet Nam. Objectives To determine the demographics, clinical presentations, radiographic and microbiologic findings, treatment regimens, and outcomes of children admitted with tuberculosis (TB) to a national referral hospital in Viet Nam. Methods We conducted a retrospective case series study of children ≤ 15 years old with bacteriologically confirmed or clinically diagnosed TB admitted to a national referral hospital in Ha Noi, Viet Nam from January through December 2007. Results One hundred three children were identified: median age 5 years (IQR 2-10), 44% female, 99% Kinh ethnicity, 27% residing in Ha Noi, 88% with BCG vaccination, 27% with known TB contact, and 38% malnourished. Intrathoracic TB was present in 62%, extrathoracic in 52%, both intra and extrathoracic in 19%, and undetermined site in 5%. The most common extrathoracic manifestation was peripheral lymphadenitis, and children under 5 were more likely to have miliary TB or both intra and extrathoracic TB. Fever and failure to thrive were common presenting symptoms among all participants (65% and 56%, respectively), 66% of those with intrathoracic TB presented with cough, and 92% of those with TB meningitis presented with severe neurologic impairment. Acid-fast bacilli smears and mycobacterial cultures were positive in 18% and 21% of children tested, and histopathology was positive in 88% of those biopsied. There were no adverse drug reactions necessitating change in therapy, and no inpatient mortality. Conclusions Extrathoracic TB was common, treatment well tolerated and clinical outcomes excellent. Culture confirmation rates were low and emphasize the need for improved diagnostics. PMID:24818967

Prevalence of suicidal behaviour & associated factors among tuberculosis patients in public primary care in South Africa

PubMed Central

Peltzer, Karl; Louw, Julia

2013-01-01

Background & objectives: In spite of the high prevalence of tuberculosis worldwide, there are only a few studies on its psychiatric complications such as suicidal behaviour. We undertook this study to assess the prevalence of suicidal behaviour and its associated factors among tuberculosis patients in public primary care in South Africa. Methods: In a cross-sectional survey conducted in three provinces of South Africa new TB and new re-treatment patients were assessed within one month of anti-tuberculosis treatment. The sample included 4900 (54.5% men and women 45.5%) consecutively selected tuberculosis patients from 42 public primary care clinics in three districts in South Africa. Results: A total of 322 patients (9.0%) reported suicidal ideation and 131 (3.1%) had a history of a suicide attempt. In multivariate analysis female gender [Odds Ratio (OR)= 0.56, Confidence Interval (CI)= 0.43-0.74], psychological distress (OR=2.36, CI=1.04-2.29), post-traumatic stress disorders (PTSD) (OR=4.98, CI=3.76-6.59), harmful alcohol use (OR=1.97, CI=1.25-3.09) and being a TB re-treatment patient (OR=1.76, CI=1.32-2.34) were associated with suicidal ideation, and psychological distress (OR=3.27, CI=1.51-7.10), PTSD symptoms (OR=4.48, CI=3.04-6.61) and harmful alcohol use (OR=3.01, CI=1.83-4.95) were associated with a suicide attempt. Interpretation & conclusions: Our findings suggest that co-morbid illnesses of psychological distress, PTSD and harmful alcohol use and HIV infection should be assessed in TB patients under TB control programmes to prevent suicidal behaviour. Clinicians should be aware about suicidality in tuberculosis patients to reduce mortality. PMID:24056595

Global Tuberculosis Report 2016

MedlinePlus

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

Diagnostic pathways and direct medical costs incurred by new adult pulmonary tuberculosis patients prior to anti-tuberculosis treatment – Tamil Nadu, India

PubMed Central

Veesa, Karun Sandeep; John, Kamalabhai Russell; Moonan, Patrick K.; Kaliappan, Saravanakumar Puthupalayam; Manjunath, Krishna; Sagili, Karuna D.; Ravichandra, Chinnappareddy; Menon, Pradeep Aravindan; Dolla, Chandrakumar; Luke, Nancy; Munshi, Kaivan; George, Kuryan; Minz, Shantidani

2018-01-01

Background Tuberculosis (TB) patients face substantial delays prior to treatment initiation, and out of pocket (OOP) expenditures often surpass the economic productivity of the household. We evaluated the pre-diagnostic cost and health seeking behaviour of new adult pulmonary TB patients registered at Primary Health Centres (PHCs) in Vellore district, Tamil Nadu, India. Methods This descriptive study, part of a randomised controlled trial conducted in three rural Tuberculosis Units from Dec 2012 to Dec 2015, collected data on number of health facilities, dates of visits prior to the initiation of anti-tuberculosis treatment, and direct OOP medical costs associated with TB diagnosis. Logistic regression analysis examined the factors associated with delays in treatment initiation and OOP expenditures. Results Of 880 TB patients interviewed, 34.7% presented to public health facilities and 65% patients sought private health facilities as their first point of care. The average monthly individual income was $77.79 (SD 57.14). About 69% incurred some pre-treatment costs at an average of $39.74. Overall, patients experienced a median of 6 days (3–11 IQR) of time to treatment initiation and 21 days (10–30 IQR) of health systems delay. Age ≤ 40 years (aOR: 1.73; CI: 1.22–2.44), diabetes (aOR: 1.63; CI: 1.08–2.44) and first visit to a private health facility (aOR: 17.2; CI: 11.1–26.4) were associated with higher direct OOP medical costs, while age ≤ 40 years (aOR: 0.64; CI: 0.48–0.85) and first visit to private health facility (aOR: 1.79, CI: 1.34–2.39) were associated with health systems delay. Conclusion The majority of rural TB patients registering at PHCs visited private health facilities first and incurred substantial direct OOP medical costs and delays prior to diagnosis and anti-tuberculosis treatment initiation. This study highlights the need for PHCs to be made as the preferred choice for first point of contact, to combat TB more efficiently. PMID:29414980

The Genotypic Population Structure of Mycobacterium tuberculosis Complex from Moroccan Patients Reveals a Predominance of Euro-American Lineages

PubMed Central

Lahlou, Ouafae; Millet, Julie; Chaoui, Imane; Sabouni, Radia; Filali-Maltouf, Abdelkarim; Akrim, Mohammed; El Mzibri, Mohammed; Rastogi, Nalin; El Aouad, Rajae

2012-01-01

Background Tuberculosis (TB) remains a major health problem in Morocco. Characterization of circulating Mycobacterium tuberculosis genotypic lineages, important to understand the dynamic of the disease, was hereby addressed for the first time at a national level. Methodology/Principal Findings Spoligotyping was performed on a panel of 592 M. tuberculosis complex strains covering a 2-year period (2004–2006). It identified 129 patterns: 105 (n = 568 strains) corresponded to a SIT number in the SITVIT2 database, while 24 patterns were labeled as orphan. A total of 523 (88.3%) strains were clustered vs. 69 or 11.7% unclustered. Classification of strains within 3 large phylogenetical groups was as follows: group 1– ancestral/TbD1+/PGG1 (EAI, Bovis, Africanum), group 2– modern/TbD1−/PGG1 group (Beijing, CAS), group 3– evolutionary recent/TbD1−/PGG2/3 (Haarlem, X, S, T, LAM; alternatively designated as the Euro-American lineage). As opposed to group 3 strains (namely LAM, Haarlem, and T) that predominated (86.5% of all isolates), 6 strains belonged to group 2 (Beijing n = 5, CAS n = 1), and 3 strains (BOV_1 n = 2, BOV_4-CAPRAE) belonged to ancestral group 1 (EAI and AFRI lineage strains were absent). 12-loci MIRU-VNTR typing of the Casablanca subgroup (n = 114 strains) identified 71 patterns: 48 MITs and 23 orphan patterns; it allowed to reduce the clustering rate from 72.8% to 29.8% and the recent transmission rate from 64% to 20.2%. Conclusion The M. tuberculosis population structure in Morocco is highly homogeneous, and is characterized by the predominance of the Euro-American lineages, namely LAM, Haarlem, and T, which belong to the “evolutionary recent” TbD1−/PGG2/3 phylogenetic group. The combination of spoligotyping and MIRUs decreased the clustering rate significantly, and should now be systematically applied in larger studies. The methods used in this study appear well suited to monitor the M. tuberculosis population structure for an enhanced TB management program in Morocco. PMID:23077552

OPC-67683, a Nitro-Dihydro-Imidazooxazole Derivative with Promising Action against Tuberculosis In Vitro and In Mice

PubMed Central

Matsumoto, Makoto; Hashizume, Hiroyuki; Tomishige, Tatsuo; Kawasaki, Masanori; Tsubouchi, Hidetsugu; Sasaki, Hirofumi; Shimokawa, Yoshihiko; Komatsu, Makoto

2006-01-01

Background Tuberculosis (TB) is still a leading cause of death worldwide. Almost a third of the world's population is infected with TB bacilli, and each year approximately 8 million people develop active TB and 2 million die as a result. Today's TB treatment, which dates back to the 1970s, is long and burdensome, requiring at least 6 mo of multidrug chemotherapy. The situation is further compounded by the emergence of multidrug-resistant TB (MDR-TB) and by the infection's lethal synergy with HIV/AIDS. Global health and philanthropic organizations are now pleading for new drug interventions that can address these unmet needs in TB treatment. Methods and Findings Here we report OPC-67683, a nitro-dihydro-imidazooxazole derivative that was screened to help combat the unmet needs in TB treatment. The compound is a mycolic acid biosynthesis inhibitor found to be free of mutagenicity and to possess highly potent activity against TB, including MDR-TB, as shown by its exceptionally low minimum inhibitory concentration (MIC) range of 0.006–0.024 μg/ml in vitro and highly effective therapeutic activity at low doses in vivo. Additionally, the results of the post-antibiotic effect of OPC-67683 on intracellular Mycobacterium tuberculosis showed the agent to be highly and dose-dependently active also against intracellular M. tuberculosis H37Rv after a 4-h pulsed exposure, and this activity at a concentration of 0.1 μg/ml was similar to that of the first-line drug rifampicin (RFP) at a concentration of 3 μg/ml. The combination of OPC-67683 with RFP and pyrazinamide (PZA) exhibited a remarkably quicker eradication (by at least 2 mo) of viable TB bacilli in the lung in comparison with the standard regimen consisting of RFP, isoniazid (INH), ethambutol (EB), and PZA. Furthermore, OPC-67683 was not affected by nor did it affect the activity of liver microsome enzymes, suggesting the possibility for OPC-67683 to be used in combination with drugs, including anti-retrovirals, that induce or are metabolized by cytochrome P450 enzymes. Conclusions We concluded that based on these properties OPC-67683 has the potential to be used as a TB drug to help combat the unmet needs in TB treatment. PMID:17132069

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

PubMed

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

2011-12-01

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

Tuberculosis of the Penis: A Review of the Literature.

PubMed

Venyo, Anthony Kodzo-Grey

2015-01-01

Background. Tuberculosis of the penis (TBP) is rare. Aim. To review the literature. Method. Various internet data bases were searched. Literature Review. TBP could be primary or secondary, may develop following circumcision performed by a person who had pulmonary Tb, and may be transmitted to the penis from ejaculation, contamination from clothing, or from contact with endometrial secretions, following an earlier pulmonary Tb or Tb elsewhere. TBP presents with a painless/painful small nodule, ulcer, mass on penis which gradually enlarges, and induration/swelling of penis, with or without erectile dysfunction. Inguinal lymph nodes may or may not be palpable. The patient's voiding is normal. There may or may not be history of circumcision, pulmonary Tb, and BCG immunization. TBP mimics penile carcinoma, granulomatous syphilis penile ulcer, genital herpes simplex, granuloma inguinale, and HIV infection. Diagnosis is established by microscopic examination finding of granulomas +/-AFB in penile discharge or biopsy of lesion or culture of Tb organism from discharge or biopsy specimens or positive Elisa serology/PCR for Tb. PTBs respond to first- or 2nd-line anti-Tb 6-month treatment. Close contacts should be screened. Extrapulmonary Tb should be excluded. Conclusions. Clinicians should consider possibility of PTB in cases of penile lesions and erectile failure.

Tuberculosis of the Penis: A Review of the Literature

PubMed Central

Venyo, Anthony Kodzo-Grey

2015-01-01

Background. Tuberculosis of the penis (TBP) is rare. Aim. To review the literature. Method. Various internet data bases were searched. Literature Review. TBP could be primary or secondary, may develop following circumcision performed by a person who had pulmonary Tb, and may be transmitted to the penis from ejaculation, contamination from clothing, or from contact with endometrial secretions, following an earlier pulmonary Tb or Tb elsewhere. TBP presents with a painless/painful small nodule, ulcer, mass on penis which gradually enlarges, and induration/swelling of penis, with or without erectile dysfunction. Inguinal lymph nodes may or may not be palpable. The patient's voiding is normal. There may or may not be history of circumcision, pulmonary Tb, and BCG immunization. TBP mimics penile carcinoma, granulomatous syphilis penile ulcer, genital herpes simplex, granuloma inguinale, and HIV infection. Diagnosis is established by microscopic examination finding of granulomas +/−AFB in penile discharge or biopsy of lesion or culture of Tb organism from discharge or biopsy specimens or positive Elisa serology/PCR for Tb. PTBs respond to first- or 2nd-line anti-Tb 6-month treatment. Close contacts should be screened. Extrapulmonary Tb should be excluded. Conclusions. Clinicians should consider possibility of PTB in cases of penile lesions and erectile failure. PMID:26435877

Drug resistant Mycobacterium tuberculosis in Mexico.

PubMed

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

2009-04-30

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

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

PubMed Central

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

2017-01-01

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

Resurrecting social infrastructure as a determinant of urban tuberculosis control in Delhi, India

PubMed Central

2014-01-01

Background The key to universal coverage in tuberculosis (TB) management lies in community participation and empowerment of the population. Social infrastructure development generates social capital and addresses the crucial social determinants of TB, thereby improving program performance. Recently, there has been renewed interest in the concept of social infrastructure development for TB control in developing countries. This study aims to revive this concept and highlight the fact that documentation on ways to operationalize urban TB control is required from a holistic development perspective. Further, it explains how development of social infrastructure impacts health and development outcomes, especially with respect to TB in urban settings. Methods A wide range of published Government records pertaining to social development parameters and TB program surveillance, between 2001 and 2011 in Delhi, were studied. Social infrastructure development parameters like human development index along with other indicators reflecting patient profile and habitation in urban settings were selected as social determinants of TB. These include adult literacy rates, per capita income, net migration rates, percentage growth in slum population, and percentage of urban population living in one-room dwelling units. The impact of the Revised National Tuberculosis Control Program on TB incidence was assessed as an annual decline in new TB cases notified under the program. Univariate linear regression was employed to examine the interrelationship between social development parameters and TB program outcomes. Results The decade saw a significant growth in most of the social development parameters in the State. TB program performance showed 46% increment in lives saved among all types of TB cases per 100,000 population. The 7% reduction in new TB case notifications from the year 2001 to 2011, translates to a logarithmic decline of 5.4 new TB cases per 100,000 population. Except per capita income, literacy, and net migration rates, other social determinants showed significant correlation with decline in new TB cases per 100,000 population. Conclusions Social infrastructure development leads to social capital generation which engenders positive growth in TB program outcomes. Strategies which promote social infrastructure development should find adequate weightage in the overall policy framework for urban TB control in developing countries. PMID:24438431

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

PubMed

Yang, Chongguang; Gao, Qian

2018-02-01

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

Altered serum microRNAs as biomarkers for the early diagnosis of pulmonary tuberculosis infection

PubMed Central

2012-01-01

Background Pulmonary tuberculosis (TB) is a highly lethal infectious disease and early diagnosis of TB is critical for the control of disease progression. The objective of this study was to profile a panel of serum microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary TB infection. Methods Using TaqMan Low-Density Array (TLDA) analysis followed by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validation, expression levels of miRNAs in serum samples from 30 patients with active tuberculosis and 60 patients with Bordetella pertussis (BP), varicella-zoster virus (VZV) and enterovirus (EV) were analyzed. Results The Low-Density Array data showed that 97 miRNAs were differentially expressed in pulmonary TB patient sera compared with healthy controls (90 up-regulated and 7 down-regulated). Following qRT-PCR confirmation and receiver operational curve (ROC) analysis, three miRNAs (miR-361-5p, miR-889 and miR-576-3p) were shown to distinguish TB infected patients from healthy controls and other microbial infections with moderate sensitivity and specificity (area under curve (AUC) value range, 0.711-0.848). Multiple logistic regression analysis of a combination of these three miRNAs showed an enhanced ability to discriminate between these two groups with an AUC value of 0.863. Conclusions Our study suggests that altered levels of serum miRNAs have great potential to serve as non-invasive biomarkers for early detection of pulmonary TB infection. PMID:23272999

HIV infection impairs Th1 and Th17 Mycobacterium tuberculosis-specific T cell responses

PubMed Central

Murray, Lyle W; Satti, Iman; Meyerowitz, Jodi; Jones, Matthew; Willberg, Christian B; Ussher, James E; Goedhals, Dominique; Hurst, Jacob; Phillips, Rodney E; McShane, Helen

2018-01-01

Background HIV-infected individuals have a higher risk of developing active tuberculosis than HIV-uninfected individuals, but the mechanisms underpinning this are unclear. We hypothesized that depletion of specific components of Mycobacterium tuberculosis (M.tb)-specific CD4+ and CD8+ T cell responses contributed to this increased risk. Methods M.tb-specific T cell responses in 147 HIV-infected and 44 HIV-uninfected control subjects in a TB-endemic setting in Bloemfontein, South Africa were evaluated. Using a whole-blood flow cytometry assay, we measured expression of IFNγ, TNFα, IL-2 and IL-17 in CD4+ and CD8+ T cells in response to M.tb antigens (PPD, ESAT-6/CFP-10 (EC) and DosR regulon-encoded α-crystallin (Rv2031c)). Results Fewer HIV-infected individuals had detectable CD4+ and CD8+ T cell responses to PPD and Rv2031c than HIV-uninfected subjects. M.tb-specific T cells showed distinct patterns of cytokine expression comprising both Th1 (CD4 and CD8) and Th17 (CD4) cytokines, the latter at highest frequency for Rv2031c. Th17 antigen-specific responses to all antigens tested were specifically impaired in HIV-infected individuals. Conclusions HIV-associated impairment of CD4+ and CD8+ M.tb-specific T cell responses is antigen-specific, particularly impacting responses to PPD and Rv2031c. Preferential depletion of Th17 cytokine-expressing CD4+ T cells suggests this T cell subset may be key to TB susceptibility in HIV-infected individuals. PMID:29546381

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

PubMed Central

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

2012-01-01

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

A Microbiological Revolution Meets an Ancient Disease: Improving the Management of Tuberculosis with Genomics

PubMed Central

Wlodarska, Marta; Johnston, James C.; Gardy, Jennifer L.

2015-01-01

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

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

PubMed

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

2015-03-01

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

Variants in toll-like receptor 9 gene influence susceptibility to tuberculosis in a Mexican population

PubMed Central

2013-01-01

Background The control of Mycobacterium tuberculosis (Mtb) infection begins with the recognition of mycobacterial structural components by toll like receptors (TLRs) and other pattern recognition receptors. Our objective was to determine the influence of TLRs polymorphisms in the susceptibility to develop tuberculosis (TB) in Amerindian individuals from a rural area of Oaxaca, Mexico with high TB incidence. Methods We carried out a case–control association community based study, genotyping 12 polymorphisms of TLR2, TLR4, TLR6 and TLR9 genes in 90 patients with confirmed pulmonary TB and 90 unrelated exposed but asymptomatic household contacts. Results We found a significant increase in the frequency of the allele A of the TLR9 gene polymorphism rs352139 (A>G) in the group of TB patients (g.f. = 0.522) when compared with controls (g.f. = 0.383), (Pcorr = 0.01, OR = 1.75). Under the recessive model (A/G + A/A vs G/G) this polymorphism was also significantly associated with TB (Pcorr = 0.01, OR= 2.37). The association of the SNP rs352139 was statistically significant after adjustment by age, gender and comorbidities by regression logistic analysis (Dominant model: p value = 0.016, OR = 2.31; Additive model: p value = 0.023, OR = 1.68). The haplotype GAA of TLR9 SNPs was also associated with TB susceptibility (Pcorr = 0.02). Differences in the genotype or allele frequencies of TLR2, TLR4 and TLR6 polymorphisms between TB patients and healthy contacts were not detected. Conclusions Our study suggests that the allele A of the intronic polymorphism rs352139 on TLR9 gene might contribute to the risk of developing TB in Mexican Amerindians. PMID:24053111

Tuberculosis and homelessness in Montreal: a retrospective cohort study

PubMed Central

2011-01-01

Background Montreal is Canada's second-largest city, where mean annual tuberculosis (TB) incidence from 1996 to 2007 was 8.9/100,000. The objectives of this study were to describe the epidemiology of TB among homeless persons in Montreal and assess patterns of transmission and sharing of key locations. Methods We reviewed demographic, clinical, and microbiologic data for all active TB cases reported in Montreal from 1996 to 2007 and identified persons who were homeless in the year prior to TB diagnosis. We genotyped all available Mycobacterium tuberculosis isolates by IS6110 restriction fragment length polymorphism (IS6110-RFLP) and spoligotyping, and used a geographic information system to identify potential locations for transmission between persons with matching isolates. Results There were 20 cases of TB in homeless persons, out of 1823 total reported from 1996-2007. 17/20 were Canadian-born, including 5 Aboriginals. Homeless persons were more likely than non-homeless persons to have pulmonary TB (20/20), smear-positive disease (17/20, odds ratio (OR) = 5.7, 95% confidence interval (CI): 1.7-20), HIV co-infection (12/20, OR = 14, 95%CI: 4.8-40), and a history of substance use. The median duration from symptom onset to diagnosis was 61 days for homeless persons vs. 28 days for non-homeless persons (P = 0.022). Eleven homeless persons with TB belonged to genotype-defined clusters (OR = 5.4, 95%CI: 2.2-13), and ten potential locations for transmission were identified, including health care facilities, homeless shelters/drop-in centres, and an Aboriginal community centre. Conclusions TB cases among homeless persons in Montreal raise concerns about delayed diagnosis and ongoing local transmission. PMID:22034944

Migrant and Refugee Patient Perspectives on Travel and Tuberculosis along the Thailand-Myanmar Border: A Qualitative Study

PubMed Central

Sein, Tabitha; Nosten, Francois; Foster, Angel M.

2016-01-01

Background The Thailand-Myanmar border separates two very different health systems. The healthcare system in eastern Myanmar remains underdeveloped as a result of decades of instability. Comparatively, Tak province, Thailand has more healthcare resources. In this Thai border province government hospitals and non-governmental organizations provide tuberculosis (TB) treatment to migrants and refugees. Objectives Our overall study aimed to explore accessibility of TB treatment, TB surveillance and health system responsiveness specific to migrant and refugee populations in Tak province. In this paper, we focus on the perspectives of migrant and refugee TB patients with respect to travel and treatment in Tak province. Methods In 2014 we conducted focus group discussions with 61 TB, Tuberculosis and Human Immunodeficiency Virus co-infection, and multidrug-resistant TB patients in Tak province. We analyzed the data for content and themes and documented individual travel trajectories. Results and Discussion Migrants are travelling with active TB within the country and between Thailand and Myanmar. Migrants primarily travelled to obtain treatment but two participants reported travelling home to seek family care in Myanmar before returning to Thailand for treatment. Travel, while expensive and arduous, is an adaptive strategy that migrants use to access healthcare. Conclusions Migrant’s need for travel points to larger difficulties associated with healthcare access in the border region. Long distance travel with an infectious disease can be seen as an indicator that local healthcare is not available or affordable. These findings suggest that public health officials from both sides of the border should discuss the factors that contribute to travel with active TB and explore potential solutions to mitigate disease transmission in migrant populations. PMID:27509036

A predictive signature gene set for discriminating active from latent tuberculosis in Warao Amerindian children

PubMed Central

2013-01-01

Background Tuberculosis (TB) continues to cause a high toll of disease and death among children worldwide. The diagnosis of childhood TB is challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. Whereas scientific and clinical research efforts to develop novel diagnostic tools have focused on TB in adults, childhood TB has been relatively neglected. Blood transcriptional profiling has improved our understanding of disease pathogenesis of adult TB and may offer future leads for diagnosis and treatment. No studies applying gene expression profiling of children with TB have been published so far. Results We identified a 116-gene signature set that showed an average prediction error of 11% for TB vs. latent TB infection (LTBI) and for TB vs. LTBI vs. healthy controls (HC) in our dataset. A minimal gene set of only 9 genes showed the same prediction error of 11% for TB vs. LTBI in our dataset. Furthermore, this minimal set showed a significant discriminatory value for TB vs. LTBI for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. In order to identify a robust representative gene set that would perform well in populations of different genetic backgrounds, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to classify 78% of the TB cases correctly with no LTBI subjects wrongly classified as TB (100% specificity). Conclusions Our data justify the further exploration of our signature set as biomarkers for potential childhood TB diagnosis. We show that, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts. PMID:23375113

Regulating the risk of tuberculosis transmission among health care workers.

PubMed

Nicas, M

2000-01-01

The 1994 Centers for Disease Control and Prevention guidelines on preventing tuberculosis (TB) transmission among health care workers (HCWs), and the 1997 Occupational Safety and Health Administration (OSHA) proposed TB standard, do not address the issue of acceptable risk. Further, many infection control personnel oppose OSHA's promulgating a standard because they believe most TB infections among HCWs are nonoccupational in origin. This article examines the relationship between TB infection and disease rates, and introduces a probability framework to apportion infection risk between occupational and nonoccupational exposure. It is argued that most TB infections among HCWs are work-related. A 0.2% overall annual risk of TB infection (accounting for both workplace and community exposure) is proposed as acceptable, because in the context of an infection surveillance program it limits an HCW's cumulative disease risk close to the value for the general United States population. Based on the probability framework, an estimate of the background community infection rate, and the traditional Wells-Riley risk model, it is shown that a target workplace infection risk value can be derived and expressed in terms of an expected pulmonary dose. The latter target dose informs risk management decision-making.

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

PubMed

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

2015-12-01

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

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

PubMed

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

2010-07-15

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

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

PubMed Central

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

2014-01-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed Central

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

2015-01-01

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

The Association Between Lung Carcinoma and Tuberculosis

PubMed Central

Cukic, Vesna

2017-01-01

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

Prevalence and Associated Factors of Tuberculosis in Prisons Settings of East Gojjam Zone, Northwest Ethiopia

PubMed Central

Hunegnaw, Emirie; Tiruneh, Moges

2017-01-01

Background Tuberculosis, mainly in prisoners, is a major public health problem in Ethiopia where there is no medical screening during prison admission. This creates scarcity of TB data in such settings. Objective To determine prevalence and associated factors of TB in prisons in East Gojjam Zone, Northwest Ethiopia. Methods A cross-sectional study was conducted from February to May 2016 among 265 prisoners in three prison sites. Sputum was processed using GeneXpert MTB/RIF. Data were analyzed using SPSS version 20.0. Multivariable logistic regression was used; p values = 0.05 were considered statistically significant. Results Of 265 prisoners, 9 (3.4%) were TB positive (males); 77.8%, 55.6%, and 55.6% of cases were rural dwellers, married, and farmers, respectively. Seven (2.6%) prisoners were HIV positive, and 3 (1.13%) had TB/HIV coinfection. One (0.4%) TB case was rifampicin resistant. Marriage (AOR = 1.5; 95% CI: 1.7, 13.03), HIV (AOR = 0.14; 95% CI: 0.001, 0.17), and sharing of rooms (AOR = 1.62; 95% CI: 2.6, 10.20) were predictors for TB. Conclusion Nine prisoners were TB positive. One case showed rifampicin resistance and three had TB/HIV coinfection. Marriage, HIV, and sharing of rooms were predictors for TB. Prevention/control and monitoring are mandatory in such settings. PMID:29226216

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2016-01-01

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

First Insights into the Phylogenetic Diversity of Mycobacterium tuberculosis in Nepal

PubMed Central

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

2012-01-01

Background Tuberculosis (TB) is a major public health problem in Nepal. Strain variation in Mycobacterium tuberculosis may influence the outcome of TB infection and disease. To date, the phylogenetic diversity of M. tuberculosis in Nepal is unknown. Methods and Findings We analyzed 261 M. tuberculosis isolates recovered from pulmonary TB patients recruited between August 2009 and August 2010 in Nepal. M. tuberculosis lineages were determined by single nucleotide polymorphisms (SNP) typing and spoligotyping. Drug resistance was determined by sequencing the hot spot regions of the relevant target genes. Overall, 164 (62.8%) TB patients were new, and 97 (37.2%) were previously treated. Any drug resistance was detected in 50 (19.2%) isolates, and 16 (6.1%) were multidrug-resistant. The most frequent M. tuberculosis lineage was Lineage 3 (CAS/Delhi) with 106 isolates (40.6%), followed by Lineage 2 (East-Asian lineage, includes Beijing genotype) with 84 isolates (32.2%), Lineage 4 (Euro-American lineage) with 41 (15.7%) isolates, and Lineage 1 (Indo-Oceanic lineage) with 30 isolates (11.5%). Based on spoligotyping, we found 45 different spoligotyping patterns that were previously described. The Beijing (83 isolates, 31.8%) and CAS spoligotype (52, 19.9%) were the dominant spoligotypes. A total of 36 (13.8%) isolates could not be assigned to any known spoligotyping pattern. Lineage 2 was associated with female sex (adjusted odds ratio [aOR] 2.58, 95% confidence interval [95% CI] 1.42–4.67, p = 0.002), and any drug resistance (aOR 2.79; 95% CI 1.43–5.45; p = 0.002). We found no evidence for an association of Lineage 2 with age or BCG vaccination status. Conclusions We found a large genetic diversity of M. tuberculosis in Nepal with representation of all four major lineages. Lineages 3 and 2 were dominating. Lineage 2 was associated with clinical characteristics. This study fills an important gap on the map of the M. tuberculosis genetic diversity in the Asian region. PMID:23300635

Obstacles for optimal tuberculosis case detection in primary health centers (PHC) in Sidoarjo district, East Java, Indonesia

PubMed Central

Wahyuni, Chatarina U; Budiono; Rahariyani, Lutfia Dwi; Sulistyowati, Muji; Rachmawati, Tety; Djuwari; Yuliwati, Sri; van der Werf, Marieke J

2007-01-01

Background Pulmonary tuberculosis (TB) is a major health problem worldwide. Detection of the most infectious cases of tuberculosis – sputum smear-positive pulmonary cases – by passive case finding is an essential component of TB control. The district of Sidoarjo in East Java reported a low case detection rate (CDR) of 14% in 2003. We evaluated the diagnostic process for TB in primary health care centers (PHC) in Sidoarjo district to assess whether problems in identification of TB suspects or in diagnosing TB patients can explain the low CDR. Methods We performed interviews with the staff (general nurse, TB worker, laboratory technician, and head of health center) of the 25 PHCs of Sidoarjo district to obtain information about the knowledge of TB, health education practices, and availability of support services for TB diagnosis. The quality of the laboratory diagnosis was examined by providing 10 slides with a known result to the laboratory technicians for re-examination. Results Eighty percent of the nurses and 84% of the TB workers knew that cough >3 weeks can be a symptom of TB. Only 40% of the nurses knew the cause of TB, few could mention complications of TB and none could mention the duration of infectiousness after start of treatment. Knowledge of TB workers was much better. Information about how to produce a good sputum sample was provided to TB suspects by 76% of the nurses and 84% of the TB workers. Only few provided all information. Fifty-five percent of the 11 laboratory technicians correctly identified all positive slides as positive and 45% correctly identified 100% of the negative slides as negative. All TB workers, one general nurses and 32% of the laboratory technicians had received specific training in TB control. There has been no shortage of TB forms and laboratory materials in 96% of the PHCs. Conclusion The quality of the diagnostic process for TB at PHC in Sidoarjo district should be improved on all levels. Training in TB control of all general nurses and the laboratory technicians that have not received training would be a good first step to enhance diagnosis of TB and to improve the case detection rate. PMID:17760984

Assessing Local Risk of Rifampicin-Resistant Tuberculosis in KwaZulu-Natal, South Africa Using Lot Quality Assurance Sampling

PubMed Central

Heidebrecht, Christine L.; Podewils, Laura J.; Pym, Alexander; Mthiyane, Thuli; Cohen, Ted

2016-01-01

Background KwaZulu-Natal (KZN) has the highest burden of notified multidrug-resistant tuberculosis (MDR TB) and extensively drug-resistant (XDR) TB cases in South Africa. A better understanding of spatial heterogeneity in the risk of drug-resistance may help to prioritize local responses. Methods Between July 2012 and June 2013, we conducted a two-way Lot Quality Assurance Sampling (LQAS) study to classify the burden of rifampicin (RIF)-resistant TB among incident TB cases notified within the catchment areas of seven laboratories in two northern and one southern district of KZN. Decision rules for classification of areas as having either a high- or low-risk of RIF resistant TB (based on proportion of RIF resistance among all TB cases) were based on consultation with local policy makers. Results We classified five areas as high-risk and two as low-risk. High-risk areas were identified in both Southern and Northern districts, with the greatest proportion of RIF resistance observed in the northernmost area, the Manguzi community situated on the Mozambique border. Conclusion Our study revealed heterogeneity in the risk of RIF resistant disease among incident TB cases in KZN. This study demonstrates the potential for LQAS to detect geographic heterogeneity in areas where access to drug susceptibility testing is limited. PMID:27050561

Association of Immune Factors with Drug-Resistant Tuberculosis: A Case-Control Study

PubMed Central

Sun, En-Tao; Xia, Dan; Li, Ben-He; Ma, Jun; Dong, Yuan-Yuan; Ding, Shu-Shu; Chen, Bai-Feng; Wen, Yu-Feng

2017-01-01

Background Presently, studies of factors associated with drug-resistant tuberculosis (TB) focus on patients’ socio-demographic characteristics and living habits, to the exclusion of biochemical indicators, especially immune factors. This study was carried out to determine whether immune factors are associated with drug-resistant TB. Material/Methods A total of 227 drug-resistant pulmonary TB patients and 225 drug-susceptible pulmonary TB patients were enrolled in this study. Information on socio-demographic characteristics and biochemical indicators were obtained through their clinical records. Non-conditional logistic regression was used to analyze the association of these indicators with drug-resistant TB. Results There were significant differences in re-treatment, marital status, alanine aminotransferase (ALT), blood uric acid (BUA), carcino-embryonic antigen (CEA), T-spot, and CD3 and CD4 counts between the 2 groups. In multivariable analysis, re-treatment [Odds Ratio (OR)=5.290, 95% Confidence Interval [CI]=2.652–10.551); CD3 (OR=1.034, 95% CI=1.001–1.068); CD4 (OR=1.035, 95% CI =1.001–1.070) and IgM (OR=1.845, 95% CI=1.153–2.952) were associated with drug-resistant TB. Conclusions These results suggest the need for greater attention to re-treatment cases and immune function when treating drug-resistant TB. PMID:29118314

Current ante-mortem techniques for diagnosis of bovine tuberculosis.

PubMed

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

2014-10-01

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

The current status, challenges, and future developments of new tuberculosis vaccines.

PubMed

Gong, Wenping; Liang, Yan; Wu, Xueqiong

2018-03-30

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.

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

PubMed

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

2018-05-11

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

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

PubMed

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

2017-07-01

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

Seasonality in pulmonary tuberculosis among migrant workers entering Kuwait

PubMed Central

Akhtar, Saeed; Mohammad, Hameed GHH

2008-01-01

Background There is paucity of data on seasonal variation in pulmonary tuberculosis (TB) in developing countries contrary to recognized seasonality in the TB notification in western societies. This study examined the seasonal pattern in TB diagnosis among migrant workers from developing countries entering Kuwait. Methods Monthly aggregates of TB diagnosis results for consecutive migrants tested between January I, 1997 and December 31, 2006 were analyzed. We assessed the amplitude (α) of the sinusoidal oscillation and the time at which maximum (θ°) TB cases were detected using Edwards' test. The adequacy of the hypothesized sinusoidal curve was assessed by χ2 goodness-of-fit test. Results During the 10 year study period, the proportion (per 100,000) of pulmonary TB cases among the migrants was 198 (4608/2328582), (95% confidence interval: 192 – 204). The adjusted mean monthly number of pulmonary TB cases was 384. Based on the observed seasonal pattern in the data, the maximum number of TB cases was expected during the last week of April (θ° = 112°; P < 0.001). The amplitude (± se) (α = 0.204 ± 0.04) of simple harmonic curve showed 20.4% difference from the mean to maximum TB cases. The peak to low ratio of adjusted number of TB cases was 1.51 (95% CI: 1.39 – 1.65). The χ2 goodness-of-test revealed that there was no significant (P > 0.1) departure of observed frequencies from the fitted simple harmonic curve. Seasonal component explained 55% of the total variation in the proportions of TB cases (100,000) among the migrants. Conclusion This regularity of peak seasonality in TB case detection may prove useful to institute measures that warrant a better attendance of migrants. Public health authorities may consider re-allocation of resources in the period of peak seasonality to minimize the risk of Mycobacterium tuberculosis infection to close contacts in this and comparable settings in the region having similar influx of immigrants from high TB burden countries. Epidemiological surveillance for the TB risk in the migrants in subsequent years and required chemotherapy of detected cases may contribute in global efforts to control this public health menace. PMID:18179720

Tuberculosis in Poland in 2014

PubMed

Korzeniewska-Koseła, Maria

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

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

PubMed

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

2015-02-01

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

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

PubMed Central

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

2013-01-01

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

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

PubMed Central

2011-01-01

Background Sudan is a large country with a diverse population and history of civil conflict. Poverty levels are high with a gross national income per capita of less than two thousand dollars. The country has a high burden of tuberculosis (TB) with an estimated 50,000 incident cases during 2009, when the estimated prevalence was 209 cases per 100,000 of the population. Few studies have been undertaken on TB in Sudan and the prevalence of drug resistant disease is not known. Methods In this study Mycobacterium tuberculosis isolates from 235 patients attending three treatment centers in Sudan were screened for susceptibility to isoniazid, rifampicin, ethambutol and streptomycin by the proportion method on Lowenstein Jensen media. 232 isolates were also genotyped by spoligotyping. Demographic details of patients were recorded using a structured questionnaire. Statistical analyses were conducted to examine the associations between drug resistance with risk ratios computed for a set of risk factors (gender, age, case status - new or relapse, geographic origin of the patient, spoligotype, number of people per room, marital status and type of housing). Results Multi drug-resistant tuberculosis (MDR-TB), being resistance to at least rifampicin and isoniazid, was found in 5% (95% CI: 2,8) of new cases and 24% (95% CI: 14,34) of previously treated patients. Drug resistance was associated with previous treatment with risk ratios of 3.51 (95% CI: 2.69-4.60; p < 0.001) for resistance to any drug and 5.23 (95% CI: 2.30-11.90; p < 0.001) for MDR-TB. Resistance was also associated with the geographic region of origin of the patient, being most frequently observed in patients from the Northern region and least in the Eastern region with risk ratios of 7.43 (95%CI:3.42,16.18; p: < 0.001) and 14.09 (95%CI:1.80,110.53; p:0.026) for resistance to any drug and MDR-TB. The major genotype observed was of the Central Asia spoligotype family (CAS1_Delhi), representing 49% of the 232 isolates examined. Conclusions We conclude that emergence of drug resistant tuberculosis has the potential to be a serious public health problem in Sudan and that strengthened tuberculosis control and improved monitoring of therapy is needed. Further surveillance is required to fully ascertain the extent of the problem. PMID:21846389

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2018-02-01

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

Urinary tuberculosis is associated with the development of urothelial carcinoma but not renal cell carcinoma: a nationwide cohort study in Taiwan

PubMed Central

Lien, Y-C; Wang, J-Y; Lee, M-C; Shu, C-C; Chen, H-Y; Hsieh, C-H; Lee, C-H; Lee, L-N; Chao, K-M

2013-01-01

Background: Obstructive uropathy and chronic urinary tract infection increase the risk of urinary tract cancer. Urinary tuberculosis (UTB) can cause chronic urinary tract inflammation, lead to obstructive uropathy, and potentially contribute to the development of urinary tract cancer. However, the association between UTB and urinary tract cancer has not been studied. Methods: This study enrolled 135 142 tuberculosis (TB) cases (male, 69%) from a nationwide health insurance research database in Taiwan and investigated the risk factors for urinary tract cancer, with emphasis on a history of UTB. The incidence of urinary tract cancer in the general population without TB was also calculated for comparison. Results: The TB patients had a mean age of 57.5±19.5 years. Of the 1287 UTB and 133 855 non-UTB patients, 15 (1.2%) and 396 (0.3%) developed urothelial carcinoma, respectively (P<0.001); and 2 (0.2%) and 96 (0.1%) developed renal cell carcinoma, respectively (P=0.240). Cox regression analysis revealed that age, male sex, end-stage renal disease, obstructive uropathy, arsenic intoxication, organ transplantation, and UTB (hazard ratio: 3.38 (2.01–5.69)) were independent risk factors for urothelial carcinoma. The hazard ratio of UTB was higher among female patients (5.26 (2.12–13.06)) than that among male patients (2.96 (1.57–5.60)). Conclusion: Urinary tuberculosis had a strong association with urothelial carcinoma, but not with renal cell carcinoma. In TB endemic areas, the urinary tract of TB patients should be scrutinised. It is also imperative that these patients be followed-up carefully in the post-treatment period, and urinalysis, ultrasonography or endoscopy should be an integral part of the follow-up. PMID:24129236

Detection of Tuberculosis in HIV-Infected and -Uninfected African Adults Using Whole Blood RNA Expression Signatures: A Case-Control Study

PubMed Central

Anderson, Suzanne T.; Bangani, Nonzwakazi; Banwell, Claire M.; Brent, Andrew J.; Crampin, Amelia C.; Dockrell, Hazel M.; Eley, Brian; Heyderman, Robert S.; Hibberd, Martin L.; Kern, Florian; Langford, Paul R.; Ling, Ling; Mendelson, Marc; Ottenhoff, Tom H.; Zgambo, Femia; Wilkinson, Robert J.; Coin, Lachlan J.; Levin, Michael

2013-01-01

Background A major impediment to tuberculosis control in Africa is the difficulty in diagnosing active tuberculosis (TB), particularly in the context of HIV infection. We hypothesized that a unique host blood RNA transcriptional signature would distinguish TB from other diseases (OD) in HIV-infected and -uninfected patients, and that this could be the basis of a simple diagnostic test. Methods and Findings Adult case-control cohorts were established in South Africa and Malawi of HIV-infected or -uninfected individuals consisting of 584 patients with either TB (confirmed by culture of Mycobacterium tuberculosis [M.TB] from sputum or tissue sample in a patient under investigation for TB), OD (i.e., TB was considered in the differential diagnosis but then excluded), or healthy individuals with latent TB infection (LTBI). Individuals were randomized into training (80%) and test (20%) cohorts. Blood transcriptional profiles were assessed and minimal sets of significantly differentially expressed transcripts distinguishing TB from LTBI and OD were identified in the training cohort. A 27 transcript signature distinguished TB from LTBI and a 44 transcript signature distinguished TB from OD. To evaluate our signatures, we used a novel computational method to calculate a disease risk score (DRS) for each patient. The classification based on this score was first evaluated in the test cohort, and then validated in an independent publically available dataset (GSE19491). In our test cohort, the DRS classified TB from LTBI (sensitivity 95%, 95% CI [87–100]; specificity 90%, 95% CI [80–97]) and TB from OD (sensitivity 93%, 95% CI [83–100]; specificity 88%, 95% CI [74–97]). In the independent validation cohort, TB patients were distinguished both from LTBI individuals (sensitivity 95%, 95% CI [85–100]; specificity 94%, 95% CI [84–100]) and OD patients (sensitivity 100%, 95% CI [100–100]; specificity 96%, 95% CI [93–100]). Limitations of our study include the use of only culture confirmed TB patients, and the potential that TB may have been misdiagnosed in a small proportion of OD patients despite the extensive clinical investigation used to assign each patient to their diagnostic group. Conclusions In our study, blood transcriptional signatures distinguished TB from other conditions prevalent in HIV-infected and -uninfected African adults. Our DRS, based on these signatures, could be developed as a test for TB suitable for use in HIV endemic countries. Further evaluation of the performance of the signatures and DRS in prospective populations of patients with symptoms consistent with TB will be needed to define their clinical value under operational conditions. Please see later in the article for the Editors' Summary PMID:24167453

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

PubMed

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

2016-01-01

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

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

PubMed

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

2017-06-01

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

Care seeking and attitudes towards treatment compliance by newly enrolled tuberculosis patients in the district treatment programme in rural western Kenya: a qualitative study

PubMed Central

2011-01-01

Background The two issues mostly affecting the success of tuberculosis (TB) control programmes are delay in presentation and non-adherence to treatment. It is important to understand the factors that contribute to these issues, particularly in resource limited settings, where rates of tuberculosis are high. The objective of this study is to assess health-seeking behaviour and health care experiences among persons with pulmonary tuberculosis, and identify the reasons patients might not complete their treatment. Methods We performed qualitative one-on-one in-depth interviews with pulmonary tuberculosis patients in nine health facilities in rural western Kenya. Thirty-one patients, 18 women and 13 men, participated in the study. All reside in an area of western Kenya with a Health and Demographic Surveillance System (HDSS). They had attended treatment for up to 4 weeks on scheduled TB clinic days in September and October 2005. The nine sites all provide diagnostic and treatment services. Eight of the facilities were public (3 hospitals and 5 health centres) and one was a mission health centre. Results Most patients initially self-treated with herbal remedies or drugs purchased from kiosks or pharmacies before seeking professional care. The reported time from initial symptoms to TB diagnosis ranged from 3 weeks to 9 years. Misinterpretation of early symptoms and financial constraints were the most common reasons reported for the delay. We also explored potential reasons that patients might discontinue their treatment before completing it. Reasons included being unaware of the duration of TB treatment, stopping treatment once symptoms subsided, and lack of family support. Conclusions This qualitative study highlighted important challenges to TB control in rural western Kenya, and provided useful information that was further validated in a quantitative study in the same area. PMID:21714895

TUBERCULOSIS BURDEN IN LEBANON: EVOLUTION AND CURRENT STATUS.

