Evaluation of genotype MTBDRplus VER 2.0 line probe assay for the detection of MDR-TB in smear positive and negative sputum samples.

PubMed

Meaza, Abyot; Kebede, Abebaw; Yaregal, Zelalem; Dagne, Zekarias; Moga, Shewki; Yenew, Bazezew; Diriba, Getu; Molalign, Helina; Tadesse, Mengistu; Adisse, Desalegn; Getahun, Muluwork; Desta, Kassu

2017-04-17

Multi drug resistant tuberculosis (MDR-TB) poses formidable challenges to TB control due to its complex diagnostic and treatment challenges and often associated with a high rate of mortality. Accurate and rapid detection of MDR-TB is critical for timely initiation of treatment. Line Probe Assay (LPA) is a qualitative in vitro diagnostic test based on DNA-STRIP technology for the identification of the M. tuberculosis complex and its resistance to rifampicin (RMP) and/or isoniazid (INH). Hain Lifescience, GmbH, Germany has improved the sensitivity of Genotype MTBDRplus VER 2.0 LPA for the detection of MDR-TB; with the possibility of applying the tool in smear negative sputum samples. A cross sectional study was conducted on 274 presumptive MDR-TB patients referred to the National TB Reference Laboratory (NTRL), Ethiopian Public Health Institute (EPHI) who submitted sputum samples for laboratory diagnosis of drug resistant-TB testing. Seventy-two smear and culture positive samples processed in smear positive direct LPA category and 197 smear negative sputum samples were processed for direct LPA. Among the smear negative samples 145 (73.6%) were culture negative and 26 (13.2%) were culture positive. All specimens were processed using NALC-NaOH method and ZN smear microscopy done from sediments. Genotype MTBDRplus VER 2.0 done from processed sputum sediments and the result was compared against the reference, BACTEC MGIT 960 culture and DST. Sensitivity, specificity, PPV and NPV of Genotype MTBDRplus VER 2.0 assay was determined and P-value <0.05 was considered as statistically significant. The sensitivity, specificity, PPV and NPV of Genotype MTBDRplus VER 2.0 LPA were 96.4, 100, 100 and 96.9%, respectively for the detection of MDR-TB from direct smear positive sputum samples. The sensitivity, specificity, PPV and NPV of Genotype MTBDR plus VER 2.0 LPA were 77.8, 97.2, 82.4 and 97.2%, respectively, for the detection of M. tuberculosis from direct smear negative sputum

Impact of Xpert MTB/RIF for TB diagnosis in a primary care clinic with high TB and HIV prevalence in South Africa: a pragmatic randomised trial.

PubMed

Cox, Helen S; Mbhele, Slindile; Mohess, Neisha; Whitelaw, Andrew; Muller, Odelia; Zemanay, Widaad; Little, Francesca; Azevedo, Virginia; Simpson, John; Boehme, Catharina C; Nicol, Mark P

2014-11-01

Xpert MTB/RIF is approved for use in tuberculosis (TB) and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert under routine conditions in settings with high TB burden. A pragmatic prospective cluster-randomised trial of Xpert for all individuals with presumptive (symptomatic) TB compared to the routine diagnostic algorithm of sputum microscopy and limited use of culture was conducted in a large TB/HIV primary care clinic. The primary outcome was the proportion of bacteriologically confirmed TB cases not initiating TB treatment by 3 mo after presentation. Secondary outcomes included time to TB treatment and mortality. Unblinded randomisation occurred on a weekly basis. Xpert and smear microscopy were performed on site. Analysis was both by intention to treat (ITT) and per protocol. Between 7 September 2010 and 28 October 2011, 1,985 participants were assigned to the Xpert (n = 982) and routine (n = 1,003) diagnostic algorithms (ITT analysis); 882 received Xpert and 1,063 routine (per protocol analysis). 13% (32/257) of individuals with bacteriologically confirmed TB (smear, culture, or Xpert) did not initiate treatment by 3 mo after presentation in the Xpert arm, compared to 25% (41/167) in the routine arm (ITT analysis, risk ratio 0.51, 95% CI 0.33-0.77, p = 0.0052). The yield of bacteriologically confirmed TB cases among patients with presumptive TB was 17% (167/1,003) with routine diagnosis and 26% (257/982) with Xpert diagnosis (ITT analysis, risk ratio 1.57, 95% CI 1.32-1.87, p<0.001). This difference in diagnosis rates resulted in a higher rate of treatment initiation in the Xpert arm: 23% (229/1,003) and 28% (277/982) in the routine and Xpert arms, respectively (ITT analysis, risk ratio 1.24, 95% CI 1.06-1.44, p = 0.013). Time to treatment initiation was improved overall (ITT analysis, hazard ratio 0.76, 95% CI 0.63-0.92, p = 0.005) and among HIV-infected participants (ITT analysis, hazard ratio 0.67, 95% CI 0.53-0.85, p = 0

Diagnostic utility of a line probe assay for multidrug resistant-TB in smear-negative pulmonary tuberculosis.

PubMed

Singh, Binit Kumar; Sharma, Surendra K; Sharma, Rohini; Sreenivas, Vishnubhatla; Myneedu, Vithal P; Kohli, Mikashmi; Bhasin, Dinkar; Sarin, Sanjay

2017-01-01

To evaluate the performance of Genotype MTBDRplus VER 2.0 in the diagnosis of Mycobacterium tuberculosis (MTB) in sputum smear-negative pulmonary TB cases. A total of 572 Ziehl-Neelsen sputum smear-negative samples were selected and subjected to line probe assay (Genotype MTBDRplus VER 2.0), and culture in mycobacterial growth indicator tube (MGIT-960). Immunochromatographic test was used to confirm the MTB-complex (MTBC) in culture-positive samples and phenotypic drug-susceptibility testing was done using MGIT-960. The line probe assay was able to diagnose MTBC in 38.2% (213/558) of specimens after excluding 14 nontuberculous mycobacteria. Sensitivity and specificity of the assay were 68.4% and 89.3% respectively, considering MGIT-960 culture as gold standard after excluding contaminated and invalid results. On comparing with composite reference standard, the assay had 71.5% sensitivity and 100% specificity in the diagnosis of tuberculosis. The sensitivity and specificity for detecting resistance to rifampicin (RMP) were 100% and 99.24% respectively and for resistance to isoniazid (INH) were 97.62% and 98.55%, respectively. Genotype MTBDRplus VER 2.0 is a rapid and precise diagnostic tool for detection of MTB in sputum smear-negative samples. It also facilitates accurate diagnosis of RMP and INH resistance within turn around-time.

Gender and socio-cultural determinants of delay to diagnosis of TB in Bangladesh, India and Malawi.

PubMed

Gosoniu, G D; Ganapathy, S; Kemp, J; Auer, C; Somma, D; Karim, F; Weiss, M G

2008-07-01

Tuberculosis (TB) control programmes in Bangladesh, India and Malawi. To compare the interval from symptom onset to diagnosis of TB for men and women, and to assess socio-cultural and gender-related features of illness explaining diagnostic delay. Semi-structured Explanatory Model Interview Catalogue (EMIC) interviews were administered to 100 or more patients at each site, assessing categories of distress, perceived causes and help seeking. Based on time from initial symptoms to diagnosis of TB, patients were classified with problem delay (>90 days), timely diagnosis (< or =30 days) or moderate delay. EMIC interview data were analysed to explain problem delay. The median interval from symptom onset to diagnosis was longest in India and shortest in Malawi. With adjustment for confounding, female sex (Bangladesh), and status of married woman (India) and housewife (Malawi) were associated with problem delay. Prominent non-specific symptoms--chest pain (Bangladesh) and breathlessness (Malawi)--were also significant. Cough in India, widely associated with TB, was associated with timely diagnosis. Sanitation as a perceived cause linked to poor urban conditions was associated with delayed diagnosis in India. Specific prior help seeking with circuitous referral patterns was identified. The study identified gender- and illness-related features of diagnostic delay. Further research distinguishing patient and provider delay is needed.

Prospective Comparison of QFT-GIT and T-SPOT.TB Assays for Diagnosis of Active Tuberculosis.

PubMed

Du, Fengjiao; Xie, Li; Zhang, Yonghong; Gao, Fei; Zhang, Huibin; Chen, Wei; Sun, Bingqi; Sha, Wei; Fang, Yong; Jia, Hongyan; Xing, Aiying; Du, Boping; Zheng, Li; Gao, Mengqiu; Zhang, Zongde

2018-04-12

T-SPOT.TB and QuantiFERON-TB Gold In-Tube (QFT-GIT) tests, as two commercial blood assays for diagnosing active tuberculosis (ATB), are not yet fully validated. Especially, there are no reports on comparing the efficacy between the two tests in the same population in China. A multicenter, prospective comparison study was undertaken at four hospitals specializing in pulmonary diseases. A total of 746 suspected pulmonary TB were enrolled and categorized, including 185 confirmed TB, 298 probable TB and 263 non-TB. Of 32 patients with indeterminate test results (ITRs), age and underlying disease were associated with the rate of ITRs. Furthermore, the rate of ITRs determined by T-SPOT.TB was lower than QFT-GIT (0.4% vs. 4.3%, P < 0.01). When excluding ITRs, the sensitivities of T-SPOT.TB and QFT-GIT were 85.2% and 84.8%, and specificities of 63.4% and 60.5%, respectively in the diagnosis of ATB. The two assays have an overall agreement of 92.3%, but exhibited a poor linear correlation (r 2  = 0.086) between the levels of interferon-γ release detected by the different assays. Although having some heterogeneity in detecting interferon-γ release, both the QFT-GIT and T-SPOT.TB demonstrated high concordance in diagnosing ATB. However, neither of them showed suitability in the definitive diagnosis of the disease.

Front-loaded smear microscopy for the diagnosis of pulmonary TB in Tripoli, Libya.

PubMed

Gammo, Mohamed; Lamaric, Widad; Hadida, Mukhtar; Abuazza, Aida; Askar, Nabil A; Yassin, Mohammed A; Cuevas, Luis E

2013-02-01

Diagnosis of pulmonary TB by conventional smear microscopy requires patient attendance on 2 consecutive days. We investigated whether collecting sputum on-the-spot for smear microscopy on the day the patient presented was as sensitive and specific for diagnosis as the conventional spot-morning-spot scheme. We enrolled 412 adults who presented between January 2009 and October 2010 at the National Centre for TB Control in Tripoli, Libya, with cough of >2 weeks' duration, into a cross-sectional survey collecting four sputum specimens: on-the-spot and Xspot on Day 1; morning and on-the-spot on Day 2. 97 (24%) of 401 culture results were culture positive. Spot-Xspot and spot-morning smear microscopy had, respectively, 65% and 66% sensitivity and 97% and 96% specificity (p > 0.5). Spot-Xspot-morning and Spot-morning-spot smear-microscopy had, respectively, 67% and 66% sensitivity and 96% and 96% specificity (p > 0.5). For the diagnosis of pulmonary TB, the sensitivity and specificity of front-loaded (same-day) smear microscopy is similar to that of the standard smear microscopy scheme.

Evaluation of a diagnostic flow chart applying medical thoracoscopy, adenosine deaminase and T-SPOT.TB in diagnosis of tuberculous pleural effusion.

PubMed

He, Y; Zhang, W; Huang, T; Wang, X; Wang, M

2015-10-01

To evaluate a diagnostic flow chart applying medical thoracoscoy (MT), adenosine deaminase (ADA) and T-SPOT.TB in diagnosis of tuberculous pleural effusion (TPE) at a high TB burden country. 136 patients with pleural effusion (PE) were enrolled and divided into TPE and Non-TPE group. MT (histology), PE ADA and T-SPOT.TB were conducted on all patients. ROC analysis was performed for the best cut-off value of PE ADA in detection of TPE. The diagnostic flow chart applying MT, ADA and T-SPOT.TB was evaluated for improving the limitations of each diagnostic method. ROC analysis showed that the best cut-off value of PE ADA was 30U/L. The sensitivity and specificity of these tests were calculated respectively to be: 71.4% (58.5%-81.6%) and 100% (95.4-100.0%) for MT, 92.9% (83.0-97.2%) and 68.8% (57.9-77.9%) for T-SPOT.TB, and 80.0% (69.6-88.1%) and 92.9% (82.7-98.0%) for PE ADA. The sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value and negative predictive value of the diagnostic flow chart were 96.4% (87.9-99.0%), 96.3% (89.6-98.7%), 25.714, 0.037, 97.4 and 94.9, respectively. The diagnostic flow chart applying MT, ADA and T-SPOT.TB is an accurate and rapid diagnostic method in detection of TPE.

Impact of Xpert MTB/RIF for TB Diagnosis in a Primary Care Clinic with High TB and HIV Prevalence in South Africa: A Pragmatic Randomised Trial

PubMed Central

Cox, Helen S.; Mbhele, Slindile; Mohess, Neisha; Whitelaw, Andrew; Muller, Odelia; Zemanay, Widaad; Little, Francesca; Azevedo, Virginia; Simpson, John; Boehme, Catharina C.; Nicol, Mark P.

2014-01-01

Background Xpert MTB/RIF is approved for use in tuberculosis (TB) and rifampicin-resistance diagnosis. However, data are limited on the impact of Xpert under routine conditions in settings with high TB burden. Methods and Findings A pragmatic prospective cluster-randomised trial of Xpert for all individuals with presumptive (symptomatic) TB compared to the routine diagnostic algorithm of sputum microscopy and limited use of culture was conducted in a large TB/HIV primary care clinic. The primary outcome was the proportion of bacteriologically confirmed TB cases not initiating TB treatment by 3 mo after presentation. Secondary outcomes included time to TB treatment and mortality. Unblinded randomisation occurred on a weekly basis. Xpert and smear microscopy were performed on site. Analysis was both by intention to treat (ITT) and per protocol. Between 7 September 2010 and 28 October 2011, 1,985 participants were assigned to the Xpert (n = 982) and routine (n = 1,003) diagnostic algorithms (ITT analysis); 882 received Xpert and 1,063 routine (per protocol analysis). 13% (32/257) of individuals with bacteriologically confirmed TB (smear, culture, or Xpert) did not initiate treatment by 3 mo after presentation in the Xpert arm, compared to 25% (41/167) in the routine arm (ITT analysis, risk ratio 0.51, 95% CI 0.33–0.77, p = 0.0052). The yield of bacteriologically confirmed TB cases among patients with presumptive TB was 17% (167/1,003) with routine diagnosis and 26% (257/982) with Xpert diagnosis (ITT analysis, risk ratio 1.57, 95% CI 1.32–1.87, p<0.001). This difference in diagnosis rates resulted in a higher rate of treatment initiation in the Xpert arm: 23% (229/1,003) and 28% (277/982) in the routine and Xpert arms, respectively (ITT analysis, risk ratio 1.24, 95% CI 1.06–1.44, p = 0.013). Time to treatment initiation was improved overall (ITT analysis, hazard ratio 0.76, 95% CI 0.63–0.92, p = 0.005) and among HIV-infected participants

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

PubMed

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

2017-06-01

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

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

PubMed Central

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

2006-01-01

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

Evaluation of FASTPlaqueTB to diagnose smear-negative tuberculosis in a peripheral clinic in Kenya.

PubMed

Bonnet, M; Gagnidze, L; Varaine, F; Ramsay, A; Githui, W; Guerin, P J

2009-09-01

To evaluate the performance and feasibility of FASTPlaqueTB in smear-negative tuberculosis (TB) suspects in a peripheral clinic after laboratory upgrading. Patients with cough > or=2 weeks, two sputum smear-negative results, no response to 1 week of amoxicillin and abnormal chest X-ray were defined as smear-negative suspects. One sputum sample was collected, decontaminated and divided into two: half was tested with FASTPlaqueTB in the clinic laboratory and the other half was cultured on Löwenstein-Jensen medium in the Kenyan Medical Research Institute. Test sensitivity and specificity were evaluated in all patients and in human immunodeficiency virus (HIV) infected patients. Feasibility was assessed by the contamination rate and the resources required to upgrade the laboratory. Of 208 patients included in the study, 56.2% were HIV-infected. Of 203 FASTPlaqueTB tests, 95 (46.8%) were contaminated, which interfered with result interpretation and led to the interruption of the study. Sensitivity and specificity were respectively 31.2% (95%CI 12.1-58.5) and 94.9% (95%CI 86.8-98.4) in all patients and 33.3% (95%CI 9.9-65.1) and 93.9% (95%CI 83.1-98.7) in HIV-infected patients. Upgrading the laboratory cost euro 20,000. FASTPlaqueTB did not perform satisfactorily in this setting. If contamination can be reduced, in addition to laboratory upgrading, its introduction in peripheral clinics would require further assessment in smear-negative and HIV co-infected patients and test adaptation for friendlier use.

The economic burden of TB diagnosis and treatment in South Africa.

PubMed

Foster, Nicola; Vassall, Anna; Cleary, Susan; Cunnama, Lucy; Churchyard, Gavin; Sinanovic, Edina

2015-04-01

Social protection against the cost of illness is a central policy objective of Universal Health Coverage and the post-2015 Global strategy for Tuberculosis (TB). Understanding the economic burden associated with TB illness and care is key to identifying appropriate interventions towards achieving this target. The aims of this study were to identify points in patient pathways from start of TB symptoms to treatment completion where interventions could be targeted to reduce the economic impact on patients and households, and to identify those most vulnerable to these costs. Two cohorts of patients accessing TB services from ten clinics in four provinces in South Africa were surveyed between July 2012 and June 2013. One cohort of 351 people with suspected TB were interviewed at the point of receiving a TB diagnostic and followed up six months later. Another cohort of 168 patients on TB treatment, at the same ten facilities, was interviewed at two-months and five-months on treatment. Patients were asked about their health-seeking behaviour, associated costs, income loss, and coping strategies used. Patients incurred the greatest share of TB episode costs (41%) prior to starting treatment, with the largest portion of these costs being due to income loss. Poorer patients incurred higher direct costs during treatment than those who were less poor but only 5% of those interviewed were accessing cash-transfers during treatment. Indirect costs accounted for 52% of total episode cost. Despite free TB diagnosis and care in South Africa, patients incur substantial direct and indirect costs particularly prior to starting treatment. The poorest group of patients were incurring higher costs, with fewer resources to pay for it. Both the direct and indirect cost of illness should be taken into account when setting levels of financial protection and social support, to prevent TB illness from pushing the poor further into poverty. Copyright © 2015 The Authors. Published by Elsevier

Nucleic Acid Amplification Testing and Sequencing Combined with Acid-Fast Staining in Needle Biopsy Lung Tissues for the Diagnosis of Smear-Negative Pulmonary Tuberculosis.