PubMed

Araj, George F; Saade, Antoine; Itani, Lina Y; Avedissian, Aline Z

2016-01-01

In the absence of surveillance data and consolidated information about tuberculosis (TB) and its drug resistance burden in Lebanon, this retrospective study was conducted to shed light on TB and its other relevant aspects over the last 15 years in this country. To generate the TB data for this retrospective study, two main sources were used: 1) the records of patients in the National Tuberculosis Program (NTP); 2) the results of the Clinical Microbiology Laboratory (CML) at the American University of Beirut Medical Center (AUBMC). The TB data review pertained to its epidemiological aspect, implementation of the directly observed therapy strategy (DOTS) all over, the gender distribution, the impact of high risk groups (non-national population, Syrian refugees, patients with multi-drug resistance-TB [MDR-TB] and the inmate population) on the trend of TB in Lebanon between 1999 and 2013. Reviewed also are TB in children, extrapulmonary tuberculosis and the mycobacterium other than tuberculosis (MOTT). During the last 15 years, 7548 TB cases were diagnosed and evaluated at the NTP. After the decreasing of TB incidence from 13/100 000 population in 2001 to 9/100 000 in 2006, the incidence started to increase in 2007, reaching 20/100 000 in 2013, mostly due to increased cases among non-national population. Fluctuations in TB rates over the years were seen among children, inmates, MDR-TB, and HIV patients. MOTT isolates recovery rates also fluctuated during the study period, M. simiae being the most common. After the decreasing trends of TB incidence between 1999 and 2006, Lebanon has been experiencing an increasing incidence in tuberculosis population since 2007. This is mainly attributed to the dramatic increase of TB patients among non-nationals and the influx of Syrian refugees. The ongoing collaboration between the public and private sectors, improvements of the surveillance system and TB control are important factors for successful elimination of TB in this country.

Demographic and Socioeconomic Disparity in Knowledge About Tuberculosis in Inner Mongolia, China

PubMed Central

Ma, Enbo; Ren, Liping; Wang, Wensheng; Takahashi, Hideto; Wagatsuma, Yukiko; Ren, Yulin; Gao, Fei; Gao, Fangfang; Wang, Wenrui; Bi, Lifu

2015-01-01

Background The aim of this study is to evaluate the awareness status, attitudes, and care-seeking behaviors concerning tuberculosis (TB) and associated factors among the public in Inner Mongolia, China. Methods A five-stage sampling was conducted, in which counties as the primary survey units and towns, villages, and households as sub-survey units were selected progressively. A standardized questionnaire was used to collect TB information. Complex survey analysis methods, including the procedures of survey frequency and survey logistic regression, were applied for analysis of TB knowledge and associated factors. The sample was weighted by survey design, non-respondent, and post-stratification adjustment. Results Among 10 581 respondents, awareness that TB is an infectious disease was 86.7%. Knowing that a cough lasting ≥3 weeks is suggestive of TB was 26.9%. Knowledge about TB dispensaries in county administrative areas was reported by 68.3% of respondents, and knowledge about the free TB detection/treatment policy was reported by 57.5% of respondents. About 52.5% of participants would stigmatize TB patients. Compared with the majority Han ethnic group, Mongolians and other minorities were 1.52–2.18 times more likely to know about TB curability, TB symptoms, the free detection/treatment policy, and TB dispensaries’ locations, but were less likely to know about the TB transmission mode (odds ratio, 0.74; 95% confidence interval, 0.65–0.84). The main sources of TB information were TV (65.6%) and other persons (47.2%). In the past year, 19.7% of TB knowledge was from acquaintances, and 16.1% was from TB institutes. Conclusions Improvement in knowledge about TB risk (symptoms and transmission), the free treatment policy, and facilities is necessary and should be provided through effective multimedia for different target populations. PMID:25797599

Mycobacterium tuberculosis causing tuberculous lymphadenitis in Maputo, Mozambique.

PubMed

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

2015-11-21

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

Molecular characterisation of Mycobacterium tuberculosis isolates in the First National Survey of Anti-tuberculosis Drug Resistance from Venezuela

PubMed Central

Aristimuño, Liselotte; Armengol, Raimond; Cebollada, Alberto; España, Mercedes; Guilarte, Alexis; Lafoz, Carmen; Lezcano, María A; Revillo, María J; Martín, Carlos; Ramírez, Carmen; Rastogi, Nalin; Rojas, Janet; de Salas, Albina Vázques; Sola, Christophe; Samper, Sofía

2006-01-01

Background Molecular typing of Mycobacterium tuberculosis strains has become a valuable tool in the epidemiology of tuberculosis (TB) by allowing detection of outbreaks, tracking of epidemics, identification of genotypes and transmission events among patients who would have remained undetected by conventional contact investigation. This is the first genetic biodiversity study of M. tuberculosis in Venezuela. Thus, we investigated the genetic patterns of strains isolated in the first survey of anti-tuberculosis drug-resistance realised as part of the Global Project of Anti-tuberculosis Drug Resistance Surveillance (WHO/IUATLD). Results Clinical isolates (670/873) were genotyped by spoligotyping. The results were compared with the international spoligotyping database (SpolDB4). Multidrug resistant (MDR) strains (14/18) were also analysed by IS6110-RFLP assays, and resistance to isoniazid and rifampicin was characterised. Spoligotyping grouped 82% (548/670) of the strains into 59 clusters. Twenty new spoligotypes (SITs) specific to Venezuela were identified. Eight new inter-regional clusters were created. The Beijing genotype was not found. The genetic network shows that the Latin American and Mediterranean family constitutes the backbone of the genetic TB population-structure in Venezuela, responsible of >60% of total TB cases studied. MDR was 0.5% in never treated patients and 13.5% in previously treated patients. Mutations in rpoB gene and katG genes were detected in 64% and 43% of the MDR strains, respectively. Two clusters were found to be identical by the four different analysis methods, presumably representing cases of recent transmission of MDR tuberculosis. Conclusion This study gives a first overview of the M. tuberculosis strains circulating in Venezuela during the first survey of anti-tuberculosis drug-resistance. It may aid in the creation of a national database that will be a valuable support for further studies. PMID:17032442

Framework for Establishment of a Comprehensive and Standardized Administration System for Prevention and Control of Tuberculosis in College Student Community in China

PubMed Central

ZHANG, Shaoru; LI, Xiaohong; ZHANG, Tianhua; WANG, Xiangni; LIU, Weiping; MA, Xuexue; LI, Yuelu; FAN, Yahui

2016-01-01

Background: College student community is the one with high risk of tuberculosis (TB). A systemic and standardized administration model for prevention and control of TB is significance in controlling TB spread in universities. Currently, the universities in China have not established the comprehensive and standardized administration system for TB prevention and control in college student community. Methods: Firstly, the literature research and brainstorming method (n=13) were used to construct the clause and sub-clause pool for the administration of TB prevention and control within college student community in 2014. Secondly, a total of twenty experts in the field of TB prevention and control who are representatives of the east, west, south and north parts of China were selected and invited to participate the Delphi letter-inquiry. After two rounds of letter-inquiry, the opinions of the experts reached a consensus and the framework for the administration system was constructed. Results: A framework for the administration system was constructed, which included 8 first class indexes, 26 second class indexes and 104 third class indexes. Conclusion: The results are highly scientific and reliable, which can be helpful for improving the systemic and standardized levels for the administration of TB prevention and control in universities in China and perhaps in other developing counties with high TB burden as well. PMID:27957436

Effect of Non-tuberculous Mycobacteria on Host Biomarkers Potentially Relevant for Tuberculosis Management

PubMed Central

Dhanasekaran, S.; Jenum, Synne; Stavrum, Ruth; Wiker, Harald G.; Kenneth, John; Vaz, Mario; Doherty, T. Mark; Grewal, Harleen M. S.

2014-01-01

Background Non-tuberculous mycobacteria (NTM) are different from Mycobacterium tuberculosis (MTB) both in their ubiquitous environmental distribution and in their reduced capacity to cause disease. While often neglected in favour of other infectious diseases, NTM may interfere with important aspects of TB control and management, namely the efficacy of new anti-tuberculosis (TB) vaccines; the immuno-diagnostic Tuberculin skin test (TST) and QuantiFERON TB Gold In Tube assay (QFTGIT); and immune biomarkers explored for their diagnostic and/or predictive potential. Our objective was therefore to explore host immune biomarkers in children who had NTM isolated from respiratory and/or gastric specimens. Methodology and Principle Findings The present study was nested within a prospective cohort study of BCG-vaccinated neonates in Southern India. In this setting, immune biomarkers from peripheral blood were analyzed in 210 children aged <3 years evaluated for TB using dual-colour-Reverse-Transcriptase-Multiple-Ligation-dependent-Probe-Amplification (dcRT-MLPA) and Bio-Plex assays. The children were classified based on clinical examination, chest X-rays and mycobacterial culture reports as either: 1) TB disease, 2) NTM present and 3) controls. The study shows a down-regulation of RAB33A (p<0.001) and up-regulation of TGFβ1, IL-2 and IL-6 (all p<0.05) in children with TB disease, and that RAB33A, TGFBR2 and IL-10 (all p<0.05) were differentially expressed in children with NTM present when compared to children that were culture negative for MTB and NTM (controls). Conclusions and Significance Carriage of NTM may reduce the specificity of future diagnostic and predictive immune biomarkers relevant to TB management. PMID:25329719

Barriers to initiating tuberculosis treatment in sub-Saharan Africa: a systematic review focused on children and youth

PubMed Central

Sullivan, Brittney J.; Esmaili, B. Emily; Cunningham, Coleen K.

2017-01-01

ABSTRACT Background: Tuberculosis (TB) is the deadliest infectious disease globally, with 10.4 million people infected and more than 1.8 million deaths in 2015. TB is a preventable, treatable, and curable disease, yet there are numerous barriers to initiating treatment. These barriers to treatment are exacerbated in low-resource settings and may be compounded by factors related to childhood. Objective: Timely initiation of tuberculosis (TB) treatment is critical to reducing disease transmission and improving patient outcomes. The aim of this paper is to describe patient- and system-level barriers to TB treatment initiation specifically for children and youth in sub-Saharan Africa through systematic review of the literature. Design: This review was conducted in October 2015 in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Six databases were searched to identify studies where primary or secondary objectives were related to barriers to TB treatment initiation and which included children or youth 0–24 years of age. Results: A total of 1490 manuscripts met screening criteria; 152 met criteria for full-text review and 47 for analysis. Patient-level barriers included limited knowledge, attitudes and beliefs regarding TB, and economic burdens. System-level barriers included centralization of services, health system delays, and geographical access to healthcare. Of the 47 studies included, 7 evaluated cost, 19 health-seeking behaviors, and 29 health system infrastructure. Only 4 studies primarily assessed pediatric cohorts yet all 47 studies were inclusive of children. Conclusions: Recognizing and removing barriers to treatment initiation for pediatric TB in sub-Saharan Africa are critical. Both patient- and system-level barriers must be better researched in order to improve patient outcomes. PMID:28598771

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

PubMed

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

2013-01-01

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

Results of the Implementation of a Pilot Model for the Bidirectional Screening and Joint Management of Patients with Pulmonary Tuberculosis and Diabetes Mellitus in Mexico

PubMed Central

Castellanos-Joya, Martín; Delgado-Sánchez, Guadalupe; Ferreyra-Reyes, Leticia; Cruz-Hervert, Pablo; Ferreira-Guerrero, Elizabeth; Ortiz-Solís, Gabriela; Jiménez, Mirtha Irene; Salazar, Leslie Lorena; Montero-Campos, Rogelio; Mongua-Rodríguez, Norma; Baez-Saldaña, Renata; Bobadilla-del-Valle, Miriam; González-Roldán, Jesús Felipe; Ponce-de-León, Alfredo; Sifuentes-Osornio, José; García-García, Lourdes

2014-01-01

Background Recently, the World Health Organisation and the International Union Against Tuberculosis and Lung Disease published a Collaborative Framework for the Care and Control of Tuberculosis (TB) and Diabetes (DM) (CFTB/DM) proposing bidirectional screening and joint management. Objective To evaluate the feasibility and effectiveness of the CFTB/DM in Mexico. Design. Prospective observational cohort. Setting. 15 primary care units in 5 states in Mexico. Participants: Patients aged ≥20 years diagnosed with DM or pulmonary TB who sought care at participating clinics. Intervention: The WHO/Union CFTB/DM was adapted and implemented according to official Mexican guidelines. We recruited participants from July 2012 to April 2013 and followed up until March 2014. Bidirectional screening was performed. Patients diagnosed with TB and DM were invited to receive TB treatment under joint management. Main outcome measures. Diagnoses of TB among DM, of DM among TB, and treatment outcomes among patients with DM and TB. Results Of 783 DM patients, 11 (1.4%) were unaware of their TB. Of 361 TB patients, 16 (4.4%) were unaware of their DM. 95 TB/DM patients accepted to be treated under joint management, of whom 85 (89.5%) successfully completed treatment. Multiple linear regression analysis with change in HbA1c and random capillary glucose as dependent variables revealed significant decrease with time (regression coefficients (β)  = −0.660, (95% confidence interval (CI), −0.96 to −0.35); and β = −1.889 (95% CI, −2.77 to −1.01, respectively)) adjusting by sex, age and having been treated for a previous TB episode. Patients treated under joint management were more likely to experience treatment success than patients treated under routine DM and TB programs as compared to historical (adjusted OR (aOR), 2.8, 95%CI 1.28–6.13) and same period (aOR 2.37, 95% CI 1.13–4.96) comparison groups. Conclusions Joint management of TB and DM is feasible and appears to improve clinical outcomes. PMID:25229236

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

PubMed

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

2018-01-01

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

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

PubMed Central

Prasad, Rajendra; Gupta, Nikhil; Banka, Amitabh

2018-01-01

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

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

PubMed

Prasad, Rajendra; Gupta, Nikhil; Banka, Amitabh

2018-01-01

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

Tuberculosis

MedlinePlus

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

Tuberculosis-resistant transgenic cattle

USDA-ARS?s Scientific Manuscript database

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

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

PubMed

Mitrzyk, Beatriz Manzor

2008-10-01

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

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

PubMed

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

2013-11-01

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

Genetic diversity of the Mycobacterium tuberculosis Complex in San Luis Potosí, México

PubMed Central

2013-01-01

Background Although epidemiologic and socioeconomic criteria and biomedical risk factors indicate high-priority for tuberculosis (TB) control in Mexico, molecular epidemiology studies of the disease in the country are scarce. Methods Complete sociodemographic and clinical data were obtained from 248 of the 432 pulmonary TB (PTB) cases confirmed from 2006 to 2010 on the population under epidemiological surveillance in the state of San Luis Potosí, México. From most PTB cases with complete data Mycobacterium tuberculosis complex (MTC) isolates were recovered and their spoligotypes, lineages and families, geographic distribution and drug resistance determined. Results Pulmonary tuberculosis incidence ranged from 2.4 to 33.4 (cases per 100,000 inhabitants) in the six state sanitary jurisdictions that were grouped in regions of low (jurisdictions I-II-III), intermediate (jurisdictions IV-V) and high incidence (jurisdiction VI) with 6.2, 17.3 and 33.4 rates, respectively. Most patients were poor, 50-years-median-age males and housewives. Among the 237 MTC spoligotyped isolates, 232 corresponded to M. tuberculosis (104 spoligotypes in 24 clusters) and five to M. bovis. The predominant Euro-American lineage was distributed all over the state, the East-Asian lineage (Beijing family) in the capital city, the Indo-Oceanic (Manila family) in eastern localities, and M. bovis in rural localities. Conclusions In San Luis Potosí TB affects mainly poor male adults and is caused by M. tuberculosis and to a minor extent by M. bovis. There is great genotypic diversity among M. tuberculosis strains, the Euro-American lineage being much more prevalent than the Indo-Oceanic and East-Asian lineages. The frequency of resistant strains is relatively low and not associated to any particular lineage. PMID:23635381

Research Questions and Priorities for Tuberculosis: A Survey of Published Systematic Reviews and Meta-Analyses

PubMed Central

Nicolau, Ioana; Ling, Daphne; Tian, Lulu; Lienhardt, Christian; Pai, Madhukar

2012-01-01

Background Systematic reviews are increasingly informing policies in tuberculosis (TB) care and control. They may also be a source of questions for future research. As part of the process of developing the International Roadmap for TB Research, we did a systematic review of published systematic reviews on TB, to identify research priorities that are most frequently suggested in reviews. Methodology/Principal Findings We searched EMBASE, MEDLINE, Web of Science, and the Cochrane Library for systematic reviews and meta-analyses on any aspect of TB published between 2005 and 2010. One reviewer extracted data and a second reviewer independently extracted data from a random subset of included studies. In total, 137 systematic reviews, with 141 research questions, were included in this review. We used the UK Health Research Classification System (HRCS) to help us classify the research questions and priorities. The three most common research topics were in the area of detection, screening and diagnosis of TB (32.6%), development and evaluation of treatments and therapeutic interventions (23.4%), and TB aetiology and risk factors (19.9%). The research priorities determined were mainly focused on the discovery and evaluation of bacteriological TB tests and drug-resistant TB tests and immunological tests. Other important topics of future research were genetic susceptibility linked to TB and disease determinants attributed to HIV/TB. Evaluation of drug treatments for TB, drug-resistant TB and HIV/TB were also frequently proposed research topics. Conclusions Systematic reviews are a good source of key research priorities. Findings from our survey have informed the development of the International Roadmap for TB Research by the TB Research Movement. PMID:22848764

Lower Pre-Treatment T Cell Activation in Early- and Late-Onset Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome

PubMed Central

Goovaerts, Odin; Jennes, Wim; Massinga-Loembé, Marguerite; Ondoa, Pascale; Ceulemans, Ann; Vereecken, Chris; Worodria, William; Mayanja-Kizza, Harriet; Colebunders, Robert; Kestens, Luc

2015-01-01

Background Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) is an inflammatory complication in HIV-TB co-infected patients receiving antiretroviral therapy (ART). The role of disturbed T cell reconstitution in TB-IRIS is not well understood. We investigated T cell activation and maturation profiles in patients who developed TB-IRIS at different intervals during ART. Methods Twenty-two HIV-TB patients who developed early-onset TB-IRIS and 10 who developed late-onset TB-IRIS were matched for age, sex and CD4 count to equal numbers of HIV-TB patients who did not develop TB-IRIS. Flow cytometry analysis was performed on fresh blood, drawn before and after ART initiation and during TB-IRIS events. T cell activation and maturation was measured on CD4+ and CD8+ T cells using CD45RO, CD38, HLA-DR, CCR7 and CD27 antibodies. Results CD8+ T cell activation before ART was decreased in both early-onset (77% vs. 82%, p = 0.014) and late-onset (71% vs. 83%, p = 0.012) TB-IRIS patients compared to non-IRIS controls. After ART initiation, the observed differences in T cell activation disappeared. During late-onset, but not early-onset TB-IRIS, we observed a skewing from memory to terminal effector CD4+ and CD8+ T cell populations (p≤0.028). Conclusion Our data provide evidence of reduced CD8+ T cell activation before ART as a common predisposing factor of early- and late-onset TB-IRIS. The occurrence of TB-IRIS itself was not marked by an over-activated CD8+ T cell compartment. Late- but not early-onset TB-IRIS was characterized by a more terminally differentiated T cell phenotype. PMID:26208109

Tuberculosis Data and Statistics

MedlinePlus

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

Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study

PubMed Central

2013-01-01

Background Identifying people at higher risk of developing tuberculosis with human immunodeficiency virus (HIV) infection may improve clinical management of co-infections. Iron influences tuberculosis (TB) pathogenesis, but understanding the exact mechanisms of how and timing of when iron is involved remains challenging since biological samples are rarely available from the disease susceptibility period due to the difficulty in predicting in who and when, if ever, TB will develop. The objective of this research was to determine how host iron status measured at HIV diagnosis and genotypes related to host iron metabolism were associated with incident TB. Methods Archived clinical data, plasma and DNA were analyzed from 1139 adult participants in a large HIV-1, HIV-2 and dual seroprevalent cohort based at the Medical Research Council Laboratories in The Gambia. Incident pulmonary and/or extrapulmonary TB diagnoses a minimum of 28 days after HIV diagnosis were independently re-confirmed using available evidence (n=152). Multiple host iron status biomarkers, Haptoglobin and solute carrier family 11, member 1 (SLC11A1) genotypes were modeled to characterize how indicators of host iron metabolism were associated with TB susceptibility. Results Hemoglobin (incidence rate ratio, IRR=0.88, 95% CI=0.79-0.98), plasma transferrin (IRR=0.53, 0.33-0.84) and ferritin (IRR=1.26, 1.05-1.51) were significantly associated with TB after adjusting for TB susceptibility factors. While genotype associations were not statistically significant, SLC11A1 associations replicated similar directions as reported in HIV-seronegative meta-analyses. Conclusions Evidence of host iron redistribution at HIV diagnosis was associated with incident TB, and genetic influences on iron homeostasis may be involved. Low hemoglobin was associated with subsequent diagnosis of TB, but when considered in combination with additional iron status biomarkers, the collective findings point to a mechanism whereby anemia and iron redistribution are likely due to viral and/or bacteria-driven processes and the host immune response to infection. As a result, iron supplementation may not be efficacious or safe under these circumstances. Clinical and nutritional management of HIV and Mycobacterium tuberculosis co-infected individuals, especially in regions where food insecurity and malnutrition co-exist, may be further improved when the iron-related TB risk factors identified here are better understood and managed to favor host rather than pathogen outcomes. PMID:23360117

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

PubMed Central

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

2012-01-01

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

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

NASA Astrophysics Data System (ADS)

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

2017-03-01

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

Activities of the Korean Institute of Tuberculosis

PubMed Central

Ryoo, Sungweon; Kim, Hee Jin

2014-01-01

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

MIC of Delamanid (OPC-67683) against Mycobacterium tuberculosis Clinical Isolates and a Proposed Critical Concentration

PubMed Central

Stinson, Kelly; Kurepina, Natalia; Venter, Amour; Fujiwara, Mamoru; Kawasaki, Masanori; Timm, Juliano; Shashkina, Elena; Kreiswirth, Barry N.; Liu, Yongge

2016-01-01

The increasing global burden of multidrug-resistant tuberculosis (MDR-TB) requires reliable drug susceptibility testing that accurately characterizes susceptibility and resistance of pathogenic bacteria to effectively treat patients with this deadly disease. Delamanid is an anti-TB agent first approved in the European Union in 2014 for the treatment of pulmonary MDR-TB in adults. Using the agar proportion method, delamanid MIC was determined for 460 isolates: 316 from patients enrolled in a phase 2 global clinical trial, 76 from two phase 2 early bactericidal activity trials conducted in South Africa, and 68 isolates obtained outside clinical trials (45 from Japanese patients and 23 from South African patients). With the exception of two isolates, MICs ranged from 0.001 to 0.05 μg/ml, resulting in an MIC50 of 0.004 μg/ml and an MIC90 of 0.012 μg/ml. Various degrees of resistance to other anti-TB drugs did not affect the distribution of MICs, nor did origin of isolates from regions/countries other than South Africa. A critical concentration/breakpoint of 0.2 μg/ml can be used to define susceptible and resistant isolates based on the distribution of MICs and available pharmacokinetic data. Thus, clinical isolates from delamanid-naive patients with tuberculosis have a very low MIC for delamanid and baseline resistance is rare, demonstrating the potential potency of delamanid and supporting its use in an optimized background treatment regimen for MDR-TB. PMID:26976868

Admixed Phylogenetic Distribution of Drug Resistant Mycobacterium tuberculosis in Saudi Arabia

PubMed Central

Varghese, Bright; Supply, Philip; Allix-Béguec, Caroline; Shoukri, Mohammed; Al-Omari, Ruba; Herbawi, Mais; Al-Hajoj, Sahal

2013-01-01

Background The phylogeographical structure of Mycobacterium tuberculosis is generally bimodal in low tuberculosis (TB) incidence countries, where genetic lineages of the isolates generally differ with little strain clustering between autochthonous and foreign-born TB patients. However, less is known on this structure in Saudi Arabia—the most important hub of human migration as it hosts a total population of expatriates and pilgrims from all over the world which is equal to that of its citizens. Methodology We explored the mycobacterial phylogenetic structure and strain molecular clustering in Saudi Arabia by genotyping 322 drug-resistant clinical isolates collected over a 12-month period in a national drug surveillance survey, using 24 locus-based MIRU-VNTR typing and spoligotyping. Principal Findings In contrast to the cosmopolitan population of the country, almost all the known phylogeographic lineages of M. tuberculosis complex (with noticeable exception of Mycobacterium africanum/West-African 1 and 2) were detected, with Delhi/CAS (21.1%), EAI (11.2%), Beijing (11.2%) and main branches of the Euro-American super-lineage such as Ghana (14.9%), Haarlem (10.6%) and Cameroon (7.8%) being represented. Statistically significant associations of strain lineages were observed with poly-drug resistance and multi drug resistance especially among previously treated cases (p value of < = 0.001 for both types of resistance), with relative over-representation of Beijing strains in the latter category. However, there was no significant difference among Saudi and non-Saudi TB patients regarding distribution of phylogenetic lineages (p = 0.311). Moreover, 59.5% (22/37) of the strain molecular clusters were shared between the Saudi born and immigrant TB patients. Conclusions Specific distribution of M. tuberculosis phylogeographic lineages is not observed between the autochthonous and foreign-born populations. These observations might reflect both socially favored ongoing TB transmission between the two population groups, and historically deep-rooted, prolonged contacts and trade relations of the peninsula with other world regions. More vigorous surveillance and strict adherence to tuberculosis control policies are urgently needed in the country. PMID:23383340

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

PubMed

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

2018-06-01

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

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

PubMed Central

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

2016-01-01

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

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

PubMed

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

2017-01-01

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

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

PubMed

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

2015-06-01

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

Tuberculosis infection among homeless persons and caregivers in a high-tuberculosis-prevalence area in Japan: a cross-sectional study

PubMed Central

2011-01-01

Background Tuberculosis (TB) is a major public health problem. The Airin district of Osaka City has a large population of homeless persons and caregivers and is estimated to be the largest TB-endemic area in the intermediate-prevalence country, Japan. However, there have been few studies of homeless persons and caregivers. The objective of this study is to detect active TB and to assess the prevalence and risk factors for latent TB infection among homeless persons and caregivers. Methods We conducted a cross-sectional study for screening TB infection (active and latent TB infections) using questionnaire, chest X-ray (CXR), newly available assay for latent TB infection (QuantiFERON-TB Gold In-Tube; QFT) and clinical evaluation by physicians at the Osaka Socio-Medical Center Hospital between July 2007 and March 2008. Homeless persons and caregivers, aged 30-74 years old, who had not received CXR examination within one year, were recruited. As for risk factors of latent TB infection, the odds ratios (OR) and 95% confidence intervals (95% CI) for QFT-positivity were calculated using logistic regression model. Results Complete responses were available from 436 individuals (263 homeless persons and 173 caregivers). Four active TB cases (1.5%) among homeless persons were found, while there were no cases among caregivers. Out of these four, three had positive QFT results. One hundred and thirty-three (50.6%) homeless persons and 42 (24.3%) caregivers had positive QFT results. In multivariate analysis, QFT-positivity was independently associated with a long time spent in the Airin district: ≥10 years versus <10 years for homeless (OR = 2.53; 95% CI, 1.39-4.61) and for caregivers (OR = 2.32; 95% CI, 1.05-5.13), and the past exposure to TB patients for caregivers (OR = 3.21; 95% CI, 1.30-7.91) but not for homeless persons (OR = 1.51; 95% CI, 0.71-3.21). Conclusions Although no active TB was found for caregivers, one-quarter of them had latent TB infection. In addition to homeless persons, caregivers need examinations for latent TB infection as well as active TB and careful follow-up, especially when they have spent a long time in a TB-endemic area and/or have been exposed to TB patients. PMID:21255421

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

PubMed Central

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

2016-01-01

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

Dilemma of managing asymptomatic children referred with “culture-confirmed” drug-resistant tuberculosis

PubMed Central

Loveday, Marian; Sunkari, Babu; Marais, Ben J; Master, Iqbal; Brust, James CM

2016-01-01

Background The diagnosis of drug-resistant tuberculosis (DR-TB) in children is challenging and treatment is associated with many adverse effects. Objective We aimed to assess if careful observation, without initiation of second-line treatment, is safe in asymptomatic children referred with “culture-confirmed” DR-TB. Setting KwaZulu-Natal, South Africa - an area with high burdens of HIV, TB and DR-TB. Design, Intervention, Main outcome measures We performed an outcome review of children with “culture-confirmed” DR-TB who were not initiated on second-line TB treatment, as they were asymptomatic with normal chest radiographs on examination at our specialist referral hospital. Children were followed up every other month for the first year, with a final outcome assessment at the end of the study. Results In total, 43 asymptomatic children with normal chest radiographs were reviewed. The median length of follow-up until final evaluation was 549 days (IQR 259-722 days); most (34; 83%) children were HIV-uninfected. Resistance patterns included 9 (21%) mono-resistant and 34 (79%) multidrug-resistant (MDR) strains. Fifteen children (35%) had been treated with first-line TB treatment, prior to presentation at our referral hospital. At the final evaluation 34 (80%) children were well, 7 (16%) were lost to follow up, 1 (2%) received MDR-TB treatment and 1 (2%) died of unknown causes. The child who received MDR-TB treatment developed new symptoms at the 12 month review and responded well to second-line treatment. Conclusion Bacteriological evaluation should not be performed in the absence of any clinical indication. If drug-resistant M. tuberculosis is detected in an asymptomatic child with a normal chest radiograph close observation may be an appropriate strategy, especially in settings where potential laboratory error and poor record keeping are constant challenges. PMID:27044259

Is TB in Your Curriculum?

ERIC Educational Resources Information Center

Kerr, Joanne; Elwell, Jack

2002-01-01

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

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

PubMed Central

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

2017-01-01

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

Investigation Outcomes of Tuberculosis Suspects in the Health Centers of Addis Ababa, Ethiopia

PubMed Central

Deribew, Amare; Negussu, Nebiyu; Melaku, Zenebe; Deribe, Kebede

2011-01-01

Background Little is known about the prevalence of tuberculosis (TB) and HIV among TB suspects in primary health care units in Ethiopia. Methods In the period of February to March, 2009, a cross sectional survey was done in 27 health centers of Addis Ababa to assess the prevalence of TB and HIV among TB suspects who have > = 2 weeks symptoms of TB such as cough, fever and weight loss. Diagnosis of TB and HIV was based on the national guidelines. Information concerning socio-demographic variables and knowledge of the respondents about TB was collected using pretested questionnaire. Results Of the 545 TB suspects, 506 (92.7%) of them participated in the study. The prevalence of both pulmonary and extra pulmonary TB was 46.0% (233/506). The smear positivity rate among pulmonary TB suspect was 21.3%. Of the TB suspects, 298 (58.9%) of them were tested for HIV and 27.2% (81/298) were HIV seropositive. Fifty percent of the HIV positive TB suspects had TB. TB suspects who had a contact history with a TB patient in the family were 9 times more likely to have TB than those who did not have a contact history, [OR = 9.1, (95%CI:4.0, 20.5)]. Individuals who had poor [OR = 5.2, (95%CI: 2.3, 11.2)] and fair knowledge [OR = 3.7, (95%CI: 1.3, 10.4)] about TB were more likely to have TB than individuals who had good knowledge. Conclusion In conclusion, the prevalence of TB among TB suspects with duration of 2 or more weeks is high. Fifty percent of the HIV positive TB suspects had TB. Case finding among TB suspects with duration of 2 or more weeks should be intensified particularly among those who have a contact history with a TB patient. PMID:21526179

Clinicopathological correlates in HIV seropositive tuberculosis cases presenting with jaundice after initiating antiretroviral therapy with a structured review of the literature

PubMed Central

2012-01-01

Background The development of jaundice after initiation of HAART in HIV-TB co-infected patients is a challenging presentation in resource constrained settings, and is often attributed to drug induced liver injury (DILI).Some investigators have described hepatic tuberculosis Immune Reconstitution Inflammatory Syndrome (TB-IRIS) as a cause of liver disease in patients initiating HAART, which could also cause jaundice. Case presentations We report the clinical and histopathological features of five HIV-TB co-infected patients presenting with a syndrome of jaundice, tender hepatomegaly, bile canalicular enzyme rise and return of constitutional symptoms within 8 weeks of initiation of highly active antiretroviral therapy (HAART) for advanced HIV infection at a rural clinic in KwaZulu Natal, South Africa. All five patients had been diagnosed with tuberculosis infection prior to HAART initiation and were on antituberculous medication at time of developing jaundice. There was evidence of multiple aetiologies of liver injury in all patients. However, based on clinical course and pathological findings, predominant hepatic injury was thought to be drug induced in one case and hepatic tuberculosis associated immune reconstitution inflammatory syndrome (TB-IRIS) in the other four. In these later 4 patients, liver biopsy findings included necrotising and non-necrotising granulomatous inflammation in the lobules and portal tracts. The granulomas demonstrated – in addition to epithelioid histiocytes and Langhans giant cells – neutrophils, plasma cells and large numbers of lymphocytes, which are not features of a conventional untreated tuberculous response. Conclusion In this high TB prevalent, low resource setting, TB-IRIS may be an important cause of jaundice post-HAART initiation. Clinicopathological correlation is essential for optimal diagnosis. Further multi-organ based histopathological studies in the context of immune reconstitution would be useful to clinicians in low resource settings dealing with this challenging presentation. PMID:23061403

Risk factors associated with default among tuberculosis patients in Darjeeling district of West Bengal, India

PubMed Central

Roy, Nirmalya; Basu, Mausumi; Das, Sibasis; Mandal, Amitava; Dutt, Debashis; Dasgupta, Samir

2015-01-01

Background: The treatment outcome “default” under Revised National Tuberculosis Control Program (RNTCP) is a patient who after treatment initiation has interrupted treatment consecutively for more than 2 months. Aims: To assess the timing, characteristics and distribution of the reasons for default with relation to some sociodemographic variables among new sputum-positive (NSP) tuberculosis (TB) patients in Darjeeling District, West Bengal. Settings and Design: A case-control study was conducted in three tuberculosis units (TUs) of Darjeeling from August’2011 to December’2011 among NSP TB patients enrolled for treatment in the TB register from 1st Qtr’09 to 2nd Qtr’10. Patients defaulted from treatment were considered as “cases” and those completed treatment as “controls” (79 cases and 79 controls). Materials and Methods: The enrolled cases and controls were interviewed by the health workers using a predesigned structured pro-forma. Statistical Analysis Used: Logistic regression analysis, odds ratios (OR), adjusted odds ratios (AOR). Results: 75% of the default occurred in the intensive phase (IP); 54.24% retrieval action was done within 1 day during IP and 75% within 1 week during continuation phase (CP); cent percent of the documented retrieval actions were undertaken by the contractual TB program staffs. Most commonly cited reasons for default were alcohol consumption (29.11%), adverse effects of drugs (25.32%), and long distance of DOT center (21.52%). In the logistic regression analysis, the factors independently associated were consumption of alcohol, inadequate knowledge about TB, inadequate patient provider interaction, instances of missed doses, adverse reactions of anti-TB drugs, Government Directly Observed Treatment (DOT) provider and smoking. Conclusions: Most defaults occurred in the intensive phase; pre-treatment counseling and initial home visit play very important role in this regard. Proper counseling by health care workers in patient provider meeting is needed. PMID:26288779

Quality Tuberculosis Care in Indonesia: Using Patient Pathway Analysis to Optimize Public–Private Collaboration

PubMed Central

Surya, Asik; Setyaningsih, Budiarti; Suryani Nasution, Helmi; Gita Parwati, Cicilia; Yuzwar, Yullita E; Osberg, Mike; Hanson, Christy L; Hymoff, Aaron; Mingkwan, Pia; Makayova, Julia; Gebhard, Agnes; Waworuntu, Wiendra

2017-01-01

Abstract Background Tuberculosis (TB) is the fourth leading cause of death in Indonesia. In 2015, the World Health Organization estimated that nearly two-thirds of the TB patients in Indonesia had not been notified, and the status of their care remained unknown. As such, Indonesia is home to nearly 20% of the world’s “missing” TB patients. Understanding where patients go for care may enable strategic planning of services to better reach them. Methods A patient pathway analysis (PPA) was conducted to assess the alignment between patient care seeking and the availability of TB diagnostic and treatment services at the national and subnational level in Indonesia. Results The PPA results revealed that only 20% of patients encountered diagnostic capacity at the location where they first sought care. Most initial care seeking occurred in the private sector and case notification lagged behind diagnostic confirmation in the public sector. Conclusions The PPA results emphasize the role that the private sector plays in TB patient care seeking and suggested a need for differentiated approaches, by province, to respond to variances in care-seeking patterns and the capacities of public and private providers. PMID:29117347

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

PubMed

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

2018-04-01

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

Diabetes mellitus and tuberculosis facts and controversies

PubMed Central

2013-01-01

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

Completeness and timeliness of tuberculosis notification in Taiwan

PubMed Central

2011-01-01

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

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

PubMed

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

2015-01-01

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

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

PubMed

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

2013-12-21

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

Factors associated to referral of tuberculosis suspects by private practitioners to community health centres in Bali Province, Indonesia

PubMed Central

2013-01-01

Background The contrast between the low proportion of tuberculosis (TB) suspects referred from private practitioners in Bali province and the high volume of TB suspects seeking care at private practices suggests problems with TB suspect referral from private practitioners to the public health sector. We aimed to identify key factors associated with the referral of TB suspects by private practitioners. Methods We conducted a case-control study conducted in Bali province, Indonesia. The cases were private practitioners who had referred at least one TB suspect to a community health centre between 1 January 2007 and the start of data collection, while the controls were private practitioners who had not referred a single TB suspect in the same time. Results The following factors were independently associated with referral of TB suspects by private practitioners: having received information about the directly observed treatment short-course (DOTS) strategy (OR 2.0; 95% CI 1.1 – 3.8), ever having been visited by a district TB program officer (OR 2.1; 95% CI 1.0 – 4.5), availability of TB suspect referral forms in the practice (OR 2.8; 95% CI 1.5-5.2), and less than 5 km distance between the private practice and the laboratory for smear examination (OR 2.2; 95% CI 1.2-4.0). Conclusions Education and exposure of private practitioners to the TB program improves referral of TB suspects from private practitioners to the national TB program. We recommend that the TB program provides all private practitioners with information about the DOTS strategy and TB suspect referral forms, and organizes regular visits to private practitioners. PMID:24165352

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

PubMed

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

2017-05-01

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

Is tuberculosis crossing borders at the Eastern boundary of the European Union?

PubMed Central

van der Werf, Marieke J.; Hollo, Vahur; Noori, Teymur

2013-01-01

Background: The Eastern border of the European Union (EU) consists of 10 countries after the expansion of the EU in 2004 and 2007. These 10 countries border to the East to countries with high tuberculosis (TB) notification rates. We analyzed the notification data of Europe to quantify the impact of cross-border TB at the Eastern border of the EU. Methods: We used TB surveillance data of 2010 submitted by 53 European Region countries to the European Centre for Disease Prevention and Control and the World Health Organization Regional Office for Europe. Notified TB cases were stratified by origin of the case (national/foreign). We calculated the contribution of foreign to overall TB notification. Results: In the 10 EU countries located at the EU Eastern border, 618 notified TB cases (1.7% of all notified TB cases) were of foreign origin. Of those 618 TB cases, 173 (28.0%) were from countries bordering the EU to the East. More specifically, 90 (52.0%) were from Russia, 33 (19.1%) from Belarus, 33 (19.1%) from Ukraine, 13 (7.5%) from Moldova and 4 (2.3%) from Turkey. Conclusions: Currently, migrants contribute little to TB notifications in the 10 EU countries at the Eastern border of the EU, but changes in migration patterns may result in an increasing contribution. Therefore, EU countries at the Eastern border of the EU should strive to provide prompt diagnostic services and adequate treatment of migrants. PMID:23813718

Short Term Advantages of a Public-Private Partnership for Tuberculosis in Guinea Bissau: Reduction of Mortality and Increased Diagnostic Capacity

PubMed Central

Vieira, Fina; Sanha, Mamadu Saliu; Riccardi, Fabio; Colombatti, Raffaella

2014-01-01

Background Tuberculosis (TB) is widespread in Africa, but weak health systems in developing countries, often display poor quality of care with delays in case identification, irrational therapy and drug shortage, clinical mismanagement, unnecessary expenditures for patients, reduced adherence and increased mortality. Public-private partnership has demonstrated to increase TB case detection, but less is known about its effects on quality of care, mortality and costs for hospitalized TB patients. Methods Clinical outcomes and costs for TB patients at the TB National Reference Center of Bissau, in Guinea Bissau, West Africa, were determined during the first 5 months of the public-private management and compared to the ones of previous years when the hospitals was under direct Government’s management. Results 215 (2009–2010) and 194 (2012–2013) patients were admitted, respectively. Improvement (p<0.05) was observed in mortality reduction (21% vs 6%), cause of death determination (50% vs 85%), treatment abandonment (15 vs 1). Direct costs for patients during TB diagnostic pathway and inpatient care were significantly reduced, 475 vs. 0 USD. Conclusions Public-private partnerships displays significant short term benefits in National TB reference centers, even in post-conflict countries. Further studies could aid in determining the overall long term benefits of this type of cooperation, and the specific characteristic of TB and concomitant hematologic and infectious diseases in TB admitted patients. PMID:25045457

Tuberculosis-diabetes co-morbidity is characterized by heightened systemic levels of circulating angiogenic factors

PubMed Central

Kumar, Nathella Pavan; Moideen, Kadar; Sivakumar, Shanmugam; Menon, Pradeep A; Viswanathan, Vijay; Kornfeld, Hardy; Babu, Subash

2016-01-01

Background Tuberculosis-diabetes co-morbidity (TB-DM) is characterized by increased inflammation with elevated circulating levels of inflammatory cytokines and other factors. Circulating angiogenic factors are intricately involved in the angiogenesis-inflammation nexus. Methods To study the association of angiogenic factors with TB-DM, we examined the systemic levels of VEGF-A, VEGF-C, VEGF-D, VEGF-R1, VEGF-R2, VEGF-R3 in individuals with either TB-DM (n=44) or TB alone (n=44). Results Circulating levels of VEGF-A, C, D, R1, R2 and R3 were significantly higher in TB-DM compared to TB individuals. Moreover, the levels of VEGF-A, C, R2 and/or R3 were significantly higher in TB-DM with bilateral or cavitary disease or with hemoptysis, suggesing an association with both disease severity and adverse clinical presentation. The levels of these factors also exhibited a significant positive relationship with bacterial burdens and HbA1c levels. In addition, VEGF-A, C and R2 levels were signifantly higher (at 2 months of treatment) in culture positive compared to culture negative TB-DM individuals. Finally, the circulating levels of VEGF-A, C, D, R1, R2 and R3 were significantly reduced following successful chemotherapy at 6 months. Conclusion Our data demonstrate that TB-DM is associated with heightened levels of circulating angiogenic factors, possibly reflecting both dysregulated angiogenesis and exaggerated inflammation. PMID:27717783

Barriers and Delays in Tuberculosis Diagnosis and Treatment Services: Does Gender Matter?

PubMed Central

Yang, Wei-Teng; Gounder, Celine R.; Akande, Tokunbo; De Neve, Jan-Walter; McIntire, Katherine N.; Chandrasekhar, Aditya; de Lima Pereira, Alan; Gummadi, Naveen; Samanta, Santanu; Gupta, Amita

2014-01-01

Background. Tuberculosis (TB) remains a global public health problem with known gender-related disparities. We reviewed the quantitative evidence for gender-related differences in accessing TB services from symptom onset to treatment initiation. Methods. Following a systematic review process, we: searched 12 electronic databases; included quantitative studies assessing gender differences in accessing TB diagnostic and treatment services; abstracted data; and assessed study validity. We defined barriers and delays at the individual and provider/system levels using a conceptual framework of the TB care continuum and examined gender-related differences. Results. Among 13,448 articles, 137 were included: many assessed individual-level barriers (52%) and delays (42%), 76% surveyed persons presenting for care with diagnosed or suspected TB, 24% surveyed community members, and two-thirds were from African and Asian regions. Many studies reported no gender differences. Among studies reporting disparities, women faced greater barriers (financial: 64% versus 36%; physical: 100% versus 0%; stigma: 85% versus 15%; health literacy: 67% versus 33%; and provider-/system-level: 100% versus 0%) and longer delays (presentation to diagnosis: 45% versus 0%) than men. Conclusions. Many studies found no quantitative gender-related differences in barriers and delays limiting access to TB services. When differences were identified, women experienced greater barriers and longer delays than men. PMID:24876956

Barriers and delays in tuberculosis diagnosis and treatment services: does gender matter?

PubMed

Yang, Wei-Teng; Gounder, Celine R; Akande, Tokunbo; De Neve, Jan-Walter; McIntire, Katherine N; Chandrasekhar, Aditya; de Lima Pereira, Alan; Gummadi, Naveen; Samanta, Santanu; Gupta, Amita

2014-01-01

Background. Tuberculosis (TB) remains a global public health problem with known gender-related disparities. We reviewed the quantitative evidence for gender-related differences in accessing TB services from symptom onset to treatment initiation. Methods. Following a systematic review process, we: searched 12 electronic databases; included quantitative studies assessing gender differences in accessing TB diagnostic and treatment services; abstracted data; and assessed study validity. We defined barriers and delays at the individual and provider/system levels using a conceptual framework of the TB care continuum and examined gender-related differences. Results. Among 13,448 articles, 137 were included: many assessed individual-level barriers (52%) and delays (42%), 76% surveyed persons presenting for care with diagnosed or suspected TB, 24% surveyed community members, and two-thirds were from African and Asian regions. Many studies reported no gender differences. Among studies reporting disparities, women faced greater barriers (financial: 64% versus 36%; physical: 100% versus 0%; stigma: 85% versus 15%; health literacy: 67% versus 33%; and provider-/system-level: 100% versus 0%) and longer delays (presentation to diagnosis: 45% versus 0%) than men. Conclusions. Many studies found no quantitative gender-related differences in barriers and delays limiting access to TB services. When differences were identified, women experienced greater barriers and longer delays than men.

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

PubMed

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

2017-12-01

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

Pros and cons of BCG vaccination in countries with low incidence of tuberculosis.

PubMed

Tala, E O; Tala-Heikkilä, M M

1994-07-01

Preventive bacille Calmette-Guérin (BCG) vaccination, together with case finding and effective chemotherapy, has formed an integral part of the tuberculosis (TB) control program in most countries. In some low-incidence countries the balance of prevention has been more on the side of chemoprophylaxis than of BCG vaccination. The time clearly has come when the strategy of mass BCG vaccination no longer is indicated medically, nor is it cost-effective. The pros and cons of the programs need to be critically evaluated against the present epidemiological background, taking into account the facts that TB, the killer disease, is recovering strength, human immunodeficiency virus infection is on the increase, and multidrug-resistant TB has changed the outcome of this previously fully curable disease. Although no longer appropriate for mass programs, BCG vaccination still should be considered for the protection of selected risk groups in low-incidence countries. The overall efficacy may be of the order 50% to 80%, but the variation is great. Therefore, further research urgently is needed on the effectiveness of BCG as an intervention in local TB programs.

The Burden of Mycobacterial Disease in Ethiopian Cattle: Implications for Public Health

PubMed Central

Berg, Stefan; Firdessa, Rebuma; Habtamu, Meseret; Gadisa, Endalamaw; Mengistu, Araya; Yamuah, Lawrence; Ameni, Gobena; Vordermeier, Martin; Robertson, Brian D.; Smith, Noel H.; Engers, Howard; Young, Douglas; Hewinson, R. Glyn; Aseffa, Abraham; Gordon, Stephen V.

2009-01-01

Background Bovine tuberculosis (bTB), caused by Mycobacterium bovis, is a debilitating disease of cattle. Ethiopia has one of the largest cattle populations in the world, with an economy highly dependent on its livestock. Furthermore, Ethiopia has one of the highest incidence rates of human extrapulmonary TB in the world, a clinical presentation that is often associated with transmission of M. bovis from cattle to humans. Methodology/Principal Findings Here we present a comprehensive investigation of the prevalence of bTB in Ethiopia based on cases identified at slaughterhouses. Out of approximately 32,800 inspected cattle, ∼4.7% showed suspect tuberculous lesions. Culture of suspect lesions yielded acid-fast bacilli in ∼11% of cases, with M. bovis accounting for 58 of 171 acid-fast cultures, while 53 isolates were non-tuberculous mycobacteria. Strikingly, M. tuberculosis was isolated from eight cattle, an unusual finding that suggests human to animal transmission. Conclusions/Significance Our analysis has revealed that bTB is widely spread throughout Ethiopia, albeit at a low prevalence, and provides underpinning evidence for public health policy formulation. PMID:19352493

Assessing Tuberculosis Case Fatality Ratio: A Meta-Analysis

PubMed Central

Straetemans, Masja; Glaziou, Philippe; Bierrenbach, Ana L.; Sismanidis, Charalambos; van der Werf, Marieke J.

2011-01-01

Background Recently, the tuberculosis (TB) Task Force Impact Measurement acknowledged the need to review the assumptions underlying the TB mortality estimates published annually by the World Health Organization (WHO). TB mortality is indirectly measured by multiplying estimated TB incidence with estimated case fatality ratio (CFR). We conducted a meta-analysis to estimate the TB case fatality ratio in TB patients having initiated TB treatment. Methods We searched for eligible studies in the PubMed and Embase databases through March 4th 2011 and by reference listing of relevant review articles. Main analyses included the estimation of the pooled percentages of: a) TB patients dying due to TB after having initiated TB treatment and b) TB patients dying during TB treatment. Pooled percentages were estimated using random effects regression models on the combined patient population from all studies. Main Results We identified 69 relevant studies of which 22 provided data on mortality due to TB and 59 provided data on mortality during TB treatment. Among HIV infected persons the pooled percentage of TB patients dying due to TB was 9.2% (95% Confidence Interval (CI): 3.7%–14.7%) and among HIV uninfected persons 3.0% (95% CI: −1.2%–7.4%) based on the results of eight and three studies respectively providing data for this analyses. The pooled percentage of TB patients dying during TB treatment was 18.8% (95% CI: 14.8%–22.8%) among HIV infected patients and 3.5% (95% CI: 2.0%–4.92%) among HIV uninfected patients based on the results of 27 and 19 studies respectively. Conclusion The results of the literature review are useful in generating prior distributions of CFR in countries with vital registration systems and have contributed towards revised estimates of TB mortality This literature review did not provide us with all data needed for a valid estimation of TB CFR in TB patients initiating TB treatment. PMID:21738585

Targeted tuberculosis contact investigation saves money without sacrificing health.

PubMed

Pisu, Maria; Gerald, Joe; Shamiyeh, James E; Bailey, William C; Gerald, Lynn B

2009-01-01

Health departments require an efficient strategy to investigate individuals exposed to Mycobacterium tuberculosis. The contact priority model (CPM) uses a decision rule to minimize testing of low-risk contacts; however, its impact on costs and disease control is unknown. A cost-effectiveness analysis compared the CPM with the traditional concentric circle approach (CCA) in a simulated population of 1000 healthy, community-dwelling adults with a 10% background rate of latent tuberculosis (TB) infection. The analysis was conducted from the perspective of the Alabama Department of Public Health. Model inputs were derived from the literature and the Alabama Department of Public Health. Lifetime costs (2004 dollars) and outcomes were discounted 3 percent annually. Incremental cost-effectiveness ratios were used to compare the strategies. Over the lifetime of 1000 simulated contacts, the CPM saved $45,000 but led to 0.5 additional TB cases and 0.24 fewer years of life. The CCA is more effective than the CPM, but it costs $92,934 to prevent one additional TB case and $185,920 to gain one additional life year. The CPM reduces costs with minimal loss of disease control and is a viable alternative to the CCA under most conditions.

Tuberculosis in Hispanics/Latinos

MedlinePlus

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

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

PubMed Central

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

2017-01-01

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

Spatial pattern and temporal trend of mortality due to tuberculosis 10

PubMed Central

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

2018-01-01

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

Understanding Latent Tuberculosis: A Moving Target

PubMed Central

Lin, Philana Ling; Flynn, JoAnne L.

2012-01-01

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

Prevalence and Risk Factors for Tuberculosis Infection among Hospital Workers in Hanoi, Viet Nam

PubMed Central

Kobayashi, Nobuyuki; Yanai, Hideki; Toyota, Emiko; Sakurada, Shinsaku; Huu Thuong, Pham; Cuong, Vu Cao; Nanri, Akiko; Mizoue, Tetsuya; Matsushita, Ikumi; Harada, Nobuyuki; Higuchi, Kazue; Tuan, Le Anh; Keicho, Naoto

2009-01-01

Background Transmission of tuberculosis (TB) to health care workers (HCWs) is a global issue. Although effective infection control measures are expected to reduce nosocomial TB, HCWs' infection has not been assessed enough in TB high burden countries. We conducted a cross-sectional study to determine the prevalence of TB infection and its risk factors among HCWs in Hanoi, Viet Nam. Methodology/Principal Findings A total of 300 HCWs including all staff members in a municipal TB referral hospital received an interferon-gamma release assay (IGRA), QuantiFERON-TB Gold In-TubeTM, followed by one- and two-step tuberculin skin test (TST) and a questionnaire-based interview. Agreement between the tests was evaluated by kappa statistics. Risk factors for TB infection were analyzed using a logistic regression model. Among the participants aged from 20 to 58 years (median = 40), prevalence of TB infection estimated by IGRA, one- and two-step TST was 47.3%, 61.1% and 66.3% respectively. Although the levels of overall agreement between IGRA and TST were moderate, the degree of agreement was low in the group with BCG history (kappa = 0.29). Working in TB hospital was associated with twofold increase in odds of TB infection estimated by IGRA. Increased age, low educational level and the high body mass index also demonstrated high odds ratios of IGRA positivity. Conclusions/Significance Prevalence of TB infection estimated by either IGRA or TST is high among HCWs in the hospital environment for TB care in Viet Nam and an infection control program should be reinforced. In communities with heterogeneous history of BCG vaccination, IGRA seems to estimate TB infection more accurately than any other criteria using TST. PMID:19710920

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

PubMed

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

2008-07-15

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

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

PubMed Central

2013-01-01

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

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

MedlinePlus

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

Tuberculosis attributed to household contacts in the Philippines.

PubMed

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

2010-01-01

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

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

PubMed

Lamar, James E; Malakooti, Mark A

2003-07-01

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

Prevalence and risk factors for infection of bovine tuberculosis in indigenous cattle in the Serengeti ecosystem, Tanzania

PubMed Central

2013-01-01

Background Bovine tuberculosis (bTB) is a chronic debilitating disease and is a cause of morbidity and mortality in livestock, wildlife and humans. This study estimated the prevalence and risk factors associated with bovine tuberculosis transmission in indigenous cattle at the human-animal interface in the Serengeti ecosystem of Tanzania. Results A total of 1,103 indigenous cattle from 32 herds were investigated for the presence of bTB using the Single Intradermal Comparative Tuberculin Test. Epidemiological data on herd structure, management and grazing system were also collected. The apparent individual animal prevalence of tuberculin reactors was 2.4% (95% confidence interval (CI), 1.7 – 3.5%), whereas the true prevalence was 0.6% CI, 0.6 – 0.7% as indicated by a reaction to avian tuberculin purified protein derivatives (PPD) which is more than 4 mm greater than the reaction to avian tuberculin PPD. The results showed that 10.6% (117/1,103) showed non-specific reactions (atypical mycobacterium). The herd prevalence of 50% (16/32) was found. Tuberculin skin test results were found to be significantly associated with age, location, size of the household and animal tested. Of 108 respondents, 70 (64.8%) individuals had not heard about bovine tuberculosis at all. Thirty five percent (38/108) of respondents at least were aware of bTB. About 60% (23/38) of respondents who were aware of bTB had some knowledge on how bTB is spread. Eighty one percent (87/108) of respondents were not aware of the presence of bTB in wildlife. There is regular contact between cattle and wild animals due to sharing of grazing land and water sources, with 99% (107/108) of households grazing cattle in communal pastures. Conclusion The study has demonstrated a high reported interaction of livestock with wildlife and poor knowledge of most cattle owners concerning bTB and its transmission pathways among people, livestock and wildlife. Although the overall proportion of animals with bTB is relatively low, herd prevalence is 50% and prevalence within herds varied considerably. Thus there is a possibility of cross transmission of bTB at wildlife-livestock interface areas that necessitates use of genetic strain typing methods to characterize them accurately. PMID:24377705

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

PubMed Central

2010-01-01

Background In many low- and middle-income countries, where tobacco use is common, tuberculosis is also a major problem. Tobacco use increases the risk of developing tuberculosis, secondary mortality, poor treatment compliance and relapses. In countries with TB epidemic, even a modest relative risk leads to a significant attributable risk. Treating tobacco dependence, therefore, is likely to have benefits for controlling tuberculosis in addition to reducing the non-communicable disease burden associated with smoking. In poorly resourced health systems which face a dual burden of disease secondary to tuberculosis and tobacco, an integrated approach to tackle tobacco dependence in TB control could be economically desirable. During TB screening, health professionals come across large numbers of patients with respiratory symptoms, a significant proportion of which are likely to be tobacco users. These clinical encounters, considered to be "teachable moments", provide a window of opportunity to offer treatment for tobacco dependence. Methods/Design We aim to develop and trial a complex intervention to reduce tobacco dependence among TB suspects based on the WHO 'five steps to quit' model. This model relies on assessing personal motivation to quit tobacco use and uses it as the basis for assessing suitability for the different therapeutic options for tobacco dependence. We will use the Medical Research Council framework approach for evaluating complex interventions to: (a) design an evidence-based treatment package (likely to consist of training materials for health professionals and education tools for patients); (b) pilot the package to determine the delivery modalities in TB programme (c) assess the incremental cost-effectiveness of the package compared to usual care using a cluster RCT design; (d) to determine barriers and drivers to the provision of treatment of tobacco dependence within TB programmes; and (e) support long term implementation. The main outcomes to assess the effectiveness would be point abstinence at 4 weeks and continuous abstinence up to 6 months. Discussion This work will be carried out in Pakistan and is expected to have relevance for other low and middle income countries with high tobacco use and TB incidence. This will enhance our knowledge of the cost-effectiveness of treating tobacco dependence in patients suspected of TB. Trial Registration Trial Registration Number: ISRCTN08829879 PMID:20338041

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

PubMed

Moynihan, Patrick Joseph; Besra, Gurdyal S

2017-10-01

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

Surveillance of Tuberculosis in Taipei: The Influence of Nontuberculous Mycobacteria

PubMed Central

Chiang, Chen-Yuan; Yu, Ming-Chih; Yang, Shiang-Lin; Yen, Muh-Yong; Bai, Kuan-Jen

2015-01-01

Background Notification of tuberculosis (TB) but not nontuberculous mycobacteria (NTM) is mandatory in Taiwan. Partly due to the strict regulation on TB notification, several patients infected with NTM were notified as TB cases. Notification of patients infected with NTM as TB cases can trigger public health actions and impose additional burdens on the public health system. We conducted a study to assess the influence of NTM infection on surveillance of TB in Taipei. Methodology/Principal Findings The study population included all individuals with a positive culture for Mycobacterium who were citizens of Taipei City and notified as TB cases in the calendar years 2007–2010. Of the 4216 notified culture-positive tuberculosis (TB) cases, 894 (21.2%) were infected with NTM. The average annual reported case rate of infection with NTM was 8.6 (95% confidence interval 7.7–9.4) per 100,000 people. The reported case rate of NTM increased with age in both males and females. The proportion of reported TB cases infected with NTM was significantly higher in females than in males (27.6% vs 17.8%, adjusted OR (adjOR) 1.93, 95% confidence interval (CI) 1.63–2.28); in smear-positive than in smear-negative (23.1% vs 19.2%, adjOR 1.26, 95% CI 1.08–1.47); and in previously treated cases than in new cases (35.7% vs 19.1%, adjOR 2.30, 95% CI 1.88–2.82). The most frequent species was M. avium complex (32.4%), followed by M. chelonae complex (17.6%), M. fortuitum complex (17.0%) and M. kansasii (9.8%). Of the 890 notified NTM cases assessed, 703 (79.0%) were treated with anti-TB drugs, and 730 (82.0%) were de-notified. Conclusions/Significance The influence of NTM on surveillance of TB in Taipei was substantial. Health authorities should take action to ensure that nucleic acid amplification tests are performed in all smear-positive cases in a timely manner to reduce the misdiagnosis of patients infected with NTM as TB cases. PMID:26544554

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

PubMed Central

2012-01-01

Background Tuberculosis (TB) indicators in South Africa currently remain well below global targets. In 2008, the National Tuberculosis Program (NTP) implemented a community mobilization program in all nine provinces to trace TB patients that had missed a treatment or clinic visit. Implementation sites were selected by TB program managers and teams liaised with health facilities to identify patients for tracing activities. The objective of this analysis was to assess the impact of the TB Tracer Project on treatment outcomes among TB patients. Methods The study population included all smear positive TB patients registered in the Electronic TB Registry from Quarter 1 2007-Quarter 1 2009 in South Africa. Subdistricts were used as the unit of analysis, with each designated as either tracer (standard TB program plus tracer project) or non-tracer (standard TB program only). Mixed linear regression models were utilized to calculate the percent quarterly change in treatment outcomes and to compare changes in treatment outcomes from Quarter 1 2007 to Quarter 1 2009 between tracer and non-tracer subdistricts. Results For all provinces combined, the percent quarterly change decreased significantly for default treatment outcomes among tracer subdistricts (−0.031%; p < 0.001) and increased significantly for successful treatment outcomes among tracer subdistricts (0.003%; p = 0.03). A significant decrease in the proportion of patient default was observed for all provinces combined over the time period comparing tracer and non-tracer subdistricts (p = 0.02). Examination in stratified models revealed the results were not consistent across all provinces; significant differences were observed between tracer and non-tracer subdistricts over time in five of nine provinces for treatment default. Conclusions Community mobilization of teams to trace TB patients that missed a clinic appointment or treatment dose may be an effective strategy to mitigate default rates and improve treatment outcomes. Additional information is necessary to identify best practices and elucidate discrepancies across provinces; these findings will help guide the NTP in optimizing the adoption of tracing activities for TB control. PMID:22871071

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

PubMed Central

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

2017-01-01

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

A rare presentation of disseminated tuberculosis: Prostatic abscess.

PubMed

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

2017-10-01

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

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

PubMed

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

2010-11-01

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

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

PubMed

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

2017-02-01

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

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

PubMed

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

2012-01-01

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

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

PubMed Central

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

2012-01-01

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

Prevalence of drug-resistant tuberculosis in Nigeria: A systematic review and meta-analysis

PubMed Central

Onyedum, Cajetan C.; Alobu, Isaac

2017-01-01

Background Drug-resistant tuberculosis (TB) undermines control efforts and its burden is poorly understood in resource-limited settings. We performed a systematic review and meta-analysis to provide an up-to-date summary of the extent of drug-resistant TB in Nigeria. Methods We searched PubMed, Scopus, Embase, HINARI, AJOL, the Cochrane library, Web of Science, and Google Scholar for reports published before January 31 2017, that included any resistance, mono-resistance or multidrug resistance to anti-TB drugs in Nigeria. Summary estimates were calculated using random effects models. Results We identified 34 anti-TB drug resistance surveys with 8002 adult TB patients consisting of 2982 new and 5020 previously-treated cases. The prevalence rate of any drug resistance among new TB cases was 32.0% (95% CI 24.0–40.0%; 734/2892) and among previously-treated cases, the rate was 53.0% (95% CI 35.0–71.0%; 1467/5020). Furthermore, multidrug resistance among new and previously-treated cases was 6.0% (95% CI 4.0–8.0%;161/2502)and 32.0% (95%CI 20.0–44.0; 357/949), respectively. There was significant heterogeneity between the studies (p<0.001, I2 tests). The prevalence of drug-resistant TB varied according to methods of drug susceptibility testing and geographic region of Nigeria. Conclusion The burden of drug-resistant TB in Nigeria is high. We recommend that a national anti-TB drug resistance survey be carried out, and strategies for case detection and programmatic management of drug-resistant TB in Nigeria need to be strengthened. PMID:28704459

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

PubMed

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

2016-01-01

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

Rationale and design of a randomized controlled trial of the effect of retinol and vitamin D supplementation on treatment in active pulmonary tuberculosis patients with diabetes

PubMed Central

2013-01-01

Background The association between pulmonary tuberculosis (PTB) and diabetes mellitus (DM) has been previously attracted much attention. Diabetes alters immunity to tuberculosis, leading to more frequent treatment failure in TB patients with DM. Moreover, TB and DM often coincide with micronutrients deficiencies, such as retinol and vitamin D, which are especially important to immunity of the body and may influence pancreas β-cell function. However, the effects of retinol and vitamin D supplementation in active TB patients with diabetes on treatment outcomes, immune and nutrition state are still uncertain. We are conducting a randomized controlled trial of vitamin A and/or D in active PTB patients with DM in a network of 4 TB treatment clinics to determine whether the supplementation could improve the outcome in the patients. Methods/design This is a 2×2 factorial trial. We plan to enroll 400 active PTB patients with DM, and randomize them to VA (2000 IU daily retinol); VD (400 IU daily cholecalciferol); VAD (2000 IU daily retinol plus 400 IU cholecalciferol) or control (placebo) group. Our primary outcome measure is the efficacy of anti-tuberculosis treatment and ameliorating of glucose metabolism, and the secondary outcome measure being immune and nutrition status of the subjects. Of the first 37 subjects enrolled: 8 have been randomized to VA, 10 to VD, 9 to VAD and 10 to control. To date, the sample is 97.3% Han Chinese and 91.9% female. The average fasting plasma glucose level is 12.19 mmol/L. Discussion This paper describes the design and rationale of a randomized clinical trial comparing VA and/or VD supplementation to active pulmonary TB patients with DM. Our trial will allow rigorous evaluation of the efficacy of the supplementation to active TB and DM therapy for improving clinical outcomes and immunological condition. This detailed description of trial methodology can serve as a template for the development of future treatment scheme for active TB patient with DM. Trial registration ChiCTR-TRC-12002546 PMID:23442225

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

PubMed

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

2017-01-01

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

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

PubMed

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

2014-04-01

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

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

USDA-ARS?s Scientific Manuscript database

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

Tuberculosis Outbreak in a Primary School, Milan, Italy

PubMed Central

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

2013-01-01

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

The arms race between man and Mycobacterium tuberculosis: Time to regroup.

PubMed

Hoal, Eileen G; Dippenaar, Anzaan; Kinnear, Craig; van Helden, Paul D; Möller, Marlo

2017-08-23

An arms race is an appropriate metaphor to use for the interaction of man and Mycobacterium tuberculosis (M.tb) through the millennia. Estimates of the time of infection of modern humans with M.tb often pre-date the Out-of-Africa migration. Humans have adapted to the changing environment during the migration with respect to climate, food sources and encounters with local pathogens. More recently, there has been adaptation to the demographic changes brought about in the majority of the human population by the Neolithic revolution. By chance and/or selection, specific variants in immune defence have arisen in different population groups. These select for M.tb strains more fit to cause disease and be transmitted, sometimes by exploiting defence systems effective on other bacteria. The different selection pressures on the M.tb lineages carried by specific human groups have resulted in a worldwide M.tb population that is geographically structured according to the humans historically found there. A similar structure is seen with pathogens such as M. leprae and Helicobacter pylori. Modern M.tb strains have emerged which may be more fit, such as the Beijing lineage, leading to their rapid spread both in the areas where they arose, and into new areas after recent introduction. The speed at which this is occurring is outpacing coevolution for the time being. By using the results of genome wide and other association studies, as well as admixture mapping and 'natural experiments' in areas where both a number of populations, admixed populations, and a variety of M.tb strains occur, we can investigate the forces that have driven the coevolution of man and M.tb. The diversity of human and bacterial genetic background may be used in the future to discover and target the specific host-pathogen interactions leading to tuberculosis diseases, which suggests the potential for rational design of vaccines and host-directed therapies. Copyright © 2017 Elsevier B.V. All rights reserved.

Evaluating the anti Mycobacterium tuberculosis activity of Alpinia galanga (L.) Willd. axenically under reducing oxygen conditions and in intracellular assays

PubMed Central

2014-01-01

Background In tuberculosis (TB), the steadily increasing bacterial resistance to existing drugs and latent TB continue to be major concerns. A combination of conventional drugs and plant derived therapeutics can serve to expand the antimicrobial spectrum, prevent the emergence of drug resistant mutants and minimize toxicity. Alpinia galanga, used in various traditional medicines, possesses broad spectrum antibacterial properties. The study was undertaken to assess the antimycobacterial potential of A. galanga in axenic (under aerobic and anaerobic conditions) and intracellular assays. Methods Phytochemical analysis was done using HPTLC. The acetone, aqueous and ethanolic extracts (1, 10, 25, 50 and 100 μg/ml) of A. galanga were tested axenically using Microplate Alamar Blue Assay (MABA) against Mycobacterium tuberculosis (M.tb) H37Rv and three drug sensitive and three multi drug resistant clinical isolates. The activity of the extracts was also evaluated intracellularly in A549 cell line against these strains. The extracts active under intracellular conditions were further tested in an axenic setup under reducing oxygen concentrations using only H37Rv. Results 1´ acetoxychavicol acetate, the reference standard used, was present in all the three extracts. The acetone and ethanolic extracts were active in axenic (aerobic and anaerobic) and intracellular assays. The aqueous extract did not demonstrate activity under the defined assay parameters. Conclusion A. galanga exhibits anti M.tb activity with multiple modes of action. Since the activity of the extracts was observed under reducing oxygen concentrations, it may be effective in treating the dormant and non-replicating bacteria of latent TB. Though the hypothesis needs further testing, A. galanga being a regular dietary component may be utilized in combination with the conventional TB therapy for enhanced efficacy. PMID:24592852

Achievements in and Challenges of Tuberculosis Control in South Korea.

PubMed

Kim, Ji Han; Yim, Jae-Joon

2015-11-01

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

Molecular Diagnosis of Tuberculosis.

PubMed

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

2018-01-01

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

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

PubMed

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

2017-07-01

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

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

PubMed

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

2009-09-01

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

A Study on the Role of Mobile Phone Communication in Tuberculosis DOTS Treatment

PubMed Central

Elangovan, R; Arulchelvan, S

2013-01-01

Background: Every year, a lot of Tuberculosis (TB) patients undergo Directly Observed Treatment Short-course (DOTS) in Salem city, one of the high TB districts in South India. Mobile phone usage among these patients and health workers is common. Mobile phone communication has a great potential in TB treatment. Objectives: To analyze the mobile phone usage and its effectiveness in TB DOTS treatment. Materials and Methods: A cross-sectional survey with 150 TB patients was followed by a focus group discussion with treatment supervisors, DOTS providers, and health workers. Results: Majority of patients use mobile phones to make calls to health workers to clarify their doubts on side effects, food, and symptoms of the disease. TB treatment supervisors effectively use mobile phones to counsel patients to adhere to the treatment regimen. Patients see mobile phones as a useful communication tool in TB treatment though they prefer direct interpersonal communication with health workers. Though the mobile ownership is 68% among the TB patients, many of them are not able to send text messages or read messages in English. Conclusion: Mobile phone possession and usage is high among the patients. Patients need to be trained to use mobile phone features such as alarm, voice mail, and interactive voice response. Incentives like free talk time and short message service (SMS) will encourage patients to communicate frequently with health workers, thereby, increasing the chances of better adherence to DOTS. SMS could be made available in the regional languages. PMID:24302824

Tuberculosis in a South African prison – a transmission modelling analysis

PubMed Central

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

2015-01-01

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

Safety and immunogenicity of candidate vaccine M72/AS01E in adolescents in a TB endemic setting

PubMed Central

Penn-Nicholson, Adam; Geldenhuys, Hennie; Burny, Wivine; van der Most, Robbert; Day, Cheryl L.; Jongert, Erik; Moris, Philippe; Hatherill, Mark; Ofori-Anyinam, Opokua; Hanekom, Willem

2018-01-01

Background Vaccination that prevents tuberculosis (TB) disease, particularly in adolescents, would have the greatest impact on the global TB epidemic. Safety, reactogenicity and immunogenicity of the vaccine candidate M72/AS01E was evaluated in healthy, HIV-negative adolescents in a TB endemic region, regardless of Mycobacterium tuberculosis (M.tb) infection status. Methods In a phase II, double-blind randomized, controlled study (NCT00950612), two doses of M72/AS01E or placebo were administered intramuscularly, one month apart. Participants were followed-up post-vaccination, for 6 months. M72-specific immunogenicity was evaluated by intracellular cytokine staining analysis of T cells and NK cells by flow cytometry. Results No serious adverse events were recorded. M72/AS01E induced robust T cell and antibody responses, including antigen-dependent NK cell IFN-γ production. CD4 and CD8 T cell responses were sustained at 6 months post vaccination. Irrespective of M.tb infection status, vaccination induced a high frequency of M72-specific CD4 T cells expressing multiple combinations of Th1 cytokines, and low level IL-17. We observed rapid boosting of immune responses in M.tb-infected participants, suggesting natural infection acts as a prime to vaccination. Conclusions The clinically acceptable safety and immunogenicity profile of M72/AS01E in adolescents living in an area with high TB burden support the move to efficacy trials. PMID:26072017

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

PubMed

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

2013-01-01

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

Smoking behavior and beliefs about the impact of smoking on anti-tuberculosis treatment among health care workers.

PubMed

Magee, M J; Darchia, L; Kipiani, M; Chakhaia, T; Kempker, R R; Tukvadze, N; Berg, C J; Blumberg, H M

2017-09-01

Tuberculosis (TB) health care facilities throughout Georgia. To describe smoking behaviors among health care workers (HCWs) at TB facilities and determine HCWs' knowledge and beliefs regarding the impact of tobacco use on anti-tuberculosis treatment. Cross-sectional survey from May to December 2014 in Georgia. Adult HCWs (age 18 years) at TB facilities were eligible. We administered a 60-question anonymous survey about tobacco use and knowledge of the effect of smoking on anti-tuberculosis treatment. Of the 431 HCWs at TB facilities who participated, 377 (87.5%) were female; the median age was 50 years (range 20-77). Overall, 59 (13.7%) HCWs were current smokers and 35 (8.1%) were past smokers. Prevalence of current smoking was more common among physicians than among nurses (18.6% vs. 7.9%, P < 0.0001). Among HCWs, 115 (26.7%) believed smoking does not impact anti-tuberculosis treatment, and only 25.3% of physicians/nurses received formal training in smoking cessation approaches. Physicians who smoked were significantly more likely to believe that smoking does not impact anti-tuberculosis treatment than non-smoking physicians (aOR 5.11, 95%CI 1.46-17.90). Additional education about the effect of smoking on TB treatment outcomes is needed for staff of TB health care facilities in Georgia. Nurses and physicians need more training about smoking cessation approaches for patients with TB.

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

PubMed

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

2018-01-01

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

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

PubMed

2006-10-01

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

[Treatment of tuberculosis].

PubMed

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

2015-01-01

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

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

PubMed Central

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

2017-01-01

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

Ursolic and oleanolic acids as antimicrobial and immunomodulatory compounds for tuberculosis treatment

PubMed Central

2013-01-01

Background New alternatives for the treatment of Tuberculosis (TB) are urgently needed and medicinal plants represent a potential option. Chamaedora tepejilote and Lantana hispida are medicinal plants from Mexico and their hexanic extracts have shown antimycobacterial activity. Bioguided investigation of these extracts showed that the active compounds were ursolic acid (UA) and oleanolic acid (OA). Methods The activity of UA and OA against Mycobacterium tuberculosis H37Rv, four monoresistant strains, and two drug-resistant clinical isolates were determined by MABA test. The intracellular activity of UA and OA against M. tuberculosis H37Rv and a MDR clinical isolate were evaluated in a macrophage cell line. Finally, the antitubercular activity of UA and OA was tested in BALB/c mice infected with M. tuberculosis H37Rv or a MDR strain, by determining pulmonary bacilli loads, tissue damage by automated histomorphometry, and expression of IFN-γ, TNF-α, and iNOS by quantitative RT-PCR. Results The in vitro assay showed that the UA/OA mixture has synergistic activity. The intracellular activity of these compounds against M. tuberculosis H37Rv and a MDR clinical isolate in a macrophage cell line showed that both compounds, alone and in combination, were active against intracellular mycobacteria even at low doses. Moreover, when both compounds were used to treat BALB/c mice with TB induced by H37Rv or MDR bacilli, a significant reduction of bacterial loads and pneumonia were observed compared to the control. Interestingly, animals treated with UA and OA showed a higher expression of IFN-γ and TNF-α in their lungs, than control animals. Conclusion UA and OA showed antimicrobial activity plus an immune-stimulatory effect that permitted the control of experimental pulmonary TB. PMID:24098949

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

PubMed

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

2017-11-01

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

Drug resistance mechanisms and novel drug targets for tuberculosis therapy.

PubMed

Islam, Md Mahmudul; Hameed, H M Adnan; Mugweru, Julius; Chhotaray, Chiranjibi; Wang, Changwei; Tan, Yaoju; Liu, Jianxiong; Li, Xinjie; Tan, Shouyong; Ojima, Iwao; Yew, Wing Wai; Nuermberger, Eric; Lamichhane, Gyanu; Zhang, Tianyu

2017-01-20

Drug-resistant tuberculosis (TB) poses a significant challenge to the successful treatment and control of TB worldwide. Resistance to anti-TB drugs has existed since the beginning of the chemotherapy era. New insights into the resistant mechanisms of anti-TB drugs have been provided. Better understanding of drug resistance mechanisms helps in the development of new tools for the rapid diagnosis of drug-resistant TB. There is also a pressing need in the development of new drugs with novel targets to improve the current treatment of TB and to prevent the emergence of drug resistance in Mycobacterium tuberculosis. This review summarizes the anti-TB drug resistance mechanisms, furnishes some possible novel drug targets in the development of new agents for TB therapy and discusses the usefulness using known targets to develop new anti-TB drugs. Whole genome sequencing is currently an advanced technology to uncover drug resistance mechanisms in M. tuberculosis. However, further research is required to unravel the significance of some newly discovered gene mutations in their contribution to drug resistance. Copyright © 2016 Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Ltd. All rights reserved.

Microarray and network-based identification of functional modules and pathways of active tuberculosis.

PubMed

Bian, Zhong-Rui; Yin, Juan; Sun, Wen; Lin, Dian-Jie

2017-04-01

Diagnose of active tuberculosis (TB) is challenging and treatment response is also difficult to efficiently monitor. The aim of this study was to use an integrated analysis of microarray and network-based method to the samples from publically available datasets to obtain a diagnostic module set and pathways in active TB. Towards this goal, background protein-protein interactions (PPI) network was generated based on global PPI information and gene expression data, following by identification of differential expression network (DEN) from the background PPI network. Then, ego genes were extracted according to the degree features in DEN. Next, module collection was conducted by ego gene expansion based on EgoNet algorithm. After that, differential expression of modules between active TB and controls was evaluated using random permutation test. Finally, biological significance of differential modules was detected by pathways enrichment analysis based on Reactome database, and Fisher's exact test was implemented to extract differential pathways for active TB. Totally, 47 ego genes and 47 candidate modules were identified from the DEN. By setting the cutoff-criteria of gene size >5 and classification accuracy ≥0.9, 7 ego modules (Module 4, Module 7, Module 9, Module 19, Module 25, Module 38 and Module 43) were extracted, and all of them had the statistical significance between active TB and controls. Then, Fisher's exact test was conducted to capture differential pathways for active TB. Interestingly, genes in Module 4, Module 25, Module 38, and Module 43 were enriched in the same pathway, formation of a pool of free 40S subunits. Significant pathway for Module 7 and Module 9 was eukaryotic translation termination, and for Module 19 was nonsense mediated decay enhanced by the exon junction complex (EJC). Accordingly, differential modules and pathways might be potential biomarkers for treating active TB, and provide valuable clues for better understanding of molecular mechanism of active TB. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

Robinson, Richard T

2017-12-12

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

Human genetic factors in tuberculosis: an update.

PubMed

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

2017-09-01

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

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

PubMed Central

Tran, Huong Thi Giang; Bui, Quyen Thi Tu

2016-01-01

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

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

PubMed

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

2016-01-01

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

Towards an empowerment approach in tuberculosis treatment in Cape Town, South Africa: a qualitative analysis of programmatic change

PubMed Central

Atkins, Salla; Lewin, Simon; Ringsberg, Karin C.; Thorson, Anna

2012-01-01

Background Tuberculosis rates in the world remain high, especially in low- and middle-income countries. International tuberculosis (TB) policy generally recommends the use of directly observed therapy (DOT) to ensure treatment adherence. Objective This article examines a change in TB treatment support that occurred in 2005 in South Africa, from DOT to the enhanced TB adherence programme (ETA). Design Seven key individuals representing academics, policy makers and service providers involved in the development of the ETA programme or knowledgeable about the issue were purposively sampled and interviewed, and participant observation was conducted at ETA programme steering group meetings. Qualitative content analysis was used to analyse the data, drawing on the Kingdon model of agenda setting. This model suggests that three independent streams – problem, policy and politics – come together at a certain point, often facilitated by policy entrepreneurs, to provide an opportunity for an issue to enter the policy agenda. Results The results suggest the empowerment-oriented programme emerged through the presence of policy entrepreneurs with access to resources. Policy entrepreneurs were influenced by a number of simultaneously occurring challenges including problems within the existing programme; a perceived mismatch between patient needs and the existing TB treatment model; and the TB-HIV co-epidemic. Policy entrepreneurs saw the ART approach as a possible solution to these challenges. Conclusions The Kingdon model contributed to describing the process of policy change. Research evidence seemed to influence this change diffusely, through the interaction of policy entrepreneurs and academics. PMID:22902052

MIC of Delamanid (OPC-67683) against Mycobacterium tuberculosis Clinical Isolates and a Proposed Critical Concentration.

PubMed

Stinson, Kelly; Kurepina, Natalia; Venter, Amour; Fujiwara, Mamoru; Kawasaki, Masanori; Timm, Juliano; Shashkina, Elena; Kreiswirth, Barry N; Liu, Yongge; Matsumoto, Makoto; Geiter, Lawrence

2016-06-01

The increasing global burden of multidrug-resistant tuberculosis (MDR-TB) requires reliable drug susceptibility testing that accurately characterizes susceptibility and resistance of pathogenic bacteria to effectively treat patients with this deadly disease. Delamanid is an anti-TB agent first approved in the European Union in 2014 for the treatment of pulmonary MDR-TB in adults. Using the agar proportion method, delamanid MIC was determined for 460 isolates: 316 from patients enrolled in a phase 2 global clinical trial, 76 from two phase 2 early bactericidal activity trials conducted in South Africa, and 68 isolates obtained outside clinical trials (45 from Japanese patients and 23 from South African patients). With the exception of two isolates, MICs ranged from 0.001 to 0.05 μg/ml, resulting in an MIC50 of 0.004 μg/ml and an MIC90 of 0.012 μg/ml. Various degrees of resistance to other anti-TB drugs did not affect the distribution of MICs, nor did origin of isolates from regions/countries other than South Africa. A critical concentration/breakpoint of 0.2 μg/ml can be used to define susceptible and resistant isolates based on the distribution of MICs and available pharmacokinetic data. Thus, clinical isolates from delamanid-naive patients with tuberculosis have a very low MIC for delamanid and baseline resistance is rare, demonstrating the potential potency of delamanid and supporting its use in an optimized background treatment regimen for MDR-TB. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

The Impact of Smoking on Airflow Limitation in Subjects with History of Asthma and Inactive Tuberculosis

PubMed Central

Kim, Hyun Jung; Baek, Seunghee; Kim, Hee Jin; Lee, Jae Seung; Oh, Yeon-Mok; Lee, Sang-Do; Lee, Sei Won

2015-01-01

Background Although smoking is the most important and modifiable cause of chronic obstructive pulmonary disease (COPD), other risk factors including asthma and tuberculosis (TB) are also associated. It is common for COPD patients to have more than one of these risk factors. The aims of this study were to determine the prevalence of airflow limitation (FEV1/FVC<0.7) according to the risk factors and to investigate their impact and interaction in airflow limitation. Methods From the Korean National Health and Nutrition Examination Survey between 2008 and 2012, we analyzed participants over 40 years of age by spirometry, chest radiograph and questionnaire about asthma and smoking history. Results Of 12,631 participants, 1,548 (12.3%) had airflow limitation. The prevalence of airflow limitation in smokers (≥10 pack-year), asthmatics, and those with inactive TB was 23.9%, 32.1%, and 33.6%. The prevalence increased with the number of risk factors: 86.1% had airflow limitation if they had all three risk factors. Impacts of inactive TB and asthma on airflow limitation were equivalent to 47 and 69 pack-years of smoking, respectively. Airflow limitation resulted from lower levels of smoking in those with inactive TB and asthma. A potential interaction between smoking and inactive tuberculosis in the development of airflow limitation was identified (p = 0.054). Conclusions Asthma and inactive TB lesions increase susceptibility to smoking in the development of airflow limitation. People with these risk factors should be seen as a major target population for anti-smoking campaigns to prevent COPD. PMID:25915938

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

NASA Astrophysics Data System (ADS)

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

2018-04-01

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

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

PubMed

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

2015-10-01

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

Tuberculosis care for pregnant women: a systematic review.

PubMed

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

2014-11-19

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

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

PubMed

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

2018-03-07

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

A rapid assessment and response approach to review and enhance Advocacy, Communication and Social Mobilisation for Tuberculosis control in Odisha state, India

PubMed Central

2011-01-01

Background Tuberculosis remains a major public health problem in India with the country accounting for 1 in 5 of all TB cases reported globally. An advocacy, communication and social mobilisation project for Tuberculosis control was implemented and evaluated in Odisha state of India. The purpose of the study was to identify the impact of project interventions including the use of 'Interface NGOs' and involvement of community groups such as women's self-help groups, local government bodies, village health sanitation committees, and general health staff in promoting TB control efforts. Methods The study utilized a rapid assessment and response (RAR) methodology. The approach combined both qualitative field work approaches, including semi-structured interviews and focus group discussions with empirical data collection and desk research. Results Results revealed that a combination of factors including the involvement of Interface NGOs, coupled with increased training and engagement of front line health workers and community groups, and dissemination of community based resources, contributed to improved awareness and knowledge about TB in the targeted districts. Project activities also contributed towards improving health worker and community effectiveness to raise the TB agenda, and improved TB literacy and treatment adherence. Engagement of successfully treated patients also assisted in reducing community stigma and discrimination. Conclusion The expanded use of advocacy, communication and social mobilisation activities in TB control has resulted in a number of benefits. These include bridging pre-existing gaps between the health system and the community through support and coordination of general health services stakeholders, NGOs and the community. The strategic use of 'tailored messages' to address specific TB problems in low performing areas also led to more positive behavioural outcomes and improved efficiencies in service delivery. Implications for future studies are that a comprehensive and well planned range of ACSM activities can enhance TB knowledge, attitudes and behaviours while also mobilising specific community groups to build community efficacy to combat TB. The use of rapid assessments combined with other complementary evaluation approaches can be effective when reviewing the impact of TB advocacy, communication and social mobilisation activities. PMID:21663623

RESULTS OF NATIONAL SURVEILLANCE OF CHILDHOOD TUBERCULOSIS: 2013–2016

PubMed Central

Giroux, R; Montgomery-Song, A; Consunji-Araneta, R; Kitai, I; Morris, S

2017-01-01

Abstract BACKGROUND: There is little detailed epidemiologic and clinical data about tuberculosis (TB) disease in children in Canada. OBJECTIVES: This study characterizes the epidemiologic, clinical, and treatment data for all cases of TB in children under age 15 in Canada surveyed through the Canadian Pediatric Surveillance Program’s (CPSP) Childhood Tuberculosis Study. Preliminary results from the study from October 2013 to September 2016 are presented here, as data collection from reported cases is still ongoing. DESIGN/METHODS: New active TB cases were identified through a monthly form sent by the CPSP to approximately 2500 active pediatricians, pediatric subspecialists, and select non-pediatricians who manage childhood TB. For cases meeting inclusion criteria, a detailed questionnaire was sent to the treating physician to collect clinical, epidemiological, and treatment data, followed by 6-month follow-up surveys until 6 months after treatment completion. RESULTS: Of 248 unique incident cases reported, 142 cases both met inclusion criteria and returned a detailed questionnaire. Selected demographic data are shown here: Intrathoracic TB was reported in 129/142 (91%) of cases of which 111 had pulmonary disease. Of 104 patients who underwent investigations for pulmonary disease (sputum in 60, brochoalveolar lavage in 6, and gastric aspirates in 56), one or more positive cultures were obtained in 42 (40%). Within age groups, the proportion of cases who underwent investigation for pulmonary disease and were culture positive was: 3/11 (27%) under 1 year of age, 14/40 (35%) 1-4 years old, 8/23 (35%) 5-9 years old, and 17/30 (57%) 10 years or older. Extrathoracic TB was reported in 35 (25%), including 16 (42%) patients 10+ years old. There was one case of multi-drug resistant TB. CONCLUSION: Preliminary results from this study suggests a high incidence of TB in Inuit and First Nations children, as well as a higher proportion of extrathoracic TB and greater success in culture positivity in children aged 10+. At completion, this study will provide the most complete picture of childhood TB in Canada and will serve to refine practice in monitoring, detecting, and treating this infection.