PubMed

Jiang, Faming; Huang, Weiwei; Wang, Ye; Tian, Panwen; Chen, Xuerong; Liang, Zongan

2016-01-01

Smear-negative pulmonary tuberculosis (PTB) is common and difficult to diagnose. In this study, we investigated the diagnostic value of nucleic acid amplification testing and sequencing combined with acid-fast bacteria (AFB) staining of needle biopsy lung tissues for patients with suspected smear-negative PTB. Patients with suspected smear-negative PTB who underwent percutaneous transthoracic needle biopsy between May 1, 2012, and June 30, 2015, were enrolled in this retrospective study. Patients with AFB in sputum smears were excluded. All lung biopsy specimens were fixed in formalin, embedded in paraffin, and subjected to acid-fast staining and tuberculous polymerase chain reaction (TB-PCR). For patients with positive AFB and negative TB-PCR results in lung tissues, probe assays and 16S rRNA sequencing were used for identification of nontuberculous mycobacteria (NTM). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of PCR and AFB staining were calculated separately and in combination. Among the 220 eligible patients, 133 were diagnosed with TB (men/women: 76/57; age range: 17-80 years, confirmed TB: 9, probable TB: 124). Forty-eight patients who were diagnosed with other specific diseases were assigned as negative controls, and 39 patients with indeterminate final diagnosis were excluded from statistical analysis. The sensitivity, specificity, PPV, NPV, and accuracy of histological AFB (HAFB) for the diagnosis of smear-negative were 61.7% (82/133), 100% (48/48), 100% (82/82), 48.5% (48/181), and 71.8% (130/181), respectively. The sensitivity, specificity, PPV, and NPV of histological PCR were 89.5% (119/133), 95.8% (46/48), 98.3% (119/121), and 76.7% (46/60), respectively, demonstrating that histological PCR had significantly higher accuracy (91.2% [165/181]) than histological acid-fast staining (71.8% [130/181]), P < 0.001. Parallel testing of histological AFB staining and PCR showed the

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

PubMed

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

2018-04-01

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

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

PubMed

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

2018-02-26

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

Cost-effectiveness of WHO-Recommended Algorithms for TB Case Finding at Ethiopian HIV Clinics.

PubMed

Adelman, Max W; McFarland, Deborah A; Tsegaye, Mulugeta; Aseffa, Abraham; Kempker, Russell R; Blumberg, Henry M

2018-01-01

The World Health Organization (WHO) recommends active tuberculosis (TB) case finding and a rapid molecular diagnostic test (Xpert MTB/RIF) to detect TB among people living with HIV (PLHIV) in high-burden settings. Information on the cost-effectiveness of these recommended strategies is crucial for their implementation. We conducted a model-based cost-effectiveness analysis comparing 2 algorithms for TB screening and diagnosis at Ethiopian HIV clinics: (1) WHO-recommended symptom screen combined with Xpert for PLHIV with a positive symptom screen and (2) current recommended practice algorithm (CRPA; based on symptom screening, smear microscopy, and clinical TB diagnosis). Our primary outcome was US$ per disability-adjusted life-year (DALY) averted. Secondary outcomes were additional true-positive diagnoses, and false-negative and false-positive diagnoses averted. Compared with CRPA, combining a WHO-recommended symptom screen with Xpert was highly cost-effective (incremental cost of $5 per DALY averted). Among a cohort of 15 000 PLHIV with a TB prevalence of 6% (900 TB cases), this algorithm detected 8 more true-positive cases than CRPA, and averted 2045 false-positive and 8 false-negative diagnoses compared with CRPA. The WHO-recommended algorithm was marginally costlier ($240 000) than CRPA ($239 000). In sensitivity analysis, the symptom screen/Xpert algorithm was dominated at low Xpert sensitivity (66%). In this model-based analysis, combining a WHO-recommended symptom screen with Xpert for TB diagnosis among PLHIV was highly cost-effective ($5 per DALY averted) and more sensitive than CRPA in a high-burden, resource-limited setting.

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

An urgent need for building technical capacity for rapid diagnosis of multidrug-resistant tuberculosis (MDR-TB) among new cases: A case report from Maharashtra, India.

PubMed

Atre, Sachin

2015-01-01

Multidrug-resistant tuberculosis (MDR-TB), the prevalence of which has increased across the globe in recent years, is a serious threat to public health. Timely diagnosis of MDR-TB, especially among new TB cases, is essential to facilitate appropriate treatment, which can prevent further emergence of drug resistance and its spread in the population. The present case report from India aims to address some operational challenges in diagnosing MDR-TB among new cases and potential measures to overcome them. It argues that even after seven years of implementing the DOTS-Plus program for controlling MDR-TB, India still lacks the technical capacity for rapid MDR-TB diagnosis. The case report underscores an urgent need to explore the use of WHO-endorsed techniques such as Xpert MTB/Rif and commercial assays such as Genotype MTBDR for rapid diagnosis of MDR-TB among new cases. Suitable applications may be found for other TB high-burden countries where MDR-TB is a major concern. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.

Cost-effectiveness of the Xpert® MTB/RIF assay for tuberculosis diagnosis in Brazil.

PubMed

Pinto, M; Steffen, R E; Cobelens, F; van den Hof, S; Entringer, A; Trajman, A

2016-05-01

The Xpert® MTB/RIF assay is being implemented as a substitute for sputum smear microscopy (SSM) in many low and high tuberculosis (TB) burden countries, including Brazil, a country with low multidrug resistance and moderate human immunodeficiency virus co-infection rates. Brazilian National TB Programme (NTP). We estimated the incremental cost-effectiveness ratio (ICER) of Xpert as a substitute for two SSM tests in the diagnosis of drug-susceptible TB. The costs for confirming each additional case and for avoiding treatment due to false-positive empirical diagnoses were estimated. The ICER was US$943 for each additional TB diagnosis and US$356 for each additional TB diagnosis with bacteriological confirmation, assuming 80% specificity of clinical diagnosis using both strategies. For every 100 000 patients with suspected TB, the NTP would spend an additional US$1.2 million per year to confirm 3344 more TB patients. The model was highly sensitive to specificity of clinical diagnosis after a negative test. Although the NTP has no threshold for cost-effectiveness, our model can provide support for decision makers in Brazil and other countries with a low prevalence of drug resistance among TB patients. Financial benefit can potentially be expected if physicians rely more on a negative Xpert result and empirical treatment is reduced.

Rapid detection of Mycobacterium tuberculosis and rifampicin resistance in extrapulmonary tuberculosis and sputum smear-negative pulmonary suspects using Xpert MTB/RIF.

PubMed

Ullah, Irfan; Javaid, Arshad; Masud, Haleema; Ali, Mazhar; Basit, Anila; Ahmad, Waqas; Younis, Faisal; Yasmin, Rehana; Khan, Afsar; Jabbar, Abdul; Husain, Masroor; Butt, Zahid Ahmad

2017-04-01

Tuberculosis (TB) is a serious public health problem in developing countries such as Pakistan. Rapid diagnosis of TB and detection of drug resistance are very important for timely and appropriate management of multidrug-resistant TB (MDR-TB). The purpose of this study was to determine the diagnostic efficacy of the Xpert MTB/RIF assay for rapid diagnosis of TB and detection of rifampicin (RIF) resistance in extrapulmonary and smear-negative pulmonary TB suspects. A total of 98 bronchoalveolar lavage fluid (BALF) and 168 extrapulmonary specimens were processed by Xpert MTB/RIF. Culture results are considered as the gold standard for diagnosis of TB, and drug susceptibility testing for detection of RIF resistance. Diagnostic efficacy was measured in terms of sensitivity, specificity and positive and negative predictive values. The Xpert MTB/RIF assay detected 40 (40.8 %) of 98 BALF of presumptive pulmonary TB and 60 (35.7 %) of 168 extrapulmonary specimens. Sensitivity and specificity of the Xpert MTB/RIF assay for detection of TB was 86 and 88.4 %, respectively. The positive predictive value was 71.5 % while negative predictive value was 95.1 %. The Xpert MTB/RIF assay is a rapid and simple technique with high sensitivity and specificity for diagnosing TB and detecting drug resistance in extrapulmonary and smear-negative TB cases.

Detection of circulating Mycobacterium tuberculosis-specific DNA by droplet digital PCR for vaccine evaluation in challenged monkeys and TB diagnosis.

PubMed

Song, Neng; Tan, Yang; Zhang, Lingyun; Luo, Wei; Guan, Qing; Yan, Ming-Zhe; Zuo, Ruiqi; Liu, Weixiang; Luo, Feng-Ling; Zhang, Xiao-Lian

2018-04-24

Mycobacterium tuberculosis (M. tb) is emerging as a more serious pathogen due to the increased multidrug-resistant TB and co-infection of human immunodeficiency virus (HIV). The development of an effective and sensitive detection method is urgently needed for bacterial load evaluation in vaccine development, early TB diagnosis, and TB treatment. Droplet digital polymerase chain reaction (ddPCR) is a newly developed sensitive PCR method for the absolute quantification of nucleic acid concentrations. Here, we used ddPCR to quantify the circulating virulent M. tb-specific CFP10 (10-kDa culture filtrate protein, Rv3874) and Rv1768 DNA copy numbers in the blood samples from Bacille Calmette-Guerin (BCG)-vaccinated and/or virulent M. tb H37Rv-challenged rhesus monkeys. We found that ddPCR was more sensitive compared to real-time fluorescence quantitative PCR (qPCR), as the detection limits of CFP10 were 1.2 copies/μl for ddPCR, but 15.8 copies/μl for qPCR. We demonstrated that ddPCR could detect CFP10 and Rv1768 DNA after 3 weeks of infection and at least two weeks earlier than qPCR in M.tb H37Rv-challenged rhesus monkey models. DdPCR could also successfully quantify CFP10 and Rv1768 DNA copy numbers in clinical TB patients' blood samples (active pulmonary TB, extrapulmonary TB (EPTB), and infant TB). To our knowledge, this study is the first to demonstrate that ddPCR is an effective and sensitive method of measuring the circulating CFP10 and Rv1768 DNA for vaccine development, bacterial load evaluation in vivo, and early TB (including EPTB and infant TB) diagnosis as well.

Quality of diagnosis and monitoring of tuberculosis in Northern Ethiopia: medical records-based retrospective study.

PubMed

Mala, George; Spigt, Mark G; Gidding, Luc G; Blanco, Roman; Dinant, Geert-Jan

2015-10-01

To determine quality of diagnosis and monitoring of treatment response of patients with smear-negative pulmonary tuberculosis (TB) compared with smear-positive cases in Ethiopia. A retrospective analysis of medical records of newly diagnosed pulmonary TB cases that were registered for taking anti-TB medication and had completed treatment between 2010 and 2012. We evaluated the percentage of cases that were managed according to the International Standards of Tuberculosis Care (ISTC) and compared smear-negative with smear-positive cases. We analysed 1168 cases of which 742 (64%) were sputum smear-negative cases. Chest radiography examination at diagnosis and microbiological testing at the end of the intensive phase of treatment was performed in a smaller proportion than in smear-positive TB cases (70% vs. 79%, P value <0.001) and (70% vs. 95%, P value <0.001), respectively. Clinical actions recommended in the ISTC are of greatest importance in minimising pitfalls in care of smear-negative TB yet were performed less often in smear-negative than smear-positive TB cases. © The Author(s) 2015.

Multiple intracranial space-occupying lesions in a renal transplant recipient from an area endemic for tuberculosis (TB): TB vs. toxoplasmosis.

PubMed

Bagchi, S; Sachdev, S S; Nalwa, A; Das, C J; Sinha, S; Suri, V; Mahajan, S; Bhowmik, D; Agarwal, S

2014-10-01

Renal transplant recipients may present with intracranial space-occupying lesions (SOLs) due to infections as well as a post-transplant lymphoproliferative disorder (PTLD). Here, we discuss a renal transplant recipient who presented with neurologic symptoms and magnetic resonance imaging (MRI) of the brain showed multiple focal SOLs. Tuberculosis (TB), toxoplasmosis, nocardiosis, fungal infections, and PTLD were considered in the differential diagnosis. MRI spectroscopy was suggestive of an infectious cause, such as toxoplasmosis or TB. Serologic tests using Toxoplasma were negative. A brain biopsy followed by immunohistochemical staining using Toxoplasma antibody demonstrated multiple intravascular cysts of toxoplasma. This case highlights the diagnostic dilemma in an immunocompromised patient with multiple focal brain lesions, especially in areas where TB is endemic. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Do adjunct tuberculosis tests, when combined with Xpert MTB/RIF, improve accuracy and the cost of diagnosis in a resource-poor setting?

PubMed Central

Theron, Grant; Pooran, Anil; Peter, Jonny; van Zyl-Smit, Richard; Mishra, Hridesh Kumar; Meldau, Richard; Calligaro, Greg; Allwood, Brian; Sharma, Surendra Kumar; Dawson, Rod; Dheda, Keertan

2017-01-01

Information regarding the utility of adjunct diagnostic tests in combination with Xpert MTB/RIF (Cepheid, Sunnyvale, CA, USA) is limited. We hypothesised adjunct tests could enhance accuracy and/or reduce the cost of tuberculosis (TB) diagnosis prior to MTB/RIF testing, and rule-in or rule-out TB in MTB/RIF-negative individuals. We assessed the accuracy and/or laboratory-associated cost of diagnosis of smear microscopy, chest radiography (CXR) and interferon-γ release assays (IGRAs; T-SPOT-TB (Oxford Immunotec, Oxford, UK) and QuantiFERON-TB Gold In-Tube (Cellestis, Chadstone, Australia)) combined with MTB/RIF for TB in 480 patients in South Africa. When conducted prior to MTB/RIF: 1) smear microscopy followed by MTB/RIF (if smear negative) had the lowest cost of diagnosis of any strategy investigated; 2) a combination of smear microscopy, CXR (if smear negative) and MTB/RIF (if imaging compatible with active TB) did not further reduce the cost per TB case diagnosed; and 3) a normal CXR ruled out TB in 18% of patients (57 out of 324; negative predictive value (NPV) 100%). When downstream adjunct tests were applied to MTB/RIF-negative individuals, radiology ruled out TB in 24% (56 out of 234; NPV 100%), smear microscopy ruled in TB in 21% (seven out of 24) of culture-positive individuals and IGRAs were not useful in either context. In resource-poor settings, smear microscopy combined with MTB/RIF had the highest accuracy and lowest cost of diagnosis compared to either technique alone. In MTB/RIF-negative individuals, CXR has poor rule-in value but can reliably rule out TB in approximately one in four cases. These data inform upon the programmatic utility of MTB/RIF in high-burden settings. PMID:22075479

Barriers to accessing TB diagnosis for rural-to-urban migrants with chronic cough in Chongqing, China: A mixed methods study

PubMed Central

Long, Qian; Li, Ying; Wang, Yang; Yue, Yong; Tang, Cheng; Tang, Shenglan; Squire, S Bertel; Tolhurst, Rachel

2008-01-01

Background China is facing a significant tuberculosis epidemic among rural-to-urban migrants, which poses a threat to TB control. This study aimed to understand the health seeking behaviour of and health systems responses to migrants and permanent urban residents suffering from chronic cough, in order to identify the factors influencing delays for both groups in receiving a TB diagnosis in urban China. Methods Combining a prospective cohort study of adult suspect TB patients and a qualitative study, the Piot model was used to analyze the health seeking behaviour of TB suspects among migrants and permanent urban residents, the factors influencing their decision and the responses by general health providers. Methods included a patient survey, focus group discussions with migrants in the general population, qualitative interviews with migrant and permanent resident TB suspects and TB patients as well as key stakeholders related to TB control and the management of migrants. Results Sixty eight percent of migrants delayed for more than two weeks before seeking care for symptoms suggestive of TB, compared to 54% of residents (p < 0.01). When they first decided to seek professional care, migrants were 1.5 times more likely than residents to use less expensive, community-level health services. Only 5% were ultimately referred to a TB dispensary. Major reasons for both patient and provider delay included lack of knowledge and mistrust of the TB control programme, lack of knowledge about TB (patients), and profit-seeking behaviour (providers). In the follow up survey, 61% of the migrants and 41% of the residents who still had symptoms gave up continuing to seek professional care, with a statistically significant difference between the two groups (p < 0.05). Conclusion Rural-to-urban migrants are more likely than permanent residents to delay in seeking care for symptoms suggestive of TB in urban Chongqing. 'Patient-' and 'provider-' related factors interact to pose barriers

Community-based MDR-TB care project improves treatment initiation in patients diagnosed with MDR-TB in Myanmar.

PubMed

Wai, Pyae Phyo; Shewade, Hemant Deepak; Kyaw, Nang Thu Thu; Thein, Saw; Si Thu, Aung; Kyaw, Khine Wut Yee; Aye, Nyein Nyein; Phyo, Aye Mon; Maung, Htet Myet Win; Soe, Kyaw Thu; Aung, Si Thu

2018-01-01

The Union in collaboration with national TB programme (NTP) started the community-based MDR-TB care (CBMDR-TBC) project in 33 townships of upper Myanmar to improve treatment initiation and treatment adherence. Patients with MDR-TB diagnosed/registered under NTP received support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each township had a project nurse exclusively for MDR-TB and 30 USD per month (max. for 4 months) were provided to the patient as a pre-treatment support. To assess whether CBMDR-TBC project's support improved treatment initiation. In this cohort study (involving record review) of all diagnosed MDR-TB between January 2015 and June 2016 in project townships, CBMDR-TBC status was categorized as "receiving support" if date of project initiation in patient's township was before the date of diagnosis and "not receiving support", if otherwise. Cox proportional hazards regression (censored on 31 Dec 2016) was done to identify predictors of treatment initiation. Of 456 patients, 57% initiated treatment: 64% and 56% among patients "receiving support (n = 208)" and "not receiving support (n = 228)" respectively (CBMDR-TBC status was not known in 20 (4%) patients due to missing diagnosis dates). Among those initiated on treatment (n = 261), median (IQR) time to initiate treatment was 38 (20, 76) days: 31 (18, 50) among patients "receiving support" and 50 (26,101) among patients "not receiving support". After adjusting other potential confounders (age, sex, region, HIV, past history of TB treatment), patients "receiving support" had 80% higher chance of initiating treatment [aHR (0.95 CI): 1.8 (1.3, 2.3)] when compared to patients "not receiving support". In addition, age 15-54 years, previous history of TB and being HIV negative were independent predictors of treatment initiation. Receiving support under CBMDR-TBC project improved treatment initiation: it not only improved the proportion initiated but also

Diagnosis of smear-negative pulmonary tuberculosis based on clinical signs in the Republic of Congo.