The epidemiology of childhood tuberculosis in the Netherlands: still room for prevention

PubMed Central

2014-01-01

Background The occurrence of tuberculosis (TB) among children has long been neglected as a public health concern. However, any child with TB is a sentinel event indicating recent transmission. Vaccination, early case finding and treatment of those latently infected with TB can prevent cases, severe morbidity and unnecessary death. Method The objective of the study was to describe the occurrence of TB events among children in the Netherlands which may be avoided through preventive measures. For this purpose we performed a trend analysis of routine Dutch TB and LTBI (surveillance data in 1993–2012 and a descriptive analysis of children with TB and with LTBI diagnosed in 2005–2012). Results Overall childhood TB incidence has declined over the last two decades from 3.6 in 1993 to 1.9 per 100,000 children in 2012. The decline was stronger among Dutch-born children compared to foreign-born children. In 2005–2012 64% of childhood TB cases were detected through active case finding. Foreign-born children with TB were less likely to be detected through active case finding, when not detected through post-entry TB screening. Childhood TB diagnosis was culture confirmed in 68% of passively detected cases and 12% of actively detected cases. Of 1,049 children with LTBI started on preventive treatment in 2005–2012, 90% completed treatment. In 37% of all childhood TB cases there was at least one ‘missed opportunity’ for prevention. Thirty nine percent of child TB patients eligible for BCG were not vaccinated. Conclusion Children with TB in the Netherlands are generally detected at an early stage and treatment completion rates are high. However, more TB cases among children can be prevented through enhancing TB case finding and screening and preventive treatment of latent TB infection among migrant children, and improving the coverage of BCG vaccination among eligible risk groups. PMID:24885314

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

PubMed

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

2011-11-01

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

Conventional and molecular epidemiology of Tuberculosis in Manitoba

PubMed Central

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

2003-01-01

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

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

PubMed

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

2017-01-01

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

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

PubMed

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

2016-06-01

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

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

PubMed Central

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

2007-01-01

Pro- and anti-inflammatory cytokines and their signaling pathways play key roles in protection from and pathogenesis of mycobacterial infection, and their balance and dynamic changes may control or predict clinical outcome. Peripheral blood cells' capacity to produce proinflammatory (tumor necrosis factor alpha [TNF-α], interleukin-12/23p40 [IL-12/23p40], and gamma interferon [IFN-γ]) and anti-inflammatory (IL-10) cytokines in response to Mycobacterium tuberculosis or unrelated stimuli (lipopolysaccharide, phytohemagglutinin) was studied in 93 pulmonary tuberculosis (TB) patients and 127 healthy controls from Indonesia. Their cells' ability to respond to IFN-γ was examined to investigate whether M. tuberculosis infection can also inhibit IFN-γ receptor (IFN-γR) signaling. Although there was interindividual variability in the observed responses, the overall results revealed that M. tuberculosis-induced TNF-α and IFN-γ levels showed opposite trends. Whereas TNF-α production was higher in active-TB patients than in controls, IFN-γ production was strongly depressed during active TB, correlated inversely with TB disease severity, and increased during therapy. By contrast, mitogen-induced IFN-γ production, although lower in patients than in controls, did not change during treatment, suggesting an M. tuberculosis-specific and reversible component in the depression of IFN-γ. Depressed IFN-γ production was not due to decreased IL-12/IL-23 production. Importantly, IFN-γ-inducible responses were also significantly depressed during active TB and normalized during treatment, revealing disease activity-related and reversible impairment in IFN-γR signaling in TB. Finally, IFN-γ/IL-10 ratios significantly correlated with TB cure. Taken together, these results show that M. tuberculosis-specific stimulation of IFN-γ (but not TNF-α) production and IFN-γR signaling are significantly depressed in active TB, correlate with TB disease severity and activity, and normalize during microbiological TB cure. The depression of both IFN-γ production and IFN-γR signaling may synergize in contributing to defective host control in active TB. PMID:17145950

High Prevalence of Latent Tuberculosis Infection in Dialysis Patients Using the Interferon-γ Release Assay and Tuberculin Skin Test

PubMed Central

Lee, Susan Shin-Jung; Chou, Kang-Ju; Dou, Horng-Yunn; Huang, Tsi-Shu; Ni, Yen-Yun; Fang, Hua-Chang; Tsai, Hung-Chin; Sy, Cheng-Len; Chen, Jui-Kuang; Wu, Kuang-Sheng; Wang, Yung-Hsin; Lin, Hsi-Hsun

2010-01-01

Background and objectives: Patients in ESRD on hemodialysis with latent tuberculosis (TB) infection have 10 to 25 times the risk of reactivation into active disease compared with healthy adults. This study investigates the prevalence of latent TB infection in dialysis patients from a country with an intermediate burden of TB and its associated risk factors using the QuantiFERON-TB Gold in-tube test (QGIT) and the tuberculin skin test (TST). Design, setting, participants, & measurements: This was a prospective, cross-sectional study performed at a medical center in Taiwan on dialysis patients. Each patient underwent QGIT, two-step TST using 2 tuberculin units (TU) of PPD RT-23, a chest x-ray to exclude active TB, and an interview to determine TB risk factors. Results: Ninety-three of 190 eligible patients were enrolled: 35 men and 58 women. 64.8% were vaccinated with the Bacille-Calmette-Guérin (BCG) vaccination. Overall, 34.4% were positive by QGIT and 10.8% were indeterminate. Using a 10-mm TST cutoff, 53.9% were positive. There was poor correlation between TST and QGIT at any TST cutoff criteria. There was a significant increasing trend of QGIT positivity with age in those younger than 70 years, and, conversely, a decreasing trend of TST reactivity with age. Significant risk factors for QGIT positivity included age and past TB disease. Conclusions: This study shows a high prevalence of latent TB infection in dialysis patients in a country with an intermediate burden of TB. QGIT in dialysis patients correlated better than TST with the risk of TB infection and past TB disease. PMID:20538837

Marked disparity in the epidemiology of tuberculosis among Aboriginal peoples on the Canadian prairies: The challenges and opportunities

PubMed Central

Long, Richard; Hoeppner, Vernon; Orr, Pamela; Ainslie, Martha; King, Malcolm; Abonyi, Sylvia; Mayan, Maria; Kunimoto, Dennis; Langlois-Klassen, Deanne; Heffernan, Courtney; Lau, Angela; Menzies, Dick

2013-01-01

BACKGROUND: While it is established that Aboriginal peoples in the prairie provinces of Canada are disproportionately affected by tuberculosis (TB), little is known about the epidemiology of TB either within or across provincial borders. METHODS: Provincial reporting systems for TB, Statistics Canada censuses and population estimates of Registered Indians provided by Aboriginal Affairs and Northern Development Canada were used to estimate the overall (2004 to 2008) and pulmonary (2007 to 2008) TB rates in the prairie provinces. The place of residence at diagnosis of pulmonary TB cases in 2007 to 2008 was also documented. RESULTS: The age- and sex-adjusted incidence of TB in Registered Indians was 52.6 per 100,000 person-years, 38 times higher than in Canadian-born ‘others’. Incidence rates in Registered Indians were highest in Manitoba and lowest in Alberta. In Alberta and Saskatchewan, on-reserve rates were more than twice that of off-reserve rates. Rates in the Métis and Registered Indians were similar in Saskatchewan (50.0 and 52.2 per 100,000 person-years, respectively). In 2007 to 2008, approximately 90% of Canadian-born pulmonary TB cases in the prairie provinces were Aboriginal. Outside of one metropolitan area (Winnipeg, Manitoba), most Registered Indian and Métis pulmonary TB cases were concentrated in a relatively small number of communities north of the 53rd parallel. Rates of pulmonary TB in 11 of these communities were >300 per 100,000 person-years. In Manitoba, 49% of off-reserve Registered Indian pulmonary cases were linked to high-incidence reserve communities. INTERPRETATION: The epidemiology of TB among Aboriginal peoples on the Canadian prairies is markedly disparate. Pulmonary TB is highly focal, which is both a concern and an opportunity. PMID:23717818

Tuberculosis Management Practices of Private Practitioners in Pune Municipal Corporation, India

PubMed Central

Bharaswadkar, Sandeep; Kanchar, Avinash; Thakur, Narendra; Shah, Shubhangi; Patnaik, Brinda; Click, Eleanor S.; Kumar, Ajay M. V.; Dewan, Puneet Kumar

2014-01-01

Background Private Practitioners (PP) are the primary source of health care for patients in India. Limited representative information is available on TB management practices of Indian PP or on the efficacy of India’s Revised National Tuberculosis Control Programme (RNTCP) to improve the quality of TB management through training of PP. Methods We conducted a cross-sectional survey of a systematic random sample of PP in one urban area in Western India (Pune, Maharashtra). We presented sample clinical vignettes and determined the proportions of PPs who reported practices consistent with International Standards of TB Care (ISTC). We examined the association between RNTCP training and adherence to ISTC by calculating odds ratios and 95% confidence intervals. Results Of 3,391 PP practicing allopathic medicine, 249 were interviewed. Of these, 55% had been exposed to RNTCP. For new pulmonary TB patients, 63% (158/249) of provider responses were consistent with ISTC diagnostic practices, and 34% (84/249) of responses were consistent with ISTC treatment practices. However, 48% (120/249) PP also reported use of serological tests for TB diagnosis. In the new TB case vignette, 38% (94/249) PP reported use of at least one second line anti-TB drug in the treatment regimen. RNTCP training was not associated with diagnostic or treatment practices. Conclusion In Pune, India, despite a decade of training activities by the RNTCP, high proportions of providers resorted to TB serology for diagnosis and second-line anti-TB drug use in new TB patients. Efforts to achieve universal access to quality TB management must account for the low quality of care by PP and the lack of demonstrated effect of current training efforts. PMID:24897374

A survey to assess the extent of public-private mix DOTS in the management of tuberculosis in Zambia

PubMed Central

Kapata, Nathan; Maboshe, Mwendaweli; Michelo, Charles; Babaniyi, Olusegun

2015-01-01

Background Involving all relevant healthcare providers in tuberculosis (TB) management through public-private mix (PPM) approaches is a vital element in the World Health Organization's (WHO) Stop TB Strategy. The control of TB in Zambia is mainly done in the public health sector, despite the high overall incidence rates. Aim We conducted a survey to determine the extent of private-sector capacity, participation, practices and adherence to national guidelines in the control of TB. Setting This survey was done in the year 2012 in 157 facilities in three provinces of Zambia where approximately 85% of the country's private health facilities are found. Methods We used a structured questionnaire to interview the heads of private health facilities to assess the participation of the private health sector in TB diagnosis, management and prevention activities. Results Out of 157 facilities surveyed, 40.5% were from the Copperbelt, 4.4% from Central province and 55.1% from Lusaka province. Only 23.8% of the facilities were able to provide full diagnosis and management of TB patients. Although 47.4% of the facilities reported that they do notify their cases to the National TB control programme, the majority (62.7%) of these facilities did not show evidence of notifications. Conclusion Our results show that the majority of the facilities that diagnose and manage TB in the private sector do not report their TB activities to the National TB Control Programme (NTP). There is a need for the NTP to improve collaboration with the private sector with respect to TB control activities and PPM for Directly Observed Treatment, Short Course (DOTS). PMID:26245591

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

USDA-ARS?s Scientific Manuscript database

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

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

PubMed

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

2016-09-01

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

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

PubMed Central

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

2009-01-01

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

Multidrug-resistant tuberculosis.

PubMed

Zager, Ellen M; McNerney, Ruth

2008-01-25

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

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

PubMed

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

2015-02-01

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

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

PubMed

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

2014-01-01

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

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

PubMed

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

2015-12-21

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

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

PubMed

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

2017-04-01

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

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

PubMed

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

2012-02-15

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

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

PubMed Central

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

2013-01-01

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

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

PubMed

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

2012-01-01

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

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2016-12-01

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

Macronutrient intake and body composition changes during anti-tuberculosis therapy in adults

PubMed Central

Frediani, Jennifer K.; Sanikidze, Ekaterina; Kipiani, Maia; Tukvadze, Nestani; Hebbar, Gautam; Ramakrishnan, Usha; Jones, Dean P.; Easley, Kirk A.; Shenvi, Neeta; Kempker, Russell R.; Tangpricha, Vin; Blumberg, Henry M.; Ziegler, Thomas R.

2015-01-01

Background Malnutrition is common in patients with active tuberculosis (TB), yet little information is available on serial dietary intake or body composition in TB disease. Objective To evaluate macronutrient intake and body composition in individuals with newly diagnosed with TB over time. Design Adults with active pulmonary TB (n=191; 23 with multidrug resistant TB (MDR-TB) and 36 culture-negative household contacts (controls) enrolled in a clinical trial of high-dose cholecalciferol (vitamin D3) were studied. Macronutrient intake was determined at baseline, 8 and 16 weeks. Serial body composition was assessed by body mass index (BMI; kg/m2) and bioelectrical impedance analysis (BIA) to estimate fat mass and fat-free mass. Descriptive statistics, repeated measures ANOVA for changes over time and linear regression were used. Results At baseline, mean daily energy, protein, fat and carbohydrate (CHO) intakes were significantly higher, and body weight, BMI, fat-free mass and fat mass were significantly lower, between TB subjects and controls. These remained significant after adjusting for age, gender, employment status and smoking. In all TB subjects, baseline mean daily intakes of energy, fat and protein were adequate when compared to the US Dietary Reference Intakes and protein significantly increased over time (p<0.0001). Body weight, BMI, and fat and fat-free mass increased over time. MDR-TB patients exhibited lower body weight and fat-free mass over time, despite similar daily intake of kcal, protein, and fat. Conclusions Macronutrient intake was higher in TB patients than controls, but TB-induced wasting was evident. As macronutrient intake of TB subjects increased over time, there was a parallel increase in BMI, while body composition proportions were maintained. However, individuals with MDR-TB demonstrated concomitantly decreased body weight and fat-free mass over time versus drug-sensitive TB patients, despite increased macronutrient intake. Thus, MDR-TB appears to blunt anabolism to macronutrient intake, likely reflecting the catabolic effects of TB. PMID:25753551

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

PubMed

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

2014-01-01

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

Examining DNA fingerprinting as an epidemiology tool in the tuberculosis program in the Northwest Territories, Canada

PubMed Central

Case, Cheryl; Kandola, Kami; Chui, Linda; Li, Vincent; Nix, Nancy; Johnson, Rhonda

2013-01-01

Background Tuberculosis (TB) is an important public health problem in the Northwest Territories (NWT), particularly among Canadian Aboriginal people. Objective To analyse the transmission patterns of tuberculosis among the population living in the NWT, a territorial jurisdiction located within Northern Canada. Methods This population-based retrospective study examined the DNA fingerprints of all laboratory confirmed cases of TB in the NWT, Canada, between 1990 and 2009. An isolate of each lab-confirmed case had genotyping done using IS6110 Restriction Fragment Length Polymorphism. DNA patterns were assigned to each DNA fingerprint, and indistinguishable fingerprints patterns were assigned a cluster. Social network analysis (SNA) was used to examine direct linkages among cases determined through conventional contact tracing (CCT), their DNA fingerprint and home community. Results Of the 225 lab-confirmed cases identified, the study was limited to 195 subjects due to DNA fingerprinting data availability. The mean age of the cases was 43.8 years (±22.6) and 120 (61.5%) males. The Dene (First Nations) encompassed 120 of the cases (87.7%), 8 cases (4.1%) were Inuit, 2 cases (1.0%) were Metis, 7 cases (3.6%) were Immigrants and 1 case had unknown ethnicity. One hundred and eighty six (95.4%) subjects were clustered, resulting in 8 clusters. Trend analysis showed significant relationships between with risk factors for unemployment (p=0.020), geographic location (p≤0.001) and homelessness (p≤0.001). Other significant risk factors included excessive alcohol consumption, prior infection with Mycobacterium tuberculosis and prior contact with a case of TB. Conclusions This study demonstrates how DNA fingerprinting and SNA can be additional epidemiological tools, along with CCT method, to determine transmission patterns of TB. PMID:23671837

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

PubMed

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

2015-01-01

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

Vitamin D: Immuno-modulation and tuberculosis treatment.

PubMed

Selvaraj, Paramasivam; Harishankar, Murugesan; Afsal, Kolloli

2015-05-01

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

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

PubMed

Denholm, Justin T; McBryde, Emma S

2014-02-01

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

Psychometric testing of the short version of the world health organization quality of life (WHOQOL-BREF) questionnaire among pulmonary tuberculosis patients in Taiwan

PubMed Central

2012-01-01

Background Studies on the effects of tuberculosis on a patient’s quality of life (QOL) are scant. The objective of this study was to evaluate the psychometric properties of the Taiwan short version of the World Health Organization Quality of Life (WHOQOL-BREF) questionnaire using patients with tuberculosis in Taiwan and healthy referents. Methods The Taiwanese short version of the WHOQOL-BREF was administered to patients with tuberculosis undergoing treatment and healthy referents from March 2007 to July 2007. Patients with tuberculosis (n = 140) and healthy referents (n = 130), matched by age, sex, and ethnicity, agreed to an interview. All participants lived in eastern Taiwan. Reliability assessments included internal consistency, whereas validity assessments included construct validity, convergent validity, and discriminant validity. Results More than half of these patients and referents were men (70.7% and 66.2%, respectively), and their average ages were 50.1 and 47.9 years, respectively. Approximately 60% of patients and referents were aboriginal Taiwanese (60.7% and 61.1%, respectively). The proportion with low socioeconomic status was greater for these patients. The internal consistency reliability coefficients were .92 and .93 for the patients and healthy referents, respectively. Exploratory factor analysis on the healthy referents displayed a 4-domain model, which was compatible with the original WHOQOL-BREF 4-domain model. However, for the TB patient group, after deleting 3 items, both exploratory and confirmatory factor analysis revealed a 6-domain model. Conclusion Psychometric evaluation of the Taiwan short version of the WHOQOL-BREF indicates that it has adequate reliability for use in research with TB patients in Taiwan. However, the factor structure generated from this TB patient sample differed from the WHO’s original 4-factor model, which raised a validity concern to apply the Taiwan short version of the WHOQOL-BREF to Taiwanese TB patients. Future research recruiting another sample to revisit this validity issue must be conducted to determine the validity of the WHOQOL-BREF TW in patients with TB. PMID:22877305

A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis

PubMed Central

Villamor, Eduardo; Mugusi, Ferdinand; Urassa, Willy; Bosch, Ronald J.; Saathoff, Elmar; Matsumoto, Kenji; Meydani, Simin N.; Fawzi, Wafaie W.

2008-01-01

Background Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. Methods We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)–infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. Results Micronutrients decreased the risk of TB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, −14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. Conclusions Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania. PMID:18471061

Prevalence of tuberculosis respiratory symptoms and associated factors in the indigenous populations of Paraguay (2012)

PubMed Central

Aguirre, Sarita; Cuellar, Celia Martínez; Herrero, María Belén; Cortesi, Gustavo Chamorro; de Romero, Nilda Gimenez; Alvarez, Mirian; Braga, Jose Ueleres

2017-01-01

BACKGROUND The prevalence of respiratory symptoms and confirmed tuberculosis (TB) among indigenous groups in Paraguay is unknown. METHODS This study assessed the prevalence of respiratory symptoms, confirmed pulmonary TB, and associated socio-economic factors among indigenous Paraguayan populations. Indigenous persons residing in selected communities were included in the study. A total of 24,352 participants were interviewed at home between October and December 2012. Respiratory symptomatic individuals were defined as those with respiratory symptoms of TB. A hierarchical Poisson regression analysis was performed with four levels: individual characteristics, living conditions and environmental characteristics, source of food, and type of nutrition. FINDINGS In this study, 1,383 participants had respiratory symptoms (5.7%), but only 10 had culture-confirmed TB (41/100,000 inhabitants). The small number of cases did not allow evaluation of the risk factors for TB. Age older than 37 years was associated with a two-fold increased risk of symptoms. Female sex; family history of TB; type of housing; home heating; a lack of hunting, fishing, or purchasing food; and a lack of vegetable consumption were also associated with the presence of symptoms. A lack of cereal consumption had a protective effect. Members of the Ayoreo or Manjui ethnic groups had a three-fold increased risk of symptoms. MAIN CONCLUSION Individual characteristics, dietary habits, and belonging to specific ethnic groups were associated with respiratory symptoms. PMID:28591308

Gender-Related Barriers and Delays in Accessing Tuberculosis Diagnostic and Treatment Services: A Systematic Review of Qualitative Studies

PubMed Central

Akande, Tokunbo; Shankar, Anita V.; McIntire, Katherine N.; Gounder, Celine R.; Gupta, Amita; Yang, Wei-Teng

2014-01-01

Background. Tuberculosis (TB) remains a significant global public health problem with known gender-related (male versus female) disparities. We reviewed the qualitative evidence (written/spoken narrative) for gender-related differences limiting TB service access from symptom onset to treatment initiation. Methods. Following a systematic process, we searched 12 electronic databases, included qualitative studies that assessed gender differences in accessing TB diagnostic and treatment services, abstracted data, and assessed study validity. Using a modified “inductive coding” system, we synthesized emergent themes within defined barriers and delays limiting access at the individual and provider/system levels and examined gender-related differences. Results. Among 13,448 studies, 28 studies were included. All were conducted in developing countries and assessed individual-level barriers; 11 (39%) assessed provider/system-level barriers, 18 (64%) surveyed persons with suspected or diagnosed TB, and 7 (25%) exclusively surveyed randomly sampled community members or health care workers. Each barrier affected both genders but had gender-variable nature and impact reflecting sociodemographic themes. Women experienced financial and physical dependence, lower general literacy, and household stigma, whereas men faced work-related financial and physical barriers and community-based stigma. Conclusions. In developing countries, barriers limiting access to TB care have context-specific gender-related differences that can inform integrated interventions to optimize TB services. PMID:24900921

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

PubMed

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

2012-12-01

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

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

PubMed

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

2005-03-01

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

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

PubMed

Di, Li; Li, Yan

2018-02-01

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

What's new in tuberculosis vaccines?

PubMed Central

Ginsberg, Ann M.

2002-01-01

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

Breath-based biomarkers for tuberculosis

NASA Astrophysics Data System (ADS)

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

2012-06-01

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

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

PubMed

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

2010-11-01

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

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

PubMed

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

2004-08-01

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

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

PubMed

Chyczewska, Elzbieta

2008-01-01

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

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

PubMed

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

2018-02-01

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

Immunogenicity of 60 novel latency-related antigens of Mycobacterium tuberculosis

PubMed Central

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

2014-01-01

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

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

PubMed

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

2014-01-01

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

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

PubMed Central

2017-01-01

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

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

PubMed

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

2012-01-01

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

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

PubMed Central

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

2018-01-01

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

Identification and Genotyping of Mycobacterium tuberculosis Isolated From Water and Soil Samples of a Metropolitan City

PubMed Central

Velayati, Ali Akbar; Farnia, Parissa; Mozafari, Mohadese; Malekshahian, Donya; Farahbod, Amir Masoud; Seif, Shima; Rahideh, Snaz

2015-01-01

BACKGROUND: The potential role of environmental Mycobacterium tuberculosis in the epidemiology of TB remains unknown. We investigated the transmission of M tuberculosis from humans to the environment and the possible transmission of M tuberculosis from the environment to humans. METHODS: A total of 1,500 samples were collected from three counties of the Tehran, Iran metropolitan area from February 2012 to January 2014. A total of 700 water samples (47%) and 800 soil samples (53%) were collected. Spoligotyping and the mycobacterial interspersed repetitive units-variable number of tandem repeats typing method were performed on DNA extracted from single colonies. Genotypes of M tuberculosis strains isolated from the environment were compared with the genotypes obtained from 55 patients with confirmed pulmonary TB diagnosed during the study period in the same three counties. RESULTS: M tuberculosis was isolated from 11 of 800 soil samples (1%) and 71 of 700 water samples (10%). T family (56 of 82, 68%) followed by Delhi/CAS (11 of 82, 13.4%) were the most frequent M tuberculosis superfamilies in both water and soil samples. Overall, 27.7% of isolates in clusters were related. No related typing patterns were detected between soil, water, and clinical isolates. The most frequent superfamily of M tuberculosis in clinical isolates was Delhi/CAS (142, 30.3%) followed by NEW-1 (127, 27%). The bacilli in contaminated soil (36%) and damp water (8.4%) remained reculturable in some samples up to 9 months. CONCLUSIONS: Although the dominant M tuberculosis superfamilies in soil and water did not correspond to the dominant M tuberculosis family in patients, the presence of circulating genotypes of M tuberculosis in soil and water highlight the risk of transmission. PMID:25340935

Radiological signs associated with pulmonary multi-drug resistant tuberculosis: an analysis of published evidences.

PubMed

Wáng, Yì Xiáng J; Chung, Myung Jin; Skrahin, Aliaksandr; Rosenthal, Alex; Gabrielian, Andrei; Tartakovsky, Michael

2018-03-01

Despite that confirmative diagnosis of pulmonary drug-sensitive tuberculosis (DS-TB) and multidrug resistant tuberculosis (MDR-TB) is determined by microbiological testing, early suspicions of MDR-TB by chest imaging are highly desirable in order to guide diagnostic process. We aim to perform an analysis of currently available literatures on radiological signs associated with pulmonary MDR-TB. A literature search was performed using PubMed on January 29, 2018. The search words combination was "((extensive* drug resistant tuberculosis) OR (multidrug-resistant tuberculosis)) AND (CT or radiograph or imaging or X-ray or computed tomography)". We analyzed English language articles reported sufficient information of radiological signs of DS-TB vs. MDR-TB. Seventeen articles were found to be sufficiently relevant and included for analysis. The reported pulmonary MDR-TB cases were grouped into four categories: (I) previously treated (or 'secondary', or 'acquired') MDR-TB in HIV negative (-) adults; (II) new (or 'primary') MDR-TB in HIV(-) adults; (III) MDR-TB in HIV positive (+) adults; and (IV) MDR-TB in child patients. The common radiological findings of pulmonary MDR-TB included centrilobular small nodules, branching linear and nodular opacities (tree-in-bud sign), patchy or lobular areas of consolidation, cavitation, and bronchiectasis. While overall MDR-TB cases tended to have more extensive disease, more likely to be bilateral, to have pleural involvement, to have bronchiectasis, and to have lung volume loss; these signs alone were not sufficient for differential diagnosis of MDR-TB. Current literatures suggest that the radiological sign which may offer good specificity for pulmonary MDR-TB diagnosis, though maybe at the cost of low sensitivity, would be thick-walled multiple cavities, particularly if the cavity number is ≥3. For adult HIV(-) patients, new MDR-TB appear to show similar prevalence of cavity lesion, which was estimated to be around 70%, compared with previously treated MDR-TB. Thick-walled multiple cavity lesions present the most promising radiological sign for MDR-TB diagnosis. For future studies cavity lesion characteristics should be quantified in details.

Risk and Timing of Tuberculosis Among Close Contacts of Persons with Infectious Tuberculosis.

PubMed

Reichler, Mary R; Khan, Awal; Sterling, Timothy R; Zhao, Hui; Moran, Joyce; McAuley, James; Bessler, Patricia; Mangura, Bonita

2018-05-15

The risk and timing of tuberculosis (TB) among recently exposed close contacts of patients with infectious TB is not well established. We prospectively enrolled culture-confirmed pulmonary TB patients ≥15 years of age and their close contacts at nine health departments in the United States and Canada. Close contacts were screened and cross-matched with TB registries to identify those who developed TB. TB was diagnosed in 158 (4%) of 4490 contacts to 718 index TB patients. Of those with TB, cumulative totals of 81 (51%), 119 (75%), 128 (81%) and 145 (92%) were diagnosed by 1, 3, 6, and 12 months after index case diagnosis, respectively. TB rates among contacts were 2644, 115, 46, 69, and 25 per 100,000 persons, respectively, in the five consecutive years after index patient diagnosis. Of the TB cases among contacts, 121 (77%) were identified by contact investigation and 37 (23%) by TB registry cross-match. Close contacts to infectious TB patients had high rates of TB, with most disease diagnosed before or within 3 months after index patient diagnosis. Contact investigations need to be prompt to detect TB and maximize the opportunity to identify and treat latent infection in order to prevent disease.

Dynamics of adrenal steroids are related to variations in Th1 and Treg populations during Mycobacterium tuberculosis infection in HIV positive persons.

PubMed

Quiroga, Maria Florencia; Angerami, Matias Tomas; Santucci, Natalia; Ameri, Diego; Francos, Jose Luis; Wallach, Jorge; Sued, Omar; Cahn, Pedro; Salomón, Horacio; Bottasso, Oscar

2012-01-01

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS.

Dynamics of Adrenal Steroids Are Related to Variations in Th1 and Treg Populations during Mycobacterium tuberculosis Infection in HIV Positive Persons

PubMed Central

Quiroga, Maria Florencia; Angerami, Matias Tomas; Santucci, Natalia; Ameri, Diego; Francos, Jose Luis; Wallach, Jorge; Sued, Omar; Cahn, Pedro; Salomón, Horacio; Bottasso, Oscar

2012-01-01

Tuberculosis (TB) remains the most frequent cause of illness and death from an infectious agent, and its interaction with HIV has devastating effects. We determined plasma levels of dehydroepiandrosterone (DHEA), its circulating form DHEA-suphate (DHEA-s) and cortisol in different stages of M. tuberculosis infection, and explored their role on the Th1 and Treg populations during different scenarios of HIV-TB coinfection, including the immune reconstitution inflammatory syndrome (IRIS), a condition related to antiretroviral treatment. DHEA levels were diminished in HIV-TB and HIV-TB IRIS patients compared to healthy donors (HD), HIV+ individuals and HIV+ individuals with latent TB (HIV-LTB), whereas dehydroepiandrosterone sulfate (DHEA-s) levels were markedly diminished in HIV-TB IRIS individuals. HIV-TB and IRIS patients presented a cortisol/DHEA ratio significantly higher than HIV+, HIV-LTB and HD individuals. A positive correlation was observed between DHEA-s and CD4 count among HIV-TB individuals. Conversely, cortisol plasma level inversely correlated with CD4 count within HIV-TB individuals. M. tuberculosis-specific Th1 lymphocyte count was increased after culturing PBMC from HIV-TB individuals in presence of DHEA. We observed an inverse correlation between DHEA-s plasma level and Treg frequency in co-infected individuals, and CD4+FoxP3+ Treg frequency was increased in HIV-TB and IRIS patients compared to other groups. Strikingly, we observed a prominent CD4+CD25-FoxP3+ population across HIV-TB and HIV-TB IRIS patients, which frequency correlated with DHEA plasma level. Finally, DHEA treatment negatively regulated FoxP3 expression without altering Treg frequency in co-infected patients. These data suggest an enhancing role for DHEA in the immune response against M. tuberculosis during HIV-TB coinfection and IRIS. PMID:22431997

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

PubMed

Mascart, Françoise; Locht, Camille

2015-01-01

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

Perinatal tuberculosis: new challenges in the diagnosis and treatment of tuberculosis in infants and the newborn.

PubMed

Whittaker, Elizabeth; Kampmann, Beate

2008-12-01

With increasing rates of tuberculosis (TB) infection and disease worldwide, the rate of perinatal TB is also affected. A high index of suspicion by health professionals, in both the developed and developing world, is required to detect and manage tuberculosis in pregnancy and the early newborn period. Differences in immune responses in the fetus and neonate add to the diagnostic difficulties already recognised in young children. Although specific guidelines for the treatment of this potentially devastating disease are lacking due to paucity of experience, outcome is favourable, if the condition is recognised and treated according to existing TB protocols. HIV co-infection, multi- and extensively-drug resistant (MDR/XDR) TB contribute to the challenges. New diagnostic and vaccine developments hold future promise, but much work is needed to completely understand the complex immune responses to tuberculosis and control this disease.

Adverse events and treatment interruption in tuberculosis patients with and without HIV co‐infection

PubMed Central

Breen, R A M; Miller, R F; Gorsuch, T; Smith, C J; Schwenk, A; Holmes, W; Ballinger, J; Swaden, L; Johnson, M A; Cropley, I; Lipman, M C I

2006-01-01

Background Serious treatment associated adverse events are thought to occur more frequently in individuals with tuberculosis (TB) who are co‐infected with HIV. A study was undertaken to assess the frequency of serious (grade III/IV) adverse events and interruption of anti‐TB treatment in the era of effective antiretroviral therapy. Methods The incidence of serious adverse events was retrospectively compared in 312 individuals treated for TB, 156 of whom were co‐infected with HIV. Results 111 HIV infected individuals (71%) received highly active antiretroviral therapy at the same time as anti‐TB treatment. Serious adverse events were recorded in 40% HIV infected and 26% HIV uninfected individuals (p = 0.008). Peripheral neuropathy and persistent vomiting were more common in co‐infected patients (p<0.001; p = 0.006), although all cause interruption of anti‐TB treatment occurred with similar frequency in the two groups (13% in HIV infected patients and 15% in HIV uninfected patients; p = 0.74). In 85% of HIV infected patients and 87% of HIV uninfected individuals this was due to hepatotoxicity, which typically presented within 2 months of starting treatment. The median delay in restarting treatment was 4 weeks, so most individuals required full TB re‐treatment. Conclusion Despite a greater rate of serious (grade III/IV) adverse events among HIV infected individuals, discontinuation of anti‐TB treatment occurred with a similar frequency in HIV infected and HIV uninfected individuals. PMID:16844730

Intragranulomatous necrosis in pulmonary granulomas is not related to resistance against Mycobacterium tuberculosis infection in experimental murine models induced by aerosol.

PubMed

Guirado, Evelyn; Gordillo, Sergi; Gil, Olga; Díaz, Jorge; Tapia, Gustavo; Vilaplana, Cristina; Ausina, Vicenç; Cardona, Pere-Joan

2006-04-01

Intragranulomatous necrosis is a primary feature in the natural history of human tuberculosis (TB). Unfortunately, this phenomenon is not usually seen in the experimental TB murine model. Artificial induction of this necrosis in pulmonary granulomas (INPG) may be achieved through aerosol inoculation of lipopolysaccharide (LPS) 3 weeks after Mycobacterium tuberculosis infection. At week 9 post-infection, the centre of primary granulomas became larger, showing eosinophilic necrosis. Interestingly, INPG induction was related to mice strains C57BL/6 and 129/Sv, but not to BALB/c and DBA/2. Furthermore, the same pattern was obtained with the induction of infection using a clinical M. tuberculosis strain (UTE 0335R) that naturally induces INPG. In all the mice strains tested, the study of pulmonary mRNA expression revealed a tendency to increase or to maintain the expression of RANTES, interferon-gamma, tumour necrosis factor and iNOS, in both LPS- and UTE 0335R-induced INPG, thus suggesting that this response must be necessary but not sufficient for inducing INPG. Our work supports that INPG induction is a local phenomenon unrelated to the resistant (C57BL/6 and BALB/c) or susceptible (129/Sv and DBA/2) background of mice strains against M. tuberculosis infection.

Human CD8 T lymphocytes recognize Mycobacterium tuberculosis antigens presented by HLA-E during active tuberculosis and express type 2 cytokines.

PubMed

Caccamo, Nadia; Pietra, Gabriella; Sullivan, Lucy C; Brooks, Andrew G; Prezzemolo, Teresa; La Manna, Marco P; Di Liberto, Diana; Joosten, Simone A; van Meijgaarden, Krista E; Di Carlo, Paola; Titone, Lucina; Moretta, Lorenzo; Mingari, Maria C; Ottenhoff, Tom H M; Dieli, Francesco

2015-04-01

CD8 T cells contribute to protective immunity against Mycobacterium tuberculosis. In humans, M. tuberculosis reactive CD8 T cells typically recognize peptides associated to classical MHC class Ia molecules, but little information is available on CD8 T cells recognizing M. tuberculosis Ags presented by nonclassical MHC class Ib molecules. We show here that CD8 T cells from tuberculosis (TB) patients recognize HLA-E-binding M. tuberculosis peptides in a CD3/TCR αβ mediated and CD8-dependent manner, and represent an additional type of effector cells playing a role in immune response to M. tuberculosis during active infection. HLA-E-restricted recognition of M. tuberculosis peptides is detectable by a significant enhanced ex vivo frequency of tetramer-specific circulating CD8 T cells during active TB. These CD8 T cells produce type 2 cytokines upon antigenic in vitro stimulation, help B cells for Ab production, and mediate limited TRAIL-dependent cytolytic and microbicidal activity toward M. tuberculosis infected target cells. Our results, together with the finding that HLA-E/M. tuberculosis peptide specific CD8 T cells are detected in TB patients with or without HIV coinfection, suggest that this is a new human T-cell population that participates in immune response in TB. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mycobacterial diversity causing multi- and extensively drug-resistant tuberculosis in Djibouti, Horn of Africa.

PubMed

Millán-Lou, M I; Ollé-Goig, J E; Tortola, M T; Martin, C; Samper, S

2016-02-01

On detecting a high prevalence of multidrug-resistant tuberculosis (TB) in Djibouti, 32 Mycobacterium tuberculosis isolates of patients hospitalised in the TB referral centre of the capital were genotyped. A high variety of M. tuberculosis lineages, including lineage 1, Indo-Oceanic, lineage 2, East-Asian, lineage 3, East-African Indian and lineage 4, Euro-American, were detected.

Alarming levels of drug-resistant tuberculosis in HIV-infected patients in metropolitan Mumbai, India.

PubMed

Isaakidis, Petros; Das, Mrinalini; Kumar, Ajay M V; Peskett, Christopher; Khetarpal, Minni; Bamne, Arun; Adsul, Balkrishna; Manglani, Mamta; Sachdeva, Kuldeep Singh; Parmar, Malik; Kanchar, Avinash; Rewari, B B; Deshpande, Alaka; Rodrigues, Camilla; Shetty, Anjali; Rebello, Lorraine; Saranchuk, Peter

2014-01-01

Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%-40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with 'presumptive TB' rather than 'presumptive DR-TB' and tailor the treatment regimen based on the resistance patterns.

Review: New Vaccine Against Tuberculosis: Current Developments and Future Challenges

NASA Astrophysics Data System (ADS)

Liu, Jun

2009-04-01

Tuberculosis (TB) continues to be a global health threat. BCG was developed as an attenuated live vaccine for tuberculosis control nearly a century ago. Despite being the most widely used vaccine in human history, BCG is not an ideal vaccine and has two major limitations: its poor efficacy against adult pulmonary TB and its disconcerting safety in immunocompromised individuals. A safer and more effective TB vaccine is urgently needed. This review article discusses current strategies to develop the next generation of TB vaccines to replace BCG. While some progresses have been made in the past decade, significant challenges lie ahead.

Multidrug-resistant tuberculosis (MDR-TB) in India: an attempt to link biosocial determinants.

PubMed

Atre, Sachin R; Mistry, Nerges F

2005-04-01

Multidrug-resistant tuberculosis (MDR-TB) has emerged as a possible threat to global tuberculosis control efforts in recent years. It is a challenge not only from a public health point of view but also in the context of global economy, especially in the absence of treatment for MDR-TB at national-level programs in developing countries. Biological accounts are insufficient to understand the emergence and dynamics of drug resistance. This article focuses essentially on the need for a holistic perspective, linking biosocial determinants that would probably lead to better insights into MDR-TB control strategies.

Achievements in and Challenges of Tuberculosis Control in South Korea

PubMed Central

Kim, Ji Han

2015-01-01

After the Korean War (1950–1953), nearly 6.5% of South Korea’s population had active tuberculosis (TB). In response, South Korea implemented the National Tuberculosis Program in 1962. From 1965 to 1995, the prevalence of bacteriologically confirmed pulmonary TB in South Korea decreased from 940 to 219 cases per 100,000 population. Astounding economic growth might have contributed to this result; however, TB incidence in South Korea remains the highest among high-income countries. The rate of decrease in TB incidence seems to have slowed over the past 15 years. A demographic shift toward an older population, many of whom have latent TB and various concurrent conditions, is challenging TB control efforts in South Korea. The increasing number of immigrants also plays a part in the prolonged battle against TB. A historical review of TB in South Korea provides an opportunity to understand national TB control efforts that are applicable to other parts of the world. PMID:26485188

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

PubMed Central

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

2013-01-01

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

Glucose Metabolism Disorder Is Associated with Pulmonary Tuberculosis in Individuals with Respiratory Symptoms from Brazil

PubMed Central

Castro, Simone; Cafezeiro, Aparecida S.; Daltro, Carla; Netto, Eduardo M.; Kornfeld, Hardy; Andrade, Bruno B.

2016-01-01

Background Diabetes mellitus (DM) has been associated with increased risk for pulmonary tuberculosis (PTB) in endemic settings but it is unknown whether PTB risk is also increased by pre-DM. Here, we prospectively examined the association between glucose metabolism disorder (GMD) and PTB in patients with respiratory symptoms at a tuberculosis primary care reference center in Brazil. Methods Oral glucose tolerance test was performed and levels of fasting plasma glucose and glycohemoglobin (HbA1c) were measured in a cohort of 892 individuals presenting with respiratory symptoms of more than two weeks duration. Patients were also tested for PTB with sputum cultures. Prevalence of pre-DM and DM (based on HbA1c) was estimated and tested for association with incident PTB. Other TB risk factors including smoking history were analyzed. Results The majority of the study population (63.1%) exhibited GMD based on HbA1c ≥5.7%. Patients with GMD had higher prevalence of PTB compared to normoglycemic patients. Individuals with DM exhibited increased frequency of TB-related symptoms and detection of acid-fast bacilli in sputum smears. Among patients with previous DM diagnosis, sustained hyperglycemia (HbA1c ≥7.0%) was associated with increased TB prevalence. Smoking history alone was not significantly associated with TB in our study population but the combination of smoking and HbA1c ≥7.0% was associated with 6 times higher odds for PTB. Conclusions Sustained hyperglycemia and pre-DM are independently associated with active PTB. This evidence raises the question whether improving glycemic control in diabetic TB patients would reduce the risk of TB transmission and simultaneously reduce the clinical burden of disease. A better understanding of mechanisms underlying these associations, especially those suggesting that pre-DM may be a factor driving susceptibility to TB is warranted. PMID:27078026

Lansoprazole use and tuberculosis incidence in the United Kingdom Clinical Practice Research Datalink: A population based cohort

PubMed Central

Yates, Tom A.; Tomlinson, Laurie A.; Bhaskaran, Krishnan; Langan, Sinead; Thomas, Sara; Smeeth, Liam

2017-01-01

Background Recent in vitro and animal studies have found the proton pump inhibitor (PPI) lansoprazole to be highly active against Mycobacterium tuberculosis. Omeprazole and pantoprazole have no activity. There is no evidence that, in clinical practice, lansoprazole can treat or prevent incident tuberculosis (TB) disease. Methods and findings We studied a cohort of new users of lansoprazole, omeprazole, or pantoprazole from the United Kingdom Clinical Practice Research Datalink to determine whether lansoprazole users have a lower incidence of TB disease than omeprazole or pantoprazole users. Negative control outcomes of myocardial infarction (MI) and herpes zoster were also studied. Multivariable Cox proportional hazards regression was used to adjust for potential confounding by a wide range of factors. We identified 527,364 lansoprazole initiators and 923,500 omeprazole or pantoprazole initiators. Lansoprazole users had a lower rate of TB disease (n = 86; 10.0 cases per 100,000 person years; 95% confidence interval 8.1–12.4) than omeprazole or pantoprazole users (n = 193; 15.3 cases per 100,000 person years; 95% confidence interval 13.3–17.7), with an adjusted hazard ratio (HR) of 0.68 (0.52–0.89). No association was found with MI (adjusted HR 1.04; 95% confidence interval 1.00–1.08) or herpes zoster (adjusted HR 1.03; 95% confidence interval 1.00–1.06). Limitations of this study are that we could not determine whether TB disease was due to reactivation of latent infection or a result of recent transmission, nor could we determine whether lansoprazole would have a beneficial effect if given to people presenting with TB disease. Conclusions In this study, use of the commonly prescribed and cheaply available PPI lansoprazole was associated with reduced incidence of TB disease. Given the serious problem of drug resistance and the adverse side effect profiles of many TB drugs, further investigation of lansoprazole as a potential antituberculosis agent is warranted. PMID:29161254

Assessing the Quality of Tuberculosis Evaluation for Children with Prolonged Cough Presenting to Routine Community Health Care Settings in Rural Uganda

PubMed Central

Marquez, Carina; Davis, J. Lucian; Katamba, Achilles; Haguma, Priscilla; Ochom, Emmanuel; Ayakaka, Irene; Chamie, Gabriel; Dorsey, Grant; Kamya, Moses R.; Charlebois, Edwin; Havlir, Diane V.; Cattamanchi, Adithya

2014-01-01

Background Improving childhood tuberculosis (TB) evaluation and care is a global priority, but data on performance at community health centers in TB endemic regions are sparse. Objective To describe the current practices and quality of TB evaluation for children with cough ≥2 weeks' duration presenting to community health centers in Uganda. Methods Cross-sectional analysis of children (<15 years) receiving care at five Level IV community health centers in rural Uganda for any reason between 2009–2012. Quality of TB care was assessed using indicators derived from the International Standards of Tuberculosis Care (ISTC). Results From 2009–2012, 1713 of 187,601 (0.9%, 95% CI: 0.4–1.4%) children presenting to community health centers had cough ≥ 2 weeks' duration. Of those children, only 299 (17.5%, 95% CI: 15.7–19.3%) were referred for sputum microscopy, but 251 (84%, 95% CI: 79.8–88.1%) completed sputum examination if referred. The yield of sputum microscopy was only 3.6% (95% CI: 1.3–5.9%), and only 55.6% (95% CI: 21.2–86.3%) of children with acid-fast bacilli positive sputum were started on treatment. Children under age 5 were less likely to be referred for sputum examination and to receive care in accordance with ISTC. The proportion of children evaluated in accordance with ISTC increased over time (4.6% in 2009 to 27.9% in 2012, p = 0.03), though this did not result in increased case-detection. Conclusion The quality of TB evaluation was poor for children with cough ≥2 weeks' duration presenting for health care. Referrals for sputum smear microscopy and linkage to TB treatment were key gaps in the TB evaluation process, especially for children under the age of five. PMID:25170875

Half of rifampicin-resistant Mycobacterium tuberculosis complex isolated from tuberculosis patients in Sub-Saharan Africa have concomitant resistance to pyrazinamide

PubMed Central

Diallo, Awa Ba; Tagliani, Elisa; Diarra, Bassirou; Kadanga, Abalo Essosimna; Togo, Antieme Combo George; Thiam, Aliou; de Rijk, Willem Bram; Alagna, Riccardo; Houeto, Sabine; Ba, Fatoumata; Dagnra, Anoumou Yaotsè; Ivan, Emil; Affolabi, Dissou; Schwoebel, Valérie; Trebucq, Arnaud; de Jong, Bouke Catherine; Rigouts, Leen; Daneau, Géraldine

2017-01-01

Background Besides inclusion in 1st line regimens against tuberculosis (TB), pyrazinamide (PZA) is used in 2nd line anti-TB regimens, including in the short regimen for multidrug-resistant TB (MDR-TB) patients. Guidelines and expert opinions are contradictory about inclusion of PZA in case of resistance. Moreover, drug susceptibility testing (DST) for PZA is not often applied in routine testing, and the prevalence of resistance is unknown in several regions, including in most African countries. Methods Six hundred and twenty-three culture isolates from rifampicin-resistant (RR) patients were collected in twelve Sub-Saharan African countries. Among those isolates, 71% were from patients included in the study on the Union short-course regimen for MDR-TB in Benin, Burkina Faso, Burundi, Cameroon, Central Africa Republic, the Democratic Republic of the Congo, Ivory Coast, Niger, and Rwanda PZA resistance, and the rest (29%) were consecutive isolates systematically stored from 2014–2015 in Mali, Rwanda, Senegal, and Togo. Besides national guidelines, the isolates were tested for PZA resistance through pncA gene sequencing. Results Over half of these RR-TB isolates (54%) showed a mutation in the pncA gene, with a significant heterogeneity between countries. Isolates with fluoroquinolone resistance (but not with injectable resistance or XDR) were more likely to have concurrent PZA resistance. The pattern of mutations in the pncA gene was quite diverse, although some isolates with an identical pattern of mutations in pncA and other drug-related genes were isolated from the same reference center, suggesting possible transmission of these strains. Conclusion Similar to findings in other regions, more than half of the patients having RR-TB in West and Central Africa present concomitant resistance to PZA. Further investigations are needed to understand the relation between resistance to PZA and resistance to fluoroquinolones, and whether continued use of PZA in the face of PZA resistance provides clinical benefit to the patients. PMID:29088294

Optimal control of a two-strain tuberculosis-HIV/AIDS co-infection model.