PubMed

Linguissi, Laure Stella Ghoma; Vouvoungui, Christevy Jeannhey; Poulain, Pierre; Essassa, Gaston Bango; Kwedi, Sylvie; Ntoumi, Francine

2015-12-18

The diagnosis of pulmonary tuberculosis (PTB) and smear-negative pulmonary tuberculosis (SNPT) in resource-limited countries is often solely based on clinical signs, chest X-ray radiography and sputum smear microscopy. We investigated currently used methods for the routine diagnosis of SNPT in the Republic of Congo (RoC) among TB suspected patients. The specific case of HIV positive patients was also studied. A cross-sectional study was conducted at the anti-tuberculosis center (CAT) of Brazzaville, RoC. Tuberculosis suspects were examined for physical signs of TB. Clinical signs, results from sputum smear microscopy, tuberculin skin test (TST) and chest X-ray were recorded. Of the 772 enrolled participants, 372 were diagnosed PTB. Cough was a common symptom for PTB and no PTB patients. Pale skin, positive TST, weight loss and chest X-ray with abnormalities compatible with PTB (PTB-CXR) were significant indicators of PTB. Thirty-six percent of PTB patients were diagnosed SNPT. This category of patients presented less persistent cough and less PTB-CXR. Anorexia and asthenia were significant indicators of SNPT. In the case of HIV+ patients, 57% were SNPT with anorexia, asthenia and shorter cough being strong indicators of SNPT. Chest X-ray abnormalities, weight loss, pale skin and positive TST were significant indicators of PTB. Anorexia and asthenia showed good diagnostic performance for SNPT, which deserve to be recommended as index indicators of SNPT diagnosis. Duration of cough is also a relevant indicator, especially for HIV+ patients.

Impact of telemonitoring approaches on integrated HIV and TB diagnosis and treatment interventions in sub-Saharan Africa: a scoping review.

PubMed

Yah, Clarence S; Tambo, Ernest; Khayeka-Wandabwa, Christopher; Ngogang, Jeanne Y

2017-01-01

Background: This paper explores telemonitoring/mhealth approaches as a promising real time and contextual strategy in overhauling HIV and TB interventions quality access and uptake, retention,adherence and coverage impact in endemic and prone-epidemic prevention and control in sub-Sahara Africa. Methods: The scoping review method was applied in acknowledged journals indexing platforms including Medline, Embase, Global Health, PubMed, MeSH PsycInfo, Scopus and Google Scholar to identify relevant articles pertaining to telemonitoring as a proxy surrogate method in reinforcing sustainability of HIV/TB prevention/treatment interventions in sub-Saharan Africa. Full papers were assessed and those selected that fosters evidence on telemonitoring/mhealth diagnosis, treatment approaches and strategies in HIV and TB prevention and control were synthesized and analyzed. Results: We found telemonitoring/mhealth approach as a more efficient and sustained proxy in HIV and TB risk reduction strategies for early diagnosis and prompt quality clinical outcomes. It can significantly contribute to decreasing health systems/patients cost, long waiting time in clinics, hospital visits, travels and time off/on from work. Improved integrated HIV and TB telemonitoring systems sustainability hold great promise in health systems strengthening including patient centered early diagnosis and care delivery systems, uptake and retention to medications/services and improving patients' survival and quality of life. Conclusion: Telemonitoring/mhealth (electronic phone text/video/materials messaging)acceptability, access and uptake are crucial in monitoring and improving uptake, retention,adherence and coverage in both local and national integrated HIV and TB programs and interventions. Moreover, telemonitoring is crucial in patient-providers-health professional partnership, real-time quality care and service delivery, antiretroviral and anti-tuberculous drugs improvement, susceptibility monitoring

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

PubMed

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

2017-01-01

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

Evaluation of Xpert® MTB/RIF and Ustar EasyNAT™ TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania: a prospective descriptive study.

PubMed

Bholla, Maira; Kapalata, Neema; Masika, Edward; Chande, Hassan; Jugheli, Levan; Sasamalo, Mohamed; Glass, Tracy R; Beck, Hans-Peter; Reither, Klaus

2016-06-06

Fine needle aspiration biopsy has become a standard approach for diagnosis of peripheral tuberculous lymphadenitis. The aim of this study was to compare the performance of Xpert MTB/RIF and Ustar EasyNAT TB IAD nucleic acid amplification assays, against acid-fast bacilli microscopy, cytology and mycobacterial culture for the diagnosis of TB lymphadenitis in children from a TB-endemic setting in Tanzania. Children of 8 weeks to 16 years of age, suspected of having TB lymphadenitis, were recruited at a district hospital in Tanzania. Fine needle aspirates of lymph nodes were analysed using acid-fast bacilli microscopy, liquid TB culture, cytology, Xpert MTB/RIF and EasyNAT. Latent class analysis and comparison against a composite reference standard comprising "culture and/or cytology" was done, to assess the performance of Xpert MTB/RIF and EasyNAT for the diagnosis of TB lymphadenitis. Seventy-nine children were recruited; 4 were excluded from analysis. Against a composite reference standard of culture and/or cytology, Xpert MTB/RIF and EasyNAT had a sensitivity and specificity of 58 % and 93 %; and 19 % and 100 % respectively. Relative to latent class definitions, cytology had a sensitivity of 100 % and specificity of 94.7 %. Combining clinical assessment, cytology and Xpert MTB/RIF may allow for a rapid and accurate diagnosis of childhood TB lymphadenitis. Larger diagnostic evaluation studies are recommended to validate these findings and on Xpert MTB/RIF to assess its use as a solitary initial test for TB lymphadenitis in children.

Cumulative False-Positive QuantiFERON-TB Interferon-γ Release Assay Results.

PubMed

Gamsky, Thomas E; Lum, Thomas; Hung-Fan, Melody; Green, Jon A

2016-05-01

Despite reports of unreliability, the QuantiFERON-TB interferon-γ release assay is increasingly used for the annual screening of individuals at risk for latent tuberculosis. Continued use of the QuantiFERON-TB assay suggests the need for more definitive evidence of its reproducibility and accuracy. To examine reproducibility and the accumulation of false-positive test results when the QuantiFERON-TB is repeated annually and to examine the validity of confirming positive test results with the performance of a second QuantiFERON-TB. We performed a retrospective, longitudinal evaluation of results from serial screening of a cohort of emergency responders from 2001 to 2013. Results of tuberculin tests and QuantiFERON-TB tests performed annually as part of a mandated first responder examination were retroactively reviewed. In this population, positive results occurred in new individuals each year. QuantiFERON-TB results were positive in 80 of 557 tuberculin test-negative individuals examined annually for a maximum of 7 years. Only 10 individuals with initially positive results remained positive when the test was repeated the next year, and 9 of these 10 were QuantiFERON-TB-negative within 3 years. The number of individuals with a positive result increased annually, and, after 7 years, 32 (27.4%) of 117 people had a positive result. When viewed in the context of the extensive literature documenting unreliable QuantiFERON-TB test performance, our findings of frequent, cumulative, sporadic, and irreproducible positive results support discontinuing the use of the QuantiFERON-TB assay for the diagnosis of latent tuberculosis in low-risk populations.

Sputum smear examination and time to diagnosis in patients with smear-negative pulmonary tuberculosis in the Pacific.

PubMed

Viney, K; Bissell, K; Tabutoa, K; Kienene, T; Linh, N N; Briand, K; Harries, A D

2012-12-21

National tuberculosis programmes (NTPs) in Kiribati and the Marshall Islands, 2006-2010. To determine the proportion of all tuberculosis (TB) cases that were pulmonary smear-negative, and for these patients to determine how many sputum smears were examined and the time from sputum smear examination to registration. A retrospective cross-sectional study involving a record review of national TB and laboratory registers. Of 2420 TB cases identified, 709 (29%) were registered as smear-negative pulmonary TB. Of the 695 (98%) with information on smear examination, 222 (32%) had no smear recorded, 61 (9%) had one smear, 86 (12%) two smears and 326 (47%) three smears. Among the 473 patients who had at least one smear, 238 (50%) were registered before sputum examination, 131 (28%) within 1 week, 72 (15%) between 1 and 4 weeks, and 34 (7%) >4 weeks after sputum examination. NTPs in Kiribati and the Marshall Islands are diagnosing 29% of all TB patients as smear-negative pulmonary TB. Many patients do not have smears done or are registered before undergoing smear examination. Corrective measures are needed.

[The usefulness of in vitro interferon-gamma assay for differential diagnosis between intestinal tuberculosis and Crohns disease].

PubMed

Lee, Jung Nam; Ryu, Dong Yup; Park, Sung Han; You, Hyun Seok; Lee, Bong Eun; Kim, Dong Uk; Kim, Tae Oh; Heo, Jeong; Kim, Gwang Ha; Song, Geun Am; Kim, Suk; Park, Do Youn

2010-06-01

It is difficult to clinically and endoscopically differentiate intestinal tuberculosis (ITB) and Crohns disease (CD). The aim of this study was to evaluate the usefulness of in vitro interferon-gamma (INF-gamma) assay for differential diagnosis between ITB and CD. Sixty patients for whom differential diagnosis between ITB and CD was difficult were enrolled between January 2007 and January 2009. The INF-gamma-producing T-cell response to early secreted antigenic target 6 and culture filtrate protein 10 were measured by T-SPOT.TB blood test in vitro. We evaluated the usefulness of T-SPOT.TB blood test by comparing its results with the final diagnosis. Twenty and forty patients were revealed to be positive and negative in T-SPOT.TB blood test, respectively. Of the 20 patients found to be positive, 12 patients (60%) were finally diagnosed as ITB, 6 patients as CD, and 2 patients as Behcets enterocolitis. Of the 40 patients with negative results, 38 patients (95%) were diagnosed as CD; one as Behcets enterocolitis; one as nonspecific colitis; none as ITB. The sensitivity and specificity of T-SPOT.TB blood test for ITB were 100% and 83.3%, respectively. Positive and negative predictive values of T-SPOT.TB blood test for ITB were 60.0% and 100%, respectively. When differential diagnosis between ITB and CD is difficult, T-SPOT.TB blood test may be a helpful and rapid diagnostic tool to exclude ITB. Prospective large-scaled studies are required for further evaluation of the usefulness of T-SPOT.TB blood test for differential diagnosis between ITB and CD.

Diagnostic usefulness of the QuantiFERON-TB gold in-tube test (QFT-GIT) for tuberculous vertebral osteomyelitis.

PubMed

Choi, Sungim; Jung, Kyung Hwa; Son, Hyo-Ju; Lee, Seung Hyun; Hong, Jung Min; Kim, Min Chul; Kim, Min Jae; Chong, Yong Pil; Sung, Heungsup; Lee, Sang-Oh; Choi, Sang-Ho; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2018-05-01

Interferon (IFN)-γ-releasing assay for diagnosing tuberculosis (TB) has shown promise; however, there are only a few reports on usefulness of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) for diagnosing TB vertebral osteomyelitis. All patients presenting at a tertiary hospital between January 2010 and July 2016 with suspected TB vertebral osteomyelitis were retrospectively enrolled to evaluate the diagnostic performance of QFT-GIT. We used QFT-GIT to measure the IFN-γ response to ESAT-6, CFP-10 and TB7.7. A total of 141 patients were enrolled; 32 (23%) were categorized as having confirmed TB, (1%) as probable TB, 14 (10%) as possible TB and 93 (66%) as not TB. Of these, 16 patients with probable and possible TB were excluded from the final analysis. Chronic granulomas with/without necrosis, acid-fast bacilli stain, M. tuberculosis polymerase chain reaction and cultures for M. tuberculosis were positive in 14 (44%), 12 (38%), 22 (69%) and 28 (88%) patients, respectively, among the 32 patients with confirmed TB. The overall sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratio for a positive result, and likelihood ratio for a negative result of the QFT-GIT for TB vertebral osteomyelitis were 91% (95% confidence interval [CI], 75-98%), 65% (95% CI, 54-75%), 50% (95% CI, 42-58%), 95% (95% CI, 86-98%), 2.59 (95% CI, 1.89-3.55) and 0.14 (95% CI, 0.05-0.43), respectively. The QFT-GIT appears to be a useful adjunct test for diagnosing TB vertebral osteomyelitis because the negative test results may be useful for excluding a diagnosis of active TB vertebral osteomyelitis.

[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.

Community-based MDR-TB care project improves treatment initiation in patients diagnosed with MDR-TB in Myanmar

PubMed Central

Shewade, Hemant Deepak; Kyaw, Nang Thu Thu; Thein, Saw; Si Thu, Aung; Kyaw, Khine Wut Yee; Aye, Nyein Nyein; Phyo, Aye Mon; Maung, Htet Myet Win; Soe, Kyaw Thu; Aung, Si Thu

2018-01-01

Background The Union in collaboration with national TB programme (NTP) started the community-based MDR-TB care (CBMDR-TBC) project in 33 townships of upper Myanmar to improve treatment initiation and treatment adherence. Patients with MDR-TB diagnosed/registered under NTP received support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each township had a project nurse exclusively for MDR-TB and 30 USD per month (max. for 4 months) were provided to the patient as a pre-treatment support. Objectives To assess whether CBMDR-TBC project’s support improved treatment initiation. Methods In this cohort study (involving record review) of all diagnosed MDR-TB between January 2015 and June 2016 in project townships, CBMDR-TBC status was categorized as “receiving support” if date of project initiation in patient’s township was before the date of diagnosis and “not receiving support”, if otherwise. Cox proportional hazards regression (censored on 31 Dec 2016) was done to identify predictors of treatment initiation. Results Of 456 patients, 57% initiated treatment: 64% and 56% among patients “receiving support (n = 208)” and “not receiving support (n = 228)” respectively (CBMDR-TBC status was not known in 20 (4%) patients due to missing diagnosis dates). Among those initiated on treatment (n = 261), median (IQR) time to initiate treatment was 38 (20, 76) days: 31 (18, 50) among patients “receiving support” and 50 (26,101) among patients “not receiving support”. After adjusting other potential confounders (age, sex, region, HIV, past history of TB treatment), patients “receiving support” had 80% higher chance of initiating treatment [aHR (0.95 CI): 1.8 (1.3, 2.3)] when compared to patients “not receiving support”. In addition, age 15–54 years, previous history of TB and being HIV negative were independent predictors of treatment initiation. Conclusion Receiving support under CBMDR-TBC project

Sputum smear examination and time to diagnosis in patients with smear-negative pulmonary tuberculosis in the Pacific

PubMed Central

Bissell, K.; Tabutoa, K.; Kienene, T.; Linh, N. N.; Briand, K.; Harries, A. D.

2012-01-01

Setting: National tuberculosis programmes (NTPs) in Kiribati and the Marshall Islands, 2006–2010. Objective: To determine the proportion of all tuberculosis (TB) cases that were pulmonary smear-negative, and for these patients to determine how many sputum smears were examined and the time from sputum smear examination to registration. Design: A retrospective cross-sectional study involving a record review of national TB and laboratory registers. Results: Of 2420 TB cases identified, 709 (29%) were registered as smear-negative pulmonary TB. Of the 695 (98%) with information on smear examination, 222 (32%) had no smear recorded, 61 (9%) had one smear, 86 (12%) two smears and 326 (47%) three smears. Among the 473 patients who had at least one smear, 238 (50%) were registered before sputum examination, 131 (28%) within 1 week, 72 (15%) between 1 and 4 weeks, and 34 (7%) >4 weeks after sputum examination. Conclusion: NTPs in Kiribati and the Marshall Islands are diagnosing 29% of all TB patients as smear-negative pulmonary TB. Many patients do not have smears done or are registered before undergoing smear examination. Corrective measures are needed. PMID:26392971

PCR colorimetric dot-blot assay and clinical pretest probability for diagnosis of Pulmonary Tuberculosis in Smear-Negative patients

PubMed Central

Scherer, Luciene Cardoso; Sperhacke, Rosa Dea; Jarczewski, Carla; Cafrune, Patrícia I; Minghelli, Simone; Ribeiro, Marta Osório; Mello, Fernanda CQ; Ruffino-Netto, Antonio; Rossetti, Maria LR; Kritski, Afrânio L

2007-01-01

-previously TB treated and HIV subjects, this approach had sensitivity, specificity, positive and negative predictive values of 91%, 79%, 81%, 90%, and 90%, 65%, 72%, 88%, respectively. Conclusion PCR dot-blot associated with a high clinical suspicion may provide an important contribution to the diagnosis of SNPTB mainly in patients that have not been previously treated attended at a TB/HIV reference hospital. PMID:18096069

Xpert MTB/RIF diagnosis of childhood tuberculosis from sputum and stool samples in a high TB-HIV-prevalent setting.

PubMed

Orikiriza, Patrick; Nansumba, Margaret; Nyehangane, Dan; Bastard, Mathieu; Mugisha, Ivan Taremwa; Nansera, Denis; Mwanga-Amumpaire, Juliet; Boum, Yap; Kumbakumba, Elias; Bonnet, Maryline

2018-05-08

The Xpert MTB/RIF assay is a major advance for diagnosis of tuberculosis (TB) in high-burden countries but is limited in children by their difficulty to produce sputum. We investigated TB in sputum and stool from children with the aim of improving paediatric TB diagnosis. A prospective cohort of children with presumptive TB, provided two sputum or induced sputum at enrolment in a regional referral hospital in Uganda. Stool was collected from those started on TB treatment. All specimen were tested for Xpert MTB/RIF, mycobacteria growth indicator tube (MGIT), Lowenstein Jensen cultures and microscopy (except stool). We compared TB detection between age categories and assessed the performance of Xpert MTB/RIF in sputum and stool. Of the 392 children enrolled, 357 (91.1%) produced at least one sputum sample. Sputum culture yield was 13/357 (3.6%): 3/109 (2.6%), 3/89 (3.2%), 3/101 (2.6%) and 4/44 (8.2%) among children of < 2, 2-5, ≥ 5-10 and > 10 years, respectively (p = 0.599). Xpert MTB/RIF yield was 14/350 (4.0%): 3/104 (2.9%), 4/92 (4.3%), 3/88 (2.9%) and 4/50 (.0%), respectively (p = 0.283). Sensitivity and specificity of Xpert MTB/RIF in sputum against sputum culture were 90.9% (95% CI 58.7-99.8) and 99.1% (99.1-99.8). In stool, it was 55.6% (21.2-86.3) and 98.2% (98.2-100) against Xpert MTB/RIF and culture in sputum. Only a minority of children had microbiologically confirmed TB with a higher proportion in children above 10 years. Although sensitivity of Xpert MTB/RIF in stool was low, with good optimization, it might be a good alternative to sputum in children.

Evaluation of the 2007 WHO guideline to improve the diagnosis of tuberculosis in ambulatory HIV-positive adults.

PubMed

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

2011-04-06

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. 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. 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.

Improving the prevention, diagnosis and treatment of TB among people living with HIV: the role of operational research

PubMed Central

2011-01-01

Operational research is necessary to improve the access to and delivery of tuberculosis prevention, diagnosis and treatment interventions for people living with HIV. We conducted an extensive review of the literature and reports from recent expert consultations and research-related meetings organized by the World Health Organization and the Stop TB Partnership to identify a TB/HIV operational research agenda. We present critical operational research questions in a series of key areas: optimizing TB prevention by enhancing the uptake of isoniazid preventive therapy and the implementation of infection control measures; assessing the effectiveness of existing diagnostic tools and scaling up new technologies; improving service delivery models; and reducing risk factors for mortality among TB patients living with HIV. We discuss the potential impact that addressing the operational research questions may have on improving programmes’ performance, assessing new strategies or interventions for TB control, or informing global or national policy formulation. Financial resources to implement these operational research questions should be mobilized from existing and new funding mechanisms. National TB and HIV/AIDS programmes should develop their operational research agendas based on these questions, and conduct the research that they consider crucial for improving TB and HIV control in their settings in collaboration with research stakeholders. PMID:21967874

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

Sensitivity and specificity of QuantiFERON-TB Gold Plus compared with QuantiFERON-TB Gold In-Tube and T-SPOT.TB on active tuberculosis in Japan.

PubMed

Takasaki, Jin; Manabe, Toshie; Morino, Eriko; Muto, Yoshikazu; Hashimoto, Masao; Iikura, Motoyasu; Izumi, Shinyu; Sugiyama, Haruhito; Kudo, Koichiro

2018-03-01

The QuantiFERON-TB Gold Plus (QFT-Plus) was introduced in 2015 as a new generation of interferon-gamma release assays (IGRAs) designed to detect Mycobacterium tuberculosis infection (TB). Examination of its diagnostic accuracy is crucial before it is launched in Japan. We examined 99 patients with laboratory-confirmed active TB (patients) and 117 healthy volunteers with no risk of TB infection (controls) at a medical center in Tokyo, Japan. Blood samples were collected from both the patients and controls and tested using three types of IGRAs: the QFT-Plus, the QuantiFERON-TB Gold In-Tube (QFT-GIT), and the T-SPOT.TB (T-SPOT). The sensitivity and specificity of each IGRA were examined and compared. The sensitivity of the QFT-Plus was 98.9% (95% confidence interval [CI], 0.934-0.998) and similar to that of the QFT-GIT (97.9%; 95% CI, 0.929-0.998) and T-SPOT (96.9%; 95% CI, 0.914-0.994). The specificity of the QFT-Plus was the same as that of the QFT-GIT and T-SPOT (98.1%; 95% CI, 0.934-0.998). One patient with uncontrolled diabetes mellitus showed negative results on all three IGRAs. The QFT-Plus showed a high degree of agreement with the QFT-GIT and T-SPOT, with high sensitivity and specificity. Severe diabetes mellitus may influence the results of IGRAs. Larger studies are needed to validate the accuracy of the GFT-Plus and determine whether it can contribute as adjunctive method for the early diagnosis of active TB in Japan. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

PubMed

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

2017-10-11

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

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

PubMed

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

2018-01-01

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

The Xpert® MTB/RIF assay in routine diagnosis of pulmonary tuberculosis: A multicentre study in Lithuania.

PubMed

Pimkina, Edita; Zablockis, Rolandas; Nikolayevskyy, Vladyslav; Danila, Edvardas; Davidaviciene, Edita

2015-11-01

Drug-resistant tuberculosis (TB) is an important public health problem in Lithuania with MDR rates in new cases reaching 11% in 2012. Currently available diagnostic tools are not fully adequate for an accurate and rapid result for diagnosis of TB and MDR-TB. To evaluate the performance of Xpert(®) MTB/RIF assay for an early diagnosis of TB and detection of rifampicin (RIF) resistance in routine settings in Lithuania. A total of 833 individual respiratory samples obtained from patients previously treated for TB and MDR-TB contacts were tested using the Xpert MTB/RIF assay. Performance characteristics of the assay for TB and RIF resistance detection were calculated using culture and phenotypical DST results as a gold standard. The overall sensitivity and specificity of the Xpert MTB/RIF assay for TB detection were 93.7% and 91.7%, respectively with the sensitivity for smear-negative specimens reaching 82.5%. Resistance to RIF was detected in 81 (20.7%) primary specimens with no false negative results; there were 4/225 (1.8%) false-positives among strains sensitive to rifampicin. Overall sensitivity and specificity of the molecular assay for detection of RIF resistance calculated against phenotypic DST results were 100% and 98.2%, respectively. Our results demonstrate very good performance of the Xpert MTB/RIF assay for the detection of TB and RIF resistance on primary respiratory specimens. It provides strong evidence that implementation of the assay for routine laboratory diagnosis in high drug-resistance settings may improve and facilitate TB diagnosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

PubMed

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

2016-03-01

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

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.

Clinical value of polymerase chain reaction in the diagnosis of joint tuberculosis by detecting the DNA of Mycobacterium tuberculosis.

PubMed

Sun, Yong-sheng; Lou, Si-quan; Wen, Jian-min; Lv, Wei-xin; Jiao, Chang-geng; Yang, Su-min; Xu, Hai-bin

2011-02-01

To assess the clinical value of polymerase chain reaction (PCR) in the diagnosis and differential diagnosis of joint tuberculosis (TB). PCR was used blindly to detect the DNA of Mycobacterium tuberculosis (M.TB) in five specimens of M.TB, 5 of BCG, and 10 of other bacteria. Then, M. TB in 98 samples from patients with joint TB and 100 samples from patients with non-tubercular joint disorders were detected by PCR, acid-fast staining and culture,. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of PCR were calculated. The χ2 test was used for statistical analysis of the frequency of various factors. At the same time, some problems with PCR were also systematically analyzed. (1) In the "standard samples", both M. TB and BCG showed positive while other bacteria were negative. (2) In 98 cases from patients with joint TB, 81 were positive by PCR, 6 by acid-fast staining, and 17 by culture. In 100 cases from patients with non-tuberculous joint disorders, 9 were positive by PCR, and none by either acid-fast staining or culture. Sensitivity, specificity, accuracy, positive and negative predictive value of PCR were 82.65% (81/98), 91.00% (91/100), 86.87% (172/198), 90.00% (81/90) and 84.26% (91/108), respectively. (3) The positive rates for PCR, acid-fast staining and culture in detection of M. TB were 82.65% (81/98), 6.12% (6/98), and 17.34% (17/98), respectively. There were statistically significant differences between the three methods (P < 0.001). (4) The process of PCR is automatic, and can be completed within 3 to 6 hours, whereas 4 to 8 weeks are required for the conventional culture of M. TB. PCR is a sensitive, specific, rapid, simple and minimally invasive method for detection of M. TB in samples from joint TB, and can play an important role in early and rapid diagnosis and differential diagnosis of joint TB. But it also has some limitations, such as false positivity and false negativity. © 2011 Tianjin Hospital

Diagnostic performance of automated liquid culture and molecular line probe assay in smear-negative pulmonary tuberculosis.

PubMed

Kotwal, Aarti; Biswas, Debasis; Raghuvanshi, Shailendra; Sindhwani, Girish; Kakati, Barnali; Sharma, Shweta

2017-04-01

The diagnosis of smear-negative pulmonary tuberculosis (PTB) is particularly challenging, and automated liquid culture and molecular line probe assays (LPA) may prove particularly useful. The objective of our study was to evaluate the diagnostic potential of automated liquid culture (ALC) technology and commercial LPA in sputum smear-negative PTB suspects. Spot sputum samples were collected from 145 chest-symptomatic smear-negative patients and subjected to ALC, direct drug susceptibility test (DST) testing and LPA, as per manufacturers' instructions. A diagnostic yield of 26.2% was observed among sputum smear-negative TB suspects with 47.4% of the culture isolates being either INH- and/or rifampicin-resistant. Complete agreement was observed between the results of ALC assay and LPA except for two isolates which demonstrated sensitivity to INH and rifampicin at direct DST but were rifampicin-resistant in LPA. Two novel mutations were also detected among the multidrug isolates by LPA. In view of the diagnostic challenges associated with the diagnosis of TB in sputum smear-negative patients, our study demonstrates the applicability of ALC and LPA in establishing diagnostic evidence of TB.

Diagnostic Value of Cerebrospinal Fluid T-SPOT.TB for Tuberculousis Meningitis in China.

PubMed

Li, Xue Lian; Xie, Na; Wang, Song Wang; Wu, Qian Hong; Ma, Yan; Shu, Wei; Chen, Hong Mei; Zhang, Li Qun; Wu, Xiao Guang; Ma, Li Ping; Che, Nan Ying; Gao, Meng Qiu

2017-09-01

The aim of this study was to evaluate the diagnostic value of the cerebrospinal fluid (CSF) T-SPOT.TB test for the diagnosis of TB meningitis (TBM). A retrospective analysis of 96 patients with manifested meningitis was conducted; T-SPOT.TB test was performed for diagnosing TBM to determine the diagnostic sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). A receiver operating characteristic (ROC) curve was also drawn to assess the diagnostic accuracy. The sensitivity, specificity, PPV, and NPV of CSF T-SPOT.TB test were 97.8%, 78.0%, 80.3%, and 97.5%, respectively, for 52 patients (54.2%) of the 96 enrolled patients. The area under the curve (AUC) was 0.910, and the sensitivities of CSF T-SPOT.TB for patients with stages I, II, and III of TBM were 96.7%, 97.2%, and 98.9%, respectively. CSF T-SPOT.TB test is a rapid and accurate diagnostic method with higher sensitivity and specificity for diagnosing TBM. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

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.

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

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.

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

PubMed

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

2015-10-01

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

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 ...

[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.

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

PubMed Central

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

2014-01-01

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

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.

Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid.

PubMed

Theron, Grant; Peter, Jonny; Meldau, Richard; Khalfey, Hoosain; Gina, Phindile; Matinyena, Brian; Lenders, Laura; Calligaro, Gregory; Allwood, Brian; Symons, Gregory; Govender, Ureshnie; Setshedi, Mashiko; Dheda, Keertan

2013-11-01

The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear. South African patients with suspected pulmonary TB (n=160) who were sputum-scarce or smear-negative underwent bronchoscopy. MTB/RIF was performed on uncentrifuged BALF (1 ml) and/or a resuspended pellet of centrifuged BALF (∼10 ml). Time to TB detection and anti-TB treatment initiation were compared between phase one, when MTB/RIF was performed as a research tool, and phase two, when it was used for patient management. 27 of 154 patients with complete data had culture-confirmed TB. Of these, a significantly lower proportion were detected by smear microscopy compared with MTB/RIF (58%, 95% CI 39% to 75% versus 93%, 77% to 98%; p<0.001). Of the 127 patients who were culture negative, 96% (91% to 98%) were MTB/RIF negative. When phase two was compared with phase one, MTB/RIF reduced the median days to TB detection (29 (18-41) to 0 (0-0); p<0.001). However, more patients initiated empirical therapy (absence of a positive test in those commencing treatment) in phase one versus phase two (79% (11/14) versus 28% (10/25); p=0.026). Consequently, there was no detectable difference in the overall proportion of patients initiating treatment (26% (17/67; 17% to 37%) versus 36% (26/73; 26% to 47%); p=0.196) or the days to treatment initiation (10 (1-49) versus 7 (0-21); p=0.330). BALF centrifugation, HIV coinfection and a second MTB/RIF did not result in detectable changes in accuracy. MTB/RIF detected TB cases more accurately and more rapidly than smear microscopy and significantly reduced the rate of empirical treatment.

Accuracy and impact of Xpert MTB/RIF for the diagnosis of smear-negative or sputum-scarce tuberculosis using bronchoalveolar lavage fluid

PubMed Central

Theron, Grant; Peter, Jonny; Meldau, Richard; Khalfey, Hoosain; Gina, Phindile; Matinyena, Brian; Lenders, Laura; Calligaro, Gregory; Allwood, Brian; Symons, Gregory; Govender, Ureshnie; Setshedi, Mashiko; Dheda, Keertan

2017-01-01

Rationale The accuracy and impact of new tuberculosis (TB) tests, such as Xpert MTB/RIF, when performed on bronchoalveolar lavage fluid (BALF) obtained from patients with sputum-scarce or smear-negative TB is unclear. Methods South African patients with suspected pulmonary TB (n=160) who were sputum-scarce or smear-negative underwent bronchoscopy. MTB/RIF was performed on uncentrifuged BALF (1 ml) and/or a resuspended pellet of centrifuged BALF (~10 ml). Time to TB detection and anti-TB treatment initiation were compared between phase one, when MTB/RIF was performed as a research tool, and phase two, when it was used for patient management. Results 27 of 154 patients with complete data had culture-confirmed TB. Of these, a significantly lower proportion were detected by smear microscopy compared with MTB/RIF (58%, 95% CI 39% to 75% versus 93%, 77% to 98%; p<0.001). Of the 127 patients who were culture negative, 96% (91% to 98%) were MTB/RIF negative. When phase two was compared with phase one, MTB/RIF reduced the median days to TB detection (29 (18–41) to 0 (0–0); p<0.001). However, more patients initiated empirical therapy (absence of a positive test in those commencing treatment) in phase one versus phase two (79% (11/14) versus 28% (10/25); p=0.026). Consequently, there was no detectable difference in the overall proportion of patients initiating treatment (26% (17/67; 17% to 37%) versus 36% (26/73; 26% to 47%); p=0.196) or the days to treatment initiation (10 (1–49) versus 7 (0–21); p=0.330). BALF centrifugation, HIV coinfection and a second MTB/RIF did not result in detectable changes in accuracy. Conclusions MTB/RIF detected TB cases more accurately and more rapidly than smear microscopy and significantly reduced the rate of empirical treatment. PMID:23811536

Is introducing rapid culture into the diagnostic algorithm of smear-negative tuberculosis cost-effective?

PubMed

Yakhelef, N; Audibert, M; Varaine, F; Chakaya, J; Sitienei, J; Huerga, H; Bonnet, M

2014-05-01

In 2007, the World Health Organization recommended introducing rapid Mycobacterium tuberculosis culture into the diagnostic algorithm of smear-negative pulmonary tuberculosis (TB). To assess the cost-effectiveness of introducing a rapid non-commercial culture method (thin-layer agar), together with Löwenstein-Jensen culture to diagnose smear-negative TB at a district hospital in Kenya. Outcomes (number of true TB cases treated) were obtained from a prospective study evaluating the effectiveness of a clinical and radiological algorithm (conventional) against the alternative algorithm (conventional plus M. tuberculosis culture) in 380 smear-negative TB suspects. The costs of implementing each algorithm were calculated using a 'micro-costing' or 'ingredient-based' method. We then compared the cost and effectiveness of conventional vs. culture-based algorithms and estimated the incremental cost-effectiveness ratio. The costs of conventional and culture-based algorithms per smear-negative TB suspect were respectively €39.5 and €144. The costs per confirmed and treated TB case were respectively €452 and €913. The culture-based algorithm led to diagnosis and treatment of 27 more cases for an additional cost of €1477 per case. Despite the increase in patients started on treatment thanks to culture, the relatively high cost of a culture-based algorithm will make it difficult for resource-limited countries to afford.

A Eu/Tb-mixed MOF for luminescent high-temperature sensing

NASA Astrophysics Data System (ADS)

Wang, Huizhen; Zhao, Dian; Cui, Yuangjing; Yang, Yu; Qian, Guodong

2017-02-01

Temperature measurements and thermal mapping using luminescent MOF operating in the high-temperature range are of great interest in the micro-electronic diagnosis. In this paper, we report a thermostable Eu/Tb-mixed MOF Eu0.37Tb0.63-BTC-a exhibiting strong luminescence at elevated temperature, which can serve as a ratiometric luminescent thermometer for high-temperature range. The high-temperature operating range (313-473 K), high relative sensitivity and accurate temperature resolution, make such a Eu/Tb-mixed MOF useful for micro-electronic diagnosis.

COMPARISON OF GeneXpert MTB/RIF ASSAY WITH CONVENTIONAL AFB SMEAR FOR DIAGNOSIS OF PULMONARY TUBERCULOSIS IN NORTHEASTERN THAILAND.

PubMed

Reechaipichitkul, Wipa; Suleesathira, Tanapong; Chaimanee, Prajaub

2017-03-01

Among infectious agents, Mycobacterium tuberculosis remains one of the most significant causes of death worldwide. Rapid and accurate diagnosis of pulmonary tuberculosis (TB) remains a great challenge. GeneXpert MTB/RIF assay is a novel integrated diagnostic system for rapid diagnosis of TB and particularly of rifampicin-resistant strains. A study was conducted between January 2010 and December 2014 to compare the performance of the sputum GeneXpert MTB/RIF assay with the conventional sputum AFB smear for diagnosis of active pulmonary TB in Thailand, a country with a high burden of this disease. Of the 125 patients who had cough and/or prolonged fever together with abnormal chest radiograph, 63 were diagnosed as having pulmonary TB by mycobacterium culture assay, while the remaining subjects were considered of having TB-like conditions, viz non-tuberculous mycobacterium infection (NTM), bacterial pneumonia or bronchogenic carcinoma. Two-thirds of the patients had underlying diseases, eg, diabetes mellitus (19 patients), autoimmune diseases (14), and HIV (6). Among patients with positive diagnosis of M. tuberculosis infection, 30 were AFB smear positive and 53 by sputum GeneXpert MTB/RIF method; among patients negative for M. tuberculosis infection, 4 were AFB smear positive and 5 by GeneXpert MTB/ RIF assay. Sensitivity and specificity of the sputum AFB smear and GeneXpertMTB/ RIF assay test were 48% (95% CI: 35-61) and 84% (95% CI: 73-92), and 94% (95% CI: 84-98) and 92% (95% CI: 82-97), respectively. Diagnostic performance of the GeneXpert MTB/RIF assay among AFB smear positive patients was higher than among AFB smear negative patients (adjusted OR 6.7; 95% CI: 2.3-19.9). Earlier diagnosis of pulmonary TB using GeneXpert MTB/RIF assay will lead to earlier appropriate treatment and provide opportunities to interrupt TB transmission.

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

PubMed Central

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

2015-01-01

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

Catching the missing million: experiences in enhancing TB & DR-TB detection by providing upfront Xpert MTB/RIF testing for people living with HIV in India.

PubMed

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9-29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6-14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV.