PubMed

Agusto, F B; Adekunle, A I

2014-05-01

Tuberculosis is a bacterial disease caused by Mycobacterium tuberculosis (TB). The risk for TB infection greatly increases with HIV infection; TB disease occurs in 7-10% of patients with HIV infection each year, increasing the potential for transmission of drug-resistant Mycobacterium tuberculosis strains. In this paper a deterministic model is presented and studied for the transmission of TB-HIV/AIDS co-infection. Optimal control theory is then applied to investigate optimal strategies for controlling the spread of the disease using treatment of infected individuals with TB as the system control variables. Various combination strategies were examined so as to investigate the impact of the controls on the spread of the disease. And incremental cost-effectiveness ratio (ICER) was used to investigate the cost effectiveness of all the control strategies. Our results show that the implementation of the combination strategy involving the prevention of treatment failure in drug-sensitive TB infectious individuals and the treatment of individuals with drug-resistant TB is the most cost-effective control strategy. Similar results were obtained with different objective functionals involving the minimization of the number of individuals with drug-sensitive TB-only and drug-resistant TB-only with the efforts involved in applying the control. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Latent tuberculous infection in household contacts of multidrug-resistant and newly diagnosed tuberculosis.

PubMed

Fox, G J; Anh, N T; Nhung, N V; Loi, N T; Hoa, N B; Ngoc Anh, L T; Cuong, N K; Buu, T N; Marks, G B; Menzies, D

2017-03-01

Differences in the prevalence of latent tuberculous infection (LTBI) and tuberculosis (TB) disease among contacts of patients with multidrug-resistant TB (MDR-TB) and drug-susceptible TB are not well understood. To compare the prevalence of tuberculin skin test (TST) positivity in household contacts of patients with MDR-TB and in contacts of patients never previously treated for TB ('new TB'). Consecutive patients with MDR-TB and their household contacts at nine urban district clinics in Viet Nam were screened for TB and LTBI, and followed up for 6 months. LTBI was defined as a TST result of at least 10 mm. A total of 167 patients with TB and their 337 household contacts were recruited. A total of 167/180 (25.8%) contacts of new TB patients and 60/147 (40.8%) contacts of MDR-TB patients were TST-positive (odds ratio [OR] 2.0, 95%CI 1.3-3.2). Contacts of MDR-TB patients were more likely to have baseline chest radiograph findings consistent with TB (OR 2.6, 95%CI 1.4-5.0). Contacts of MDR-TB patients have a high risk of developing TB. Measures to reduce Mycobacterium tuberculosis transmission and accelerate the detection of disease among high-risk contacts should be prioritised to curb the MDR-TB epidemic.

High Prevalence of Tuberculosis and Serious Bloodstream Infections in Ambulatory Individuals Presenting for Antiretroviral Therapy in Malawi

PubMed Central

Bedell, Richard A.; Anderson, Suzanne T. B.; van Lettow, Monique; Åkesson, Ann; Corbett, Elizabeth L.; Kumwenda, Moses; Chan, Adrienne K.; Heyderman, Robert S.; Zachariah, Rony; Harries, Anthony D.; Ramsay, Andrew R.

2012-01-01

Background Tuberculosis (TB) and serious bloodstream infections (BSI) may contribute to the high early mortality observed among patients qualifying for antiretroviral therapy (ART) with unexplained weight loss, chronic fever or chronic diarrhea. Methods and Findings A prospective cohort study determined the prevalence of undiagnosed TB or BSI among ambulatory HIV-infected adults with unexplained weight loss and/or chronic fever, or diarrhea in two routine program settings in Malawi. Subjects with positive expectorated sputum smears for AFB were excluded. Investigations Bacterial and mycobacterial blood cultures, cryptococcal antigen test (CrAg), induced sputum (IS) for TB microscopy and solid culture, full blood count and CD4 lymphocyte count. Among 469 subjects, 52 (11%) had microbiological evidence of TB; 50 (11%) had a positive (non-TB) blood culture and/or positive CrAg. Sixty-five additional TB cases were diagnosed on clinical and radiological grounds. Nontyphoidal Salmonellae (NTS) were the most common blood culture pathogens (29 cases; 6% of participants and 52% of bloodstream isolates). Multivariate analysis of baseline clinical and hematological characteristics found significant independent associations between oral candidiasis or lymphadenopathy and TB, marked CD4 lymphopenia and NTS infection, and severe anemia and either infection, but low positive likelihood ratios (<2 for all combinations). Conclusions We observed a high prevalence of TB and serious BSI, particularly NTS, in a program cohort of chronically ill HIV-infected outpatients. Baseline clinical and hematological characteristics were inadequate predictors of infection. HIV clinics need better rapid screening tools for TB and BSI. Clinical trials to evaluate empiric TB or NTS treatment are required in similar populations. PMID:22761767

Bovine tuberculosis slaughter surveillance in the United States 2001–2010: assessment of its traceback investigation function

PubMed Central

2014-01-01

Background The success of tracing cattle to the herd of origin after the detection and confirmation of bovine tuberculosis (TB) lesions in cattle at slaughter is a critical component of the national bovine TB eradication program in the United States (U.S.). The aims of this study were to 1) quantify the number of bovine TB cases identified at slaughter that were successfully traced to their herd of origin in the U.S. during 2001–2010, 2) quantify the number of successful traceback investigations that found additional TB infected animals in the herd of origin or epidemiologically linked herds, and 3) describe the forms of animal identification present on domestic bovine TB cases and their association with traceback success. Results We analyzed 2001–2010 data in which 371 granulomatous lesions were confirmed as bovine TB. From these 114 bovine TB cases, 78 adults (i.e. sexually intact bovines greater than two years of age), and 36 fed (i.e. less than or equal to two years of age) were classified as domestic cattle (U.S. originated). Of these adults and fed cases, 83% and 13% were successfully traced, respectively. Of these traceback investigations, 70% of adult cases and 50% of fed cases identified additional bovine TB infected animals in the herd of origin or an epidemiologically linked herd. We found that the presence of various forms of animal identification on domestic bovine TB cases at slaughter may facilitate successful traceback investigations; however, they do not guarantee it. Conclusions These results provide valuable information with regard to epidemiological traceback investigations and serve as a baseline to aid U.S. officials when assessing the impact of newly implemented strategies as part of the national bovine TB eradication in the U.S. PMID:25123050

Patient- and provider-level risk factors associated with default from tuberculosis treatment, South Africa, 2002: a case-control study

PubMed Central

2012-01-01

Background Persons who default from tuberculosis treatment are at risk for clinical deterioration and complications including worsening drug resistance and death. Our objective was to identify risk factors associated with tuberculosis (TB) treatment default in South Africa. Methods We conducted a national retrospective case control study to identify factors associated with treatment default using program data from 2002 and a standardized patient questionnaire. We defined default as interrupting TB treatment for two or more consecutive months during treatment. Cases were a sample of registered TB patients receiving treatment under DOTS that defaulted from treatment. Controls were those who began therapy and were cured, completed or failed treatment. Two respective multivariable models were constructed, stratified by history of TB treatment (new and re-treatment patients), to identify independent risk factors associated with default. Results The sample included 3165 TB patients from 8 provinces; 1164 were traceable and interviewed (232 cases and 932 controls). Significant risk factors associated with default among both groups included poor health care worker attitude (new: AOR 2.1, 95% CI 1.1-4.4; re-treatment: AOR 12, 95% CI 2.2-66.0) and changing residence during TB treatment (new: AOR 2.0, 95% CI 1.1-3.7; re-treatment: AOR 3.4, 95% CI 1.1-9.9). Among new patients, cases were more likely than controls to report having no formal education (AOR 2.3, 95% CI 1.2-4.2), feeling ashamed to have TB (AOR 2.0, 95% CI 1.3-3.0), not receiving adequate counseling about their treatment (AOR 1.9, 95% CI 1.2-2.8), drinking any alcohol during TB treatment (AOR 1.9, 95% CI 1.2-3.0), and seeing a traditional healer during TB treatment (AOR 1.9, 95% CI 1.1-3.4). Among re-treatment patients, risk factors included stopping TB treatment because they felt better (AOR 21, 95% CI 5.2-84), having a previous history of TB treatment default (AOR 6.4, 95% CI 2.9-14), and feeling that food provisions might have helped them finish treatment (AOR 5.0, 95% CI 1.3-19). Conclusions Risk factors for default differ between new and re-treatment TB patients in South Africa. Addressing default in both populations with targeted interventions is critical to overall program success. PMID:22264339

Prevalence of pulmonary tuberculosis among prison inmates: A cross-sectional survey at the Correctional and Detention Facility of Abidjan, Côte d'Ivoire

PubMed Central

Koffi, Ange; Danel, Christine; Ouassa, Timothée; Blehoué, Marcel-Angora; Ouattara, Eric; Assemien, Jeanne-d’Arc; Masumbuko, Jean-Marie; Coffie, Patrick; Cartier, Nathalie; Laurent, Arnaud; Raguin, Gilles; Malvy, Denis; N’Dri-Yoman, Thérèse; Eholié, Serge P.; Domoua, Serge K.

2017-01-01

Background In Côte d’Ivoire, a TB prison program has been developed since 1999. This program includes offering TB screening to prisoners who show up with TB symptoms at the infirmary. Our objective was to estimate the prevalence of pulmonary TB among inmates at the Correctional and Detention Facility of Abidjan, the largest prison of Côte d’Ivoire, 16 years after this TB program was implemented. Methods Between March and September 2015, inmates, were screened for pulmonary TB using systematic direct smear microscopy, culture and chest X-ray. All participants were also proposed HIV testing. TB was defined as either confirmed (positive culture), probable (positive microscopy and/or chest X-ray findings suggestive of TB) or possible (signs or symptoms suggestive of TB, no X-Ray or microbiological evidence). Factors associated with confirmed tuberculosis were analysed using multivariable logistic regression. Results Among the 943 inmates screened, 88 (9.3%) met the TB case definition, including 19 (2.0%) with confirmed TB, 40 (4.2%) with probable TB and 29 (3.1%) with possible TB. Of the 19 isolated TB strains, 10 (53%) were TB drug resistant, including 7 (37%) with multi-resistance. Of the 10 patients with TB resistant strain, only one had a past history of TB treatment. HIV prevalence was 3.1% overall, and 9.6%among TB cases. Factors associated with confirmed TB were age ≥30 years (Odds Ratio 3.8; 95% CI 1.1–13.3), prolonged cough (Odds Ratio 3.6; 95% CI 1.3–9.5) and fever (Odds Ratio 2.7; 95% CI 1.0–7.5). Conclusion In the country largest prison, pulmonary TB is still 10 (confirmed) to 44 times (confirmed, probable or possible) as frequent as in the Côte d’Ivoire general population, despite a long-time running symptom-based program of TB detection. Decreasing TB prevalence and limiting the risk of MDR may require the implementation of annual in-cell TB screening campaigns that systematically target all prison inmates. PMID:28759620

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

PubMed Central

2013-01-01

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

The impact of migration on tuberculosis epidemiology and control in high-income countries: a review.

PubMed

Pareek, Manish; Greenaway, Christina; Noori, Teymur; Munoz, Jose; Zenner, Dominik

2016-03-23

Tuberculosis (TB) causes significant morbidity and mortality in high-income countries with foreign-born individuals bearing a disproportionate burden of the overall TB case burden in these countries. In this review of tuberculosis and migration we discuss the impact of migration on the epidemiology of TB in low burden countries, describe the various screening strategies to address this issue, review the yield and cost-effectiveness of these programs and describe the gaps in knowledge as well as possible future solutions.The reasons for the TB burden in the migrant population are likely to be the reactivation of remotely-acquired latent tuberculosis infection (LTBI) following migration from low/intermediate-income high TB burden settings to high-income, low TB burden countries.TB control in high-income countries has historically focused on the early identification and treatment of active TB with accompanying contact-tracing. In the face of the TB case-load in migrant populations, however, there is ongoing discussion about how best to identify TB in migrant populations. In general, countries have generally focused on two methods: identification of active TB (either at/post-arrival or increasingly pre-arrival in countries of origin) and secondly, conditionally supported by WHO guidance, through identifying LTBI in migrants from high TB burden countries. Although health-economic analyses have shown that TB control in high income settings would benefit from providing targeted LTBI screening and treatment to certain migrants from high TB burden countries, implementation issues and barriers such as sub-optimal treatment completion will need to be addressed to ensure program efficacy.

Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis in children: a prospective, multi-centre evaluation.

PubMed

Reither, Klaus; Manyama, Christina; Clowes, Petra; Rachow, Andrea; Mapamba, Daniel; Steiner, Andreas; Ross, Amanda; Mfinanga, Elirehema; Sasamalo, Mohamed; Nsubuga, Martin; Aloi, Francesco; Cirillo, Daniela; Jugheli, Levan; Lwilla, Fred

2015-04-01

Following endorsement by the World Health Organisation, the Xpert MTB/RIF assay has been widely incorporated into algorithms for the diagnosis of adult tuberculosis (TB). However, data on its performance in children remain scarce. This prospective, multi-centre study evaluated the performance of Xpert MTB/RIF to diagnose pulmonary tuberculosis in children. Children older than eight weeks and younger than 16 years with suspected pulmonary tuberculosis were enrolled at three TB endemic settings in Tanzania and Uganda, and assigned to five well-defined case definition categories: culture-confirmed TB, highly probable TB, probable TB, not TB, or indeterminate. The diagnostic accuracy of Xpert MTB/RIF was assessed using culture-confirmed TB cases as reference standard. In total, 451 children were enrolled. 37 (8%) had culture-confirmed TB, 48 (11%) highly probably TB and 62 probable TB (13%). The Xpert MTB/RIF assay had a sensitivity of 68% (95% CI, 50%-82%) and specificity of 100% (95% CI, 97%-100%); detecting 1.7 times more culture-confirmed cases than smear microscopy with a similar time to detection. Xpert MTB/RIF was positive in 2% (1/48) of highly probable and in 3% (2/62) of probable TB cases. Xpert MTB/RIF provided timely results with moderate sensitivity and excellent specificity compared to culture. Low yields in children with highly probable and probable TB remain problematic. Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Analysis of host responses to Mycobacterium tuberculosis antigens in a multi-site study of subjects with different TB and HIV infection states in sub-Saharan Africa.

PubMed

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

2013-01-01

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 trials.

A case risk study of lactic acidosis risk by metformin use in type 2 diabetes mellitus tuberculosis coinfection patients.

PubMed

Novita, Bernadette Dian; Pranoto, Agung; Wuryani; Soediono, Endang Isbandiati; Mertaniasih, Ni Made

2018-07-01

Metformin (MET) has possibilities to be utilized as an adjunct of tuberculosis (TB) therapy for controlling the growth of Mycobacterium tuberculosis (M. tuberculosis). MET enhances the production of mitochondrial reactive oxygen species and facilitates phagosome-lysosome fusion; those mechanism are important in M. tuberculosis elimination. Moreover, MET-associated lactic acidosis (MALA) needs to be considered and the incidence of MALA in patients with type 2 DM-TB coinfection remains unknown. This result contributes much to our understanding about the clinical effect of MET use in type 2 DM-TB coinfection. For the purpose of understanding the MET effect as an adjuvant therapy in TB therapy and insulin simultaneous therapy, an observational clinical study was done in type 2 DM newly TB coinfection outpatients at Surabaya Paru Hospital. Patients were divided into two groups. First group was MET group, in which the patients were given MET accompanying insulin and TB treatment regimens, the golden standard therapy of DM-TB coinfection. MET therapy was given for at least 2 months. Second group was non-MET group, in which the patients were given insulin and TB treatment regimens. The lactate levels in both groups were measured after 2 months. Among 42 participants, there was no case of lactic acidosis during this study period. Data were normally distributed; thus, we continued analysis of the difference using paired T-test with 95% confidence. There was no difference in lactate levels (p=0.396) after MET therapy compared to non-MET group. In this study involving patients with TB pulmonary diseases, there is neither evidence that MET therapy induced lactic acidosis event nor that it increased lactate blood level. Thus, we concluded that MET use in type 2 DM-TB coinfection did not induce lactic acidosis. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Factors associated with tuberculosis treatment outcomes among tuberculosis patients attending tuberculosis treatment centres in 2016-2017 in Mogadishu, Somalia.

PubMed

Ali, Marian Khalif; Karanja, Simon; Karama, Mohammed

2017-01-01

World Health Organization (WHO) reported that tuberculosis (TB) was a major health problem and the second leading cause of mortality globally. An estimated 1.8 million TB deaths were reported in 2015. In Somalia, the average TB incidence was 274 cases per 100,000 people in 2014; prevalence was 513 per 100,000 population; and mortality rate excluding human immune deficiency virus (HIV)/TB co-infection was 64/100,000. In addition, the prevalence rates of multi-drug resistant (MDR)-TB are still high, 5.2% among new cases and 40.7% for retreatment cases. The objective of this study was to determine individual and institutional level factors associated with TB treatment outcomes (TB-TOs) among patients attending TBTCs in Mogadishu. The study design was cross-sectional, using quantitative and qualitative methods. Data was collected using interviewer administered semi-structured questionnaires and key in-depth interviews in 2016/2017. Qualitative data was coded using NVIVO8 and quantitative data analyzed using descriptive and inferential statistics at 95% confidence interval using SPSS20 software. The study used a sample of 385 TB patients. There were 315(81.8%) successful TB-TOs. Individual level factors-marital status, education level, HIV status, treatment category and knowledge on TB influenced TB-TOs (p-value < 0.05). Being married, educated, HIV-negative, new treatment case and knowledgeable on TB increased odds of successful TB-TOs (OR > 0, p value < 0.05) compared to other patients. TBTCs factors did not influence TB-TOs (p-value > 0.05). TB-TOs were mainly affected by patient individual factors. There was need for patient education on TB management and treatment; and improved patient-health provider relationship.

Factors associated with tuberculosis treatment outcomes among tuberculosis patients attending tuberculosis treatment centres in 2016-2017 in Mogadishu, Somalia

PubMed Central

Ali, Marian Khalif; Karanja, Simon; Karama, Mohammed

2017-01-01

Introduction World Health Organization (WHO) reported that tuberculosis (TB) was a major health problem and the second leading cause of mortality globally. An estimated 1.8 million TB deaths were reported in 2015. In Somalia, the average TB incidence was 274 cases per 100,000 people in 2014; prevalence was 513 per 100,000 population; and mortality rate excluding human immune deficiency virus (HIV)/TB co-infection was 64/100,000. In addition, the prevalence rates of multi-drug resistant (MDR)-TB are still high, 5.2% among new cases and 40.7% for retreatment cases. The objective of this study was to determine individual and institutional level factors associated with TB treatment outcomes (TB-TOs) among patients attending TBTCs in Mogadishu. Methods The study design was cross-sectional, using quantitative and qualitative methods. Data was collected using interviewer administered semi-structured questionnaires and key in-depth interviews in 2016/2017. Qualitative data was coded using NVIVO8 and quantitative data analyzed using descriptive and inferential statistics at 95% confidence interval using SPSS20 software. Results The study used a sample of 385 TB patients. There were 315(81.8%) successful TB-TOs. Individual level factors-marital status, education level, HIV status, treatment category and knowledge on TB influenced TB-TOs (p-value < 0.05). Being married, educated, HIV-negative, new treatment case and knowledgeable on TB increased odds of successful TB-TOs (OR > 0, p value < 0.05) compared to other patients. TBTCs factors did not influence TB-TOs (p-value > 0.05). Conclusion TB-TOs were mainly affected by patient individual factors. There was need for patient education on TB management and treatment; and improved patient-health provider relationship. PMID:29610635

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

PubMed Central

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

2017-01-01

Background & objectives: A complicated epidemiological situation characterized by significantly high tuberculosis (TB) morbidity is observed in West Siberia. This study was aimed to investigate the genetic characteristics of Mycobacterium tuberculosis circulating in the southern part of West Siberia (in the Omsk region). Methods: From March 2013 to January 2015, 100 isolates of M. tuberculosis were obtained from patients with pulmonary TB living in the Omsk region. Drug susceptibility testing was performed on Lowenstein-Jensen medium (absolute concentration method). Genetic typing of isolates was carried out by variable number tandem repeats of mycobacterial interspersed repetitive units (MIRU-VNTR) typing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. The genetic types and characteristics of cluster strains were determined using 15 MIRU-VNTR loci. Results: Thirty six VNTR types were found. Twenty six (26.0%) isolates had a unique profile, and the remaining 74 were grouped in 10 clusters containing from 2 to 23 isolates. The Beijing genotype was found in 72 isolates, 61 (85.0%) of which were part of five clusters that included two large clusters containing 23 isolates. Other genetic families, such as Latin-American Mediterranean (LAM, 11.0%), S family (2.0%) and Haarlem (4.0%), were also detected. The genetic family of 11 isolates could not be determined. Six different VNTR profiles were found in these non-classified isolates. Only 16 per cent of isolates were sensitive to anti-TB drugs. The katG315 (94.8%) and rpoB531 (92.2%) mutations were identified in 77 multidrug-resistant M. tuberculosis isolates. Interpretation & conclusions: This study showed that the M. tuberculosis population in the Omsk region was heterogeneous. The Beijing genotype predominated and was actively spreading. The findings obtained point to the need for the implementation of more effective preventive measures to stop the spread of drug-resistant M. tuberculosis strains. PMID:29168460

Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

PubMed

Gómez-Reino, Juan J; Carmona, Loreto; Valverde, Vicente Rodríguez; Mola, Emilio Martín; Montero, Maria Dolores

2003-08-01

The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

Electronic recording and reporting system for tuberculosis in China: experience and opportunities

PubMed Central

Huang, Fei; Cheng, ShiMing; Du, Xin; Chen, Wei; Scano, Fabio; Falzon, Dennis; Wang, Lixia

2014-01-01

Tuberculosis (TB) surveillance in China is organized through a nationwide network of about 3200 hospitals and health facilities. In 2005, an electronic Tuberculosis Information Management System (TBIMS) started to be phased in to replace paper recording. The TBIMS collects key information on TB cases notified in TB care facilities, and exchanges real-time data with the Infectious Disease Reporting System, which covers the country’s 37 notifiable diseases. The system is accessible to authorized users at every level of the TB network through a password-protected website. By 2009 the TBIMS achieved nationwide coverage. Completeness of data on patient bacteriological end points improved remarkably over time. Data on about a million active TB cases, including drug-resistant TB, are included each year. The sheer scale of the data handling and the intricate functions that the China TBIMS performs makes it stand apart from the electronic information systems for TB adopted in other countries. PMID:24326537

Childhood tuberculosis: progress requires an advocacy strategy now

PubMed Central

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

2012-01-01

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

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

PubMed

Yükseltürk, Neriman; Dinç, Leyla

2013-02-01

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

Clinical Diagnostic Utility of IP-10 and LAM Antigen Levels for the Diagnosis of Tuberculous Pleural Effusions in a High Burden Setting

PubMed Central

Dheda, Keertan; Van-Zyl Smit, Richard N.; Sechi, Leonardo A.; Badri, Motasim; Meldau, Richard; Symons, Gregory; Khalfey, Hoosein; Carr, Igshaan; Maredza, Alice; Dawson, Rodney; Wainright, Helen; Whitelaw, Andrew; Bateman, Eric D.; Zumla, Alimuddin

2009-01-01

Background Current tools for the diagnosis of tuberculosis pleural effusions are sub-optimal. Data about the value of new diagnostic technologies are limited, particularly, in high burden settings. Preliminary case control studies have identified IFN-γ-inducible-10kDa protein (IP-10) as a promising diagnostic marker; however, its diagnostic utility in a day-to-day clinical setting is unclear. Detection of LAM antigen has not previously been evaluated in pleural fluid. Methods We investigated the comparative diagnostic utility of established (adenosine deaminase [ADA]), more recent (standardized nucleic-acid-amplification-test [NAAT]) and newer technologies (a standardized LAM mycobacterial antigen-detection assay and IP-10 levels) for the evaluation of pleural effusions in 78 consecutively recruited South African tuberculosis suspects. All consenting participants underwent pleural biopsy unless contra-indicated or refused. The reference standard comprised culture positivity for M. tuberculosis or histology suggestive of tuberculosis. Principal Findings Of 74 evaluable subjects 48, 7 and 19 had definite, probable and non-TB, respectively. IP-10 levels were significantly higher in TB vs non-TB participants (p<0.0001). The respective outcomes [sensitivity, specificity, PPV, NPV %] for the different diagnostic modalities were: ADA at the 30 IU/L cut-point [96; 69; 90; 85], NAAT [6; 93; 67; 28], IP-10 at the 28,170 pg/ml ROC-derived cut-point [80; 82; 91; 64], and IP-10 at the 4035 pg/ml cut-point [100; 53; 83; 100]. Thus IP-10, using the ROC-derived cut-point, missed ∼20% of TB cases and mis-diagnosed ∼20% of non-TB cases. By contrast, when a lower cut-point was used a negative test excluded TB. The NAAT had a poor sensitivity but high specificity. LAM antigen-detection was not diagnostically useful. Conclusion Although IP-10, like ADA, has sub-optimal specificity, it may be a clinically useful rule-out test for tuberculous pleural effusions. Larger multi-centric studies are now required to confirm our findings. PMID:19277111

Traffic-Related Air Pollution and All-Cause Mortality during Tuberculosis Treatment in California

PubMed Central

Pascopella, Lisa; Catanzaro, Donald G.; Barry, Pennan M.; English, Paul B.; Segal, Mark R.; Flood, Jennifer; Meltzer, Dan; Jones, Brenda; Balmes, John; Nahid, Payam

2017-01-01

Background: Ambient air pollution and tuberculosis (TB) have an impact on public health worldwide, yet associations between the two remain uncertain. Objective: We determined the impact of residential traffic on mortality during treatment of active TB. Methods: From 2000–2012, we enrolled 32,875 patients in California with active TB and followed them throughout treatment. We obtained patient data from the California Tuberculosis Registry and calculated traffic volumes and traffic densities in 100- to 400-m radius buffers around residential addresses. We used Cox models to determine mortality hazard ratios, controlling for demographic, socioeconomic, and clinical potential confounders. We categorized traffic exposures as quintiles and determined trends using Wald tests. Results: Participants contributed 22,576 person-years at risk. There were 2,305 deaths during treatment for a crude mortality rate of 1,021 deaths per 10,000 person-years. Traffic volumes and traffic densities in all buffers around patient residences were associated with increased mortality during TB treatment, although the findings were not statistically significant in all buffers. As the buffer size decreased, fifth-quintile mortality hazards increased, and trends across quintiles of traffic exposure became more statistically significant. Increasing quintiles of nearest-road traffic volumes in the 100-m buffer were associated with 3%, 14%, 19%, and 28% increased risk of death during TB treatment [first quintile, referent; second quintile hazard ratio (HR)=1.03 [95% confidence interval (CI): 0.86, 1.25]; third quintile HR=1.14 (95% CI: 0.95, 1.37); fourth quintile HR=1.19 (95% CI: 0.99, 1.43); fifth quintile HR=1.28 (95% CI: 1.07, 1.53), respectively; p-trend=0.002]. Conclusions: Residential proximity to road traffic volumes and traffic density were associated with increased all-cause mortality in patients undergoing treatment for active tuberculosis even after adjusting for multiple demographic, socioeconomic, and clinical factors, suggesting that TB patients are susceptible to the adverse health effects of traffic-related air pollution. https://doi.org/10.1289/EHP1699 PMID:28963088

[Tuberculous abscess of the thoracic wall secondary to nodular tuberculosis: Atypical presentation in an older adult].

PubMed

Cajuste-Sequeira, Fritz; Bueno-Wong, Juan Luis; Rosas-Carrasco, Óscar; González-Vergara, Carolina; Bieletto-Trejo, Olivia

2017-01-01

Tuberculosis (tb) of the chest wall is uncommon and it represents less than 5% of all cases of musculoskeletal tb and only 1-2% of tb. We present the case of an elderly woman with tb of the chest wall secondary to a nodal tb with an unusual presentation. The diagnosis of this entity is difficult because the disease often mimics other diseases such as pyogenic abscess, chest wall.

Extensively Drug-Resistant Tuberculosis in Women, KwaZulu-Natal, South Africa

PubMed Central

Zelnick, Jennifer; Werner, Lise; Master, Iqbal; Loveday, Marian; Horsburgh, C. Robert; Padayatchi, Nesri

2011-01-01

To determine whether women in KwaZulu-Natal, South Africa, with drug-resistant tuberculosis (TB) were more likely than men to have extensively drug-resistant TB, we reviewed 4,514 adults admitted during 2003–2008 for drug-resistant TB. Female sex independently predicted extensively drug-resistant TB, even after we controlled for HIV infection. This association needs further study. PMID:22000378

Vaccination of white-tailed deer (Odocoileus virginianus) for protection against bovine tuberculosis

USDA-ARS?s Scientific Manuscript database

Bovine tuberculosis (bTB), caused by Mycobacterium bovis and other related species in the M. tuberculosis complex, pose a serious continual threat to the health and economic wellbeing of wildlife, livestock, and humans worldwide. Wildlife reservoirs of bTB play a very important role in the epidemio...

Risk factors for default from tuberculosis treatment in HIV-infected individuals in the state of Pernambuco, Brazil: a prospective cohort study

PubMed Central

2011-01-01

Background Concomitant treatment of Human Immunodeficiency Virus (HIV) infection and tuberculosis (TB) presents a series of challenges for treatment compliance for both providers and patients. We carried out this study to identify risk factors for default from TB treatment in people living with HIV. Methods We conducted a cohort study to monitor HIV/TB co-infected subjects in Pernambuco, Brazil, on a monthly basis, until completion or default of treatment for TB. Logistic regression was used to calculate crude and adjusted odds ratios, 95% confidence intervals and P-values. Results From a cohort of 2310 HIV subjects, 390 individuals (16.9%) who had started treatment after a diagnosis of TB were selected, and data on 273 individuals who completed or defaulted on treatment for TB were analyzed. The default rate was 21.7% and the following risk factors were identified: male gender, smoking and CD4 T-cell count less than 200 cells/mm3. Age over 29 years, complete or incomplete secondary or university education and the use of highly active antiretroviral therapy (HAART) were identified as protective factors for the outcome. Conclusion The results point to the need for more specific actions, aiming to reduce the default from TB treatment in males, younger adults with low education, smokers and people with CD4 T-cell counts < 200 cells/mm3. Default was less likely to occur in patients under HAART, reinforcing the strategy of early initiation of HAART in individuals with TB. PMID:22176628

Antituberculosis IgG Antibodies as a Marker of Active Mycobacterium tuberculosis Disease

PubMed Central

Welch, Ryan J.; Lawless, Kathleen M.

2012-01-01

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

Assessing the Consequences of Stigma for Tuberculosis Patients in Urban Zambia

PubMed Central

Cremers, Anne Lia; de Laat, Myrthe Manon; Kapata, Nathan; Gerrets, Rene; Klipstein-Grobusch, Kerstin; Grobusch, Martin Peter

2015-01-01

Background Stigma is one of the many factors hindering tuberculosis (TB) control by negatively affecting hospital delay and treatment compliance. In Zambia, the morbidity and mortality due to TB remains high, despite extended public health attempts to control the epidemic and to diminish stigma. Study Aim To enhance understanding of TB-related stigmatizing perceptions and to describe TB patients’ experiences of stigma in order to point out recommendations to improve TB policy. Methods We conducted a mixed method study at Kanyama clinic and surrounding areas, in Lusaka, Zambia; structured interviews with 300 TB patients, multiple in-depth interviews with 30 TB patients and 10 biomedical health workers, 3 focus group discussions with TB patients and treatment supporters, complemented by participant observation and policy analysis of the TB control program. Predictors of stigma were identified by use of multivariate regression analyses; qualitative analysis of the in-depth interviews, focus group discussions and participant observation was used for triangulation of the study findings. Results We focused on the 138/300 patients that described TB-related perceptions and attitudes, of whom 113 (82%) reported stigma. Stigma provoking TB conceptions were associated with human immunodeficiency virus (HIV)-infection, alleged immoral behaviour, (perceived) incurability, and (traditional) myths about TB aetiology. Consequences of stigma prevailed both among children and adults and included low self-esteem, insults, ridicule, discrimination, social exclusion, and isolation leading to a decreased quality of life and social status, non-disclosure, and/or difficulties with treatment compliance and adherence. Women had significantly more stigma-related problems than men. Conclusions The findings illustrate that many TB patients faced stigma-related issues, often hindering effective TB control and suggesting that current efforts to reduce stigma are not yet optimal. The content and implementation of sensitization programs should be improved and more emphasis needs to be placed on women and children. PMID:25806955

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

PubMed Central

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

2013-01-01

Background Tuberculosis (TB) and human immunodeficiency virus (HIV) represent two of the greatest health threats in African prisons. In 2010, collaboration between the Centre for Infectious Disease Research in Zambia, the Zambia Prisons Service, and the National TB Program established a TB and HIV screening program in six Zambian prisons. We report data on the prevalence of TB and HIV in one of the largest facilities: Lusaka Central Prison. Methods Between November 2010 and April 2011, we assessed the prevalence of TB and HIV amongst inmates entering, residing, and exiting the prison, as well as in the surrounding community. The screening protocol included complete history and physical exam, digital radiography, opt-out HIV counseling and testing, sputum smear and culture. A TB case was defined as either bacteriologically confirmed or clinically diagnosed. Results A total of 2323 participants completed screening. A majority (88%) were male, median age 31 years and body mass index 21.9. TB symptoms were found in 1430 (62%). TB was diagnosed in 176 (7.6%) individuals and 52 people were already on TB treatment at time of screening. TB was bacteriologically confirmed in 88 cases (3.8%) and clinically diagnosed in 88 cases (3.8%). Confirmed TB at entry and exit interventions were 4.6% and 5.3% respectively. Smear was positive in only 25% (n = 22) of bacteriologically confirmed cases. HIV prevalence among inmates currently residing in prison was 27.4%. Conclusion Ineffective TB and HIV screening programs deter successful disease control strategies in prison facilities and their surrounding communities. We found rates of TB and HIV in Lusaka Central Prison that are substantially higher than the Zambian average, with a trend towards concentration and potential transmission of both diseases within the facility and to the general population. Investment in institutional and criminal justice reform as well as prison-specific health systems is urgently required. PMID:23967048

Direct Application of the INNO-LiPA Rif.TB Line-Probe Assay for Rapid Identification of Mycobacterium tuberculosis Complex Strains and Detection of Rifampin Resistance in 360 Smear-Positive Respiratory Specimens from an Area of High Incidence of Multidrug-Resistant Tuberculosis

PubMed Central

Viveiros, Miguel; Leandro, Clara; Rodrigues, Liliana; Almeida, Josefina; Bettencourt, Rosário; Couto, Isabel; Carrilho, Lurdes; Diogo, José; Fonseca, Ana; Lito, Luís; Lopes, João; Pacheco, Teresa; Pessanha, Mariana; Quirim, Judite; Sancho, Luísa; Salfinger, Max; Amaral, Leonard

2005-01-01

The INNO-LiPA Rif.TB assay for the identification of Mycobacterium tuberculosis complex strains and the detection of rifampin (RIF) resistance has been evaluated with 360 smear-positive respiratory specimens from an area of high incidence of multidrug-resistant tuberculosis (MDR-TB). The sensitivity when compared to conventional identification/culture methods was 82.2%, and the specificity was 66.7%; the sensitivity and specificity were 100.0% and 96.9%, respectively, for the detection of RIF resistance. This assay has the potential to provide rapid information that is essential for the effective management of MDR-TB. PMID:16145166

Multidrug-resistant tuberculosis in Lisbon, Portugal: a molecular epidemiological perspective.

PubMed

Perdigão, João; Macedo, Rita; João, Inês; Fernandes, Elisabete; Brum, Laura; Portugal, Isabel

2008-06-01

Portugal has the fourth highest tuberculosis (TB) incidence rate in the European Union (EU). Thirty-nine percent of all cases originate in Lisbon Health Region. Portugal also presents high levels of multidrug-resistant tuberculosis (MDR-TB) (1.5%, primary rate and 2.4%, in retreatment cases). In the present study we have characterized 58 MDR-TB clinical isolates by: (i) determining the resistance profile to first- and second-line drugs used in the treatment of tuberculosis; (ii) genotyping all isolates by MIRU-VNTR; (iii) analyzing mutations conferring resistance to isoniazid, rifampicin, streptomycin, and ethambutol, in katG, mabA-inhA, rpoB, rpsL, rrs, and pncA genes. We have therefore established the prevalence of the most common mutations associated with drug resistance in the Lisbon Health Region: C-15T in mabA-inhA for isoniazid; S531L in rpoB for rifampicin; K43R in rpsL for streptomycin; and V125G in pncA for pyrazinamide. By genotyping all isolates and combining with the mutational results, we were able to assess the isolates' genetic relatedness and determine possible transmission events. Strains belonging to family Lisboa, characterized several years ago, are still responsible for the majority of the MDR-TB. Even more alarming is the high prevalence of extensive drug-resistant tuberculosis (XDR-TB) among the MDR-TB isolates, which was found to be 53%. The TB status in Portugal therefore requires urgent attention to contain the strains continuously responsible for MDR-TB and now, XDR-TB.

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

PubMed

Maeda, Hideo; Shirai, Chika

2013-03-01

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

Resistance Patterns among Multidrug-Resistant Tuberculosis Patients in Greater Metropolitan Mumbai: Trends over Time

PubMed Central

Dalal, Alpa; Pawaskar, Akshay; Das, Mrinalini; Desai, Ranjan; Prabhudesai, Pralhad; Chhajed, Prashant; Rajan, Sujeet; Reddy, Deepesh; Babu, Sajit; Jayalakshmi, T. K.; Saranchuk, Peter; Rodrigues, Camilla; Isaakidis, Petros

2015-01-01

Background While the high burden of multidrug-resistant tuberculosis (MDR-TB) itself is a matter of great concern, the emergence and rise of advanced forms of drug-resistance such as extensively drug-resistant TB (XDR-TB) and extremely drug-resistant TB (XXDR-TB) is more troubling. The aim of this study was to investigate the trends over time of patterns of drug resistance in a sample of MDR-TB patients in greater metropolitan Mumbai, India. Methods This was a retrospective, observational study of drug susceptibility testing (DST) results among MDR-TB patients from eight health care facilities in greater Mumbai between 2005 and 2013. We classified resistance patterns into four categories: MDR-TB, pre-XDR-TB, XDR-TB and XXDR-TB. Results A total of 340 MDR-TB patients were included in the study. Pre-XDR-TB was the most common form of drug-resistant TB observed overall in this Mumbai population at 56.8% compared to 29.4% for MDR-TB. The proportion of patients with MDR-TB was 39.4% in the period 2005–2007 and 27.8% in 2011–2013, while the proportion of those with XDR-TB and XXDR-TB was changed from 6.1% and 0% respectively to 10.6% and 5.6% during the same time period. During the same periods, the proportions of patients with ofloxacin, moxifloxacin and ethionamide resistance significantly increased from 57.6% to 75.3%, from 60.0% to 69.5% and from 24.2% to 52.5% respectively (p<0.05). Discussion The observed trends in TB drug-resistance patterns in Mumbai highlight the need for individualized drug regimens, designed on the basis of DST results involving first- and second-line anti-TB drugs and treatment history of the patient. A drug-resistant TB case-finding strategy based on molecular techniques that identify only rifampicin resistance will lead to initiation of suboptimal treatment regimens for a significant number of patients, which may in turn contribute to amplification of resistance and transmission of strains with increasingly advanced resistance within the community. PMID:25606853

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

PubMed Central

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

2015-01-01

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

Plan to combat extensively drug-resistant tuberculosis: recommendations of the Federal Tuberculosis Task Force.

PubMed

2009-02-13

An estimated one third of the world's population is infected with Mycobacterium tuberculosis, and nearly 9 million persons develop disease caused by M. tuberculosis each year. Although tuberculosis (TB) occurs predominantly in resource-limited countries, it also occurs in the United States. During 1985-1992, the United States was confronted with an unprecedented TB resurgence. This resurgence was accompanied by a rise in multidrug-resistant TB (MDR TB), which is defined as TB that is resistant to the two most effective first-line therapeutic drugs, isoniazid and rifampin. In addition, virtually untreatable strains of M. tuberculosis are emerging globally. Extensively drug-resistant (XDR) TB is defined as MDR TB that also is resistant to the most effective second-line therapeutic drugs used commonly to treat MDR TB: fluoroquinolones and at least one of three injectable second-line drugs used to treat TB (amikacin, kanamycin, or capreomycin). XDR TB has been identified in all regions of the world, including the United States. In the United States, the cost of hospitalization for one XDR TB patient is estimated to average $483,000, approximately twice the cost for MDR TB patients. Because of the limited responsiveness of XDR TB to available antibiotics, mortality rates among patients with XDR TB are similar to those of TB patients in the preantibiotic era. In January 1992, CDC convened a Federal TB Task Force to draft an action plan to improve prevention and control of drug-resistant TB in the United States (CDC. National action plan to combat multidrug-resistant tuberculosis. MMWR 1992;41([No. RR-11]). In November 2006, CDC reconvened the Task Force to draft an updated action plan to address the issue of MDR TB and XDR TB. Task Force members were divided into nine response areas and charged with articulating the most pressing problems, identifying barriers to improvement, and recommending specific action steps to improve prevention and control of XDR TB within their respective areas. Although the first priority of the Federal TB Task Force convened in 2006 was to delineate objectives and action steps to address MDR TB and XDR TB domestically, members recognized the necessity for TB experts in the United States to work with the international community to help strengthen TB control efforts globally. TB represents a substantial public health problem in low- and middle-income countries, many of which might benefit from assistance by the United States. In addition, the global TB epidemic directly affects the United States because the majority of all cases of TB and 80% of cases of MDR TB reported in the United States occur among foreign-born persons. For these reasons, the Action Plan also outlines potential steps that U.S. government agencies can take to help solve global XDR TB problems. Unless the fundamental causes of MDR TB and XDR TB are addressed in the United States and internationally, the United States is likely to experience a growing number of cases of MDR TB and XDR TB that will be difficult, if not impossible, to treat or prevent. The recommendations provided in this report include specific action steps and new activities that will require additional funding and a renewed commitment by government and nongovernment organizations involved in domestic and international TB control efforts to be implemented effectively. The Federal TB Task Force will coordinate activities of various federal agencies and partner with state and local health departments, nonprofit and TB advocacy organizations in implementing this plan to control and prevent XDR TB in the United States and to contribute to global efforts in the fight against this emerging public health crisis.

Tuberculosis among the homeless, United States, 1994-2010.