Catching the Missing Million: Experiences in Enhancing TB & DR-TB Detection by Providing Upfront Xpert MTB/RIF Testing for People Living with HIV in India

PubMed Central

Raizada, Neeraj; Sachdeva, Kuldeep Singh; Sreenivas, Achuthan; Kulsange, Shubhangi; Gupta, Radhey Shyam; Thakur, Rahul; Dewan, Puneet; Boehme, Catharina; Paramsivan, Chinnambedu Nainarappan

2015-01-01

Background A critical challenge in providing TB care to People Living with HIV (PLHIV) is establishing an accurate bacteriological diagnosis. Xpert MTB/RIF, a highly sensitive and specific rapid tool, offers a promising solution in addressing these challenges. This study presents results from PLHIV taking part in a large demonstration study across India wherein upfront Xpert MTB/RIF testing was offered to all presumptive PTB cases in public health facilities. Method The study covered a population of 8.8 million across 18 sub-district level tuberculosis units (TU), with one Xpert MTB/RIF platform established at each TU. All HIV-infected patients suspected of TB (both TB and Drug Resistant TB (DR-TB)) accessing public health facilities in study area were prospectively enrolled and provided upfront Xpert MTB/RIF testing. Result 2,787 HIV-infected presumptive pulmonary TB cases were enrolled and 867 (31.1%, 95% Confidence Interval (CI) 29.4‒32.8) HIV-infected TB cases were diagnosed under the study. Overall 27.6% (CI 25.9–29.3) of HIV-infected presumptive PTB cases were positive by Xpert MTB/RIF, compared with 12.9% (CI 11.6–14.1) who had positive sputum smears. Upfront Xpert MTB/RIF testing of presumptive PTB and DR-TB cases resulted in diagnosis of 73 (9.5%, CI 7.6‒11.8) and 16 (11.2%, CI 6.7‒17.1) rifampicin resistance cases, respectively. Positive predictive value (PPV) for rifampicin resistance detection was high 97.7% (CI 89.3‒99.8), with no significant difference with or without prior history of TB treatment. Conclusion The study results strongly demonstrate limitations of using smear microscopy for TB diagnosis in PLHIV, leading to low TB and DR-TB detection which can potentially lead to either delayed or sub-optimal TB treatment. Our findings demonstrate the usefulness and feasibility of addressing this diagnostic gap with upfront of Xpert MTB/RIF testing, leading to overall strengthening of care and support package for PLHIV. PMID:25658091

Scale-up of collaborative TB/HIV activities in Guyana.

PubMed

Baker, Brian J; Peterson, Brandy; Mohanlall, Jeetendra; Singh, Shanti; Hicks, Collene; Jacobs, Ruth; Ramos, Ruth; Allen, Barbara; Pevzner, Eric

2017-04-20

To assess scale-up of recommended tuberculosis (TB)/HIV activities in Guyana and to identify specific strategies for further expansion. Medical records and clinic registers were reviewed at nine TB clinics and 10 HIV clinics. At TB clinics, data were collected on HIV testing and antiretroviral therapy (ART) for patients with TB/HIV; at HIV clinics, data were collected on intensified case finding (ICF), tuberculin skin test (TST) results, and provision of isoniazid preventive therapy (IPT). At TB clinics, among 461 patients newly diagnosed with TB, 419 (90.9%) had a known HIV status and 121 (28.9%) were HIV-infected. Among the 63 patients with TB/HIV, 33 (52.4%) received ART. Among the 45 patients with TB/HIV for whom dates of HIV diagnosis were available, 38 (84.4%) individuals knew their HIV status prior to TB diagnosis. At HIV clinics, among 127 patients eligible to receive a TST, 87 (68.5%) received a TST, 66 (75.9%) had a TST result, seven (10.6%) had a newly positive result, two had a previously positive result, and six of nine patients with positive results (66.7%) received IPT. ICF could not be assessed because of incomplete or discrepant documentation. An in-depth evaluation of TB/HIV activities successfully identified areas of success and remaining challenges. At TB clinics, HIV testing rates are high; further scale-up of ART for persons with TB/HIV is needed. At HIV clinics, use of TST to focus IPT is a feasible and efficient strategy; improving rates of annual TST screening will allow for further expansion of IPT.

[A study of the value of three molecular diagnostic techniques in the diagnosis of tuberculosis].

PubMed

Huang, Fang; Dang, Liyun; Sun, Huiping; Yang, Han; Wu, Xia

2015-09-01

To evaluate the diagnostic value of real-time fluorescent RNA isothermal amplification detection technology (simultaneous amplification and testing, SAT), Mycobacterium nucleic acid detection (PCR-fluorescence probe)method (TB-NTM-PCR) and Xpert MTB/RIF detection in the diagnosis of tuberculosis. A total of 378 sputum specimens from pulmonary tuberculosis patients were collected between April to July 2014 in Xi'an Thoracic Tumor and Tuberculosis Hospital. The specimens were detected by 5 methods at the same time including acid-fast stain, SAT method, TB-NTM-PCR method, TB 960 rapid liquid culture and Xpert MTB/RIF. The sensitivity and specificity of SAT method, TB-NTM-PCR method and Xpert MTB/RIF were calculated according to the results of TB 960 rapid liquid culture and staining. The difference among all the 3 methods was analyzed by Chi-squared test. The positive rate of SAT-TB,TB-NTM-PCR and Xpert MTB/RIF were 37.6% (142/378), 37.8% (143/378) and 53.4% (202/378), respectively. In specimens both positive for acid-fast stain and culture, the positive rate of SAT method was 84.6% (77/91), that of TB-NTM-PCR was 91.2% (83/91), and that of Xpert MTB/RIF was 96.7% (88/91), the difference being significant (P=0.018 2). In specimens negative for acid-fast stain but positive for culture, the positive rate of SAT method was 61.9% (60 /97), that of TB-NTM-PCR was 44.3% (43/97), and that of Xpert MTB/RIF was 80.4% (78/97), the difference being significant (P<0.000 1). In specimens both negative for acid-fast stain and culture, the positive rate of SAT method was 1.6% (3/185), that of TB-NTM-PCR was 6.5% (12/185), and that of Xpert MTB/RIF was 16.8% (31/185), the difference being significant (P=0.018). In specimens positive for acid-fast stain but negative for culture, the number of positive samples of SAT,TB-NTM-PCR and Xpert MTB/RIF were 3 (3/5), 5 (5/5),and 5 (5/5), respectively. With the result of TB 960 rapid liquid culture and staining as the reference, Xpert MTB

Tuberculin skin testing and T-SPOT.TB in internationally adopted children.

PubMed

Spicer, Kevin B; Turner, Joanne; Wang, Shu-Hua; Koranyi, Katalin; Powell, Dwight A

2015-06-01

Diagnosis of latent tuberculosis infection is a problem in children because of lack of a diagnostic standard and potential impact of previous Bacille Calmette-Guérin vaccination and exposure to environmental mycobacteria. Effectiveness and usefulness of interferon-gamma release assays in infants and younger children have yet to be clearly demonstrated. Prospective cohort study including 109 children (4 months to 16 years) seen in an international adoption clinic at Nationwide Children's Hospital, Columbus, OH. Children were adopted from 14 countries, mostly (72.5%) from China, Russia and Ethiopia. Correspondence between tuberculin skin test (TST) and the T-SPOT.TB assay was evaluated. Factors associated with positive results on the TST and T-SPOT.TB were determined, and the impact of age on test performance was specifically addressed. TST was positive in 23.4% (25 of 107). T-SPOT.TB was positive in 4.6% (5 of 109). Overall agreement between TST and T-SPOT.TB was 71%, with prevalence-adjusted, bias-adjusted Kappa of 0.68. History of Mycobacterium tuberculosis exposure was associated with positive results on TST (odds ratio: 25.4, 95% confidence interval: 4.8-261.6, exact logistic regression) and T-SPOT.TB (odds ratio: 78.9, 95% confidence interval: 9.7-∞). All 5 children with positive T-SPOT.TB had TST induration ≥15 mm. No patient less than 1 year of age (n = 17) had positive TST or T-SPOT.TB. Positive TST was not associated with Bacille Calmette-Guérin vaccination or scar. TST was positive in a significant percentage of international adoptees. T-SPOT.TB was rarely positive and discordant results reflected negative T-SPOT.TB with positive TST. In this population latent tuberculosis infection may be over-estimated by TST. Regardless, in our context at the time of the study, treatment decisions were based upon TST results, not results of the T-SPOT.TB assay. Age was consistently associated with findings on TST and T-SPOT.TB with no positive result on either

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

PubMed

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

2017-05-01

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

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

PubMed

Rahman, Md Arifur; Sarkar, Atanu

2017-07-01

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

LPA or GeneXpert in the diagnosis of multidrug-resistant tuberculosis.

PubMed

Mindru, Roxana; Spinu, Victor; Popescu, Oana

2016-01-01

Facing a constant increase of multidrug-resistant tuberculosis (MDR-TB), there is large need for routine use of new diagnostic tests, based on molecular techniques that allow both a rapid diagnosis for TB complex and rapid identification of resistance mutations. The resistances are due to genetic factors: accumulation of changes within the genome structure, acquisition or loss of genes, spontaneous mutations in chromosomal genes, and changes that induce selection of resistant strains during a suboptimal treatment. The bacteriology laboratory plays a crucial role in the making of the diagnosis, monitoring and preventing TB transmission. World Health Organization offers consistent recommendations in favour of use of Xpert MTB/RIF, GeneXpert platform, as initial diagnostic test in adults and children suspected of TB, because it can simultaneously determine the presence of Mycobacterium tuberculosis and the Rifampicin resistance, which is a surrogate marker of MDR strains. The very high sensibility and specificity, also in the smear negative samples, as well as the short time needed for the results, make Xpert MTB/RIF a valuable tool in the fight against TB. Other recommended tests are: LPA, which identifies M. Tuberculosis complex, the Rifancim and Isoniazid resistance; MTBDR plus or, for second line anti-TB drugs, the MTBDRsl.

The impact of HIV status and antiretroviral treatment on TB treatment outcomes of new tuberculosis patients attending co-located TB and ART services in South Africa: a retrospective cohort study.

PubMed

Nglazi, Mweete D; Bekker, Linda-Gail; Wood, Robin; Kaplan, Richard

2015-11-19

The implementation of collaborative TB-HIV services is challenging. We, therefore, assessed TB treatment outcomes in relation to HIV infection and antiretroviral therapy (ART) among TB patients attending a primary care service with co-located ART and TB clinics in Cape Town, South Africa. In this retrospective cohort study, all new TB patients aged ≥ 15 years who registered and initiated TB treatment between 1 October 2009 and 30 June 2011 were identified from an electronic database. The effects of HIV-infection and ART on TB treatment outcomes were analysed using a multinomial logistic regression model, in which treatment success was the reference outcome. The 797 new TB patients included in the analysis were categorized as follows: HIV- negative, in 325 patients (40.8 %); HIV-positive on ART, in 339 patients (42.5 %) and HIV-positive not on ART, in 133 patients (16.7 %). Overall, bivariate analyses showed no significant difference in death and default rates between HIV-positive TB patients on ART and HIV-negative patients. Statistically significant higher mortality rates were found among HIV-positive patients not on ART compared to HIV-negative patients (unadjusted odds ratio (OR) 3.25; 95 % confidence interval (CI) 1.53-6.91). When multivariate analyses were conducted, the only significant difference between the patient categories on TB treatment outcomes was that HIV-positive TB patients not on ART had significantly higher mortality rates than HIV-negative patients (adjusted OR 4.12; 95 % CI 1.76-9.66). Among HIV-positive TB patients (n = 472), 28.2 % deemed eligible did not initiate ART in spite of the co-location of TB and ART services. When multivariate analyses were restricted to HIV-positive patients in the cohort, we found that being HIV-positive not on ART was associated with higher mortality (adjusted OR 7.12; 95 % CI 2.95-18.47) and higher default rates (adjusted OR 2.27; 95 % CI 1.15-4.47). There was no significant difference in death and

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

PubMed

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

2018-01-01

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

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

PubMed Central

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

2018-01-01

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

Diagnosing TB infection in children: analysis of discordances using in vitro tests and the tuberculin skin test.

PubMed

Altet-Gómez, N; De Souza-Galvao, M; Latorre, I; Milà, C; Jiménez, M A; Solsona, J; Cantos, A; Zamora, J J; Ruiz-Manzano, J; Ausina, V; Domínguez, J

2011-05-01

The aim of the present study was to compare the performance of the interferon (IFN)-γ tests (QuantiFERON®-TB Gold In-Tube (QFT-G-IT) and T-SPOT®.TB) with the tuberculin skin test (TST) in diagnosing tuberculosis (TB) infection in children, and to analyse discordant results. This was a prospective study including 98 children from contact-tracing studies and 68 children with TST indurations ≥ 5 mm recruited during public health screenings. Positive IFN-γ tests results were associated with risk of exposure (p<0.0001). T-SPOT.TB was positive in 11 (78.6%) out of 14 cases with active TB and QFT-G-IT in nine (64.3%) out of 14 cases. Sensitised T-cells against Mycobacterium avium were detected in six out of 12 children not vaccinated with bacille Calmette-Guérin (BCG), a TST induration 5-9 mm in diameter and both IFN-γ tests negative. In concordant IFN-γ tests results, a positive correlation was found (p = 0.0001) between the number of responding cells and the amount of IFN-γ released. However, in discordant IFN-γ tests results this correlation was negative (p = 0.371): an increase in the number of spot-forming cells correlated with a decrease in the amount of IFN-γ released. The use of IFN-γ tests is helpful for the diagnosis of TB infection, avoiding cross-reactions with BCG immunisation and nontuberculous mycobacterial infections. The analysis of highly discordant results requires further investigation to elucidate possible clinical implications.

Diagnosis of Pulmonary Tuberculosis in HIV-Positive Patients by Microscopic Observation Drug Susceptibility Assay ▿

PubMed Central

Ha, Dang Thi Minh; Lan, Nguyen Thi Ngoc; Kiet, Vo Sy; Wolbers, Marcel; Hang, Hoang Thi Thanh; Day, Jeremy; Hien, Nguyen Quang; Tien, Nguyen Anh; An, Pham Thuy; Anh, Truong Thi; Oanh, Do Thi Tuong; Hoa, Chau Luong; Chau, Nguyen Thi Minh; Hai, Nguyen Ngoc; Binh, Ngo Thanh; Ngoc, Le Hong; Phuong, Doan Thanh; Quyet, Tran Van; Tuyen, Nguyen Thi Bich; Ha, Vo Thi; Nho, Nguyen Thi; Hoa, Dai Viet; Anh, Phan Thi Hoang; Dung, Nguyen Huy; Farrar, Jeremy; Caws, Maxine

2010-01-01

The microscopic observation drug susceptibility assay (MODS) is a novel and promising test for the early diagnosis of tuberculosis (TB). We evaluated the MODS assay for the early diagnosis of TB in HIV-positive patients presenting to Pham Ngoc Thach Hospital for Tuberculosis and Lung Diseases in southern Vietnam. A total of 738 consecutive sputum samples collected from 307 HIV-positive individuals suspected of TB were tested by smear, MODS, and the mycobacteria growth indicator tube method (MGIT). The diagnostic sensitivity and specificity of MODS compared to the microbiological gold standard (either smear or MGIT) were 87 and 93%, respectively. The sensitivities of smear, MODS, and MGIT were 57, 71, and 75%, respectively, against clinical gold standard (MODS versus smear, P < 0.001; MODS versus MGIT, P = 0.03). The clinical gold standard was defined as patients who had a clinical examination and treatment consistent with TB, with or without microbiological confirmation. For the diagnosis of smear-negative patients, the sensitivities of MODS and MGIT were 38 and 45%, respectively (P = 0.08). The median times to detection using MODS and MGIT were 8 and 11 days, respectively, and they were 11 and 17 days, respectively, for smear-negative samples. The original bacterial/fungal contamination rate of MODS was 1.1%, while it was 2.6% for MGIT. The cross-contamination rate of MODS was 4.7%. In conclusion, MODS is a sensitive, specific, and rapid test that is appropriate for the detection of HIV-associated TB; its cost and ease of use make it particularly useful in resource-limited settings. PMID:20926704

[Diagnostic performance of T-SPOT.TB on peripheral blood in combination with adenosine deaminase on pleural fluid for the diagnosis of tuberculous pleurisy within different age group].

PubMed

Xu, H Y; Zhang, D Q; Ye, J R; Su, S S; Xie, Y P; Chen, C S; Li, Y P

2017-06-27

Objective: To evaluate the performance of T cell enzyme-linked immuno-spot assay (T-SPOT) on peripheral blood in combination with adenosine deaminase (ADA) on pleural fluid for diagnosis of tuberculous (TB) pleurisy within different age groups. Methods: The data of patients with pleural effusion from the Department of Pulmonary and Critical Care Medicine of the First Affiliated Hospital of Wenzhou Medical University from April 2012 to November 2016 were retrospectively analyzed, and the diagnoses of these patients were histopathologically confirmed through medical thoracoscopy. The cases who had confirmed diagnosis, in the same time, received peripheral blood T-SPOT.TB were enrolled. The performance of peripheral blood T-SPOT.TB in combination with pleural fluid ADA on diagnosing TB pleurisy in the younger patients (16-59 years old) and elderly patients (≥60 years old) were analyzed respectively. The sensitivity, specificity and the receiver operating characteristic (ROC) curve were adopted for statistical analysis. Results: A total of 448 cases were finally enrolled, 341(76.1%) confirmed with TB pleurisy, 224 males, 117 females, (47±19) years old; and 107 (23.9%) classified as non-TB pleurisy, 65 males, 42 females, (61±14) years old. There were 285 cases who were classified as younger group, and the other 163 cases were classified as elderly group. The sensitivity and specificity of peripheral blood T-SPOT.TB were 85.4% (204/239) and 71.7% (33/46) in the younger patients, 76.5% (78/102) and 59.0% (36/61) respectively in the elderly patients. The sensitivity of peripheral blood T-SPOT.TB in the younger patients was significantly higher than that in the elderly patients ( P =0.047). The sensitivity and specificity were 99.2% and 95.7% in combination with peripheral blood T-SPOT.TB and pleural fluid ADA respectively in the younger patients. The area under ROC curve (AUC) of T-SPOT.TB in the younger patients was 0.833, AUC of T-SPOT.TB combined with ADA was 0

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

PubMed

Binesh, Fariba; Halvani, Abolhassan

2013-01-01

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

Rapid molecular TB diagnosis: evidence, policy making and global implementation of Xpert MTB/RIF.