PubMed

Bamrah, S; Yelk Woodruff, R S; Powell, K; Ghosh, S; Kammerer, J S; Haddad, M B

2013-11-01

1) To describe homeless persons diagnosed with tuberculosis (TB) during the period 1994-2010, and 2) to estimate a TB incidence rate among homeless persons in the United States. TB cases reported to the National Tuberculosis Surveillance System were analyzed by origin of birth. Incidence rates were calculated using the US Department of Housing and Urban Development homeless population estimates. Analysis of genotyping results identified clustering as a marker for transmission among homeless TB patients. Of 270,948 reported TB cases, 16,527 (6%) were homeless. The TB incidence rate among homeless persons ranged from 36 to 47 cases per 100,000 population in 2006-2010. Homeless TB patients had over twice the odds of not completing treatment and of belonging to a genotype cluster. US- and foreign-born homeless TB patients had respectively 8 and 12 times the odds of substance abuse. Compared to the general population, homeless persons had an approximately 10-fold increase in TB incidence, were less likely to complete treatment and more likely to abuse substances. Public health outreach should target homeless populations to reduce the excess burden of TB in this population.

LOWER LEVELS OF INTERLEUKIN-12 PRECEDE THE DEVELOPMENT OF TUBERCULOSIS AMONG HIV-INFECTED WOMEN

PubMed Central

Bordón, José; Plankey, Michael W.; Young, Mary; Greenblatt, Ruth M.; Villacres, Maria C.; French, Audrey L.; Zhang, Jie; Brock, Guy; Appana, Savitri; Herold, Betsy; Durkin, Helen; Golub, Jonathan E.; Fernandez-Botran, Rafael

2012-01-01

Tuberculosis (TB) is the worldwide leading cause of death among HIV-infected individuals, accounting for more than half of AIDS-related deaths. A high risk of tuberculosis (TB) has been shown in early stages of the HIV disease, even in the presence of normal CD4+ cell counts. Moreover, the factors that determine protective immunity vs. susceptibility to M. tuberculosis cannot be fully explained by simple changes in IFNγ levels or a shift from Th1 to Th2 cytokines. This work investigated the relationship between cytokine expression profiles in peripheral blood mononuclear cells (PBMC) and susceptibility to M. tuberculosis in ten HIV+ women who went on to develop TB. RNA transcripts for IL-4, IL-4δ2, IL-10, IL-12(p35), IL-13, IL-17A, IFNγ and TNFα were measured by real-time quantitative PCR in unstimulated or TB peptide antigen-stimulated PBMCs from ten HIV+ women with positive tuberculin skin tests (TST) and compared with HIV-seropositive and seronegative women without previous TB and negative TST. Stimulated PBMC cultures showed significantly lower expression of IL-12p35 (p=0.004) and IL-10 (p=0.026) in the HIV+TB+ group six to twelve months before onset of TB compared to HIV+TB− women. Unstimulated PBMC from HIV+TB+ women also had lower expression of Th2 cytokines [IL-4 (p=0.056) and IL-13 (p=0.050)] compared to HIV+TB− women. These results suggest that lower IL-12 production by PBMC in response to TB antigens and lower levels of both Th1 and Th2 cytokines by PBMC correlate with future development of TB in HIV-infected women and may be responsible for their increased susceptibility. PMID:21880503

Is systematic screening and treatment for latent tuberculosis infection in HIV patients useful in a low endemic setting?

PubMed

Maniewski, Ula; Payen, Marie-Christine; Delforge, Marc; De Wit, Stephane

2017-08-01

A decreasing incidence of tuberculosis (TB) among HIV patients has been documented in high-income settings and screening for tuberculosis is not systematically performed in many clinics (such as ours). Our objectives are to evaluate whether a same decline of incidence was seen in our Belgian tertiary center and to evaluate whether systematic screening and prophylaxis of tuberculosis should remain part of routine practice. Between 2005 and 2012, the annual incidence of tuberculosis among adult HIV patients was measured. The impact of demographic characteristics and CD 4 nadir on the incidence of active TB was evaluated. Among the 1167 patients who entered the cohort, 42 developed active TB with a significant decrease of annual incidence from 28/1000 patient-years in 2005 to 3/1000 patient-years in 2012. Among the 42 cases, 83% were of sub-Saharan origin. Median CD4 cell count upon HIV diagnosis was significantly lower in TB cases and 60% had a nadir CD4 below 200/μl. Thirty-six percent of incident TB occurred within 14 days after HIV diagnosis. A significant decline of TB incidence in HIV patients was observed. Incident TB occurred mainly in African patients, with low CD4 upon HIV diagnosis. A significant proportion of TB cases were discovered early in follow-up which probably reflects TB already present upon HIV diagnosis. In a low endemic setting, exclusion of active TB upon HIV diagnosis remains a priority and screening for LTBI should focus on HIV patients from high risk groups such as migrants from endemic regions, especially in patients with low CD4 nadir.

Evaluation of two line probe assays for rapid detection of Mycobacterium tuberculosis, tuberculosis (TB) drug resistance, and non-TB Mycobacteria in HIV-infected individuals with suspected TB.

PubMed

Luetkemeyer, Anne F; Kendall, Michelle A; Wu, Xingye; Lourenço, Maria Cristina; Jentsch, Ute; Swindells, Susan; Qasba, Sarojini S; Sanchez, Jorge; Havlir, Diane V; Grinsztejn, Beatriz; Sanne, Ian M; Firnhaber, Cynthia

2014-04-01

Limited performance data from line probe assays (LPAs), nucleic acid tests used for the rapid diagnosis of tuberculosis (TB), nontuberculosis mycobacteria (NTM), and Mycobacterium tuberculosis drug resistance are available for HIV-infected individuals, in whom paucibacillary TB is common. In this study, the strategy of testing sputum with GenoType MTBDRplus (MTBDR-Plus) and GenoType Direct LPA (Direct LPA) was compared to a gold standard of one mycobacterial growth indicator tube (MGIT) liquid culture. HIV-positive (HIV(+)) individuals with suspected TB from southern Africa and South America with <7 days of TB treatment had 1 sputum specimen tested with Direct LPA, MTBDR-Plus LPA, smear microscopy, MGIT, biochemical identification of mycobacterial species, and culture-based drug-susceptibility testing (DST). Of 639 participants, 59.3% were MGIT M. tuberculosis culture positive, of which 276 (72.8%) were acid-fast bacillus (AFB) smear positive. MTBDR-Plus had a sensitivity of 81.0% and a specificity of 100%, with sensitivities of 44.1% in AFB smear-negative versus 94.6% in AFB smear-positive specimens. For specimens that were positive for M. tuberculosis by MTBDR-Plus, the sensitivity and specificity for rifampin resistance were 91.7% and 96.6%, respectively, and for isoniazid (INH) they were 70.6% and 99.1%. The Direct LPA had a sensitivity of 88.4% and a specificity of 94.6% for M. tuberculosis detection, with a sensitivity of 72.5% in smear-negative specimens. Ten of 639 MGIT cultures grew Mycobacterium avium complex or Mycobacterium kansasii, half of which were detected by Direct LPA. Both LPA assays performed well in specimens from HIV-infected individuals, including in AFB smear-negative specimens, with 72.5% sensitivity for M. tuberculosis identification with the Direct LPA and 44.1% sensitivity with MTBDR-Plus. LPAs have a continued role for use in settings where rapid identification of INH resistance and clinically relevant NTM are priorities.

Nontuberculous Mycobacteria (NTM)

MedlinePlus

... human disease. NTM is an infectious disease like tuberculosis (TB), but it does not cause TB. There ... founded more than 100 years ago as a tuberculosis hospital. Since that time, we have grown to ...

First national survey of anti-tuberculosis drug resistance in Azerbaijan and risk factors analysis

PubMed Central

Akhundova, I.; Seyfaddinova, M.; Mammadbayov, E.; Mirtskulava, V.; Rüsch-Gerdes, S.; Bayramov, R.; Suleymanova, J.; Kremer, K.; Dadu, A.; Acosta, C. D.; Harries, A. D.; Dara, M.

2014-01-01

Setting: Civilian population of the Republic of Azerbaijan. Objectives: To determine patterns of anti-tuberculosis drug resistance among new and previously treated pulmonary tuberculosis (TB) cases, and explore their association with socio-demographic and clinical characteristics. Design: National cross-sectional survey conducted in 2012–2013. Results: Of 789 patients (549 new and 240 previously treated) who met the enrolment criteria, 231 (42%) new and 146 (61%) previously treated patients were resistant to any anti-tuberculosis drug; 72 (13%) new and 66 (28%) previously treated patients had multidrug-resistant TB (MDR-TB). Among MDR-TB cases, 38% of new and 46% of previously treated cases had pre-extensively drug-resistant TB (pre-XDR-TB) or XDR-TB. In previously treated cases, 51% of those who had failed treatment had MDR-TB, which was 15 times higher than in relapse cases (OR 15.2, 95%CI 6–39). The only characteristic significantly associated with MDR-TB was a history of previous treatment (OR 3.1, 95%CI 2.1–4.7); for this group, history of incarceration was an additional risk factor for MDR-TB (OR 2.8, 95%CI 1.1–7.4). Conclusion: Azerbaijan remains a high MDR-TB burden country. There is a need to implement countrywide control and innovative measures to accelerate early diagnosis of drug resistance in individual patients, improve treatment adherence and strengthen routine surveillance of drug resistance. PMID:26393092

Characterisation of Mycobacterium tuberculosis isolates lacking IS6110 in Viet Nam.

PubMed

Huyen, M N T; Tiemersma, E W; Kremer, K; de Haas, P; Lan, N T N; Buu, T N; Sola, C; Cobelens, F G J; van Soolingen, D

2013-11-01

The molecular diagnosis of tuberculosis (TB) in Viet Nam is often based on the detection of insertion sequence (IS) 6110 in Mycobacterium tuberculosis. However, 8-11% of M. tuberculosis strains in South-East Asia do not contain this target and this undermines the validity of these molecular tests. We quantified the frequency of M. tuberculosis strains lacking IS6110 in rural Viet Nam and studied their epidemiological and clinical characteristics. Consecutively diagnosed adult TB patients in rural Southern Viet Nam submitted two sputum samples for culture, IS6110 restriction fragment length polymorphism (RFLP) spoligotyping and 15-loci variable number tandem repeat typing. Polymerase chain reaction (PCR) was performed to confirm the absence of IS6110 elements in strains lacking IS6110 hybridisation in RFLP. Among 2664 TB patient isolates examined, 109 (4.1%) had no IS6110 element. Compared to other strains, these no-copy strains were less often resistant to anti-tuberculosis drugs, particularly to streptomycin (adjusted OR 0.2, 95%CI 0.1-0.5), and showed significant geographic variation. No associations with TB history or demographic factors were found. Strains without the IS6110 target pose a problem in Viet Nam as regards false-negative molecular TB diagnosis in PCR. Compared to other strains circulating in Viet Nam, no-copy strains are more susceptible to anti-tuberculosis drugs.

Tuberculosis in the elderly: Why inflammation matters.

PubMed

Piergallini, Tucker J; Turner, Joanne

2018-05-01

Growing old is associated with an increase in the basal inflammatory state of an individual and susceptibility to many diseases, including infectious diseases. Evidence is growing to support the concept that inflammation and disease susceptibility in the elderly is linked. Our studies focus on the infectious disease tuberculosis (TB), which is caused by Mycobacterium tuberculosis (M.tb), a pathogen that infects approximately one fourth of the world's population. Aging is a major risk factor for developing TB, and inflammation has been strongly implicated. In this review we will discuss the relationship between inflammation in the lung and susceptibility to develop and succumb to TB in old age. Further understanding of the relationship between inflammation, age, and M.tb will lead to informed decisions about TB prevention and treatment strategies that are uniquely designed for the elderly. Copyright © 2017 Elsevier Inc. All rights reserved.

TB Anywhere Is TB Everywhere: The Intersection of U.S. Immigration Enforcement Policy and TB

DTIC Science & Technology

2016-09-01

born population.40 One region of special concern in the United States is the area along the border with Mexico . Tuberculosis rates in the border ...Controlling Tuberculosis along the US- Mexico Border ,” Morbidity and Mortality Weekly Report 50, no. RR1 (2001): 1–2, http://www.cdc.gov/mmwr/ preview/mmwrhtml...Ramirez, “Health Departments Fight Tuberculosis on both Sides of the U.S. Border with Mexico : Mexican Immigrants Often Contract the Disease before

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

PubMed Central

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

2008-01-01

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

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

PubMed Central

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

2015-01-01

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

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

PubMed

Bates, Matthew; Zumla, Alimuddin

2016-01-01

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

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

PubMed Central

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

2015-01-01

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

[Riddles in human tuberculous infection].

PubMed

Tsuyuguchi, I

2000-10-01

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

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

PubMed Central

Kozakiewicz, Lee; Phuah, Jiayao; Flynn, JoAnne

2014-01-01

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

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

PubMed

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

2013-08-23

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

Prevalence of Pulmonary Tuberculosis among Prison Inmates in Ethiopia, a Cross-Sectional Study

PubMed Central

Ali, Solomon; Haileamlak, Abraham; Wieser, Andreas; Pritsch, Michael; Heinrich, Norbert; Loscher, Thomas; Hoelscher, Michael; Rachow, Andrea

2015-01-01

Setting Tuberculosis (TB) is one of the major health problems in prisons. Objective This study was done to assess the prevalence and determinants of active tuberculosis in Ethiopian prisons. Design A cross-sectional study was conducted from January 2013 to December 2013 in 13 zonal prisons. All incarcerated inmates underwent TB symptom screening according to WHO criteria. From identified TB-suspects two sputum samples were analyzed using smear microscopy and solid culture. A standardized questionnaire assessing TB risk factors was completed for each TB suspect. Results 765 (4.9%) TB suspects were identified among 15,495 inmates. 51 suspects were already on anti-TB treatment (6.67%) and 20 (2.8%) new culture-confirmed TB cases were identified in the study, resulting in an overall TB prevalence of 458.1/100,000 (95%CI: 350-560/100,000). Risk factors for active TB were alcohol consumption, contact with a TB case before incarceration and no window in prison cell. HIV prevalence was not different between TB suspects and active TB cases. Further, the TB burden in prisons increased with advancing distance from the capital Addis Ababa. Conclusions The overall TB prevalence in Ethiopian prisons was high and extremely variable among different prisons. TB risk factors related to conditions of prison facilities and the impact of implemented TB control measures need to be further studied in order to improve TB control among inmates. PMID:26641654

The prevalence and factors associated for anti-tuberculosis treatment non-adherence among pulmonary tuberculosis patients in public health care facilities in South Ethiopia: a cross-sectional study.

PubMed

Woimo, Tadele Teshome; Yimer, Wondwossen Kassahun; Bati, Temesgen; Gesesew, Hailay Abrha

2017-03-20

Evidence exists pointing out how non-adherence to treatment remains a major hurdle to efficient tuberculosis control in developing countries. Many tuberculosis (Tb) patients do not complete their six-month course of anti-tuberculosis medications and are not aware of the importance of sputum re-examinations, thereby putting themselves at risk of developing multidrug-resistant and extensively drug-resistant forms of tuberculosis and relapse. However, there is a dearth of publications about non-adherence towards anti-Tb medication in these settings. We assessed the prevalence of and associated factors for anti-Tb treatment non-adherence in public health care facilities of South Ethiopia. This was a cross-sectional survey using both quantitative and qualitative methods. The quantitative study was conducted among 261 Tb patients from 17 health centers and one general hospital. The qualitative aspect included an in-depth interview of 14 key informants. For quantitative data, the analysis of descriptive statistics, bivariate and multiple logistic regression was carried out, while thematic framework analysis was applied for the qualitative data. The prevalence of non-adherence towards anti-Tb treatment was 24.5%. Multiple logistic regression analysis demonstrated that poor knowledge towards tuberculosis and its treatment (AOR = 4.6, 95%CI: 1.4-15.6), cost of medication other than Tb (AOR = 4.7, 95%CI: 1.7-13.4), having of health information at every visit (AOR = 3, 95% CI: 1.1-8.4) and distance of DOTS center from individual home (AOR = 5.7, 95%CI: 1.9-16.8) showed statistically significant association with non-adherence towards anti- tuberculosis treatment. Qualitative study also revealed that distance, lack of awareness about importance of treatment completion and cost of transportation were the major barriers for adherence. A quarter of Tb patients interrupted their treatment due to knowledge, availability and accessibility of DOTS service. We recommend creating awareness about anti-Tb treatment, and decentralization of drug pick-ups to the lowest level of health institutions.

Improving quality of tuberculosis care in India.

PubMed

Pai, Madhukar; Satyanarayana, Srinath; Hopewell, Phil

2014-01-01

In India, the quality of care that tuberculosis (TB) patients receive varies considerably and is often not in accordance with the national and international standards. In this article, we provide an overview of the third (latest) edition of the International Standards of Tuberculosis Care (ISTC). These standards are supported by the existing World Health Organization guidelines and policy statements pertaining to TB care and have been endorsed by a number of international organizations. We call upon all health care providers in the country to practice TB care that is consistent with these standards, as well as the upcoming Standards for TB Care in India (STCI).

Survey of the Diagnostic Retooling Process in National TB Reference Laboratories, with Special Focus on Rapid Speciation Tests Endorsed by WHO in 2007

PubMed Central

van Kampen, Sanne C.; Oskam, Linda; Tuijn, Coosje J.; Klatser, Paul R.

2012-01-01

Background Successful integration of new diagnostics in national tuberculosis (TB) control programs, also called ‘retooling’, is highly dependent on operational aspects related to test availability, accessibility and affordability. This survey aimed to find out whether recommendations to use new diagnostics lead to successful retooling in high TB endemic countries, using immunochromatographic tests (ICTs) for TB culture speciation as a case study. ICTs are recommended to accurately confirm the presence of bacteria of the Mycobacterium tuberculosis complex in liquid culture isolates. Methods and Findings Questionnaires were sent to national TB reference laboratories (NRLs) in 42 high TB endemic countries to address their access to information on ICT implementation, logistics related to availability, accessibility and affordability of ICTs, and testing algorithms. Results from 16 responding countries indicated that half of the NRLs were aware of the contents of WHO guidance documents on liquid culture and ICT implementation, as well as their eligibility for a negotiated pricing agreement for ICT procurement. No major issues with availability and accessibility of ICTs were raised. When asked about testing algorithms, ICTs were not used as stand-alone or first test for TB culture identification as recommended by WHO. Conclusions The low response rate was a limitation of this survey and together with NRLs managers' unawareness of global guidance, suggests a lack of effective communication between partners of the global laboratory network and NRLs. TB tests could become more affordable to high TB endemic countries, if the possibility to negotiate lower prices for commercial products is communicated to them more successfully. NRLs need additional guidance to identify where available technologies can be most usefully implemented and in what order, taking into account long-term laboratory strategies. PMID:22937050

Traditional healers and the potential for collaboration with the national tuberculosis programme in Vanuatu: results from a mixed methods study

PubMed Central

2014-01-01

Background This study was conducted in the Pacific island nation of Vanuatu. Our objective was to assess knowledge, attitudes and practice of traditional healers who treat lung diseases and tuberculosis (TB), including their willingness to collaborate with the national TB programme. Methods This was a descriptive study using both qualitative and quantitative methods. Quantitative analysis was based on the responses provided to closed-ended questions, and we used descriptive analysis (frequencies) to describe the knowledge, attitudes and practice of the traditional healers towards TB. Qualitative analysis was based on open-ended questions permitting fuller explanations. We used thematic analysis and developed a posteriori inductive categories to draw original and unbiased conclusions. Results Nineteen traditional healers were interviewed; 18 were male. Fifteen of the healers reported treating short wind (a local term to describe lung, chest or breathing illnesses) which they attributed to food, alcohol, smoking or pollution from contact with menstrual blood, and a range of other physical and spiritual causes. Ten said that they would treat TB with leaf medicine. Four traditional healers said that they would not treat TB. Twelve of the healers had referred someone to a hospital for a strong wet-cough and just over half of the healers (9) reported a previous collaboration with the Government health care system. Eighteen of the traditional healers would be willing to collaborate with the national TB programme, with or without compensation. Conclusions Traditional healers in Vanuatu treat lung diseases including TB. Many have previously collaborated with the Government funded health care system, and almost all of them indicated a willingness to collaborate with the national TB programme. The engagement of traditional healers in TB management should be considered, using an evidence based and culturally sensitive approach. PMID:24758174

Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis

PubMed Central

Roe, Jennifer K; Thomas, Niclas; Gil, Eliza; Best, Katharine; Tsaliki, Evdokia; Morris‑Jones, Stephen; Stafford, Sian; Simpson, Nandi; Witt, Karolina D; Chain, Benjamin; Miller, Robert F; Martineau, Adrian

2016-01-01

BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. METHODS. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. RESULTS. We identified and validated elevated blood basic leucine zipper transcription factor 2 (BATF2) transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1–negative individuals, and 0.85 in HIV-1–infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. CONCLUSIONS. Elevated blood BATF2 transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. FUNDING. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR. PMID:27734027

Blood transcriptomic diagnosis of pulmonary and extrapulmonary tuberculosis.

PubMed

Roe, Jennifer K; Thomas, Niclas; Gil, Eliza; Best, Katharine; Tsaliki, Evdokia; Morris-Jones, Stephen; Stafford, Sian; Simpson, Nandi; Witt, Karolina D; Chain, Benjamin; Miller, Robert F; Martineau, Adrian; Noursadeghi, Mahdad

2016-10-06

BACKGROUND. Novel rapid diagnostics for active tuberculosis (TB) are required to overcome the time delays and inadequate sensitivity of current microbiological tests that are critically dependent on sampling the site of disease. Multiparametric blood transcriptomic signatures of TB have been described as potential diagnostic tests. We sought to identify the best transcript candidates as host biomarkers for active TB, extend the evaluation of their specificity by comparison with other infectious diseases, and to test their performance in both pulmonary and extrapulmonary TB. METHODS. Support vector machine learning, combined with feature selection, was applied to new and previously published blood transcriptional profiles in order to identify the minimal TB‑specific transcriptional signature shared by multiple patient cohorts including pulmonary and extrapulmonary TB, and individuals with and without HIV-1 coinfection. RESULTS. We identified and validated elevated blood basic leucine zipper transcription factor 2 ( BATF2 ) transcript levels as a single sensitive biomarker that discriminated active pulmonary and extrapulmonary TB from healthy individuals, with receiver operating characteristic (ROC) area under the curve (AUC) scores of 0.93 to 0.99 in multiple cohorts of HIV-1-negative individuals, and 0.85 in HIV-1-infected individuals. In addition, we identified and validated a potentially novel 4-gene signature comprising CD177, haptoglobin, immunoglobin J chain, and galectin 10 that discriminated active pulmonary and extrapulmonary TB from other febrile infections, giving ROC AUCs of 0.94 to 1. CONCLUSIONS. Elevated blood BATF2 transcript levels provide a sensitive biomarker that discriminates active TB from healthy individuals, and a potentially novel 4-gene transcriptional signature differentiates between active TB and other infectious diseases in individuals presenting with fever. FUNDING. MRC, Wellcome Trust, Rosetrees Trust, British Lung Foundation, NIHR.

Evaluation of a Tuberculosis Skin Testing Program

ERIC Educational Resources Information Center

Kahn, Pamela

2009-01-01

There has been a recent slowdown in the decline of rates of tuberculosis (TB) in the United States. However, there are disparities in TB diagnosis between U.S.-born and foreign-born persons and between Whites and minorities. Measures for achieving TB elimination include identification of high-risk persons, including children and adolescents, at…

Multidrug-resistant tuberculosis, Somalia, 2010-2011.

PubMed

Sindani, Ireneaus; Fitzpatrick, Christopher; Falzon, Dennis; Suleiman, Bashir; Arube, Peter; Adam, Ismail; Baghdadi, Samiha; Bassili, Amal; Zignol, Matteo

2013-03-01

In a nationwide survey in 2011, multidrug-resistant tuberculosis (MDR TB) was found in 5.2% and 40.8% of patients with new and previously treated TB, respectively. These levels of drug resistance are among the highest ever documented in Africa and the Middle East. This finding presents a serious challenge for TB control in Somalia.

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

PubMed

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

2007-02-01

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

Community empowerment program for increasing knowledge and awareness of tuberculosis patients, cadres and community in Medan city

NASA Astrophysics Data System (ADS)

Harahap, J.; Amelia, R.; Wahyuni, A. S.; Andayani, L. S.

2018-03-01

Tuberculosis is one of a major health problem in Indonesia. WHO expressed the need for the participation of various stakeholders in addition to government. TB CEPAT Program aimed to increase knowledge and awareness in combating tuberculosis. This study aimed to compare the knowledge and awareness of community, cadres and TB patients in the program areas and non-program areas, and assess the role of the program in combating tuberculosis in Medan. The study used quantitative and qualitative methods, where 300 people (community, cadres, TB patients) as respondents and three key persons as informants. The findings revealed that in the program areas the knowledge, attitude and practice of the respondents generally are better compare to those in the non-program areas. There was a significant difference in knowledge and practice for community, cadres, and TB patients (p<0.05) and there was a significant difference in attitude for community, cadres (p<0.05), but no significant difference for TB patients (p>0.05) in program areas and non-program areas. The community empowerment through TB CEPAT Program plays an important role in improving knowledge, attitude, and practice of community, cadres, and TB patients. It would help the effort of TB control and prevention in Medan City.

Influence of diabetes mellitus on immunity to human tuberculosis.

PubMed

Kumar Nathella, Pavan; Babu, Subash

2017-09-01

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

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries.

PubMed

Getahun, Haileyesus; Matteelli, Alberto; Abubakar, Ibrahim; Aziz, Mohamed Abdel; Baddeley, Annabel; Barreira, Draurio; Den Boon, Saskia; Borroto Gutierrez, Susana Marta; Bruchfeld, Judith; Burhan, Erlina; Cavalcante, Solange; Cedillos, Rolando; Chaisson, Richard; Chee, Cynthia Bin-Eng; Chesire, Lucy; Corbett, Elizabeth; Dara, Masoud; Denholm, Justin; de Vries, Gerard; Falzon, Dennis; Ford, Nathan; Gale-Rowe, Margaret; Gilpin, Chris; Girardi, Enrico; Go, Un-Yeong; Govindasamy, Darshini; D Grant, Alison; Grzemska, Malgorzata; Harris, Ross; Horsburgh, C Robert; Ismayilov, Asker; Jaramillo, Ernesto; Kik, Sandra; Kranzer, Katharina; Lienhardt, Christian; LoBue, Philip; Lönnroth, Knut; Marks, Guy; Menzies, Dick; Migliori, Giovanni Battista; Mosca, Davide; Mukadi, Ya Diul; Mwinga, Alwyn; Nelson, Lisa; Nishikiori, Nobuyuki; Oordt-Speets, Anouk; Rangaka, Molebogeng Xheedha; Reis, Andreas; Rotz, Lisa; Sandgren, Andreas; Sañé Schepisi, Monica; Schünemann, Holger J; Sharma, Surender Kumar; Sotgiu, Giovanni; Stagg, Helen R; Sterling, Timothy R; Tayeb, Tamara; Uplekar, Mukund; van der Werf, Marieke J; Vandevelde, Wim; van Kessel, Femke; van't Hoog, Anna; Varma, Jay K; Vezhnina, Natalia; Voniatis, Constantia; Vonk Noordegraaf-Schouten, Marije; Weil, Diana; Weyer, Karin; Wilkinson, Robert John; Yoshiyama, Takashi; Zellweger, Jean Pierre; Raviglione, Mario

2015-12-01

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3-4 month isoniazid plus rifampicin; or 3-4 month rifampicin alone. Copyright ©ERS 2015.

Spoligotyping of Mycobacterium tuberculosis isolates at a tertiary care hospital in India.

PubMed

Suzana, Shirly; Shanmugam, Sivakumar; Uma Devi, K R; Swarna Latha, P N; Michael, Joy S

2017-06-01

Spoligotyping is a valuable genotyping tool to study the genetic diversity and molecular epidemiology of Mycobacterium tuberculosis (M. tb). The aim of this study was to analyse different spoligotype patterns of M. tb strains isolated from patients with tuberculosis from different parts of India. A total of 163 M. tb isolates were spoligotyped between January 2014 and January 2015. About 47% (n = 77) were from patients with extrapulmonary tuberculosis; of these, 10 were MDR, and seven were Pre-XDR. Of the 86 M. tb isolates from patients with pulmonary tuberculosis, 25 were MDR, and 25 were Pre-XDR. We found 61 spoligo patterns, 128 clusters in the spoligotype data base (spoldb4 data base) with spoligo international type (SIT) number and 35 true unique isolates. The most pre-dominant spoligotype was EAI lineage (56), followed by Beijing (28), CAS (20), T(9), U(7), X(3), H(3), BOVIS_1 BCG(1) and LAM(1). Although our study identified EAI, CAS and Beijing strain lineages as pre-dominant, we also found a large number of orphan strains (20%) in our study. Beijing strains were more significantly associated with MDR TB than CAS and EAI lineages. Further studies on large sample sizes would help to clearly describe the epidemiology of M. tb in India. © 2017 John Wiley & Sons Ltd.

Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries

PubMed Central

Matteelli, Alberto; Abubakar, Ibrahim; Aziz, Mohamed Abdel; Baddeley, Annabel; Barreira, Draurio; Den Boon, Saskia; Borroto Gutierrez, Susana Marta; Bruchfeld, Judith; Burhan, Erlina; Cavalcante, Solange; Cedillos, Rolando; Chaisson, Richard; Chee, Cynthia Bin-Eng; Chesire, Lucy; Corbett, Elizabeth; Dara, Masoud; Denholm, Justin; de Vries, Gerard; Falzon, Dennis; Ford, Nathan; Gale-Rowe, Margaret; Gilpin, Chris; Girardi, Enrico; Go, Un-Yeong; Govindasamy, Darshini; D. Grant, Alison; Grzemska, Malgorzata; Harris, Ross; Horsburgh Jr, C. Robert; Ismayilov, Asker; Jaramillo, Ernesto; Kik, Sandra; Kranzer, Katharina; Lienhardt, Christian; LoBue, Philip; Lönnroth, Knut; Marks, Guy; Menzies, Dick; Migliori, Giovanni Battista; Mosca, Davide; Mukadi, Ya Diul; Mwinga, Alwyn; Nelson, Lisa; Nishikiori, Nobuyuki; Oordt-Speets, Anouk; Rangaka, Molebogeng Xheedha; Reis, Andreas; Rotz, Lisa; Sandgren, Andreas; Sañé Schepisi, Monica; Schünemann, Holger J.; Sharma, Surender Kumar; Sotgiu, Giovanni; Stagg, Helen R.; Sterling, Timothy R.; Tayeb, Tamara; Uplekar, Mukund; van der Werf, Marieke J.; Vandevelde, Wim; van Kessel, Femke; van't Hoog, Anna; Varma, Jay K.; Vezhnina, Natalia; Voniatis, Constantia; Vonk Noordegraaf-Schouten, Marije; Weil, Diana; Weyer, Karin; Wilkinson, Robert John; Yoshiyama, Takashi; Zellweger, Jean Pierre; Raviglione, Mario

2015-01-01

Latent tuberculosis infection (LTBI) is characterised by the presence of immune responses to previously acquired Mycobacterium tuberculosis infection without clinical evidence of active tuberculosis (TB). Here we report evidence-based guidelines from the World Health Organization for a public health approach to the management of LTBI in high risk individuals in countries with high or middle upper income and TB incidence of <100 per 100 000 per year. The guidelines strongly recommend systematic testing and treatment of LTBI in people living with HIV, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor treatment, patients receiving dialysis, patients preparing for organ or haematological transplantation, and patients with silicosis. In prisoners, healthcare workers, immigrants from high TB burden countries, homeless persons and illicit drug users, systematic testing and treatment of LTBI is conditionally recommended, according to TB epidemiology and resource availability. Either commercial interferon-gamma release assays or Mantoux tuberculin skin testing could be used to test for LTBI. Chest radiography should be performed before LTBI treatment to rule out active TB disease. Recommended treatment regimens for LTBI include: 6 or 9 month isoniazid; 12 week rifapentine plus isoniazid; 3–4 month isoniazid plus rifampicin; or 3–4 month rifampicin alone. PMID:26405286

Structural measurements and cell line studies of the copper-PEG-Rifampicin complex against Mycobacterium tuberculosis.

PubMed

Manning, Thomas; Mikula, Rachel; Wylie, Greg; Phillips, Dennis; Jarvis, Jackie; Zhang, Fengli

2015-02-01

The bacterium responsible for tuberculosis is increasing its resistance to antibiotics resulting in new multidrug-resistant Mycobacterium tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). In this study, several analytical techniques including NMR, FT-ICR, MALDI-MS, LC-MS and UV/Vis are used to study the copper-Rifampicin-Polyethylene glycol (PEG-3350) complex. The copper (II) cation is a carrier for the antibiotic Rifampicin as well as nutrients for the bacterium. The NIH-NIAID cell line containing several Tb strains (including antibiotic resistant strains) is tested against seven copper-PEG-RIF complex variations. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Management of multidrug-resistant tuberculosis].

PubMed

Tritar, F; Daghfous, H; Ben Saad, S; Slim-Saidi, L

2015-01-01

The emergence of drug-resistant TB in many countries has become a major public health problem and an obstacle to effective tuberculosis control. Multidrug-resistant tuberculosis (MDR-TB), which is most often the result of poor adherence, is a particularly dangerous form of tuberculosis because it is caused by bacilli resistant to at least isoniazid and rifampicin, the two most effective anti-tuberculosis drugs. Techniques for rapid diagnosis of resistance have greatly improved the care of patients by allowing early treatment which remains complex and costly establishment, and requires skills and resources. The treatment is not standardized but it includes in all cases attack phase with five drugs (there must be an injectable agent and a fluoroquinolone that form the basis of the regimen) for eight months and a maintenance phase (without injectable agent) with a total duration of 20 months on average. Surgery may be beneficial as long as the lesions are localized and the patient has a good cardiorespiratory function. Evolution of MDR-TB treated is less favorable than tuberculosis with germ sensitive. The cure rate varies from 60 to 75% for MDR-TB, and drops to 30 to 40% for XDR-TB. Mortality remains high, ranging from 20 to 40% even up to 70-90% in people co-infected with HIV. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Humoral immune profiling of mycobacterial antigen recognition in sarcoidosis and Löfgren's syndrome using high-content peptide microarrays.

PubMed

Ferrara, Giovanni; Valentini, Davide; Rao, Martin; Wahlström, Jan; Grunewald, Johan; Larsson, Lars-Olof; Brighenti, Susanna; Dodoo, Ernest; Zumla, Alimuddin; Maeurer, Markus

2017-03-01

Sarcoidosis is considered an idiopathic granulomatous disease, although similar immunological and clinical features with tuberculosis (TB) suggest mycobacterial involvement in its pathogenesis. High-content peptide microarrays (HCPM) may help to decipher mycobacteria-specific antibody reactivity in sarcoidosis. Serum samples from patients with sarcoidosis, Löfgren's syndrome, and TB, as well as from healthy individuals (12/group), were tested on HCPM containing 5964 individual peptides spanning 154 Mycobacterium tuberculosis proteins displayed as 15-amino acid stretches. Inclusion/exclusion and significance analyses were performed according to published methods. Each study group recognized 68-78% M. tuberculosis peptides at least once. M. tuberculosis epitope recognition by sarcoidosis patient sera was 42.7%, and by TB patient sera was 39.1%. Seven and 16 peptides were recognized in 9/12 (75%) and 8/12 (67%) sarcoidosis patient sera but not in TB patient sera, respectively. Nine (75%) and eight (67%) out of twelve TB patient sera, respectively recognized M. tuberculosis peptides that were not recognized in sarcoidosis patient sera. Specific IgG recognition patterns for M. tuberculosis antigens in sarcoidosis patients re-affirm mycobacterial involvement in sarcoidosis, providing biologically relevant targets for future studies pertaining to diagnostics and immunotherapy. Copyright © 2017. Published by Elsevier Ltd.

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

PubMed

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

2017-06-01

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

Lateral Flow Urine Lipoarabinomannan Assay (LF-LAM) for Diagnosis of Active Tuberculosis in HIV-Infected Adults: a Prospective Cohort Study

PubMed Central

Na Songkhla, Munjit; Tantipong, Hutsaya; Tongsai, Sasima; Angkasekwinai, Nasikarn

2017-01-01

Abstract Background Early diagnosis and treatment of active tuberculosis (TB) in HIV-positive patients is challenging. Tests based on the detection of mycobacterial lipoarabinomannan (LAM) antigen in urine have emerged as potential point-of-care tests for TB. However, limited data exists on their performance among HIV-TB co-infected patients from Southeast Asian countries. Methods We prospectively recruited HIV-positive adult patients with CD4 count less than or equal to 200/mm3 and symptoms suspected of active TB from two tertiary hospitals between December 2015 and March 2017. Freshly collected urine was applied to the Determine®-TB LAM Ag test strip (4 bands of graded intensity), using grade 1 cutoff. Diagnostic accuracy of urine LAM strip test were assessed against microbiological reference standard, defined as positive Mycobacterium tuberculosis cultured from one or more clinical specimens (definite TB) or composite reference standard including definite TB and probable TB, defined as those have symptoms consistent with TB and response to anti-TB treatment. Results A total of 280 patients were enrolled. Of whom, 72 (25.7%) and 65 (23.2%) had definite and probable TB. Amongst those with definite TB, LF-LAM test gave a sensitivity of 75.0% (95% CI 63.9–83.6), specificity of 86.0% (95% CI 79.4–90.8) and accuracy of 82.3% (95% CI 76.7–86.8). When compared with the composite reference standard, the test yielded a lower sensitivity (61.3%, 95% CI 53.0–69.1) and accuracy (73.9%, 95% CI 68.5–78.7), with equal specificity. The test showed the highest sensitivity (90.5%, 95% CI 77.9–96.2) and accuracy (85.9%, 95% CI 79.2–90.7) but lower specificity (84.0%, 95% CI 75.6–89.9) in HIV-infected patients with CD4 count less than 50/mm3. The sensitivity of the combined LF-LAM or sputum microscopy was higher than that of either test alone (86.1% vs. 75.0%, 61.1%, respectively). Mycobacterium avium complex (MAC) was cultured in 7 out of 20 with false positive result. Urine LAM strip test can remain positive for up to 4 weeks even after anti-TB treatment. Conclusion Urine LAM assay gave the best performance for diagnosis of active TB in advanced HIV-infected patients and provide an additional benefit of a greater simplicity, speed, with a more easily obtainable sample. Disclosures All authors: No reported disclosures.

Immunology of bovine tuberculosis: Perspectives on one health approaches and defining correlates of protection versus infection

USDA-ARS?s Scientific Manuscript database

Tuberculosis (TB), primarily due to Mycobacterium tuberculosis in humans and Mycobacterium bovis in cattle, is an exemplary model of the One Health Concept. The human TB vaccine, M. bovis bacille Calmette-Guerin (BCG), was first proven effective in cattle prior to use in humans. Recent experimental ...

Treatment compliance and challenges among tuberculosis patients across selected health facilities in Osun State Nigeria.

PubMed

Ajao, K O; Ogundun, O A; Afolabi, O T; Ojo, T O; Atiba, B P; Oguntunase, D O

2014-12-01

Tuberculosis (TB) is a major public health problem in the world and Africa has approximately one quarter of the world's cases. One of the greatest challenges facing most TB programmes is the non-compliance to TB treatment among TB patients. This study aimed at determining the challenges of management of tuberculosis (TB) across selected Osun State health facilities. The study employed a descriptive cross-sectional design. A semi-structured questionnaire was used to collect data from 102 TB patients in the health facilities. The instrument measured socio-demographic variables, patient related factors, socio-economic variables, health care system related factors to TB disease and treatment. Data were analysed and summarized using descriptive and inferential statistics. Statistical significance was placed at p < 0.05. TB patients who had no formal education (χ2 = 12.941, p < 0.05), who were smoking during treatment (χ2 = 13.194, p < 0.001), who consumed alcohol during TB treatment (χ2 = 6.371, p < 0.05) and those who were HIV positive (χ2 = 23.039, p < 0.001) significantly failed to comply with TB treatment. TB patients who waited for one hour or more at heath facilities (χ2 = 21.761, p < 0.001), who reported that TB treatment should be stopped before six month (χ2 = 9.804, p < 0.05) or when patient felt better (χ2 = 35.185, p < 0.001) and travelled for 10 km or more (χ2 = 13.610, p < 0.001) significantly failed to comply with TB treatment. This study concluded that non-compliance rate to tuberculosis treatment among TB patients in this study is high. Both health facility and patient-related factors were largely responsible.

Performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.

PubMed

Manga, Selene; Perales, Rocio; Reaño, Maria; D'Ambrosio, Lia; Migliori, Giovanni Battista; Amicosante, Massimo

2016-11-01

Tuberculosis (TB) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. Serological tests have the potentially to impact TB diagnosis, in particular in extreme clinical settings. The diagnostic performances of the TB-XT HEMA EXPRESS (HEMA-EXPRESS) immunochromatographic rapid test for active TB diagnosis, based on use of multiple Mycobacterium tuberculosis (MTB) specific antigens, have been evaluated in a large study multicentre TB case-finding study, in populations with different exposure level to TB. A total of 1,386 subjects were enrolled in the six participating centres in Peru: 290 active-TB and 1,096 unaffected subjects. The TB prevalence (overall 20.5%) varied between 4.0% and 41.1% in the different study groups. Overall, the HEMA-EXPRESS test had 30.6% sensitivity (range 3.9-77.9%) and 84.6% specificity (range 51.6-97.3%). A significant inverse correlation between test accuracy (overall 73.5%, range 40.4-96.4%) and TB prevalence in the various study populations was observed (Pearson's r=-0.7985; P=0.05). HEMA-EXPRESS, is rapid and relatively inexpensive test suitable for routine use in TB diagnosis. In low TB prevalence conditions, test performance appears in line with WHO Target Product Profile for TB diagnostics. Performances appear suboptimal in high TB prevalence settings. Appropriate set-up in operative clinical settings has to be considered for novel serological tests for TB diagnosis, particularly for formats suitable for point-of-care use.

Tuberculosis Treatment Outcome and Drug Resistance in Lambaréné, Gabon: A Prospective Cohort Study

PubMed Central

Bélard, Sabine; Remppis, Jonathan; Bootsma, Sanne; Janssen, Saskia; Kombila, Davy U.; Beyeme, Justin O.; Rossatanga, Elie G.; Kokou, Cosme; Osbak, Kara K.; Obiang Mba, Régis M.; Kaba, Harry M.; Traoré, Afsatou N.; Ehrhardt, Jonas; Bache, Emmanuel B.; Flamen, Arnaud; Rüsch-Gerdes, Sabine; Frank, Matthias; Adegnika, Ayôla A.; Lell, Bertrand; Niemann, Stefan; Kremsner, Peter G.; Loembé, Marguerite M.; Alabi, Abraham S.; Grobusch, Martin P.

2016-01-01

Despite overall global progress in tuberculosis (TB) control, TB remains one of the deadliest communicable diseases. This study prospectively assessed TB epidemiology in Lambaréné, Gabon, a Central African country ranking 10th in terms of TB incidence rate in the 2014 World Health Organization TB report. In Lambaréné, between 2012 and 2014, 201 adult and pediatric TB patients were enrolled and followed up; 66% had bacteriologically confirmed TB and 95% had pulmonary TB. The human immunodeficiency virus (HIV) coinfection rate was 42% in adults and 16% in children. Mycobacterium tuberculosis and Mycobacterium africanum were identified in 82% and 16% of 108 culture-confirmed TB cases, respectively. Isoniazid (INH) and streptomycin yielded the highest resistance rates (13% and 12%, respectively). The multidrug resistant TB (MDR-TB) rate was 4/91 (4%) and 4/13 (31%) in new and retreatment TB cases, respectively. Treatment success was achieved in 53% of patients. In TB/HIV coinfected patients, mortality rate was 25%. In this setting, TB epidemiology is characterized by a high rate of TB/HIV coinfection and low treatment success rates. MDR-TB is a major public health concern; the need to step-up in-country diagnostic capacity for culture and drug susceptibility testing as well as access to second-line TB drugs urgently requires action. PMID:27352879

Research on tuberculosis in tribal areas in India: A systematic review.

PubMed

Rao, V G; Muniyandi, M; Bhat, J; Yadav, R; Sharma, R

2018-01-01

Tuberculosis (TB) remains a major public health problem in resource-poor countries including India. Scientific knowledge is used to guide policy and practice. There is however, a limited, systematically collected data required for guiding the scale-up of interventions particularly amongst vulnerable populations including tribal groups in the country. In view of this, a systematic review of the TB research studies carried out in tribal areas of different parts of the country was undertaken. To undertake a systematic review of the TB research studies carried out in tribal areas of India between 1996 and 2016. A systematic review of English articles published between 1996 and 2016 on any aspect of TB was done through internet searches using Literature search EndNote programme. The words used for searching were tuberculosis, India, tribal, indigenous, disadvantaged, adivasi. The most common topics classified as annual risk of tuberculosis infection (ARTI), prevalence of TB, laboratory studies, clinical symptoms of TB, risk factors for TB, knowledge attitude practice, community Directly Observed Treatment (DOT) providers, performance of Revised National Tuberculosis Control Programme (RNTCP), and drug resistant TB. Classification was also done on the basis of the type of tribe studied and place of study conducted. A total of 47 studies identified through the search were included in the review. Of the 47 studies reviewed, 12 were on TB prevalence, 7 were laboratory studies, four on ARTI and 5 on performance of RNTCP in tribal areas. Among these, majority (23 studies) of the tribal studies did not mention the type of tribe. Ten studies were conducted among Saharia, a particularly vulnerable tribal group in the Indian state of Madhya Pradesh mainly by the National Institute for Research on Tribal Health, five were among the mixed tribes and very few on other tribes. The systematic review indicates that the research studies on TB among tribal population are very few. There is a need to invest and encourage researcher to work on the research plans for the control of TB in tribal areas. Copyright © 2017 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.

Exogenous reinfection of tuberculosis in a low-burden area.

PubMed

Schiroli, Consuelo; Carugati, Manuela; Zanini, Fabio; Bandera, Alessandra; Di Nardo Stuppino, Silvia; Monge, Elisa; Morosi, Manuela; Gori, Andrea; Matteelli, Alberto; Codecasa, Luigi; Franzetti, Fabio

2015-12-01

Recurrence of tuberculosis (TB) can be the consequence of relapse or exogenous reinfection. The study aimed to assess the factors associated with exogenous TB reinfection. Prospective cohort study based on the TB database, maintained at the Division of Infectious Diseases, Luigi Sacco Hospital (Milan, Italy). Time period: 1995-2010. (1) ≥2 episodes of culture-confirmed TB; (2) cure of the first episode of TB; (3) availability of one Mycobacterium tuberculosis isolate for each episode. Genotyping of the M. tuberculosis strains to differentiate relapse and exogenous reinfection. Logistic regression analysis was used to assess the influence of risk factors on exogenous reinfections. Of the 4682 patients with TB, 83 were included. Of these, exogenous reinfection was diagnosed in 19 (23 %). It was independently associated with absence of multidrug resistance at the first episode [0, 10 (0.01-0.95), p = 0.045] and with prolonged interval between the first TB episode and its recurrence [7.38 (1.92-28.32) p = 0.004]. However, TB relapses occurred until 4 years after the first episode. The risk associated with being foreign born, extrapulmonary site of TB, and HIV infection was not statistically significant. In the relapse and re-infection cohort, one-third of the patients showed a worsened drug resistance profile during the recurrent TB episode. Exogenous TB reinfections have been documented in low endemic areas, such as Italy. A causal association with HIV infection could not be confirmed. Relapses and exogenous reinfections shared an augmented risk of multidrug resistance development, frequently requiring the use of second-line anti-TB regimens.

Tuberculosis vaccine development at a divide.

PubMed

Kaufmann, Stefan H E

2014-05-01

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

Under-reporting of tuberculosis in Praia, Cape Verde, from 2006 to 2012.

PubMed

Furtado da Luz, E; Braga, J U

2018-03-01

According to World Health Organization (WHO) estimates, the under-reporting rate for tuberculosis (TB) in Cape Verde between 2006 and 2012 was 49%. However, the WHO recognises the challenges associated with this estimation process and recommends implementing other methods, such as record linkage, to combat TB under-reporting. To estimate and analyse under-reporting of cases by TB surveillance health units and to evaluate TB cases retrieved from other TB diagnostic sources in Praia, Cape Verde, from 2006 to 2012. This cross-sectional study evaluated under-reporting using the following data: 1) the under-reporting index from TB reporting health units (RHUs), where the number of validated TB cases from RHUs was compared with data from the National Programme for the Fight against Tuberculosis and Leprosy (NPFTL); and 2) the under-reporting index among overall data sources, or a comparison of the number of all validated TB cases from all sources with NPFTL data. The TB under-reporting rate was 40% in Praia during the study period, and results were influenced by laboratory findings. The TB under-reporting rate was very similar to the rate estimated by the WHO. TB surveillance must be improved to reduce under-reporting.

Tuberculosis: Is the landscape changing?

PubMed

Khatua, Sutapa; Geltemeyer, Abby M; Gourishankar, Anand

2017-01-01

Robert Heinrich Herman Koch, a German physician and microbiologist, received Nobel Prize in 1905 for identifying the specific causative agent of tuberculosis (TB). During his time it was believed that TB was an inherited disease. However he was convinced that the disease was caused by a bacterium and was infectious, tested his postulates using guinea pigs, and found the causative agent to be slow growing mycobacterium tuberculosis. TB is the second most common cause of death from infectious diseases after HIV/AIDS. Drug-resistant TB poses serious challenge to effective management of TB worldwide. Multidrug-resistant TB accounted for about half a million new cases and over 200,000 deaths in 2013. Whole-genome sequencing (first done in 1998) technologies have provided new insight into the mechanism of drug resistance. For the first time in 50 y, new anti TB drugs have been developed. The World Health Organization (WHO) has recently revised their treatment guidelines based on 32 studies. In United States, latent TB affects between 10 and 15 million people, 10% of whom may develop active TB disease. QuantiFERON TB Gold and T-SPOT.TB test are used for diagnosis. Further research will look into the importance of newly discovered gene mutations in causing drug resistance.

Upper-Room Ultraviolet Light and Negative Air Ionization to Prevent Tuberculosis Transmission

PubMed Central

Escombe, A. Roderick; Moore, David A. J; Gilman, Robert H; Navincopa, Marcos; Ticona, Eduardo; Mitchell, Bailey; Noakes, Catherine; Martínez, Carlos; Sheen, Patricia; Ramirez, Rocio; Quino, Willi; Gonzalez, Armando; Friedland, Jon S; Evans, Carlton A

2009-01-01

Background Institutional tuberculosis (TB) transmission is an important public health problem highlighted by the HIV/AIDS pandemic and the emergence of multidrug- and extensively drug-resistant TB. Effective TB infection control measures are urgently needed. We evaluated the efficacy of upper-room ultraviolet (UV) lights and negative air ionization for preventing airborne TB transmission using a guinea pig air-sampling model to measure the TB infectiousness of ward air. Methods and Findings For 535 consecutive days, exhaust air from an HIV-TB ward in Lima, Perú, was passed through three guinea pig air-sampling enclosures each housing approximately 150 guinea pigs, using a 2-d cycle. On UV-off days, ward air passed in parallel through a control animal enclosure and a similar enclosure containing negative ionizers. On UV-on days, UV lights and mixing fans were turned on in the ward, and a third animal enclosure alone received ward air. TB infection in guinea pigs was defined by monthly tuberculin skin tests. All guinea pigs underwent autopsy to test for TB disease, defined by characteristic autopsy changes or by the culture of Mycobacterium tuberculosis from organs. 35% (106/304) of guinea pigs in the control group developed TB infection, and this was reduced to 14% (43/303) by ionizers, and to 9.5% (29/307) by UV lights (both p < 0.0001 compared with the control group). TB disease was confirmed in 8.6% (26/304) of control group animals, and this was reduced to 4.3% (13/303) by ionizers, and to 3.6% (11/307) by UV lights (both p < 0.03 compared with the control group). Time-to-event analysis demonstrated that TB infection was prevented by ionizers (log-rank 27; p < 0.0001) and by UV lights (log-rank 46; p < 0.0001). Time-to-event analysis also demonstrated that TB disease was prevented by ionizers (log-rank 3.7; p = 0.055) and by UV lights (log-rank 5.4; p = 0.02). An alternative analysis using an airborne infection model demonstrated that ionizers prevented 60% of TB infection and 51% of TB disease, and that UV lights prevented 70% of TB infection and 54% of TB disease. In all analysis strategies, UV lights tended to be more protective than ionizers. Conclusions Upper-room UV lights and negative air ionization each prevented most airborne TB transmission detectable by guinea pig air sampling. Provided there is adequate mixing of room air, upper-room UV light is an effective, low-cost intervention for use in TB infection control in high-risk clinical settings. PMID:19296717

Rapid detection of Mycobacterium tuberculosis complex in sputum Samples using PURE TB-LAMP assay.

PubMed

N'guessan, K; Horo, K; Coulibaly, I; Adegbele, J; Kouame-Adjei, N; Seck-Angu, H; Guei, A; Kouakou, J; Dosso, M

2016-12-01

Lack of rapid and accurate diagnostic testing is a critical obstacle to global tuberculosis (TB) control. Sensitivity of sputum smear microscopy (SSM) is not optimal; however, it remains the most prevalent tool for TB confirmation in poor countries. As a part of passive case finding of TB detection, this study was conducted to determine the clinical performance of PURE TB-LAMP assay using liquid culture medium as the gold standard. Centre Antituberculeux de Yopougon is one of the 17 intermediate Tuberculosis centers in Côte d'Ivoire. A standardized questionnaire was submitted to patients with signs and symptoms consistent with tuberculosis by a trained caregiver. After obtaining signed consent forms, sputum samples were collected according to National TB Control Programme guidelines (spot-morning). SSM after Ziehl-Neelsen staining and TB-LAMP assay were blindly performed on the first sample. Samples transported to Institut Pasteur de Côte d'Ivoire were decontaminated according to the N-acetyl-L-Cystein method. In Mycobacteria Growth Indicator Tube (MGIT), 500mL of pellets were inoculated and incubated in the MGIT 960 system. MPT64 antigen was detected in positive cultures. Of the 500 patients enrolled, 469 (232men and 239 women) patients were included. The mean ages of men and women were 36.9 (15-86) and 37.3 (15-37.3) years, respectively. There were 56 (12.2%) HIV-infected patients, including 14 women. Clinical isolates of M. tuberculosis complex were detected for 157 (33.5%) patients. Compared with culturing, the overall sensitivity and specificity of SSM were 86% (95% confidence interval [CI]=81-91) and 96% (95% CI=94-98), respectively. The overall sensitivity and specificity for TB-LAMP was 92% (95% CI=0.88-0.96) and 94% (95% CI=0.91-0.97), respectively. Positive likelihood ratios for TB-LAMP and SSM were 15.3 and 21.5, respectively, and negative likelihood ratios for TB-LAMP and SSM were 0.09 and 0.15, respectively. Among the 469 patients, active tuberculosis was detected using TB-LAMP assay and SSM in 162 (34.5%) and 147 (31.3%) patients, respectively. For accurate diagnostic of pulmonary TB, TB-LAMP could be used as a tool of the first intention. Copyright © 2016.

High Rates of Mycobacterium tuberculosis among Socially Marginalized Immigrants in Low-Incidence Area, 1991–2010, Italy

PubMed Central

Mercadante, Silvio; Pareek, Manish; Lalvani, Ajit; Bugiani, Massimiliano

2013-01-01

Migration from low- and middle-income countries to high-income countries increasingly determines the severity of tuberculosis (TB) cases in the adopted country. Socially marginalized groups, about whom little is known, may account for a reservoir of TB among the immigrant populations. We investigated the rates of and risk factors for Mycobacterium tuberculosis transmission, infection, and disease in a cohort of 27,358 socially marginalized immigrants who were systematically screened (1991–2010) in an area of Italy with low TB incidence. Overall TB and latent TB infection prevalence and annual tuberculin skin testing conversion rates (i.e., incidence of new infection) were 2.7%, 34.6%, and 1.7%, respectively. Prevalence of both TB and latent TB infection and incidence of infection increased as a function of the estimated TB incidence in the immigrants’ countries of origin. Annual infection incidence decreased with time elapsed since immigration. These findings have implications for control policy and immigrant screening in countries with a low prevalence of TB. PMID:23965807

Mobility patterns of persons at risk for drug-resistant tuberculosis in Mumbai, India.

PubMed

Conners, E; Garfein, R S; Rodwell, T C; Udwadia, Z F; Catanzaro, D G

2016-12-01

Tuberculosis (TB) hospital in Mumbai, India. To describe the mobility patterns of persons with suspected drug-resistant tuberculosis (DR-TB) and to assess whether there were significant differences in demographic or risk characteristics based on mobility. Observational cohort study of TB clinic patients at risk for DR-TB. Among 602 participants, 37% had ever moved from their place of birth; 14% were local movers (within state), and 23% were distant movers, between states or countries. Univariate multinomial logistic regression models showed that distant movers were more likely than non-movers to have lower income, less education, a greater number of previous TB episodes, and to have ever smoked. Compared to non-movers, local movers were more likely to have lower income and were more likely to have seen a doctor in the past 2 years. Clinical outcomes, including DR-TB, diabetes, and human immunodeficiency virus (HIV), did not differ between the three mobility groups. Mobility was common among patients at risk for DR-TB in Mumbai. TB programs should consider the implications of mobility on the protracted treatment for DR-TB in India.

Emerging technologies for monitoring drug-resistant tuberculosis at the point-of-care.

PubMed

Mani, Vigneshwaran; Wang, ShuQi; Inci, Fatih; De Libero, Gennaro; Singhal, Amit; Demirci, Utkan

2014-11-30

Infectious diseases are the leading cause of death worldwide. Among them, tuberculosis (TB) remains a major threat to public health, exacerbated by the emergence of multiple drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (Mtb). MDR-Mtb strains are resistant to first-line anti-TB drugs such as isoniazid and rifampicin; whereas XDR-Mtb strains are resistant to additional drugs including at least to any fluoroquinolone and one of the second-line anti-TB injectable drugs such as kanamycin, capreomycin, or amikacin. Clinically, these strains have significantly impacted the management of TB in high-incidence developing countries, where systemic surveillance of TB drug resistance is lacking. For effective management of TB on-site, early detection of drug resistance is critical to initiate treatment, to reduce mortality, and to thwart drug-resistant TB transmission. In this review, we discuss the diagnostic challenges to detect drug-resistant TB at the point-of-care (POC). Moreover, we present the latest advances in nano/microscale technologies that can potentially detect TB drug resistance to improve on-site patient care. Copyright © 2014 Elsevier B.V. All rights reserved.

Emerging Technologies for Monitoring Drug-Resistant Tuberculosis at the Point-of-Care

PubMed Central

Mani, Vigneshwaran; Wang, ShuQi; Inci, Fatih; De Libero, Gennaro; Singhal, Amit; Demirci, Utkan

2014-01-01

Infectious diseases are the leading cause of death worldwide. Among them, tuberculosis (TB) remains a major threat to public health, exacerbated by the emergence of multiple drug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis (Mtb). MDR-Mtb strains are resistant to first-line anti-TB drugs such as isoniazid and rifampicin; whereas XDR-Mtb strains are resistant to additional drugs including at least to any fluoroquinolone and at least one of the second-line anti-TB injectable drugs such as kanamycin, capreomycin, or amikacin. Clinically, these strains have significantly impacted the management of TB in high-incidence developing countries, where systemic surveillance of TB drug resistance is lacking. For effective management of TB on-site, early detection of drug resistance is critical to initiate treatment, to reduce mortality, and to thwart drug-resistant TB transmission. In this review, we discuss the diagnostic challenges to detect drug-resistant TB at the point-of-care (POC). Moreover, we present the latest advances in nano/microscale technologies that can potentially detect TB drug resistance to improve on-site patient care. PMID:24882226

Mycobacterial lipolytic enzymes: a gold mine for tuberculosis research.

PubMed

Dedieu, L; Serveau-Avesque, C; Kremer, L; Canaan, S

2013-01-01

Tuberculosis (TB) is one of the deadliest infectious diseases worldwide with a strong impact in developing countries. Mycobacterium tuberculosis, the etiological agent of TB, has a high capacity to evade the host immune system and establish a chronic, asymptomatic and latent infection. In a latent TB infection, persistent bacilli are present in a non-replicating dormant state within host granulomas. During reactivation, bacilli start replicating again leading to an active TB infection that can be highly contagious. Mycobacterial lipids and lipolytic enzymes are thought to play important physiological roles during dormancy and reactivation. The role of lipolytic enzymes in the physiology of M. tuberculosis and physiopathology of the disease will be discussed in this review, with an emphasis on the secreted or cell wall-associated, surface exposed lipolytic enzymes characterized to date. Studies on the localization, enzymatic activity and immunological properties of these enzymes highlighted their possible usefulness as new diagnostic markers in the fight against TB. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Fast and efficient detection of tuberculosis antigens using liposome encapsulated secretory proteins of Mycobacterium tuberculosis.

PubMed

Tiwari, Dileep; Haque, Shafiul; Tiwari, Ram P; Jawed, Arshad; Govender, Thavendran; Kruger, Hendrik G

2017-04-01

A rapid and efficient diagnostic test was developed for the detection of Mycobacterium tuberculosis antigens in serum samples of active tuberculosis (TB) and extrapulmonary TB patients via a liposomal agglutination-based method. A rapid card test has been developed to facilitate the recognition of high-affinity binding rabbit raised purified culture filtrate protein antibodies coupled on the surface of activated liposomal preparation. In the presence of TB antigens, the polyclonal antibodies bound to the liposomal particles demonstrate a visible agglutination reaction. The developed assay was simple, rapid, reliable, sensitive, and specific as a diagnostic test for the detection of antigens in serum samples of clinically confirmed cases of TB within 4-5 minutes' duration. The test was evaluated at different hospitals, medical colleges, and pathology centers, and involved 1483 participants. This investigation was conducted to detect the presence of these antigens during the period of active growth of the microorganism in serum samples for pulmonary TB and processed tissue biopsy for other extrapulmonary TB. Results obtained using this test were compared with acid-fast bacilli smear and culture results. Our study demonstrated that the newly developed liposome tuberculosis antigen card test detected antigens in our study population with approximately 97.48% sensitivity and 95.79% specificity. This is the first study to report the liposomal encapsulation of culture filtrate proteins from M. tuberculosis for diagnostic application. Copyright © 2015. Published by Elsevier B.V.

Drug Resistance in Newly Presenting and Previously Treated Tuberculosis Patients in Guangxi Province, People's Republic of China.

PubMed

Luo, Dan; Zhao, Jinming; Lin, Mei; Liu, Feiying; Huang, Shuhai; Zhang, Yingkun; Huang, Minying; Li, Juan; Zhou, Yang; Lan, Rushu; Zhao, Yanlin

2017-05-01

Drug-resistant Mycobacterium tuberculosis strains are a major threat to the control of tuberculosis (TB), but the prevalence of drug-resistant TB is still unknown in the southern ethnic region of China. A cluster-randomized sampling method was used to include the study population. Isolates were tested for resistance to 6 antituberculosis drugs, and genotyped to identify Beijing strains. Overall, 11.3% (139/1229) of new cases and 33.0% (126/382) of retreated cases had drug-resistant tuberculosis. Multiple previous TB treatment episodes and multiple treatment interruptions were risk factors for both drug-resistant and multidrug-resistant TB among retreated cases. A total of 53.2% of the patients were infected with a Beijing strain of M tuberculosis. Infection with a Beijing strain was significantly associated with drug resistance among new cases (odds ratio, 1.44; 95% CI, 1.01-2.07). Novel strategies to rapid diagnosis and effective treatment are urgently needed to prevent the development of drug resistance.

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

PubMed

2007-01-05

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

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

PubMed

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

2018-05-08

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

TB & HIV: the deadly intersection.

PubMed

MacDougall, D S

1999-05-01

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

Detection of IS6110 and HupB gene sequences of Mycobacterium tuberculosis and bovis in the aortic tissue of patients with Takayasu’s arteritis

PubMed Central

2012-01-01

Background Takayasu’s arteritis (TA) is a chronic inflammatory disease affecting the large arteries and their branches; its etiology is still unknown. In individuals suffering from TA, arterial inflammation progresses to stenosis and/or occlusion, leading to organ damage and affecting survival. Relation of TA with Mycobacterium tuberculosis has been known, but there have been only a few systematic studies focusing on this association. The IS6110 sequence identifies the Mycobacterium tuberculosis complex and the HupB establishes the differences between M. tuberculosis and M. bovis. Our objective was to search the presence of IS6110 and HupB genes in aorta of patients with TA. Methods We analyzed aorta tissues embedded in paraffin from 5760 autopsies obtained from our institution, we divided the selected samples as cases and controls; Cases: aortic tissues of individuals with Takayasu’s arteritis. Control positive: aortic tissues (with tuberculosis disease confirmed) and control negative with other disease aortic (atherosclerosis). Results Of 181 selected aorta tissues, 119 fulfilled the corresponding criteria for TA, TB or atherosclerosis. Thus 33 corresponded to TA, 33 to tuberculosis (TB) and 53 to atherosclerosis. The mean age was 22 ± 13, 41 ± 19, and 57 ± 10, respectively. IS6110 and HupB sequences were detected in 70% of TA tissues, 82% in tuberculosis, and in 32% with atherosclerosis. Important statistical differences between groups with TA, tuberculosis versus atherosclerosis (p = 0.004 and 0.0001, respectively) were found. Conclusion We identified a higher frequency of IS6110 and HupB genes in aortic tissues of TA patients. This data suggests that arterial damage could occur due to previous infection with M. tuberculosis. PMID:22905864

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

PubMed Central

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

2016-01-01

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

Tuberculosis along the United States-Mexico border, 1993-2001.

PubMed

Schneider, Eileen; Laserson, Kayla F; Wells, Charles D; Moore, Marisa

2004-07-01

Tuberculosis (TB) is a leading public health problem and a recognized priority for the federal Governments of both Mexico and the United States of America. The objectives of this research, primarily for the four states in the United States that are along the border with Mexico, were to: (1) describe the epidemiological situation of TB, (2) identify TB risk factors, and (3) discuss tuberculosis program strategies. We analyzed tuberculosis case reports collected from 1993 through 2001 by the tuberculosis surveillance system of the United States. We used those data to compare TB cases mainly among three groups: (1) Mexican-born persons in the four United States border states (Arizona, California, New Mexico, and Texas), (2) persons in those four border states who had been born in the United States, and (3) Mexican-born persons in the 46 other states of the United States, which do not border Mexico. For the period from 1993 through 2001, of the 16 223 TB cases reported for Mexican-born persons in the United States, 12 450 of them (76.7%) were reported by Arizona, California, New Mexico, and Texas. In those four border states overall in 2001, tuberculosis case rates for Mexican-born persons were 5.0 times as high as the rates for persons born in the United States; those four states have 23 counties that directly border on Mexico, and the ratio in those counties was 5.8. HIV seropositivity, drug and alcohol use, unemployment, and incarceration were significantly less likely to be reported in Mexican-born TB patients from the four border states and the nonborder states than in patients born in the United States from the four border states (P < 0.001). Multivariate analysis revealed that among pulmonary tuberculosis patients who were 18-64 years of age and residing in the four border states, the Mexican-born patients were 3.6 times as likely as the United States-born patients were to have resistance to at least isoniazid and rifampin (i. e., to have multidrug-resistant TB) and twice as likely to have isoniazid resistance. Mexican-born TB patients from the four border states and the nonborder states were significantly more likely to have moved or to be lost to follow-up than were the TB patients born in the United States from the four border states (P < 0.001). Increased collaborative tuberculosis control efforts by the federal Governments of both Mexico and the United States along the border that they share are needed if tuberculosis is to be eliminated in the United States.

Mycobacteriophages: an important tool for the diagnosis of Mycobacterium tuberculosis (review).

PubMed

Fu, Xiaoyan; Ding, Mingxing; Zhang, Ning; Li, Jicheng

2015-07-01

The prevention and control of tuberculosis (TB) on a global scale has become increasingly important with the emergence of multidrug‑resistant TB. Mycobacterium tuberculosis phages have been identified as an important investigative tool. Phage genomes exhibit a significant level of diversity and mosaic genome architecture, however, they are simple structures, which are amenable to genetic manipulation. Based on these characteristics, the phages may be used to construct a shuttle plasmid, which is an indispensable tool in the investigation of TB. Furthermore, they may be used for rapid diagnosis and assessing drug susceptibility of TB, including phage amplified assessment and reporter phage technology. With an improved understanding of mycobacteriophages, further clarification of the pathogenesis of TB, and of the implications for its diagnosis and therapy, may be elucidated.

Mycobacterium tuberculosis complex transmission is not associated with recent immigration (≤5 years) in Florida.

PubMed

Séraphin, Marie Nancy; Lauzardo, Michael

2015-12-01

As tuberculosis (TB) incidence decreases in the US, foreign-born persons continue to account for a larger proportion of the burden. In these cross-sectional analyses of 1149 culture-confirmed TB cases genotyped using spoligotyping and 24-locus MIRU, we show that over a quarter of cases among the foreign-born population in Florida resulted from recent transmission of the Mycobacterium tuberculosis complex. In addition, over a third of these cases occurred among persons who had immigrated 5 years or less prior to their diagnosis. Although recent immigration was not a significant predictor of TB transmission, younger age, birthplace in the Americas, homelessness, drug use and TB lineage are risk factors for TB transmission among the foreign-born population in Florida. These data provide actionable insights into TB transmission among the foreign-born population in Florida. Copyright © 2015 Elsevier B.V. All rights reserved.

Infection of the Invisible: Impressions of a Tuberculosis Intervention Program for Migrants in Istanbul.

PubMed

Yasin, Yesim; Biehl, Kristen; Erol, Maral

2015-10-01

This paper reviews the experience of the Istanbul Tuberculosis Aid Program, which targeted tuberculosis (TB) disease in the growing irregular migrant populations of Istanbul. This experience illustrated the importance of community-based public health interventions when dealing with an infectious disease like TB among vulnerable groups. Our data is derived primarily from a qualitative study carried out with program stakeholders. We summarize lessons for success of ITAP as: (1) Strengthening impact and outreach of TB intervention among irregular migrant communities through involvement of multiple stakeholders (2) Increasing TB awareness through a community targeted approach (3) Increasing TB contact tracing and treatment success among infected irregular migrants, and, (4) Improving overall health seeking behavior of irregular migrants through empowerment and trust. Given these particularities we list our policy suggestions for revision of regulations regarding TB control and healthcare needs of irregular migrant populations.

Knowledge of tuberculosis among drug users. Relationship to return rates for tuberculosis screening at a syringe exchange.

PubMed

Salomon, N; Perlman, D C; Friedmann, P; Perkins, M P; Ziluck, V; Jarlais, D C; Paone, D

1999-04-01

Tuberculosis is an important health issue among drug users. We sought to evaluate active drug users' (DUs) knowledge of tuberculosis (TB) and to assess the relationship between TB knowledge and attitudes and tuberculin skin test (TST) return rates at a syringe exchange program. DUs were recruited at a syringe exchange program in New York City, were interviewed and offered TSTs, and received $15.00 upon returning for TST reading. The questionnaire evaluated knowledge of TB transmission, prevention, and treatment. From March 13, 1995 to January 31, 1996, 610 of 650 (94%) of DUs approached agreed to participate. Of these, 80% had previous TSTs within the past 2 years and 20% were known to be HIV infected. Almost all knew that TB is contagious and more than two thirds knew that TB is treatable and that TB preventive therapy existed. However, fewer than half knew that HIV-related TB could be treated, 30% thought TB could be treated without a medical doctor, and the majority (70%) thought a reactive TST implied infectivity. The rate of return for TST reading was 93%. In multivariate analysis, those who knew that HIV-related TB was curable were more likely to return for TST reading (odds ratio 2.0; 95% confidence interval 1.04 to 3.95; p = .03). The high acceptance and return rates suggest that TB services can be incorporated into syringe exchange programs. However, several important gaps in TB knowledge existed in this population at high risk of TB, which may impact on adherence and which support the need for TB education for drug users.

Co-evolution of Mycobacterium tuberculosis and Homo sapiens

PubMed Central

Brites, Daniela; Gagneux, Sebastien

2015-01-01

The causative agent of human tuberculosis (TB), Mycobacterium tuberculosis, is an obligate pathogen that evolved to exclusively persist in human populations. For M. tuberculosis to transmit from person to person, it has to cause pulmonary disease. Therefore, M. tuberculosis virulence has likely been a significant determinant of the association between M. tuberculosis and humans. Indeed, the evolutionary success of some M. tuberculosis genotypes seems at least partially attributable to their increased virulence. The latter possibly evolved as a consequence of human demographic expansions. If co-evolution occurred, humans would have counteracted to minimize the deleterious effects of M. tuberculosis virulence. The fact that human resistance to infection has a strong genetic basis is a likely consequence of such a counter-response. The genetic architecture underlying human resistance to M. tuberculosis remains largely elusive. However, interactions between human genetic polymorphisms and M. tuberculosis genotypes have been reported. Such interactions are consistent with local adaptation and allow for a better understanding of protective immunity in TB. Future ‘genome-to-genome’ studies, in which locally associated human and M. tuberculosis genotypes are interrogated in conjunction, will help identify new protective antigens for the development of better TB vaccines. PMID:25703549

Multidrug-resistant tuberculosis outbreak among US-bound Hmong refugees, Thailand, 2005.

PubMed

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

2008-11-01

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.

The minipig as an animal model to study Mycobacterium tuberculosis infection and natural transmission

USDA-ARS?s Scientific Manuscript database

Infants and children with tuberculosis (TB) account for more than 20% of cases in endemic countries. Current animal models study TB during adulthood but animal models for adolescent and infant TB are scarce. Here we propose that minipigs can be used as an animal model to study adult, adolescent and ...

Tuberculosis Screening on a Health Science Campus: Use of QuantiFERON-TB Gold Test for Students and Employees

ERIC Educational Resources Information Center

Veeser, Peggy Ingram; Smith, Phillip Karl; Handy, Barry; Martin, Sharon R.

2007-01-01

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…

Multidrug-Resistant Tuberculosis, Somalia, 2010–2011

PubMed Central

Sindani, Ireneaus; Fitzpatrick, Christopher; Falzon, Dennis; Suleiman, Bashir; Arube, Peter; Adam, Ismail; Baghdadi, Samiha; Bassili, Amal

2013-01-01

In a nationwide survey in 2011, multidrug-resistant tuberculosis (MDR TB) was found in 5.2% and 40.8% of patients with new and previously treated TB, respectively. These levels of drug resistance are among the highest ever documented in Africa and the Middle East. This finding presents a serious challenge for TB control in Somalia. PMID:23621911

Convergent ethical issues in HIV/AIDS, tuberculosis and malaria vaccine trials in Africa: Report from the WHO/UNAIDS African AIDS Vaccine Programme's Ethics, Law and Human Rights Collaborating Centre consultation, 10-11 February 2009, Durban, South Africa

PubMed Central

2010-01-01

Background Africa continues to bear a disproportionate share of the global HIV/AIDS, tuberculosis (TB) and malaria burden. The development and distribution of safe, effective and affordable vaccines is critical to reduce these epidemics. However, conducting HIV/AIDS, TB, and/or malaria vaccine trials simultaneously in developing countries, or in populations affected by all three diseases, is likely to result in numerous ethical challenges. Methods In order to explore convergent ethical issues in HIV/AIDS, TB and malaria vaccine trials in Africa, the Ethics, Law and Human Rights Collaborating Centre of the WHO/UNAIDS African AIDS Vaccine Programme hosted a consultation on the Convergent Ethical Issues in HIV/AIDS, TB and Malaria Vaccine Trials in Africa in Durban, South Africa on the 10-11 February 2009. Results Key cross cutting ethical issues were prioritized during the consultation as community engagement; ancillary care obligations; care and treatment; informed consent; and resource sharing. Conclusion The consultation revealed that while there have been few attempts to find convergence on ethical issues between HIV/AIDS, TB and malaria vaccine trial fields to date, there is much common ground and scope for convergence work between stakeholders in the three fields. PMID:20211030

Influenza Pandemics and Tuberculosis Mortality in 1889 and 1918: Analysis of Historical Data from Switzerland

PubMed Central

Zürcher, Kathrin; Zwahlen, Marcel; Ballif, Marie; Rieder, Hans L.; Egger, Matthias

2016-01-01

Background Tuberculosis (TB) mortality declined in the northern hemisphere over the last 200 years, but peaked during the Russian (1889) and the Spanish (1918) influenza pandemics. We studied the impact of these two pandemics on TB mortality. Methods We retrieved historic data from mortality registers for the city of Bern and countrywide for Switzerland. We used Poisson regression models to quantify the excess pulmonary TB (PTB) mortality attributable to influenza. Results Yearly PTB mortality rates increased during both influenza pandemics. Monthly influenza and PTB mortality rates peaked during winter and early spring. In Bern, for an increase of 100 influenza deaths (per 100,000 population) monthly PTB mortality rates increased by a factor of 1.5 (95%Cl 1.4–1.6, p<0.001) during the Russian, and 3.6 (95%Cl 0.7–18.0, p = 0.13) during the Spanish pandemic. Nationally, the factor was 2.0 (95%Cl 1.8–2.2, p<0.001) and 1.5 (95%Cl 1.1–1.9, p = 0.004), respectively. We did not observe any excess cancer or extrapulmonary TB mortality (as a negative control) during the influenza pandemics. Conclusions We demonstrate excess PTB mortality during historic influenza pandemics in Switzerland, which supports a role for influenza vaccination in PTB patients in high TB incidence countries. PMID:27706149

Tuberculosis prevalence in forensic autopsies.

PubMed

Ozsoy, Sait; Demirel, Birol; Albay, Ali; Kisa, Ozgul; Dinc, Ahmet H; Safali, Mukerrem

2010-03-01

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.

Protein-calorie malnutrition, macronutrient supplements, and tuberculosis.

PubMed

Koethe, J R; von Reyn, C F

2016-07-01

Protein-calorie malnutrition (PCM) is a risk factor for tuberculosis (TB) disease and may affect treatment outcomes. There is currently no recommended macronutrient intervention for improving the outcome of anti-tuberculosis treatment. We reviewed current literature on PCM and low body mass index (BMI) as risk factors for tuberculous infection and TB disease, and their effects on anti-tuberculosis treatment. We summarize clinical trials of macronutrient supplementation in the treatment of TB. PCM is a well-established risk factor for TB disease; however, data on malnutrition and the risk of tuberculous infection are limited. Malnutrition is associated with an increased risk of mortality and relapse of active TB. Clinical trials of macronutrient supplementation during treatment confirm a 2-3 kg improvement in weight gain at 2 months, and may result in improvement in physical function, sputum conversion and treatment completion, but they have not been powered to assess effects on mortality or relapse. Assessment of dietary intake, food security, and baseline BMI should be standard practice in anti-tuberculosis treatment, along with dietary counselling. As macronutrient supplementation may have modest benefits and is not associated with adverse events, patients with BMI values <18.5 kg/m(2) should be provided with balanced macronutrient supplementation whenever possible.

[Prevalence of HIV-Tuberculosis co-infection and HIV impact on patients with tuberculosis in the Lubumbashi Health Zone from 2014 to 2015].

PubMed

Wa Ilunga, E N; Muya, R K; Kaponda, A A; Kaput, C M A; Kalonji, S M; Chiribagula, V B; Nshikala, B N; N'sasi, A N; Simbi, J-B L

2018-02-01

Tuberculosis and HIV/AIDS are a dangerous couple in sub-Saharan Africa. The aim of this paper is to evaluate the prevalence of the co-infection tuberculosis/HIV/AIDS and its impact on issues of tuberculosis patients treated in Lubumbashi Heath Zone (LHZ). A retrospective and transversal study was conducted through the analysis of tuberculosis patients' data admitted in the tuberculosis Health Centers for Diagnosis and treatment (HCDT) in the LHZ from January 2014 to December 2015. TB-HIV co-infection cases will be identified and the outcome will be analyzed. Data of 1368 patients were noted from three HCDT of the TB of the Lubumbashi ZS and among them 334 cases of co-infections were recorded. The most incriminated age range is 40-50 years. The mean of age of our patients is 32.84±15.32 years and the man/women sex ratio is 1.70. The most predominant clinical tuberculosis form is the extra pulmonary [EPT (52.70 %)]. Among co-infected patients, the predominant form is pulmonary (TPM-). Out of the 51 cases of deaths recorded, 23 (45.10 %) also had HIV while 28 (54.90 %) were HIV-negative. There was an increase of 11.6 % in TB-HIV/AIDS co-infection from 2014 to 2015. TB-HIV/AIDS co-infection is a reality in the LHZ, especially in patients with negative bacterial TB (TPM-) and we have to pay a particular attention on the impact of HIV on the death of tuberculosis patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2016-04-01

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

Correlation between tuberculin skin test and IGRAs with risk factors for the spread of infection in close contacts with sputum smear positive in pulmonary tuberculosis

PubMed Central

2014-01-01

Background The aim of the study was to assess the correlation between the tuberculin skin test (TST) and in vitro interferon-gamma released assays (IGRAs) with risk factors for the spread of infection in smear positive pulmonary tuberculosis (TB) contacts. Methods We recruited prospective contacts with smear positive pulmonary TB cases. We looked at human immunodeficiency virus (HIV) infection and other conditions of immunosuppression, presence of BCG vaccination and the degree of exposure to the index case. Patients underwent the TST, chest radiography, sputum analysis when necessary, and IGRA assays (QFN-G-IT and T-SPOT.TB). Presence of cough, diagnostic delay (days between first symptoms and TB diagnostic), contact conditions: room size (square meters) and index of overcrowding (square meters per person) were investigated in the index case. Results 156 contacts (119 adults, 37 children) of 66 TB patients were enrolled, 2.4 (1-14) contacts per TB case. The positivity of the TST did not correlate with the risk factors studied: presence of cough (p = 0.929); delayed diagnosis (p = 0.244); room size (p = 0.462); overcrowding (p = 0.800). Both QFN-G-IT and T-SPOT.TB, showed significant association with cough (p = 0.001, and p = 0.007) and room size (p = 0.020, and p = 0.023), respectively. Conclusions Both IGRA associated better than TST with certain host-related risk factors involved in the transmission of disease, such as the presence of cough. PMID:24885850

Tuberculosis risk factors among tuberculosis patients in Kampala, Uganda: implications for tuberculosis control.

PubMed

Kirenga, Bruce J; Ssengooba, Willy; Muwonge, Catherine; Nakiyingi, Lydia; Kyaligonza, Stephen; Kasozi, Samuel; Mugabe, Frank; Boeree, Martin; Joloba, Moses; Okwera, Alphonse

2015-01-21

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 mycobacteriological study patient characteristics. Among TB patients in Kampala, Uganda, there is high prevalence of the known TB risk factors. Targeting reducing their prevalence may lead to better TB control in the country. Tuberculosis, risk factors, Uganda.

Tuberculosis: will it infect wild elk?

USGS Publications Warehouse

Roffe, T.J.; Smith, B.

1992-01-01

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.

A predictive signature gene set for discriminating active from latent tuberculosis in Warao Amerindian children.

PubMed

Verhagen, Lilly M; Zomer, Aldert; Maes, Mailis; Villalba, Julian A; Del Nogal, Berenice; Eleveld, Marc; van Hijum, Sacha Aft; de Waard, Jacobus H; Hermans, Peter Wm

2013-02-01

Tuberculosis (TB) continues to cause a high toll of disease and death among children worldwide. The diagnosis of childhood TB is challenged by the paucibacillary nature of the disease and the difficulties in obtaining specimens. Whereas scientific and clinical research efforts to develop novel diagnostic tools have focused on TB in adults, childhood TB has been relatively neglected. Blood transcriptional profiling has improved our understanding of disease pathogenesis of adult TB and may offer future leads for diagnosis and treatment. No studies applying gene expression profiling of children with TB have been published so far. We identified a 116-gene signature set that showed an average prediction error of 11% for TB vs. latent TB infection (LTBI) and for TB vs. LTBI vs. healthy controls (HC) in our dataset. A minimal gene set of only 9 genes showed the same prediction error of 11% for TB vs. LTBI in our dataset. Furthermore, this minimal set showed a significant discriminatory value for TB vs. LTBI for all previously published adult studies using whole blood gene expression, with average prediction errors between 17% and 23%. In order to identify a robust representative gene set that would perform well in populations of different genetic backgrounds, we selected ten genes that were highly discriminative between TB, LTBI and HC in all literature datasets as well as in our dataset. Functional annotation of these genes highlights a possible role for genes involved in calcium signaling and calcium metabolism as biomarkers for active TB. These ten genes were validated by quantitative real-time polymerase chain reaction in an additional cohort of 54 Warao Amerindian children with LTBI, HC and non-TB pneumonia. Decision tree analysis indicated that five of the ten genes were sufficient to classify 78% of the TB cases correctly with no LTBI subjects wrongly classified as TB (100% specificity). Our data justify the further exploration of our signature set as biomarkers for potential childhood TB diagnosis. We show that, as the identification of different biomarkers in ethnically distinct cohorts is apparent, it is important to cross-validate newly identified markers in all available cohorts.

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

PubMed Central

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

2015-01-01

Background Contact tracing, to identify source cases with untreated tuberculosis (TB), is rarely performed in high disease burden settings when the index case is a young child with TB. As TB is strongly associated with HIV infection in these settings, we used source case investigation to determine the prevalence of undiagnosed TB and HIV in the caregivers and household contacts of hospitalised young children diagnosed with TB in South Africa. Methods Caregivers and household contacts of 576 young children (age ≤7 years) with TB diagnosed between May 2010 and August 2012 were screened for TB and HIV. The primary outcome was the detection of laboratory-confirmed, newly-diagnosed TB disease and/or HIV-infection in close contacts. Results Of 576 caregivers, 301 (52·3%) self-reported HIV-positivity. Newly-diagnosed HIV infection was detected in 63 (22·9%) of the remaining 275 caregivers who self-reported an unknown or negative HIV status. Screening identified 133 (23·1%) caregivers eligible for immediate anti-retroviral therapy (ART). Newly-diagnosed TB disease was detected in 23 (4·0%) caregivers. In non-caregiver household contacts (n = 1341), the prevalence of newly-diagnosed HIV infection and TB disease was 10·0% and 3·2% respectively. On average, screening contacts of every nine children with TB resulted in the identification of one case of newly-diagnosed TB disease, three cases of newly diagnosed HIV-infection, and three HIV-infected persons eligible for ART. Conclusion In high burden countries, source case investigation yields high rates of previously undiagnosed HIV and TB infection in the close contacts of hospitalised young children diagnosed with TB. Furthermore, integrated screening identifies many individuals who are eligible for immediate ART. Similar studies, with costing analyses, should be undertaken in other high burden settings–integrated source case investigation for TB and HIV should be routinely undertaken if our findings are confirmed. PMID:26378909

Changing patterns and trends of multidrug-resistant tuberculosis at referral centre in Northern India: a 4-year experience.

PubMed

Maurya, A K; Singh, A K; Kumar, M; Umrao, J; Kant, S; Nag, V L; Kushwaha, R A S; Dhole, T N

2013-01-01

India has a high burden of drug-resistant tuberculosis (TB), although there is little data on multidrug-resistant tuberculosis (MDR-TB). Although MDR-TB has existed for long time in India, very few diagnostic laboratories are well-equipped to test drug sensitivity. The objectives of this study were to determine the prevalence of MDR-TB, first-line drug resistance patterns and its changing trends in northern India in the 4 years. This was a prospective study from July 2007 to December 2010. Microscopy, culture by Bactec460 and p-nitro-α-acetylamino-β-hydroxypropiophenone (NAP) test was performed to isolate and identify Mycobacterium tuberculosis (M. tb) complex (MTBC). Drug sensitivity testing (DST) was performed by 1% proportional method (Bactec460) for four drugs: Rifampicin, isoniazid, ethambutol and streptomycin. Various clinical and demographical profiles were evaluated to analyse risk factors for development of drug resistance. We found the overall prevalence rate of MDR-TB to be 38.8%, increasing from 36.4% in 2007 to 40.8% in 2010. we found that the prevalence of MDR-TB in new and previously treated cases was 29.1% and 43.3% ( P < 0.05; CI 95%). The increasing trend of MDR-TB was more likely in pulmonary TB when compared with extra-pulmonary TB ( P < 0.05; CI 95%). we found a high prevalence (38.8%) of MDR-TB both in new cases (29.1%) and previously treated cases (43.3%).This study strongly highlights the need to make strategies for testing, surveillance, monitoring and management of such drug-resistant cases.

Tuberculosis of hip in children: A retrospective analysis

PubMed Central

Moon, Myung-Sang; Kim, Sung-Soo; Lee, Sung-Rak; Moon, Young-Wan; Moon, Jeong-Lim; Moon, Seog-In

2012-01-01

Background: Tuberculosis (TB) of hip constitutes nearly 15% of all cases of osteoarticular tuberculosis. We report a retrospective study carried out on 43 children with hip TB. Materials and Methods: Forty-three children of TB hip treated between 1971 and 2000 were analysed. Twenty-four children of the early series were treated with streptomycin (S), isoniazid (H) and PAS (Pa) for 18 months (3HPaS, 15 HPa), while 19 children in the later series were treated with isoniazid (H), rifampicin (R) and ethambutol (E) or pyrazinamide (Z) for 12 months [(12 RHE(Z)]. Five out of 18 children with radiologically normal appearing type hip TB were treated with chemotherapy alone and 38 children were subjected to surgery; simple synovectomy alone in 31 hips, joint debridement in six hips, and proximal femoral varisation osteotomy in one. After surgery hips were immobilized in cast for one to three months according to the severity of the disease and patients pain tolerance, and then were mobilized under leg traction in bed gradually till pain subsided completely. Results: TB of hip healed with minimum sequelae in all children. In 18 Type one hip TB, normal hip (synovial form) anatomy was maintained, and in 25 patients with advanced lesions some defect in the femoral head and acetabulum was noticed, though painless good hip motion was maintained. Excellent to good results were obtained in 31 children (73.1%), fair in eight (18.6%), and poor in four (9.3%). In four patients with poor results, there was some residual morphological defect in the hip. None developed ankylosis of hip. Conclusion: We achieved good outcome with minimum sequelae in this series. The management goal should be aimed not only to heal the disease but also to maintain a painless mobile hip and anatomical cephalocotyloid relationship until maturity, and retard the development of secondary osteoarthritis. PMID:22448058

Socio-demographic determinants and prevalence of Tuberculosis knowledge in three slum populations of Uganda.