PubMed

Weyer, Karin; Mirzayev, Fuad; Migliori, Giovanni Battista; Van Gemert, Wayne; D'Ambrosio, Lia; Zignol, Matteo; Floyd, Katherine; Centis, Rosella; Cirillo, Daniela M; Tortoli, Enrico; Gilpin, Chris; de Dieu Iragena, Jean; Falzon, Dennis; Raviglione, Mario

2013-07-01

If tuberculosis (TB) is to be eliminated as a global health problem in the foreseeable future, improved detection of patients, earlier diagnosis and timely identification of rifampicin resistance will be critical. New diagnostics released in recent years have improved this perspective but they require investments in laboratory infrastructure, biosafety and staff specialisation beyond the means of many resource-constrained settings where most patients live. Xpert MTB/RIF, a new assay employing automated nucleic acid amplification to detect Mycobacterium tuberculosis, as well as mutations that confer rifampicin resistance, holds the promise to largely overcome these operational challenges. In this article we position Xpert MTB/RIF in today's TB diagnostic landscape and describe its additional potential as an adjunct to surveillance and surveys, taking into account considerations of pricing and ethics. In what could serve as a model for the future formulation of new policy on diagnostics, we trace the unique process by which the World Health Organization consulted international expertise and systematically assessed published evidence and freshly emerging experience from the field ahead of its endorsement of the Xpert MTB/RIF technology in 2010, summarise subsequent research findings and guidance on who to test and how, and provide perspectives on scaling up the new technology.

Epidemiology of HIV-TB in Asia.

PubMed

Narain, Jai P; Lo, Ying-Ru

2004-10-01

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

Performance of the TB-LAMP diagnostic assay in reference laboratories: Results from a multicentre study.

PubMed

Pham, Thu Hang; Peter, Jonathan; Mello, Fernanda C Q; Parraga, Tommy; Lan, Nguyen Thi Ngoc; Nabeta, Pamela; Valli, Eloise; Caceres, Tatiana; Dheda, Keertan; Dorman, Susan E; Hillemann, Doris; Gray, Christen M; Perkins, Mark D

2018-03-01

To evaluate the diagnostic performance of TB-LAMP, a manual molecular tuberculosis (TB) detection method, and provide comparison to the Xpert MTB/RIF assay. In a large multicentre study, two sputum samples were collected from participants with TB symptoms in reference laboratories in Peru, South Africa, Brazil, and Vietnam. Each sample was tested with TB-LAMP. The reference standard consisted of four direct smears, four cultures, and clinical and radiological findings. Individuals negative on conventional tests were followed up after 8 weeks. The Xpert MTB/RIF assay was performed on fresh or frozen samples as a molecular test comparison. A total of 1036 adults with suspected TB were enrolled. Among 375 culture-confirmed TB cases with 750 sputum samples, TB-LAMP detected 75.6% (95% confidence interval (CI) 71.8-79.4%), including 97.9% (95% CI 96.4-99.4%) of smear-positive TB samples and 46.6% (95% CI 40.6-52.7%) of smear-negative TB samples. Specificity in 477 culture-negative participants not treated for TB (954 sputum samples) was 98.7% (95% CI 97.9-99.6%). TB-LAMP test results were indeterminate in 0.3% of cases. TB-LAMP detects nearly all smear-positive and half of smear-negative TB cases and has a high specificity when performed in reference laboratories. Performance was similar to the Xpert MTB/RIF assay. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Evaluation of a New IFN-γ Release Assay for Rapid Diagnosis of Active Tuberculosis in a High-Incidence Setting.

PubMed

Li, Gen; Li, Feng; Zhao, Hui-Min; Wen, Han-Li; Li, Hai-Cong; Li, Chun-Ling; Ji, Ping; Xu, Peng; Wu, Kang; Hu, Zhi-Dong; Lu, Shui-Hua; Lowrie, Douglas B; Lv, Jian-Xin; Fan, Xiao-Yong

2017-01-01

Blood-based interferon-gamma (IFN-γ) release assays (IGRAs) have been proven to be useful in the diagnosis of Mycobacterium tuberculosis ( Mtb ) infection. However, IGRAs have not been recommended for clinical practice in most low-income settings due to cost-intensive limitations and shortage of clinical data available. The established T-SPOT. TB assay containing Mtb -specific antigens ESAT-6 and CFP10 are widely used for immunodiagonsis of Mtb infection, but the high cost is one of the restricting factors against its clinical application in the developing countries. More recently, a cost-saving IGRA assay, TS-SPOT, was approved in China. This new assay contains an additional antigen Rv3615c. Rv3615c contains broadly recognized CD4 + and CD8 + epitopes, and T-cell responses to Rv3615c are as specific for Mtb infection as the responses to ESAT-6 and CFP10 in both Mtb -infected humans and M. bovis -infected cattle. Therefore, we assessed the likely effect of inclusion of Rv3615c as stimulus besides ESAT-6 and CFP10 in an IGRA assay and evaluated the performance of TS-SPOT for diagnosis of Mtb infection and active TB compared with T-SPOT. TB . We tested 155 active TB patients, 90 non-TB lung disease patients, and 55 healthy individuals. The results presented an improved positive rate for diagnosis of active TB and Mtb infection, that could be attributable to inclusion of Rv3615c in the mixture of stimulatory antigens. The diagnostic efficiency of TS-SPOT assay for active TB was as follows: sensitivity 80.00%, specificity 83.45%, positive predictive value (PPV) 83.78%, negative predictive value (NPV) 83.45%, positive likelihood ratio (LR+) 4.83, and negative likelihood ratio (LR-) 0.24. The results were similar to those of T-SPOT. TB , with an excellent agreement (κ = 0.91, 95% CI: 0.85-0.95) being observed between these two assays. The sensitivities of the TS-SPOT assay varied for patients with different forms of active TB, with the highest sensitivity for patients

Diagnosis of Tuberculosis Following World Health Organization–Recommended Criteria in Severely Malnourished Children Presenting With Pneumonia

PubMed Central

Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Shahid, Abu S. M. S. B.; Shahunja, K. M.; Das, Sumon Kumar; Faruque, Abu Syed Golam; Bardhan, Pradip Kumar; Ahmed, Tahmeed

2017-01-01

Evidences on diagnosis of tuberculosis (TB) following the World Health Organization (WHO) criteria in children with severe acute malnutrition (SAM) are lacking. We sought to evaluate the WHO criteria for the diagnosis of TB in such children. In this prospective study, we enrolled SAM children aged <5 with radiological pneumonia. We collected induced sputum and gastric lavage for smear microscopy, mycobacterial culture, and Xpert MTB/RIF. Using the last 2 methods as the gold standard, we determined sensitivity, specificity, and positive and negative predictive values of WHO criteria (n = 388). However, Xpert MTB/RIF was performed on the last 214 children. Compared to mycobacterial culture–confirmed TB, sensitivity and specificity (95% confidence interval) of WHO criteria were 40 (14% to 73%) and 84 (80% to 87%), respectively. Compared to culture- and/or Xpert MTB/RIF-confirmed TB, the values were 22% (9% to 43%) and 83 (79% to 87%), respectively. Thus, the good specificity of the WHO criteria may help minimize overtreatment with anti-TB therapy in SAM children, especially in resource-limited settings. PMID:28229100

Diagnosis of Tuberculosis Following World Health Organization-Recommended Criteria in Severely Malnourished Children Presenting With Pneumonia.

PubMed

Chisti, Mohammod Jobayer; Salam, Mohammed Abdus; Shahid, Abu S M S B; Shahunja, K M; Das, Sumon Kumar; Faruque, Abu Syed Golam; Bardhan, Pradip Kumar; Ahmed, Tahmeed

2017-01-01

Evidences on diagnosis of tuberculosis (TB) following the World Health Organization (WHO) criteria in children with severe acute malnutrition (SAM) are lacking. We sought to evaluate the WHO criteria for the diagnosis of TB in such children. In this prospective study, we enrolled SAM children aged <5 with radiological pneumonia. We collected induced sputum and gastric lavage for smear microscopy, mycobacterial culture, and Xpert MTB/RIF. Using the last 2 methods as the gold standard, we determined sensitivity, specificity, and positive and negative predictive values of WHO criteria (n = 388). However, Xpert MTB/RIF was performed on the last 214 children. Compared to mycobacterial culture-confirmed TB, sensitivity and specificity (95% confidence interval) of WHO criteria were 40 (14% to 73%) and 84 (80% to 87%), respectively. Compared to culture- and/or Xpert MTB/RIF-confirmed TB, the values were 22% (9% to 43%) and 83 (79% to 87%), respectively. Thus, the good specificity of the WHO criteria may help minimize overtreatment with anti-TB therapy in SAM children, especially in resource-limited settings.

Implementation Research to Inform the Use of Xpert MTB/RIF in Primary Health Care Facilities in High TB and HIV Settings in Resource Constrained Settings.

PubMed

Muyoyeta, Monde; Moyo, Maureen; Kasese, Nkatya; Ndhlovu, Mapopa; Milimo, Deborah; Mwanza, Winfridah; Kapata, Nathan; Schaap, Albertus; Godfrey Faussett, Peter; Ayles, Helen

2015-01-01

The current cost of Xpert MTB RIF (Xpert) consumables is such that algorithms are needed to select which patients to prioritise for testing with Xpert. To evaluate two algorithms for prioritisation of Xpert in primary health care settings in a high TB and HIV burden setting. Consecutive, presumptive TB patients with a cough of any duration were offered either Xpert or Fluorescence microscopy (FM) test depending on their CXR score or HIV status. In one facility, sputa from patients with an abnormal CXR were tested with Xpert and those with a normal CXR were tested with FM ("CXR algorithm"). CXR was scored automatically using a Computer Aided Diagnosis (CAD) program. In the other facility, patients who were HIV positive were tested using Xpert and those who were HIV negative were tested with FM ("HIV algorithm"). Of 9482 individuals pre-screened with CXR, Xpert detected TB in 2090/6568 (31.8%) with an abnormal CXR, and FM was AFB positive in 8/2455 (0.3%) with a normal CXR. Of 4444 pre-screened with HIV, Xpert detected TB in 508/2265 (22.4%) HIV positive and FM was AFB positive in 212/1920 (11.0%) in HIV negative individuals. The notification rate of new bacteriologically confirmed TB increased; from 366 to 620/ 100,000/yr and from 145 to 261/100,000/yr at the CXR and HIV algorithm sites respectively. The median time to starting TB treatment at the CXR site compared to the HIV algorithm site was; 1(IQR 1-3 days) and 3 (2-5 days) (p<0.0001) respectively. Use of Xpert in a resource-limited setting at primary care level in conjunction with pre-screening tests reduced the number of Xpert tests performed. The routine use of Xpert resulted in additional cases of confirmed TB patients starting treatment. However, there was no increase in absolute numbers of patients starting TB treatment. Same day diagnosis and treatment commencement was achieved for both bacteriologically confirmed and empirically diagnosed patients where Xpert was used in conjunction with CXR.

The sensitivity and specificity of using a computer aided diagnosis program for automatically scoring chest X-rays of presumptive TB patients compared with Xpert MTB/RIF in Lusaka Zambia.

PubMed

Muyoyeta, Monde; Maduskar, Pragnya; Moyo, Maureen; Kasese, Nkatya; Milimo, Deborah; Spooner, Rosanna; Kapata, Nathan; Hogeweg, Laurens; van Ginneken, Bram; Ayles, Helen

2014-01-01

To determine the sensitivity and specificity of a Computer Aided Diagnosis (CAD) program for scoring chest x-rays (CXRs) of presumptive tuberculosis (TB) patients compared to Xpert MTB/RIF (Xpert). Consecutive presumptive TB patients with a cough of any duration were offered digital CXR, and opt out HIV testing. CXRs were electronically scored as normal (CAD score ≤ 60) or abnormal (CAD score > 60) using a CAD program. All patients regardless of CAD score were requested to submit a spot sputum sample for testing with Xpert and a spot and morning sample for testing with LED Fluorescence Microscopy-(FM). Of 350 patients with evaluable data, 291 (83.1%) had an abnormal CXR score by CAD. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of CXR compared to Xpert were 100% (95%CI 96.2-100), 23.2% (95%CI 18.2-28.9), 33.0% (95%CI 27.6-38.7) and 100% (95% 93.9-100), respectively. The area under the receiver operator curve (AUC) for CAD was 0.71 (95%CI 0.66-0.77). CXR abnormality correlated with smear grade (r = 0.30, p<0.0001) and with Xpert CT(r = 0.37, p<0.0001). To our knowledge this is the first time that a CAD program for TB has been successfully tested in a real world setting. The study shows that the CAD program had high sensitivity but low specificity and PPV. The use of CAD with digital CXR has the potential to increase the use and availability of chest radiography in screening for TB where trained human resources are scarce.

Cost-Effectiveness of Automated Digital Microscopy for Diagnosis of Active Tuberculosis.

PubMed

Jha, Swati; Ismail, Nazir; Clark, David; Lewis, James J; Omar, Shaheed; Dreyer, Andries; Chihota, Violet; Churchyard, Gavin; Dowdy, David W

2016-01-01

Automated digital microscopy has the potential to improve the diagnosis of tuberculosis (TB), particularly in settings where molecular testing is too expensive to perform routinely. The cost-effectiveness of TB diagnostic algorithms using automated digital microscopy remains uncertain. Using data from a demonstration study of an automated digital microscopy system (TBDx, Applied Visual Systems, Inc.), we performed an economic evaluation of TB diagnosis in South Africa from the health system perspective. The primary outcome was the incremental cost per new TB diagnosis made. We considered costs and effectiveness of different algorithms for automated digital microscopy, including as a stand-alone test and with confirmation of positive results with Xpert MTB/RIF ('Xpert', Cepheid, Inc.). Results were compared against both manual microscopy and universal Xpert testing. In settings willing to pay $2000 per incremental TB diagnosis, universal Xpert was the preferred strategy. However, where resources were not sufficient to support universal Xpert, and a testing volume of at least 30 specimens per day could be ensured, automated digital microscopy with Xpert confirmation of low-positive results could facilitate the diagnosis of 79-84% of all Xpert-positive TB cases, at 50-60% of the total cost. The cost-effectiveness of this strategy was $1280 per incremental TB diagnosis (95% uncertainty range, UR: $340-$3440) in the base case, but improved under conditions likely reflective of many settings in sub-Saharan Africa: $677 per diagnosis (95% UR: $450-$935) when sensitivity of manual smear microscopy was lowered to 0.5, and $956 per diagnosis (95% UR: $40-$2910) when the prevalence of multidrug-resistant TB was lowered to 1%. Although universal Xpert testing is the preferred algorithm for TB diagnosis when resources are sufficient, automated digital microscopy can identify the majority of cases and halve the cost of diagnosis and treatment when resources are more scarce and

Evaluating the Auto-MODS Assay, a Novel Tool for Tuberculosis Diagnosis for Use in Resource-Limited Settings

PubMed Central

Wang, Linwei; Mohammad, Sohaib H.; Li, Qiaozhi; Rienthong, Somsak; Rienthong, Dhanida; Nedsuwan, Supalert; Mahasirimongkol, Surakameth; Yasui, Yutaka

2014-01-01

There is an urgent need for simple, rapid, and affordable diagnostic tests for tuberculosis (TB) to combat the great burden of the disease in developing countries. The microscopic observation drug susceptibility assay (MODS) is a promising tool to fill this need, but it is not widely used due to concerns regarding its biosafety and efficiency. This study evaluated the automated MODS (Auto-MODS), which operates on principles similar to those of MODS but with several key modifications, making it an appealing alternative to MODS in resource-limited settings. In the operational setting of Chiang Rai, Thailand, we compared the performance of Auto-MODS with the gold standard liquid culture method in Thailand, mycobacterial growth indicator tube (MGIT) 960 plus the SD Bioline TB Ag MPT64 test, in terms of accuracy and efficiency in differentiating TB and non-TB samples as well as distinguishing TB and multidrug-resistant (MDR) TB samples. Sputum samples from clinically diagnosed TB and non-TB subjects across 17 hospitals in Chiang Rai were consecutively collected from May 2011 to September 2012. A total of 360 samples were available for evaluation, of which 221 (61.4%) were positive and 139 (38.6%) were negative for mycobacterial cultures according to MGIT 960. Of the 221 true-positive samples, Auto-MODS identified 212 as positive and 9 as negative (sensitivity, 95.9%; 95% confidence interval [CI], 92.4% to 98.1%). Of the 139 true-negative samples, Auto-MODS identified 135 as negative and 4 as positive (specificity, 97.1%; 95% CI, 92.8% to 99.2%). The median time to culture positivity was 10 days, with an interquartile range of 8 to 13 days for Auto-MODS. Auto-MODS is an effective and cost-sensitive alternative diagnostic tool for TB diagnosis in resource-limited settings. PMID:25378569

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

PubMed

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

2018-02-01

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

Extensively Drug-Resistant Tuberculosis (XDR-TB) - A Potential Threat in Ireland

PubMed Central

Mc Laughlin, Anne Marie; O’Donnell, Rory A; Gibbons, Noel; Scully, Mary; O’Flangan, Darina; Keane, Joseph

2007-01-01

We describe a case of a 25 year old female from Lithuania who presented with a productive cough. Chest radiograph demonstrated an infiltrate in the left upper lobe and a cavitating lesion in the right middle lobe. Sensitivity testing of her sputum led to a diagnosis of extensively drug-resistant tuberculosis (XDR-TB). This is the first case in Ireland and highlights the need for physicians to be aware of the possibility of XDR-TB. Moreover it underlines the need for improvement in service provision in terms of a TB reference laboratory and TB clinics. PMID:19340317

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

PubMed

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

2015-02-01

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

Implementation of new TB screening requirements for U.S.-bound immigrants and refugees - 2007-2014.

PubMed

Posey, Drew L; Naughton, Mary P; Willacy, Erika A; Russell, Michelle; Olson, Christine K; Godwin, Courtney M; McSpadden, Pamela S; White, Zachary A; Comans, Terry W; Ortega, Luis S; Guterbock, Michael; Weinberg, Michelle S; Cetron, Martin S

2014-03-21

For more than two decades, as the number of tuberculosis (TB) cases overall in the United States has declined, the proportion of cases among foreign-born persons has increased. In 2013, the percentage of TB cases among those born outside the country was 64.6%. To address this trend, CDC has developed strategies to identify and treat TB in U.S.-bound immigrants and refugees overseas. Each year, approximately 450,000 persons are admitted to the United States on an immigrant visa, and 50,000-70,000 are admitted as refugees. Applicants for either an immigrant visa or refugee status are required to undergo a medical examination overseas before being allowed to travel to the United States. CDC is the federal agency with regulatory oversight of the overseas medical examination, and panel physicians appointed by the U.S. Department of State perform the examinations in accordance with Technical Instructions (TI) provided by CDC's Division of Global Migration and Quarantine (DGMQ). Beginning in 1991, the algorithm for TB TI relied on chest radiographs for applicants aged ≥15 years, followed by sputum smears for those with findings suggestive of TB; no additional diagnostics were used. In 2007, CDC issued enhanced standards for TB diagnosis and treatment, including the addition of sputum cultures (which are more sensitive than smears) as a diagnostic tool and treatment delivered as directly observed therapy (DOT). This report summarizes worldwide implementation of the new screening requirements since 2007. In 2012, the year for which the most recent data are available, 60% of the TB cases diagnosed were in persons with smear-negative, but culture-positive, test results. The results demonstrate that rigorous diagnostic and treatment programs can be implemented in areas with high TB incidence overseas.