PubMed

Obuku, Ekwaro A; Meynell, Clea; Kiboss-Kyeyune, Jemimah; Blankley, Simon; Atuhairwe, Christine; Nabankema, Evelyn; Lab, Morris; Jeffrey, Nikki; Ndungutse, David

2012-07-23

Knowledge of tuberculosis has been shown to influence health seeking behaviour; and urban slum dwellers are at a higher risk of acquiring tuberculosis than the general population. The study aim was to assess knowledge of tuberculosis and identify the associated socio-demographic determinants, in order to inform tailored interventions for advocacy, communication and social mobilisation in three urban-slum communities of Uganda. A cross-sectional survey of 1361 adults between April and October 2011. Data was analyzed by descriptive statistics. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) of potential determinants of tuberculosis (TB) knowledge were estimated by multivariable ordinal logistic regression using Stata 11.2 software. We found low knowledge of TB cause (26.7%); symptoms (46.8%), transmission (54.3%), prevention (34%) and free treatment (35%). Knowledge about TB treatment (69.4) and cure (85.1) was relatively high. Independent determinants of poor knowledge of TB in the multivariable analysis included (aOR, 95% CI) lack of formal education (0.56; 0.38 - 0.83, P = 0.004), unemployment (0.67; 0.49 - 0.90, P = 0.010) and never testing for HIV (0.69; 0.51 - 0.92, P < 0.012). Whilst, older age (1.73; 1.30 - 2.29, P < 0.001) and residing in Lira (2.02; 1.50 - 2.72, P < 0.001) were independent determinants of higher knowledge of TB. This study revealed deficiencies in the public health knowledge about TB symptoms, diagnosis and treatment among urban-slum dwellers in Uganda. Tuberculosis control programmes in similar settings should consider innovative strategies for TB education, advocacy, communication and social mobilisation to reach the youth, unemployed and less-educated; as well as those who have never tested for HIV.

Mycobacterium tuberculosis Transmission in a Country with Low Tuberculosis Incidence: Role of Immigration and HIV Infection

PubMed Central

Gagneux, Sebastien; Helbling, Peter; Battegay, Manuel; Rieder, Hans L.; Pfyffer, Gaby E.; Zwahlen, Marcel; Furrer, Hansjakob; Siegrist, Hans H.; Fehr, Jan; Dolina, Marisa; Calmy, Alexandra; Stucki, David; Jaton, Katia; Janssens, Jean-Paul; Stalder, Jesica Mazza; Bodmer, Thomas; Ninet, Beatrice; Böttger, Erik C.; Egger, Matthias; Barth, J.; Battegay, M.; Bernasconi, E.; Böni, J.; Bucher, H. C.; Burton-Jeangros, A. Calmy; Cavassini, M.; Cellerai, C.; Egger, M.; Elzi, L.; Fehr, J.; Fellay, J.; Flepp, M.; Francioli, P.; Furrer, H.; Fux, C. A.; Gorgievski, M.; Günthard, H.; Haerry, D.; Hasse, B.; Hirschel, B.; Hirsch, H. H.; Hirschel, B.; Hoffmann, M.; Hösli, I.; Kahlert, C.; Kaiser, L.; Kaiser, O.; Kind, C.; Klimkait, T.; Kovari, H.; Ledergerber, B.; Lugano, A. P.; Martinetti, G.; Martinez de Tejada, B.; Metzner, K.; Müller, N.; Nadal, D.; Pantaleo, G.; Rauch, A.; Regenass, S.; Rickenbach, M.; Rudin, C.; Schmid, P.; Schultze, D.; Schöni-Affolter, F.; Schüpbach, J.; Speck, R.; Taffé, P.; Tarr, P.; Telenti, A.; Trkola, A.; Vernazza, P.; Weber, R.; Yerly, S.

2012-01-01

Immigrants from high-burden countries and HIV-coinfected individuals are risk groups for tuberculosis (TB) in countries with low TB incidence. Therefore, we studied their role in transmission of Mycobacterium tuberculosis in Switzerland. We included all TB patients from the Swiss HIV Cohort and a sample of patients from the national TB registry. We identified molecular clusters by spoligotyping and mycobacterial interspersed repetitive-unit–variable-number tandem-repeat (MIRU-VNTR) analysis and used weighted logistic regression adjusted for age and sex to identify risk factors for clustering, taking sampling proportions into account. In total, we analyzed 520 TB cases diagnosed between 2000 and 2008; 401 were foreign born, and 113 were HIV coinfected. The Euro-American M. tuberculosis lineage dominated throughout the study period (378 strains; 72.7%), with no evidence for another lineage, such as the Beijing genotype, emerging. We identified 35 molecular clusters with 90 patients, indicating recent transmission; 31 clusters involved foreign-born patients, and 15 involved HIV-infected patients. Birth origin was not associated with clustering (adjusted odds ratio [aOR], 1.58; 95% confidence interval [CI], 0.73 to 3.43; P = 0.25, comparing Swiss-born with foreign-born patients), but clustering was reduced in HIV-infected patients (aOR, 0.49; 95% CI, 0.26 to 0.93; P = 0.030). Cavitary disease, male sex, and younger age were all associated with molecular clustering. In conclusion, most TB patients in Switzerland were foreign born, but transmission of M. tuberculosis was not more common among immigrants and was reduced in HIV-infected patients followed up in the national HIV cohort study. Continued access to health services and clinical follow-up will be essential to control TB in this population. PMID:22116153

Synchronous oral paracoccidioidomycosis and pulmonary tuberculosis in an immunocompetent patient.

PubMed

Amorim Pellicioli, Ana Carolina; Neves-Silva, Rodrigo; Santos-Silva, Alan Roger; Vargas, Pablo Agustin; Lopes, Márcio Ajudarte

2015-06-01

Paracoccidioidomycosis (PCM) and tuberculosis (TB) are chronic granulomatous infectious diseases, in which the main form of contraction is through inhalation of the microorganism-Paracoccidioides brasiliensis and Mycobacterium tuberculosis. Oral involvement of PCM is observed in up to 70 % of the cases and usually presents clinically as ulcerations with granular surface showing tiny hemorrhagic areas. Oral presentation of TB is rare with prevalence smaller than 0.5 % of all cases. Clinical presentation of oral TB mainly consists of single ulcers with irregular limits and necrotic base. A 70-year-old immunocompetent man presented simultaneously oral PCM and pulmonary TB. Medical history revealed a previous diagnosis of pulmonary TB; however, even under treatment for TB, the patient remained with oral lesions and intense pulmonary fibrosis. The physician requested P. brasiliensis serological analysis, which resulted positive. Although the combination of PCM and TB has been reported in the literature, it is still considered an uncommon condition and their diagnosis may represent a challenge to healthcare professionals because of the similarity between their clinical and radiological presentations.

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

PubMed

Restrepo, Blanca I

2016-12-01

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

Genital tuberculosis in females

PubMed Central

Grace, G. Angeline; Devaleenal, D. Bella; Natrajan, Mohan

2017-01-01

The morbidity and mortality due to tuberculosis (TB) is high worldwide, and the burden of disease among women is significant, especially in developing countries. Mycobacterium tuberculosis bacilli reach the genital tract primarily by haematogenous spread and dissemination from foci outside the genitalia with lungs as the common primary focus. Genital TB in females is a chronic disease with low-grade symptoms. The fallopian tubes are affected in almost all cases of genital TB, and along with endometrial involvement, it causes infertility in patients. Many women present with atypical symptoms which mimic other gynaecological conditions. A combination of investigations is needed to establish the diagnosis of female genital TB (FGTB). Multidrug anti-TB treatment is the mainstay of management and surgery may be required in advanced cases. Conception rates are low among infertile women with genital TB even after multidrug therapy for TB, and the risk of complications such as ectopic pregnancy and miscarriage is high. More research is needed on the changing trends in the prevalence and on the appropriate methods for diagnosis of FGTB. PMID:28862174

Tuberculosis in HIV patient.

PubMed

Paudel, Bidhan Nidhi; Paudel, Punya; Paudel, Luna; Dhungana, Govinda; Amatya, Gyanendra Lal; Aryal, Choodamani; Kandel, Prakash

2013-01-01

Strict monitoring ofanti tuberculosis therapy and antiretroviral therapyis crucial for proper management of TB/HIV co-infected patients. Between December 2006 and December 2008 a prospective observational study was conducted among 135 TB/HIV co-infected patients visiting antiretroviral therapy in Seti Zonal Hospital, Dhangadi. The diagnosed TB patients were subjected to ATT through directly observed treatment short-course (DOTS) and its response was evaluated as per WHO guidelines. Among 135 studied subjects, 97 (71.9%) were males and over 119 (88 %) of the patients were in the age group 21 to 50. Of the total TB cases 92 (68.1%) presented pulmonary TB and 37.20% of the Extra-pulmonary Tuberculosis cases were lymph node TB. 72 (53.33%) of them had completed ATT, 11 (8.2%) transfer out and 17 (12.6%) were default. Majority of the patients presented PTB, and lymph node TB was found to be the most common EPTB. Comparatively, high efficacy of ATT was found in HIV patients visiting this resource poor setting.

[Biologics and mycobacterial diseases].

PubMed

Tsuyuguchi, Kazunari; Matsumoto, Tomoshige

2013-03-01

Various biologics such as TNF-alpha inhibitor or IL-6 inhibitor are now widely used for treatment of rheumatoid arthritis. Many reports suggested that one of the major issues is high risk of developing tuberculosis (TB) associated with using these agents, which is especially important in Japan where tuberculosis still remains endemic. Another concern is the risk of development of nontuberculous mycobacterial (NTM) diseases and we have only scanty information about it. The purpose of this symposium is to elucidate the role of biologics in the development of mycobacterial diseases and to establish the strategy to control them. First, Dr. Tohma showed the epidemiologic data of TB risks associated with using biologics calculated from the clinical database on National Database of Rheumatic Diseases by iR-net in Japan. He estimated TB risks in rheumatoid arthritis (RA) patients to be about four times higher compared with general populations and to become even higher by using biologics. He also pointed out a low rate of implementation of QuantiFERON test (QFT) as screening test for TB infection. Next, Dr. Tokuda discussed the issue of NTM disease associated with using biologics. He suggested the airway disease in RA patients might play some role in the development of NTM disease, which may conversely lead to overdiagnosis of NTM disease in RA patients. He suggested that NTM disease should not be uniformly considered a contraindication to treatment with biologics, considering from the results of recent multicenter study showing relatively favorable outcome of NTM patients receiving biologics. Patients with latent tuberculosis infection (LTBI) should receive LTBI treatment before starting biologics. Dr. Kato, a chairperson of the Prevention Committee of the Japanese Society for Tuberculosis, proposed a new LTBI guideline including active implementation of LTBI treatment, introducing interferon gamma release assay, and appropriate selection of persons at high risk for developing TB. Lastly, Dr. Matsumoto stressed the risk of discontinuing TNF-alpha inhibitor during treatment for tuberculosis. He showed from his clinical experience that TNF-alpha inhibitor can be safely used in active TB patient receiving effective antituberculosis chemotherapy and it is even more effective for prevention of paradoxical response. Active discussion was done about the four topics, including the matter beyond present guidelines. We hope these discussions will form the basis for the establishment of new guideline for the management of mycobacterial disease when using immunosuppressive agents including biologics. 1. The risk of developing tuberculosis (TB) and situations of screening for TB risk at administration of biologics-the case of rheumatoid arthritis: Shigeto TOHMA (Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital) We calculated the standardized incidence ratio (SIR) of TB from the clinical data on National Database of Rheumatic Diseases by iR-net in Japan (NinJa) and compared with the SIR of TB from the data of the post-marketing surveillances of five biologics. Among 43584 patient-years, forty patients developed TB. The SIR of TB in NinJa was 4.34 (95%CI: 3.00-5.69). According to the post-marketing surveillances of 5 biologics, the SIR of TB were 3.62-34.4. The incidence of TB in patients with RA was higher than general population in Japan, and was increased more by some biologics. We have to recognize the risk of TB when we start biologics therapy to patients with RA. Although the frequency of implementation of QuantiFERON test (QFT) had gradually increased, it was still limited to 41%. In order to predict the risk of developing TB and to prevent TB, it might be better to check all RA patients by QFT at time time of biologics administration. 2. Biologics and nontuberculous mycobacterial diseases: Hitoshi TOKUDA (Social Insurance Central General Hospital) Several topics about the relationship between RA and nontuberculous mycobacterial (NTM) diseases were discussed, which is still poorly understood. It is well known that airway diseases often accompany RA, which may be considered as a possible etiology for development of NTM diseases, but conversely it may lead to overdiagnosis of NTM disease. Next, we evaluated justification for the contraindication of biologics in patients with NTM diseases. Recent multicenter study showed that prognosis of patients developing NTM diseases during treatment with biologics were not always poor, which throws doubt on uniform prohibition of biologics in NTM diseases. 3. Future guideline for treating latent tuberculosis infection: Seiya KATO (Research Institute of Tuberculosis, Japan AntiTuberculosis Association) The Japanese Society for Tuberculosis issued a joint statement on chemoprophylaxis with the Japan College of Rheumatology in 2004. However, issues and challenges due to changing circumstance indicate application of interferon gamma release assay (IGRA), increased variety and indication of biologics, dissemination of knowledge on strategy and system for latent tuberculosis infection (LTBI), etc. Future guideline should include 1) promoting LTBI treatment to achieve low incidence, 2) updated information on IGRAs, 3) treatment strategy and target: contact to infectious cases, immunosuppressive cases (especially HIV and patients treated with biologics), high risk groups, etc. 4) fundamental information on tuberculosis control strategies, especially DOTS. 4. Therapy for RA and tuberculosis in patients with RA and TB activated by anti-TNF treatment: Tomoshige MATSUMOTO (Osaka Prefectural Medical Center for Respiratory and Allergic Diseases) Biologics targeting TNF, including infliximab, have brought about a paradigm shift in the treatment of rheumatoid arthritis (RA). In 2001, tuberculosis, an ancient and also modem scourge, became spotlighted again, because Keane reported in the New England Journal of Medicine that infliximab administration induced reactivation of tuberculosis. How should we treat RA after we successfully treated tuberculosis? Decisions regarding the treatment of patients with refractory RA in the setting of active tuberculosis remain difficult. We successfully treated RA in patients with tuberculosis by anti-TNF therapy. These demonstrate that anti-TNF therapy can be considered for patients with refractory RA who have tuberculosis and in whom antituberculosis therapy can be maintained.

Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement.

PubMed

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

2016-01-01

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.

Tuberculosis among the homeless, United States, 1994–2010

PubMed Central

Bamrah, S.; Yelk Woodruff, R. S.; Powell, K.; Ghosh, S.; Kammerer, J. S.; Haddad, M. B.

2016-01-01

SUMMARY OBJECTIVES 1) To describe homeless persons diagnosed with tuberculosis (TB) during the period 1994–2010, and 2) to estimate a TB incidence rate among homeless persons in the United States. METHODS TB cases reported to the National Tuberculosis Surveillance System were analyzed by origin of birth. Incidence rates were calculated using the US Department of Housing and Urban Development homeless population estimates. Analysis of genotyping results identified clustering as a marker for transmission among homeless TB patients. RESULTS Of 270 948 reported TB cases, 16 527 (6%) were homeless. The TB incidence rate among homeless persons ranged from 36 to 47 cases per 100 000 population in 2006–2010. Homeless TB patients had over twice the odds of not completing treatment and of belonging to a genotype cluster. US- and foreign-born homeless TB patients had respectively 8 and 12 times the odds of substance abuse. CONCLUSIONS Compared to the general population, homeless persons had an approximately 10-fold increase in TB incidence, were less likely to complete treatment and more likely to abuse substances. Public health outreach should target homeless populations to reduce the excess burden of TB in this population. PMID:24125444

XDR-TB: an outcome of programmatic management of TB in India.

PubMed

Mishra, Gyanshankar; Ghorpade, S V; Mulani, Jasmin

2014-01-01

A significantly strengthened Revised National Tuberculosis Control Programme (RNTCP) is currently operational in India. In this case-based commentary, we describe the plight of a patient who developed extensive drug-resistant tuberculosis (XDR-TB) despite having received treatment under the RNTCP for a long period. Our aim is to analyse the programmatic management of tuberculosis in India by highlighting and discussing various issues related to the treatment received by the patient. Further, the article explores whether there is a need to incorporate an ethical element into the RNTCP as it stands today.

Treatment outcome of tuberculosis patients in a clinic of Bangalore.

PubMed

Subramaniyam, S; Chadha, V K; Manuvel, C; Praseeja, P; Sharada, M A; Nagendra, N; Gupta, J

2014-07-01

A total of 112 cases (New = 101, previously treated = 11) were diagnosed as suffering from tuberculosis (TB) at a private clinic in Bangalore city. The clinic identified TB suspects, established diagnosis of TB, administered direct observation of treatment (DOT), maintained treatment cards and undertook defaulter retrieval actions as and when required. The Revised National Tuberculosis Control Programme (RNTCP) provided support in terms of sputum microscopy supply of patient-wise drug boxes and registration of patients. Ninety six (95.1%) of new cases and 10 (90.9%) of previously treated cases had successful treatment outcome. Most patients completed treatment within the prescribed period. No TB deaths were reported during the period of treatment.

Advances in Mycobacterium tuberculosis therapeutics discovery utlizing structural biology

PubMed Central

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

2013-01-01

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

Achievements and challenges of the World Bank Loan/Department for International Development grant-assisted Tuberculosis Control Project in China.

PubMed

Kong, Peng; Jiang, Xu; Zhang, Ben; Jiang, Shi-wen; Liu, Bo

2011-07-01

In March 2002, the government of China launched the World Bank Loan/ Department for International Development-supported Tuberculosis (TB) Control Project to reduce the prevalence and mortality of TB. The project generated promising results in policy development, strengthening of TB control systems, patient treatment success, funds management, and the introduction of legislation. In light of the global TB epidemic and control environment, it is useful to review the TB control priorities of the project, summarize the achievements and experiences around its implementation.

Paraspinal tuberculosis mimicking malignancy.

PubMed

Alherabi, Ameen Z; Marglani, Osama A; Gazzaz, Malak J; Abbas, Mohammed M

2013-12-01

Tuberculosis (TB) of the paraspinal muscles is a rare clinical entity. We present a case of an 18-year-old, Saudi male patient presenting with the clinical picture of a paraspinal mass that turned out to be paraspinal TB. It originated from the paraspinal tissues and muscles, and invaded the C6 and C7 vertebrae. Initially, it was highly suspicious for malignancy. A biopsy confirmed the diagnosis of TB, and the patient was treated successfully with anti-TB therapy. It is important to be aware that paraspinal TB can mimic malignancy.

Comparison of pulmonary and extrapulmonary tuberculosis in Nepal- a hospital-based retrospective study

PubMed Central

Sreeramareddy, Chandrashekhar T; Panduru, Kishore V; Verma, Sharat C; Joshi, Hari S; Bates, Michael N

2008-01-01

Background Studies from developed countries have reported on host-related risk factors for extra-pulmonary tuberculosis (EPTB). However, similar studies from high-burden countries like Nepal are lacking. Therefore, we carried out this study to compare demographic, life-style and clinical characteristics between EPTB and PTB patients. Methods A retrospective analysis was carried out on 474 Tuberculosis (TB) patients diagnosed in a tertiary care hospital in western Nepal. Characteristics of demography, life-style and clinical features were obtained from medical case records. Risk factors for being an EPTB patient relative to a PTB patient were identified using logistic regression analysis. Results The age distribution of the TB patients had a bimodal distribution. The male to female ratio for PTB was 2.29. EPTB was more common at younger ages (< 25 years) and in females. Common sites for EPTB were lymph nodes (42.6%) and peritoneum and/or intestines (14.8%). By logistic regression analysis, age less than 25 years (OR 2.11 95% CI 1.12–3.68) and female gender (OR 1.69, 95% CI 1.12–2.56) were associated with EPTB. Smoking, use of immunosuppressive drugs/steroids, diabetes and past history of TB were more likely to be associated with PTB. Conclusion Results suggest that younger age and female gender may be independent risk factors for EPTB in a high-burden country like Nepal. TB control programmes may target young and female populations for EPTB case-finding. Further studies are necessary in other high-burden countries to confirm our findings. PMID:18218115

Evaluating clinicians’ user experience and acceptability of LearnTB, a smartphone application for tuberculosis in India

PubMed Central

Pande, Tripti; Saravu, Kavitha; Temesgen, Zelalem; Seyoum, Al; Rai, Shipra; Rao, Raghavendra; Mahadev, Deekshith; Pai, Madhukar

2017-01-01

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<0.0001). Logistic regression analysis helped target items strongly influencing IU, such as “The use of the LearnTB application is compatible with my work habits” [OR =3.20 (1.04–9.84), P=0.004] and “The use of the LearnTB application could promote good clinical practice” [OR =5.23 (1.35–20.29); P=0.016]. Conclusion The first part of the study indicated high user experience of the LearnTB application. The TAM questionnaire (second part) explained a significant portion of the variance in clinicians’ IU the LearnTB application. The PU of the application has the highest impact on the clinicians’ IU the Learn TB application. This study provides a preliminary analysis of mobile health interventions for tuberculosis in India, and emphasizes the need for future research in this domain. PMID:28828377

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

PubMed

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

2018-01-01

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

Combination of gene expression patterns in whole blood discriminate between tuberculosis infection states

PubMed Central

2014-01-01

Background Genetic factors are involved in susceptibility or protection to tuberculosis (TB). Apart from gene polymorphisms and mutations, changes in levels of gene expression, induced by non-genetic factors, may also determine whether individuals progress to active TB. Methods We analysed the expression level of 45 genes in a total of 47 individuals (23 healthy household contacts and 24 new smear-positive pulmonary TB patients) in Addis Ababa using a dual colour multiplex ligation-dependent probe amplification (dcRT-MLPA) technique to assess gene expression profiles that may be used to distinguish TB cases and their contacts and also latently infected (LTBI) and uninfected household contacts. Results The gene expression level of BLR1, Bcl2, IL4d2, IL7R, FCGR1A, MARCO, MMP9, CCL19, and LTF had significant discriminatory power between sputum smear-positive TB cases and household contacts, with AUCs of 0.84, 0.81, 0.79, 0.79, 0.78, 0.76, 0.75, 0.75 and 0.68 respectively. The combination of Bcl2, BLR1, FCGR1A, IL4d2 and MARCO identified 91.66% of active TB cases and 95.65% of household contacts without active TB. The expression of CCL19, TGFB1, and Foxp3 showed significant difference between LTBI and uninfected contacts, with AUCs of 0.85, 0.82, and 0.75, respectively, whereas the combination of BPI, CCL19, FoxP3, FPR1 and TGFB1 identified 90.9% of QFT- and 91.6% of QFT+ household contacts. Conclusions Expression of single and especially combinations of host genes can accurately differentiate between active TB cases and healthy individuals as well as between LTBI and uninfected contacts. PMID:24885723

Tuberculosis and Indoor Biomass and Kerosene Use in Nepal: A Case–Control Study

PubMed Central

Pokhrel, Amod K.; Bates, Michael N.; Verma, Sharat C.; Joshi, Hari S.; Sreeramareddy, Chandrashekhar T.; Smith, Kirk R.

2010-01-01

Background In Nepal, tuberculosis (TB) is a major problem. Worldwide, six previous epidemiologic studies have investigated whether indoor cooking with biomass fuel such as wood or agricultural wastes is associated with TB with inconsistent results. Objectives Using detailed information on potential confounders, we investigated the associations between TB and the use of biomass and kerosene fuels. Methods A hospital-based case–control study was conducted in Pokhara, Nepal. Cases (n = 125) were women, 20–65 years old, with a confirmed diagnosis of TB. Age-matched controls (n = 250) were female patients without TB. Detailed exposure histories were collected with a standardized questionnaire. Results Compared with using a clean-burning fuel stove (liquefied petroleum gas, biogas), the adjusted odds ratio (OR) for using a biomass-fuel stove was 1.21 [95% confidence interval (CI), 0.48–3.05], whereas use of a kerosene-fuel stove had an OR of 3.36 (95% CI, 1.01–11.22). The OR for use of biomass fuel for heating was 3.45 (95% CI, 1.44–8.27) and for use of kerosene lamps for lighting was 9.43 (95% CI, 1.45–61.32). Conclusions This study provides evidence that the use of indoor biomass fuel, particularly as a source of heating, is associated with TB in women. It also provides the first evidence that using kerosene stoves and wick lamps is associated with TB. These associations require confirmation in other studies. If using kerosene lamps is a risk factor for TB, it would provide strong justification for promoting clean lighting sources, such as solar lamps. PMID:20368124

The social determinants of tuberculosis treatment adherence in a remote region of Papua New Guinea.

PubMed

Diefenbach-Elstob, Tanya; Plummer, David; Dowi, Robert; Wamagi, Sinba; Gula, Bisato; Siwaeya, Keyanato; Pelowa, Daniel; Siba, Peter; Warner, Jeffrey

2017-01-13

Papua New Guinea (PNG) is a diverse and culturally-rich country with severe infrastructural and health problems. Tuberculosis (TB) is widespread, and the number of cases with drug resistance is rising. Treatment adherence is known to be important for both effective treatment and limiting the emergence of drug resistance. The aim of this study was to construct a matrix of the factors that act as facilitators or barriers to TB treatment adherence in a remote region of PNG. The study was based in the Balimo region of the Western Province. People known to have undergone TB treatment, as well as staff involved in managing people with TB, were asked to participate in an in-depth interview about their experiences. Purposive sampling was used to identify a diverse range of participants, from different geographic locations, social backgrounds, and with successful and unsuccessful treatment outcomes. The interview data was analysed based on grounded theory methodology. The study identified a range of factors that influence TB treatment adherence, with these being classified as personal, systems, and sociocultural. These factors are presented along with suggested recommendations for adaptations to DOTS-based treatment in this region. Barriers included the challenges associated with travel to treatment sites, and the difficulties of undertaking treatment alongside the daily need to maintain subsistence food production. However, facilitators were also identified, including the positive influence of religious beliefs, and high confidence in the ability of DOTS-based treatment to cure TB. Documenting the wide range of factors that influence treatment adherence in a severely affected remote population will assist in improving TB control. These results provide impetus for further community-based efforts aimed at improving access to TB diagnosis and treatment, and maintaining successful treatment outcomes in the face of emerging drug resistance.

Pilot randomized trial of nutritional supplementation in patients with tuberculosis and HIV-tuberculosis coinfection receiving directly observed short-course chemotherapy for tuberculosis.

PubMed

Sudarsanam, T D; John, J; Kang, G; Mahendri, V; Gerrior, J; Franciosa, M; Gopal, S; John, K R; Wanke, C A; Muliyil, J

2011-06-01

To investigate the effects of nutritional supplementation on the outcome and nutritional status of south Indian patients with tuberculosis (TB) with and without human immunodeficiency virus (HIV) coinfection on anti-tuberculous therapy. Randomized controlled trial on the effect of a locally prepared cereal-lentil mixture providing 930 kcal and a multivitamin micronutrient supplement during anti-tuberculous therapy in 81 newly diagnosed TB alone and 22 TB-HIV-coinfected patients, among whom 51 received and 52 did not receive the supplement. The primary outcome evaluated at completion of TB therapy was outcome of TB treatment, as classified by the national programme. Secondary outcomes were body composition, compliance and condition on follow-up 1 year after cessation of TB therapy and supplementation. There was no significant difference in TB outcomes at the end of treatment, but HIV-TB coinfected individuals had four times greater odds of poor outcome than those with TB alone. Among patients with TB, 1/35 (2.9%) supplemented and 5/42(12%) of those not supplemented had poor outcomes, while among TB-HIV-coinfected individuals, 4/13 (31%) supplemented and 3/7 (42.8%) non-supplemented patients had poor outcomes at the end of treatment, and the differences were more marked after 1 year of follow-up. Although there was some trend of benefit for both TB alone and TB-HIV coinfection, the results were not statistically significant at the end of TB treatment, possibly because of limited sample size. Nutritional supplements in patients are a potentially feasible, low-cost intervention, which could impact patients with TB and TB-HIV. The public health importance of these diseases in resource-limited settings suggests the need for large, multi-centre randomized control trials on nutritional supplementation. © 2011 Blackwell Publishing Ltd.

Drug resistant tuberculosis in Saudi Arabia: an analysis of surveillance data 2014-2015.

PubMed

Al Ammari, Maha; Al Turaiki, Abdulrahman; Al Essa, Mohammed; Kashkary, Abdulhameed M; Eltigani, Sara A; Ahmed, Anwar E

2018-01-01

There is limited data that investigates the national rates of drug-resistant tuberculosis (TB) in Saudi Arabia.This study aimed to estimate the rates of multi-drug-resistant tuberculosis (MDR-TB), rifampicin-resistant tuberculosis (RR-TB), and monoresistance (MR) in Saudi Arabia. A retrospective cohort study was conducted on all TB cases reported to the National TB Control and Prevention Program (NTCPP) registry at the Saudi Ministry of Health between January 1, 2014 and December 31, 2015. A total of 2098 TB patients with positive TB cultures were included in the study. Subgroup analyses and multivariate binary logistic regression models were performed with IBM SPSS 23.0. Of the total TB cases, 4.4% (95% CI: 3.59%-5.40%) were found to have MDR-TB. The rates of MR were 3.8% (95% CI: 2.99%-4.67%) for ethambutol, 5.4% (95% CI: 4.50%-6.49%) for pyrazinamide, 10.2% (95% CI: 5.89%-11.52%) for isoniazid, 11% (95% CI: 9.70%-12.43%) for streptomycin, and 5.9% (95% CI: 4.90%-6.96%) for rifampicin. The high rates of MDR and RR-TB were found among the younger age group, female gender, and those who had a previous history of TB. We also discovered that renal failure tends to increase the risk of rifampicin resistance. National TB data in Saudi Arabia shows that the rate of MDR-TB was similar to the global rate reported by the World Health Organization (WHO). It is a relatively high rate as compared to Western countries. The proportion of MDR/RR-TB patients tends to be higher in the younger age group, female gender, and in patients with a previous history of TB treatment. Effective strategies for prevention of all multi-drug-resistant TB cases are warranted.

Low Dose Aerosol Fitness at the Innate Phase of Murine Infection Better Predicts Virulence amongst Clinical Strains of Mycobacterium tuberculosis

PubMed Central

Caceres, Neus; Llopis, Isaac; Marzo, Elena; Prats, Clara; Vilaplana, Cristina; de Viedma, Dario Garcia; Samper, Sofía; Lopez, Daniel; Cardona, Pere-Joan

2012-01-01

Background Evaluation of a quick and easy model to determine the intrinsic ability of clinical strains to generate active TB has been set by assuming that this is linked to the fitness of Mycobacterium tuberculosis strain at the innate phase of the infection. Thus, the higher the bacillary load, the greater the possibility of inducting liquefaction, and thus active TB, once the adaptive response is set. Methodology/Principal Findings The virulence of seven clinical Mycobacterium tuberculosis strains isolated in Spain was tested by determining the bacillary concentration in the spleen and lung of mice at weeks 0, 1 and 2 after intravenous (IV) inoculation of 104 CFU, and by determining the growth in vitro until the stationary phase had been reached. Cord distribution automated analysis showed two clear patterns related to the high and low fitness in the lung after IV infection. This pattern was not seen in the in vitro fitness tests, which clearly favored the reference strain (H37Rv). Subsequent determination using a more physiological low-dose aerosol (AER) inoculation with 102 CFU showed a third pattern in which the three best values coincided with the highest dissemination capacity according to epidemiological data. Conclusions/Significance The fitness obtained after low dose aerosol administration in the presence of the innate immune response is the most predictive factor for determining the virulence of clinical strains. This gives support to a mechanism of the induction of active TB derived from the dynamic hypothesis of latent tuberculosis infection. PMID:22235258

Migration-related tuberculosis: epidemiology and characteristics of tuberculosis cases originating outside the European Union and European Economic Area, 2007 to 2013.

PubMed

Ködmön, Csaba; Zucs, Phillip; van der Werf, Marieke J

2016-01-01

Migrants arriving from high tuberculosis (TB)-incidence countries may pose a significant challenge to TB control programmes in the host country. TB surveillance data for 2007-2013 submitted to the European Surveillance System were analysed. Notified TB cases were stratified by origin and reporting country. The contribution of migrant TB cases to the TB epidemiology in EU/EEA countries was analysed. Migrant TB cases accounted for 17.4% (n = 92,039) of all TB cases reported in the EU/EEA in 2007-2013, continuously increasing from 13.6% in 2007 to 21.8% in 2013. Of 91,925 migrant cases with known country of origin, 29.3% were from the Eastern Mediterranean, 23.0% from south-east Asia, 21.4% from Africa, 13.4% from the World Health Organization European Region (excluding EU/EEA), and 12.9% from other regions. Of 46,499 migrant cases with known drug-susceptibility test results, 2.9% had multidrug-resistant TB, mainly (51.7%) originating from the European Region. The increasing contribution of TB in migrants from outside the EU/EEA to the TB burden in the EU/EEA is mainly due to a decrease in native TB cases. Especially in countries with a high proportion of TB cases in non-EU/EEA migrants, targeted prevention and control initiatives may be needed to progress towards TB elimination.

[Factors associated to pulmonary tuberculosis in patients with diabetes mellitus from Veracruz, México].

PubMed

Pérez-Navarro, Lucía Montserrat; Fuentes-Domínguez, Francisco; Morales-Romero, Jaime; Zenteno-Cuevas, Roberto

2011-01-01

In Mexico, 20% of cases of tuberculosis (TB) are associated with diabetes mellitus (DM). However, the behavior of the factors related to this comorbidity is unknown, so the aim of this study was to estimate the risk factors and outcome for TB-DM in a population from the state of Veracruz, Mexico. We developed a double-design study: cases and controls for the estimation of risk factors, and a retrospective cohort for the outcome factors. The populations surveyed were 67 patients with the comorbidity TB-DB and 109 with TB. The risk factors for tuberculosis in the diabetic population studied were: age ≥ 35 with an OR of 2.5 (95% CI: 1.4-4.3) and IMC ≥ 25 with an OR of 8.5 (95% CI: 3.1-23.3). According to the outcome variables, the patients with TB-DM showed an increased risk of 2.8 (95% CI: 2.2-3.4) for the development of drug resistance against tuberculosis. In conclusion, age and overweight are important risk factors, and drug resistance is an important outcome factor for the binomial TB-DM in the population from Veracruz. This information will have important effects on the development of surveillance programs against TB, with emphasis on the characteristics of the diabetic population.

Risk factors and timing of default from treatment for non-multidrug-resistant tuberculosis in Moldova.

PubMed

Jenkins, H E; Ciobanu, A; Plesca, V; Crudu, V; Galusca, I; Soltan, V; Cohen, T

2013-03-01

The Republic of Moldova, in Eastern Europe, has among the highest reported nationwide proportions of tuberculosis (TB) patients with multidrug-resistant tuberculosis (MDR-TB) worldwide. Default has been associated with increased mortality and amplification of drug resistance, and may contribute to the high MDR-TB rates in Moldova. To assess risk factors and timing of default from treatment for non-MDR-TB from 2007 to 2010. A retrospective analysis of routine surveillance data on all non-MDR-TB patients reported. A total of 14.7% of non-MDR-TB patients defaulted from treatment during the study period. Independent risk factors for default included sociodemographic factors, such as homelessness, living alone, less formal education and spending substantial time outside Moldova in the year prior to diagnosis; and health-related factors such as human immunodeficiency virus co-infection, greater lung pathology and increasing TB drug resistance. Anti-tuberculosis treatment is usually initiated within an institutional setting in Moldova, and the default risk was highest in the month following the phase of hospitalized treatment (among civilians) and after leaving prison (among those diagnosed while incarcerated). Targeted interventions to increase treatment adherence for patients at highest risk of default, and improving the continuity of care for patients transitioning from institutional to community care may substantially reduce risk of default.

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

PubMed Central

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

2014-01-01

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

[Cluster of multidrug-resistant tuberculosis cases in a school of the district of Ica, Peru].

PubMed

Torres, Julio; Sardón, Victoria; Soto, Mirtha G; Anicama, Rolado; Arroyo-Hernández, Hugo; Munayco, César V

2011-01-01

We describe the evolution and features of a cluster of Multidrug-resistant tuberculosis (MDR TB) cases that occurred in 2001, in a school located in a sub-urban area of the district of Ica, Peru. We identified 15 students related before becoming infected with tuberculosis. The mean age of the cluster was 15 years. A total of 12 students were MDR-TB cases and 7 were drug-resistant to 5 first-line drugs (RHEZS). Five out of the 15 cases received at least 3 different anti-tuberculosis treatment schemes. The average treatment duration was 37 months (minimum 21 and maximum 59 months). A total of 13 cases recovered and 2 died. This study describes a cluster of MDR -TB cases in an educational facility, which due to the epidemiological link and time presentation, is probably an outbreak of MDR TB with a satisfactory outcome after prolonged treatment.

Fighting an old disease with modern tools: characteristics and molecular detection methods of drug-resistant Mycobacterium tuberculosis.

PubMed

Engström, Anna

2016-01-01

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.

Modulation of dendritic cell and monocyte subsets in tuberculosis-diabetes co-morbidity upon standard tuberculosis treatment

PubMed Central

Kumar, Nathella Pavan; Moideen, Kadar; Sivakumar, Shanmugam; Menon, Pradeep A; Viswanathan, Vijay; Kornfeld, Hardy; Babu, Subash

2016-01-01

Type 2 diabetes mellitus (DM) is a major risk factor for the development of active pulmonary tuberculosis (PTB), with development of DM pandemic in countries where tuberculosis (TB) is also endemic. However, the effect of anti-TB treatment on the changes in dentritic cell (DC) and monocyte subset phenotype in TB-DM co-morbidity is not well understood. In this study, we characterized the frequency of DC and monocyte subsets in individuals with PTB with (PTB-DM) or without coincident diabetes mellitus (PTB-NDM) before, during and after completion of anti-TB treatment. PTB-DM is characterized by diminished frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes at baseline and 2 months of anti-TB treatment but not following 6 months of treatment completion in comparison to PTB-NDM. DC and monocyte subsets exhibit significant but borderline correlation with fasting blood glucose and glycated hemoglobin levels. Finally, while minor changes in the DC and monocyte compartment were observed at 2 months of treatment, significantly increased frequencies of plasmacytoid and myeloid DCs and classical and intermediate monocytes were observed at the successful completion of anti-TB treatment. Our data show that coincident diabetes alters the frequencies of innate subset distribution of DC and monocytes in TB-DM co-morbidity and suggests that most of these changes are reversible following anti-TB therapy. PMID:27865391

Striking the right immunological balance prevents progression of tuberculosis.

PubMed

Vyas, Shachi Pranjal; Goswami, Ritobrata

2017-12-01

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

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

PubMed Central

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

2015-01-01

Background Xpert MTB/RIF, the first automated molecular test for tuberculosis, is transforming the diagnostic landscape in high-burden settings. This study assessed the impact of up-front Xpert MTB/RIF testing on detection of pulmonary tuberculosis (PTB) and rifampicin-resistant PTB (DR-TB) cases in India. Methods This demonstration study was implemented in 18 sub-district level TB programme units (TUs) in India in diverse geographic and demographic settings covering a population of 8.8 million. A baseline phase in 14 TUs captured programmatic baseline data, and an intervention phase in 18 TUs had Xpert MTB/RIF offered to all presumptive TB patients. We estimated changes in detection of TB and DR-TB, the former using binomial regression models to adjust for clustering and covariates. Results In the 14 study TUs, which participated in both phases, 10,675 and 70,556 presumptive TB patients were enrolled in the baseline and intervention phase, respectively, and 1,532 (14.4%) and 14,299 (20.3%) bacteriologically confirmed PTB cases were detected. The implementation of Xpert MTB/RIF was associated with increases in both notification rates of bacteriologically confirmed TB cases (adjusted incidence rate ratio [aIRR] 1.39; CI 1.18-1.64), and proportion of bacteriological confirmed TB cases among presumptive TB cases (adjusted risk ratio (aRR) 1.33; CI 1.6-1.52). Compared with the baseline strategy of selective drug-susceptibility testing only for PTB cases at high risk of drug-resistant TB, Xpert MTB/RIF implementation increased rifampicin resistant TB case detection by over fivefold. Among, 2765 rifampicin resistance cases detected, 1055 were retested with conventional drug susceptibility testing (DST). Positive predictive value (PPV) of rifampicin resistance detected by Xpert MTB/RIF was 94.7% (CI 91.3-98.1), in comparison to conventional DST. Conclusion Introduction of Xpert MTB/RIF as initial diagnostic test for TB in public health facilities significantly increased case-notification rates of all bacteriologically confirmed TB by 39% and rifampicin-resistant TB case notification by fivefold. PMID:25996389

Heparin-Binding Haemagglutinin, a New Tool for the Detection of Latent Mycobacterium tuberculosis Infection in Hemodialysis Patients

PubMed Central

Dessein, Rodrigue; Corbière, Véronique; Nortier, Joëlle; Dratwa, Max; Gastaldello, Karine; Pozdzik, Agnieszka; Lecher, Sophie; Grandbastien, Bruno; Locht, Camille; Mascart, Françoise

2013-01-01

Background Patients with end-stage renal disease (ESRD) and latently infected with Mycobacterium tuberculosis (LTBI) are at higher risk to develop tuberculosis (TB) than healthy subjects. Interferon-gamma release assays (IGRAs) were reported to be more sensitive than tuberculin skin tests for the detection of infected individuals in dialysis patients. Methods On 143 dialysis patients prospectively enrolled, we compared the results from the QuantiFERON®-TB Gold assay (QFT), to those of an IGRA in response to in vitro stimulation of circulating mononuclear cells with the mycobacterial latency antigen Heparin-Binding Haemagglutinin purified from Mycobacterium bovis BCG (native HBHA, nHBHA). Results Seven patients had a past history of active TB and 1 had an undetermined result with both IGRAs. Among the other 135 patients, 94 had concordant results with the QFT and nHBHA-IGRA, 40.0% being negative and therefore not latently infected, and 29.6% being positive and thus LTBI. Discrepant results between these tests were found for 36 patients positive only with the nHBHA-IGRA and 5 only with the QFT. Conclusions The nHBHA-IGRA is more sensitive than the QFT for the detection of LTBI dialysis patients, and follow-up of the patients will allow us to define the clinical significance of discrepant results between the nHBHA-IGRA and the QFT. PMID:23940693

MIRU-VNTR typing of drug-resistant tuberculosis isolates in Greece.

PubMed

Rovina, Nikoletta; Karabela, Simona; Constantoulakis, Pantelis; Michou, Vassiliki; Konstantinou, Konstantinos; Sgountzos, Vassileios; Roussos, Charis; Poulakis, Nikolaos

2011-08-01

The increasing immigration rate in Greece from countries with a high prevalence of Mycobacterium tuberculosis (MTB) and multidrug-resistant tuberculosis (MDR-TB) may have an impact οn the number of MDR-TB cases in Greece. The aim of this study was to genotypically characterize the MTB isolates from patients with pulmonary drug-resistant tuberculosis (DR-TB) in Greece, and to determine whether there is any association between the prevalent genotypes and drug resistance. Fifty-three drug-resistant MTB strains isolated from culture specimens of clinical material from native Greeks and immigrant patients with pulmonary tuberculosis were genotyped using the mycobacterial interspersed repetitive units-variable number of tandem repeats (MIRU-VNTR) method. The phylogenetically distinct groups of isolates identified were: the Beijing (34%), the LAM (11%), the Haarlem (24.5%), the Uganda I (9.4%), the Ural (3.8%), the Delhi/CAS (9.4%) and the Cameroon (3.8%) families. Greek patients were more likely to have monoresistant and polyresistant TB with the most prevalent isolates belonging to the Haarlem family. Among foreign-born patients with MDR-TB, the most prevalent genotypes belonged to the Beijing family. MIRU-VNTR rapidly obtained clinically useful genotyping data, by characterizing clonal MTB heterogeneity in the isolated strains. Our results underline the need for more effective antituberculosis control programs in order to control the expansion of DR-TB in Greece.

[Access barriers to comprehensive care for people affected by tuberculosis and human immunodeficiency virus coinfection in Peru, 2010-2015].

PubMed

García-Fernández, Lisset; Benites, Carlos; Huamán, Byelca

2017-05-25

Identify the programmatic barriers that hinder access to comprehensive care of patients with tuberculosis and human immunodeficiency virus (TB/HIV) coinfection. This is a mixed-method study. Qualitative research was conducted via in-depth interviews with key actors and the quantitative component involved cross-sectional descriptive analysis of programmatic data from 2010-2015 on tuberculosis and HIV programs at health facilities in the cities of Lima and Iquitos. Twenty-two key actors in seven establishments were interviewed. The identified barriers were: little or no coordination between tuberculosis and HIV teams, separate management of tuberculosis and HIV cases at different levels of care, insufficient financing, limited or poorly trained human resources, and lack of an integrated information system. It was found that HIV screening in TB patients increased (from 18.8% in 2011 to 95.2% in 2015), isoniazid coverage of HIV patients declined (from 62% to 9%), and the proportion of deaths among TB/HIV coinfection cases averaged 20%. There is poor coordination between HIV and TB health strategies. Management of TB/HIV coinfection is fragmented into different levels of care, which has an impact on comprehensive patient care. As a result of this research, a technical document was prepared to establish joint procedures that should be implemented to improve comprehensive care of TB/HIV coinfection.

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

PubMed

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

2018-05-01

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