Rapid Diagnosis of Tuberculosis with the Xpert MTB/RIF Assay in High Burden Countries: A Cost-Effectiveness Analysis

PubMed Central

Vassall, Anna; van Kampen, Sanne; Sohn, Hojoon; Michael, Joy S.; John, K. R.; den Boon, Saskia; Davis, J. Lucian; Whitelaw, Andrew; Nicol, Mark P.; Gler, Maria Tarcela; Khaliqov, Anar; Zamudio, Carlos; Perkins, Mark D.; Boehme, Catharina C.; Cobelens, Frank

2011-01-01

Background Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings. Methods and Findings We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%–85% to 95%–99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28–US$49 to US$133–US$146 and US$137–US$151 per TB case detected when Xpert is used “in addition to” and “as a replacement of” smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert “in addition to” smear microscopy, compared to the base case, range from US$41–$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert “as a replacement of” smear microscopy range from US$52–$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold. Conclusions Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during

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

PubMed Central

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

2014-01-01

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

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

PubMed

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

2015-01-01

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

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

PubMed Central

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

2015-01-01

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

Minimum package for cross-border TB control and care in the WHO European region: a Wolfheze consensus statement

PubMed Central

Dara, Masoud; de Colombani, Pierpaolo; Petrova-Benedict, Roumyana; Centis, Rosella; Zellweger, Jean-Pierre; Sandgren, Andreas; Heldal, Einar; Sotgiu, Giovanni; Jansen, Niesje; Bahtijarevic, Rankica; Migliori, Giovanni Battista

2012-01-01

The World Health Organization (WHO) European region estimates that more than 400,000 tuberculosis (TB) cases occur in Europe, a large proportion of them among migrants. A coordinated public health mechanism to guarantee TB prevention, diagnosis, treatment and care across borders is not in place. A consensus paper describing the minimum package of cross-border TB control and care was prepared by a task force following a literature review, and with input from the national TB control programme managers of the WHO European region and the Wolfheze 2011 conference. A literature review focused on the subject of TB in migrants was carried out, selecting documents published during the 11-yr period 2001–2011. Several issues were identified in cross-border TB control and care, varying from the limited access to early TB diagnosis, to the lack of continuity of care and information during migration, and the availability of, and access to, health services in the new country. The recommended minimum package addresses the current shortcomings and intends to improve the situation by covering several areas: political commitment (including the implementation of a legal framework for TB cross-border collaboration), financial mechanisms and adequate health service delivery (prevention, infection control, contact management, diagnosis and treatment, and psychosocial support). PMID:22653772

Implementation Research to Inform the Use of Xpert MTB/RIF in Primary Health Care Facilities in High TB and HIV Settings in Resource Constrained Settings

PubMed Central

Muyoyeta, Monde; Moyo, Maureen; Kasese, Nkatya; Ndhlovu, Mapopa; Milimo, Deborah; Mwanza, Winfridah; Kapata, Nathan; Schaap, Albertus; Godfrey Faussett, Peter; Ayles, Helen

2015-01-01

Background The current cost of Xpert MTB RIF (Xpert) consumables is such that algorithms are needed to select which patients to prioritise for testing with Xpert. Objective To evaluate two algorithms for prioritisation of Xpert in primary health care settings in a high TB and HIV burden setting. Method Consecutive, presumptive TB patients with a cough of any duration were offered either Xpert or Fluorescence microscopy (FM) test depending on their CXR score or HIV status. In one facility, sputa from patients with an abnormal CXR were tested with Xpert and those with a normal CXR were tested with FM (“CXR algorithm”). CXR was scored automatically using a Computer Aided Diagnosis (CAD) program. In the other facility, patients who were HIV positive were tested using Xpert and those who were HIV negative were tested with FM (“HIV algorithm”). Results Of 9482 individuals pre-screened with CXR, Xpert detected TB in 2090/6568 (31.8%) with an abnormal CXR, and FM was AFB positive in 8/2455 (0.3%) with a normal CXR. Of 4444 pre-screened with HIV, Xpert detected TB in 508/2265 (22.4%) HIV positive and FM was AFB positive in 212/1920 (11.0%) in HIV negative individuals. The notification rate of new bacteriologically confirmed TB increased; from 366 to 620/ 100,000/yr and from 145 to 261/100,000/yr at the CXR and HIV algorithm sites respectively. The median time to starting TB treatment at the CXR site compared to the HIV algorithm site was; 1(IQR 1-3 days) and 3 (2-5 days) (p<0.0001) respectively. Conclusion Use of Xpert in a resource-limited setting at primary care level in conjunction with pre-screening tests reduced the number of Xpert tests performed. The routine use of Xpert resulted in additional cases of confirmed TB patients starting treatment. However, there was no increase in absolute numbers of patients starting TB treatment. Same day diagnosis and treatment commencement was achieved for both bacteriologically confirmed and empirically diagnosed patients

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

PubMed

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

2016-01-01

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

Treatment: Latent TB Infection (LTBI) and TB Disease

MedlinePlus

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MPT64 antigen detection test improves routine diagnosis of extrapulmonary tuberculosis in a low-resource setting: A study from the tertiary care hospital in Zanzibar.

PubMed

Jørstad, Melissa Davidsen; Marijani, Msafiri; Dyrhol-Riise, Anne Ma; Sviland, Lisbet; Mustafa, Tehmina

2018-01-01

Extrapulmonary tuberculosis (EPTB) is a diagnostic challenge. An immunochemistry-based MPT64 antigen detection test (MPT64 test) has reported higher sensitivity in the diagnosis of EPTB compared with conventional methods. The objective of this study was to implement and evaluate the MPT64 test in routine diagnostics in a low-resource setting. Patients with presumptive EPTB were prospectively enrolled at Mnazi Mmoja Hospital, Zanzibar, and followed to the end of treatment. Specimens collected were subjected to routine diagnostics, GeneXpert® MTB/RIF assay and the MPT64 test. The performance of the MPT64 test was assessed using a composite reference standard, defining the patients as tuberculosis (TB) cases or non-TB cases. Patients (n = 132) were classified as confirmed TB (n = 12), probable TB (n = 34), possible TB (n = 18), non-TB (n = 62) and uncategorized (n = 6) cases. Overall, in comparison to the composite reference standard for diagnosis, the sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the MPT64 test was 69%, 95%, 94%, 75% and 82%, respectively. The MPT64 test performance was best in TB lymphadenitis cases (n = 67, sensitivity 79%, specificity 97%) and in paediatric TB (n = 41, sensitivity 100%, specificity 96%). We show that the MPT64 test can be implemented in routine diagnostics in a low-resource setting and improves the diagnosis of EPTB, especially in TB lymphadenitis and in children.

Diagnosis and treatment of paediatric tuberculosis: An insight review.

PubMed

Mandal, Nityananda; Anand, Parveen Kumar; Gautam, Subhash; Das, Shritam; Hussain, Tahziba

2017-08-01

Tuberculosis (TB) is a major public health problem, invading all age groups world-wide. It is an opportunistic infection affecting the individuals alone or with co-infections. Childhood TB is a neglected aspect and a significant health problem in epidemic areas. It constitutes more than 20% of TB incidence. Pediatric TB exists in the shadow of adult TB. The clinicians concentrate on pulmonary manifestation of TB, whereas it is a major problem in both pulmonary and extra-pulmonary infections. The rate of infection with this disease is mostly associated with poverty, social disruption and human immunodeficiency virus (HIV) infection. The diagnosis of extra-pulmonary TB (EPTB) is more difficult than pulmonary TB (PTB). Delayed diagnosis and executive treatment contribute to increase in the mortality rate in endemic areas. This article provides the evidence-based simple and safe screening method, indicating rapid, highly sensitive and specific diagnostic tests for pulmonary and EPTB in children. The most important aspect of treatment is the correct course of anti-tubercular drugs. This review serves the purpose of quick reference for microbiologists, epidemiologists, academicians, students and researchers. It provides guidance regarding early diagnosis and treatment accuracy of pediatric TB.

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

PubMed

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

2016-01-01

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

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

PubMed

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

2017-08-10

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

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

PubMed

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

2016-01-01

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

Costs of providing tuberculosis diagnosis and treatment services in Viet Nam.

PubMed

Minh, H V; Mai, V Q; Nhung, N V; Hoi, L V; Giang, K B; Chung, L H; Kien, V D; Duyen, N T; Ngoc, N B; Anh, T T; Phuong, T B; Ngan, T T; Khanh, P H

2017-09-01

To estimate the cost of providing tuberculosis (TB) diagnosis and treatment packages at different levels of health facilities in Viet Nam. This was a retrospective costing study from the providers' perspective using a standard costing approach. We included typical services for TB diagnosis and treatment based on standard protocols. The least expensive TB service was the 6-month isoniazid preventive therapy regimen for latent tuberculous infection provided by district health centres (US$7.20-14.30, accounting for 0.3-0.7% of Viet Nam's per capita gross domestic product [GDP] of US$2052.30 in 2014). The cost of diagnosing and treating a patient with drug-susceptible TB (the most common type of TB) ranged between US$51.20 and US$180.70, and represented 2.5-8.8% of Viet Nam's per capita GDP in 2014. The most expensive TB service was the diagnosis and treatment of a multidrug-resistant TB case (US$1568.20-2391.20), accounting for 76.4-116.5% of Viet Nam's per capita GDP in 2014). The cost of TB diagnosis and treatment services in Viet Nam varied according to level of health facility, type of TB, different costing options, and different staff cost scenarios.

TB Terms

MedlinePlus

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Impact of Fluoroquinolone Exposure Prior to Tuberculosis Diagnosis on Clinical Outcomes in Immunocompromised Patients.

PubMed

Lee, Ju Young; Lee, Hyun Jung; Kim, Yong Kyun; Yu, Shinae; Jung, Jiwon; Chong, Yong Pil; Lee, Sang-Oh; Choi, Sang-Ho; Shim, Tae Sun; Kim, Yang Soo; Woo, Jun Hee; Kim, Sung-Han

2016-07-01

There have been concerns about an association of fluoroquinolone (FQ) use prior to tuberculosis (TB) diagnosis with adverse outcomes. However, FQ use might prevent clinical deterioration in missed TB patients, especially in those who are immunocompromised, until they receive definitive anti-TB treatment. All adult immunocompromised patients with smear-negative and culture-positive TB at a tertiary care hospital in Korea over a 2-year period were included in this study. Long-term FQ (≥7 days) use was defined as exposure to FQ for at least 7 days prior to TB diagnosis. A total of 194 patients were identified: 33 (17%) in the long-term FQ group and 161 (83%) in the comparator, including a short-term FQ group (n = 23), non-FQ group (n = 78), and a group receiving no antibiotics (n = 60). Patients in the long-term FQ group presented with atypical chest radiologic pattern more frequently than those in the comparator (77% [24/31] versus 46% [63/138]; P = 0.001). The median time from mycobacterial test to positive mycobacterial culture appeared to be longer in the long-term FQ group (8.1 weeks versus 7.7 weeks; P = 0.09), although the difference was not statistically significant. Patients in the long-term FQ group were less likely to receive empirical anti-TB treatment (55% versus 74%; P = 0.03). The median time from mycobacterial test to anti-TB therapy was longer in the long-term FQ group (4.6 weeks versus 2.2 weeks; P < 0.001), but there was no significant difference in FQ resistance (0% versus 3%; P > 0.99) or in the 30-day (6% versus 6%; P > 0.99) or 90-day (12% versus 12%; P > 0.99) mortality rate between the two groups. FQ exposure (≥7 days) prior to TB diagnosis in immunocompromised patients appears not to be associated with adverse outcomes. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

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

PubMed

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

2015-06-04

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

Diagnostic value of ex vivo pleural fluid interferon-gamma versus adapted whole-blood quantiferon-TB gold in tube assays in tuberculous pleural effusion

PubMed Central

Eldin, Eman N.; Omar, Asmaa; Khairy, Mahmoud; Mekawy, Adel H. M.; Ghanem, Maha K.

2012-01-01

BACKGROUND: Noninvasive diagnosis of pleural tuberculosis (TB) remains a challenge due to the paucibacillary nature of the disease. As Mycobacterium tuberculosis (MTB)-specific T cells are recruited into pleural space in TB effusion; their indirect detection may provide useful clinical information. OBJECTIVES: Evaluation of pleural fluid interferon (INF)-γ levels vs Quantiferon–TB Gold In tube assay (QFT- IT) in blood and its adapted variants, using pleural fluid or isolated pleural fluid cells in the diagnosis of pleural TB. METHODS: Thirty-eight patients with pleural effusion of unknown etiology presented at Assiut University Hospital, Egypt, were recruited. Blood and pleural fluid were collected at presentation for INF-γ assays. Ex vivo pleural fluid INF-γ levels, QFT-IT in blood and its adapted variants were compared with final diagnosis as confirmed by other tools including blind and/or thoracoscopic pleural biopsy. RESULTS: The final clinical diagnosis was TB in 20 (53%), malignancy in 10 (26%), and effusion due to other causes in eight patients (21%). Ex vivo pleural fluid INF-γ levels accurately identified TB in all patients and were superior to the QFT-IT assays using blood or pleural fluid (70 and 78% sensitivity, with 60 and 83% specificity, respectively). QFT-IT assay applied to isolated pleural fluid cells had 100% sensitivity and 72% specificity. The optimal cut-off obtained with ROC analysis was 0.73 for TB Gold assay in blood assay, 0.82 IU/ml for the cultured pleural fluid assay, and 0.94 for isolated pleural cells assay. CONCLUSION: The ex vivo pleural fluid INF-γ level is an accurate marker for the diagnosis of pleural TB. QFT- IT assay in peripheral blood or its adapted versions of the assay using pleural fluid and/or washed pleural fluid cells had no diagnostic advantage over pleural fluid INF-γ in the diagnosis of pleural TB. PMID:23189099

Role of Negative Trans-Thoracic Echocardiography in the Diagnosis of Infective Endocarditis.

PubMed

Leitman, Marina; Peleg, Eli; Shmueli, Ruthie; Vered, Zvi

2016-07-01

The search for the presence of vegetations in patients with suspected infective endocarditis is a major indication for trans-esophageal echocardiographic (TEE) examinations. Advances in harmonic imaging and ongoing improvement in modern echocardiographic systems allow adequate quality of diagnostic images in most patients. To investigate whether TEE examinations are always necessary for the assessment of patients with suspected infective endocarditis. During 2012-2014 230 trans-thoracic echo (TTE) exams in patients with suspected infective endocarditis were performed at our center. Demographic, epidemiological, clinical and echocardiographic data were collected and analyzed, and the final clinical diagnosis and outcome were determined. Of 230 patients, 24 had definite infective endocarditis by clinical assessment. TEE examination was undertaken in 76 of the 230 patients based on the clinical decision of the attending physician. All TTE exams were classified as: (i) positive, i.e., vegetations present; (ii) clearly negative; or (iii) non-conclusive. Of the 92 with clearly negative TTE exams, 20 underwent TEE and all were negative. All clearly negative patients had native valves, adequate quality images, and in all 92 the final diagnosis was not infective endocarditis. Thus, the negative predictive value of a clearly negative TTE examination was 100%. In patients with native cardiac valves referred for evaluation for infective endocarditis, an adequate quality TTE with clearly negative examination may be sufficient for the diagnosis.

TB Meningitis in HIV-Positive Patients in Europe and Argentina: Clinical Outcome and Factors Associated with Mortality

PubMed Central

Efsen, Anne Marie W.; Panteleev, Alexander M.; Grint, Daniel; Podlekareva, Daria N.; Vassilenko, Anna; Rakhmanova, Aza; Zeltina, Indra; Losso, Marcelo H.; Miller, Robert F.; Caylá, Joan; Post, Frank A.; Miro, Jose M.; Bruyand, Mathias; Lundgren, Jens D.; Mocroft, Amanda; Kirk, Ole

2013-01-01

Objectives. The study aimed at describing characteristics and outcome of tuberculous meningitis (TBM) in HIV-positive patients and comparing these parameters with those of extrapulmonary TB (TBEP) and pulmonary TB (TBP). Methods. Kaplan-Meier estimation and Poisson regression models were used to assess the mortality following TB diagnosis and to evaluate potential prognostic factors for the 3 groups of TB patients separately. Results. A total of 100 patients with TBM, 601 with TBEP, and 371 TBP were included. Patients with TBM had lower CD4 cell counts and only 17.0% received antiretroviral therapy (ART) at TB diagnosis. The cumulative probability of death at 12 months following TB was 51.2% for TBM (95% CI 41.4–61.6%), 12.3% for TBP (8.9–15.7%), and 19.4% for TBEP (16.1–22.6) (P < 0.0001; log-rank test). For TBM, factors associated with a poorer prognosis were not being on ART (adjusted incidence rate ratio (aIRR) 4.00 (1.72–9.09), a prior AIDS diagnosis (aIRR = 4.82 (2.61–8.92)), and receiving care in Eastern Europe (aIRR = 5.41 (2.58–11.34))). Conclusions. TBM among HIV-positive patients was associated with a high mortality rate, especially for patients from Eastern Europe and patients with advanced HIV-infection, which urgently calls for public health interventions to improve both TB and HIV aspects of patient management. PMID:24699884

Poor outcome is associated with delayed tuberculosis diagnosis in HIV-infected children in Baja California, Mexico.

PubMed

Viani, R M; Lopez, G; Chacón-Cruz, E; Hubbard, P; Spector, S A

2008-04-01

To describe the morbidity and mortality associated with tuberculosis (TB) in human immunodeficiency virus (HIV) infected children in Baja California, Mexico. Retrospective review of the medical records of all children with perinatally acquired HIV infection evaluated at Tijuana General Hospital with a diagnosis of TB between 1998 and 2007. The Stegen-Toledo (ST) clinical criteria for the diagnosis of TB were used. A total of 73 HIV-infected children were followed during the study period. Thirteen (18%) children were diagnosed with TB; one was confirmed by culture to be positive. Among these children, the mean ages at HIV and TB diagnosis were respectively 3.6 and 5.3 years. The mean ST score was 8.1; 10/13 had a score of >or=7, or highly probable TB. There were a cumulative 29 hospital admissions prior to TB diagnosis; 24 of these were due to pneumonia. The mean duration of symptoms at TB diagnosis was 73 days. The most common symptoms were cough (92%) and anorexia (85%). Seven patients (54%) had disseminated TB and five (39%) died as a consequence of TB. We observed high morbidity, hospital utilization and high mortality associated with TB among HIV-infected children in Baja California.

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

PubMed

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

2018-03-01

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

Impact of the Mycobaterium africanum West Africa 2 Lineage on TB Diagnostics in West Africa: Decreased Sensitivity of Rapid Identification Tests in The Gambia.

PubMed

Ofori-Anyinam, Boatema; Kanuteh, Fatoumatta; Agbla, Schadrac C; Adetifa, Ifedayo; Okoi, Catherine; Dolganov, Gregory; Schoolnik, Gary; Secka, Ousman; Antonio, Martin; de Jong, Bouke C; Gehre, Florian

2016-07-01

MPT64 rapid speciation tests are increasingly being used in diagnosis of tuberculosis (TB). Mycobacterium africanum West Africa 2 (Maf 2) remains an important cause of TB in West Africa and causes one third of disease in The Gambia. Since the introduction of MPT64 antigen tests, a higher than expected rate of suspected non-tuberculous mycobacteria (NTM) was seen among AFB smear positive TB suspects, which led us to prospectively assess sensitivity of the MPT64 antigen test in our setting. We compared the abundance of mRNA encoded by the mpt64 gene in sputa of patients with untreated pulmonary TB caused by Maf 2 and Mycobacterium tuberculosis (Mtb). Subsequently, prospectively collected sputum samples from presumptive TB patients were inoculated in the BACTEC MGIT 960 System. One hundred and seventy-three acid fast bacilli (AFB)-positive and blood agar negative MGIT cultures were included in the study. Cultures were tested on the day of MGIT positivity with the BD MGIT TBc Identification Test. A random set of positives and all negatives were additionally tested with the SD Bioline Ag MPT64 Rapid. MPT64 negative cultures were further incubated at 37°C and retested until positive. Bacteria were spoligotyped and assigned to different lineages. Maf 2 isolates were 2.52-fold less likely to produce a positive test result and sensitivity ranged from 78.4% to 84.3% at the beginning and end of the recommended 10 day testing window, respectively. There was no significant difference between the tests. We further showed that the decreased rapid test sensitivity was attributable to variations in mycobacterial growth behavior and the smear grades of the patient. In areas where Maf 2 is endemic MPT64 tests should be cautiously used and MPT64 negative results confirmed by a second technique, such as nucleic acid amplification tests, to avoid their misclassification as NTMs.

TB treatment outcomes following directly-observed treatment at an urban outpatient specialist TB facility in South Africa.

PubMed

Kharsany, A B M; Connolly, C; Olowolagba, A; Abdool Karim, S S; Abdool Karim, Q

2006-01-01

The treatment of 450 consecutive new patients with pulmonary TB was evaluated to determine outcome following directly-observed treatment. In all, 176 (39.1%) patients were cured, 23 (5.1%) completed treatment, 80 (17.8%) defaulted treatment, 24 (5.3%) died, 54 (12.0%) were lost to follow-up and 93 (20.7%) were transferred out. Increasing age was significant for death. Males were more likely to default and those with negative pretreatment sputum smears and those who were unemployed were more likely to be lost to follow-up. The overall treatment success rate remains low. Our data suggests that greater emphasis is needed to improve TB treatment success.

Assessment of the influence of direct tobacco smoke on infection and active TB management

PubMed Central

Jiménez-Fuentes, María Ángeles; Maldonado, José; Molina, Israel; González-Díaz, Yoel; Milà, Celia; García-García, Esther; Muriel, Beatriz; Villar-Hernández, Raquel; Laabei, Maisem; Gómez, Andromeda-Celeste; Godoy, Pere; de Souza-Galvão, Maria Luiza; Solano, Segismundo; Jiménez-Ruiz, Carlos A.

2017-01-01

Background Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs). Objective In the present study, we assess the impact of direct tobacco smoking on radiological manifestations, sputum conversion and immune response to Mycobacterium tuberculosis, analyzing IFN-γ secretion by IGRAs. Methods A total of 525 participants were studied: (i) 175 active pulmonary TB patients and (ii) 350 individuals coming from contact tracing studies, 41 of whom were secondary TB cases. Clinical, radiological and microbiological data were collected. T-SPOT.TB and QFN-G-IT were processed according manufacturer’s instructions. Results In smoking patients with active TB, QFN-G-IT (34.4%) and T-SPOT.TB (19.5%) had high frequencies of negative results. In addition, by means of an unconditional logistic regression, smoking was a main factor associated with IGRAs’ false-negative results (aOR: 3.35; 95%CI:1.47–7.61; p<0.05). Smoking patients with active TB presented a high probability of having cavitary lesions (aOR: 1.88; 95%CI:1.02–3.46;p<0.05). Mean culture negativization (months) ± standard deviation (SD) was higher in smokers than in non-smokers (2.47±1.3 versus 1.69±1.4). Latent TB infection (LTBI) was favored in smoking contacts, being a risk factor associated with infection (aOR: 11.57; 95%CI:5.97–22.41; p<0.00005). The IFN-γ response was significantly higher in non-smokers than in smokers. Smoking quantity and IFN-γ response analyzed by IGRAs were dose-dependent related. Conclusions Smoking had a negative effect on radiological manifestations, delaying time of sputum conversion. Our data establish a link between tobacco smoking and TB due to a weakened IFN-γ response caused by direct tobacco smoke. PMID:28837570

Assessment of the influence of direct tobacco smoke on infection and active TB management.

PubMed

Altet, Neus; Latorre, Irene; Jiménez-Fuentes, María Ángeles; Maldonado, José; Molina, Israel; González-Díaz, Yoel; Milà, Celia; García-García, Esther; Muriel, Beatriz; Villar-Hernández, Raquel; Laabei, Maisem; Gómez, Andromeda-Celeste; Godoy, Pere; de Souza-Galvão, Maria Luiza; Solano, Segismundo; Jiménez-Ruiz, Carlos A; Domínguez, Jose

2017-01-01

Smoking is a risk factor for tuberculosis (TB) infection and disease progression. Tobacco smoking increases susceptibility to TB in a variety of ways, one of which is due to a reduction of the IFN-γ response. Consequently, an impaired immune response could affect performance of IFN-γ Release Assays (IGRAs). In the present study, we assess the impact of direct tobacco smoking on radiological manifestations, sputum conversion and immune response to Mycobacterium tuberculosis, analyzing IFN-γ secretion by IGRAs. A total of 525 participants were studied: (i) 175 active pulmonary TB patients and (ii) 350 individuals coming from contact tracing studies, 41 of whom were secondary TB cases. Clinical, radiological and microbiological data were collected. T-SPOT.TB and QFN-G-IT were processed according manufacturer's instructions. In smoking patients with active TB, QFN-G-IT (34.4%) and T-SPOT.TB (19.5%) had high frequencies of negative results. In addition, by means of an unconditional logistic regression, smoking was a main factor associated with IGRAs' false-negative results (aOR: 3.35; 95%CI:1.47-7.61; p<0.05). Smoking patients with active TB presented a high probability of having cavitary lesions (aOR: 1.88; 95%CI:1.02-3.46;p<0.05). Mean culture negativization (months) ± standard deviation (SD) was higher in smokers than in non-smokers (2.47±1.3 versus 1.69±1.4). Latent TB infection (LTBI) was favored in smoking contacts, being a risk factor associated with infection (aOR: 11.57; 95%CI:5.97-22.41; p<0.00005). The IFN-γ response was significantly higher in non-smokers than in smokers. Smoking quantity and IFN-γ response analyzed by IGRAs were dose-dependent related. Smoking had a negative effect on radiological manifestations, delaying time of sputum conversion. Our data establish a link between tobacco smoking and TB due to a weakened IFN-γ response caused by direct tobacco smoke.

Novel behaviors of anomalous Hall effect in TbFeCo ferrimagnetic thin films

NASA Astrophysics Data System (ADS)

Ando, Ryo; Komine, Takashi; Sato, Shiori; Kaneta, Shingo; Hara, Yoshiaki

2018-05-01

We investigate the temperature dependence and the thickness dependence of anomalous Hall effect (AHE) of TbFeCo ultra-thin films under high magnetic field. The sign change on temperature dependence of AHE in 20nm-thick TbFeCo film with rare-earth (RE) rich composition was observed. The AHE sign at low temperature is negative while it gradually becomes positive as the temperature increases. Moreover, the AHE sign for 5nm-thick TbFeCo film remains positive while that for 50nm-thick TbFeCo film remains negative at temperature in the range from 5 K to 400 K. The similar thickness dependence of AHE in TM-rich samples was also observed. From the mean-field approximation, the sign change temperature in AHE is related to the compensation temperature and the existence of interfacial region, which has the TM-rich composition and the weak anisotropy. Therefore, We clarified that the novel behavior of AHE sign changes in TbFeCo thin films with different thickness can be explained by the interfacial layer with weak anisotropy and two phase model.

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

PubMed

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

2017-01-10

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

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

PubMed

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

2018-04-12

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

Determinants of PCR performance (Xpert MTB/RIF), including bacterial load and inhibition, for TB diagnosis using specimens from different body compartments

PubMed Central

Theron, Grant; Peter, Jonny; Calligaro, Greg; Meldau, Richard; Hanrahan, Colleen; Khalfey, Hoosain; Matinyenya, Brian; Muchinga, Tapuwa; Smith, Liezel; Pandie, Shaheen; Lenders, Laura; Patel, Vinod; Mayosi, Bongani M.; Dheda, Keertan

2014-01-01

The determinants of Xpert MTB/RIF sensitivity, a widely used PCR test for the diagnosis of tuberculosis (TB) are poorly understood. We compared culture time-to-positivity (TTP; a surrogate of bacterial load), MTB/RIF TB-specific and internal positive control (IPC)-specific CT values, and clinical characteristics in patients with suspected TB who provided expectorated (n = 438) or induced sputum (n = 128), tracheal aspirates (n = 71), bronchoalveolar lavage fluid (n = 152), pleural fluid (n = 76), cerebral spinal fluid (CSF; n = 152), pericardial fluid (n = 131), or urine (n = 173) specimens. Median bacterial load (TTP in days) was the strongest associate of MTB/RIF positivity in each fluid. TTP correlated with CT values in pulmonary specimens but not extrapulmonary specimens (Spearman's coefficient 0.5043 versus 0.1437; p = 0.030). Inhibition affected a greater proportion of pulmonary specimens than extrapulmonary specimens (IPC CT > 34: 6% (47/731) versus 1% (4/381; p < 0.0001). Pulmonary specimens had greater load than extrapulmonary specimens [TTPs (interquartile range) of 11 (7–16) versus 22 (18–33.5) days; p < 0.0001]. HIV-infection was associated with a decreased likelihood of MTB/RIF-positivity in pulmonary specimens but an increased likelihood in extrapulmonary specimens. Mycobacterial load, which displays significant variation across different body compartments, is the main determinant of MTB/RIF-positivity rather than PCR inhibition. MTB/RIF CT is a poor surrogate of load in extrapulmonary specimens. PMID:25014250

Assessment of current practices in management of childhood TB among frontline clinicians in Southern Nigeria.

PubMed

Chukwu, Joseph N; Ukwaja, Kingsley N; Ekeke, Ngozi; Nwafor, Charles C; Meka, Anthony O; Madichie, Nelson O; Anyim, Moses C; Ogbudebe, Chidubem; Adegbesan, Julie; Ikebudu, Joy; Oshi, Daniel C

2016-07-01

Poor competence of clinicians may be a critical factor responsible for the under-diagnosis of childhood TB in high-burden settings. Our objective was to assess the current practices of management of childhood TB among clinicians in Nigeria. A cross-sectional survey was conducted among clinicians recruited through a three-stage sampling technique from 76 health facilities in Southern Nigeria. A semi-structured questionnaire was administered to all participants. Of 106 clinicians who completed the survey, 73 (68.9%) were <40 years and 67 (63.2%) were males. Also, 14 (13.2%) were paediatricians, 22 (20.8%) were paediatric specialist trainees and 70 (66%) were medical officers in primary and secondary care health facilities. About 94% of the respondents perceived diagnosis of childhood TB a challenge in Nigeria. The overall mean (SD) knowledge score was 3.8±0.9 (maximum 5), and 68 (64.2%) had good knowledge of childhood TB. The mean (SD) appropriate practice score was 4.0±1.7 (maximum 10) and, only 8 (7.5%) of them were considered to have adopted appropriate practices regarding childhood TB care. There are gaps in practices adopted by frontline clinicians in the management of childhood TB in Nigeria. Focused training of health workers on childhood TB care is urgently recommended. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Index-TB Guidelines: Guidelines on extrapulmonary tuberculosis for India

PubMed Central

Sharma, Surendra K.; Ryan, H.; Khaparde, Sunil; Sachdeva, K. S.; Singh, Achintya D.; Mohan, Alladi; Sarin, Rohit; Paramasivan, C N; Kumar, Prahlad; Nischal, Neeraj; Khatiwada, Saurav; Garner, Paul; Tharyan, Prathap

2017-01-01

Extrapulmonary tuberculosis (EPTB) is frequently a diagnostic and therapeutic challenge. It is a common opportunistic infection in people living with HIV/AIDS and other immunocompromised states such as diabetes mellitus and malnutrition. There is a paucity of data from clinical trials in EPTB and most of the information regarding diagnosis and management is extrapolated from pulmonary TB. Further, there are no formal national or international guidelines on EPTB. To address these concerns, Indian EPTB guidelines were developed under the auspices of Central TB Division and Directorate of Health Services, Ministry of Health and Family Welfare, Government of India. The objective was to provide guidance on uniform, evidence-informed practices for suspecting, diagnosing and managing EPTB at all levels of healthcare delivery. The guidelines describe agreed principles relevant to 10 key areas of EPTB which are complementary to the existing country standards of TB care and technical operational guidelines for pulmonary TB. These guidelines provide recommendations on three priority areas for EPTB: (i) use of Xpert MTB/RIF in diagnosis, (ii) use of adjunct corticosteroids in treatment, and (iii) duration of treatment. The guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria, which were evidence based, and due consideration was given to various healthcare settings across India. Further, for those forms of EPTB in which evidence regarding best practice was lacking, clinical practice points were developed by consensus on accumulated knowledge and experience of specialists who participated in the working groups. This would also reflect the needs of healthcare providers and develop a platform for future research. PMID:28862176

Are We Doing Enough to Stem the Tide of Acquired MDR-TB in Countries with High TB Burden? Results of a Mixed Method Study in Chongqing, China

PubMed Central

Li, Ying; Ehiri, John; Oren, Eyal; Hu, Daiyu; Luo, Xingneng; Liu, Ying; Li, Daikun; Wang, Qingya

2014-01-01

Multi-drug resistant tuberculosis (MDR-TB) represents a threat to health and development in countries with high TB burden. China’s MDR-TB prevalence rate of 6.8% is the highest in the world. Interventions to remove barriers against effective TB control, and prevention of MDR-TB are urgently needed in the country. This paper reports a cross-sectional questionnaire survey of 513 pulmonary TB (PTB) patients, and qualitative interviews of 10 healthcare workers (HCWs), and 15 PTB patients. The objective was to assess barriers against effective control of PTB and prevention of MDR-TB by elucidating the perspectives of patients and healthcare providers. Results showed that more than half of the patients experienced patient delay of over 12.5 days. A similar proportion also experienced detection delay of over 30 days, and delay in initiating treatment of over 31 days. Consulting a non-TB health facility ≥3 times before seeking care at TB dispensary was a risk factor for both detection delay [AOR (95% CI): 1.89(1.07, 3.34) and delay in initiating treatment[AOR (95% CI): 1.88 (1.06, 3.36). Results revealed poor implementation of Directly Observed Therapy (DOT), whereby treatment of 34.3% patients was never monitored by HCWs. Only 31.8% patients had ever accessed TB health education before their TB diagnosis. Qualitative data consistently disclosed long patient delay, and indicated that patient’s poor TB knowledge and socioeconomic barriers were primary reasons for patient delay. Seeking care and being treated at a non-TB hospital was an important reason for detection delay. Patient’s long work hours and low income increased risk for treatment non-adherence. Evidence-based measures to improve TB health seeking behavior, reduce patient and detection delays, improve the quality of DOT, address financial and system barriers, and increase access to TB health promotion are urgently needed to address the burgeoning prevalence of MDR-TB in China. PMID:24505476

Cost of Tuberculosis Diagnosis and Treatment in Patients with HIV: A Systematic Literature Review.

PubMed

de Siqueira-Filha, Noemia Teixeira; Legood, Rosa; Cavalcanti, Aracele; Santos, Andreia Costa

2018-04-01

To summarize the costs of tuberculosis (TB) diagnosis and treatment in human immunodeficiency virus (HIV)-infected patients and to assess the methodological quality of these studies. We included cost, cost-effectiveness, and cost-utility studies that reported primary costing data, conducted worldwide and published between 1990 and August 2016. We retrieved articles in PubMed, Embase, EconLit, CINAHL plus, and LILACS databases. The quality assessment was performed using two guidelines-the Consolidated Health Economic Evaluation Reporting Standards and the Tool to Estimate Patient's Costs. TB diagnosis was reported as cost per positive result or per suspect case. TB treatment was reported as cost of TB drugs, TB/HIV hospitalization, and treatment. We analyzed the data per level of TB/HIV endemicity and perspective of analysis. We included 34 articles, with 24 addressing TB/HIV treatment and 10 addressing TB diagnosis. Most of the studies were carried out in high TB/HIV burden countries (82%). The cost of TB diagnosis per suspect case varied from $0.5 for sputum smear microscopy to $175 for intensified case finding. The cost of TB/HIV hospitalization was higher in low/medium TB/HIV burden countries than in high TB/HIV burden countries ($75,406 vs. $2,474). TB/HIV co-infection presented higher costs than TB from the provider perspective ($814 vs. $604 vs. $454). Items such as "choice of discount rate," "patient interview procedures," and "methods used for valuing indirect costs" did not achieve a good score in the quality assessment. Our findings point to the need of generation of more standardized methods for cost data collection to generate more robust estimates and thus, support decision-making process. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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

PubMed

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

2012-01-01

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

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

PubMed

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

2016-11-24

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

A Field Evaluation of the Hardy TB MODS Kit™ for the Rapid Phenotypic Diagnosis of Tuberculosis and Multi-Drug Resistant Tuberculosis

PubMed Central

Martin, Laura; Coronel, Jorge; Faulx, Dunia; Valdez, Melissa; Metzler, Mutsumi; Crudder, Chris; Castillo, Edith; Caviedes, Luz; Grandjean, Louis; Rodriguez, Mitzi; Friedland, Jon S.; Gilman, Robert H.; Moore, David A. J.

2014-01-01

Background Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory. Methods & Findings 2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ), conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct) DST and proportion method (indirect) DST. 778 samples (31.8%) were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals) of the MODS Kit were 99.3% (98.3–99.8%), 98.3% (97.5–98.8%), 95.8% (94.0–97.1%), and 99.7% (99.3–99.9%). Median (interquartile ranges) time to culture-positivity (and rifampicin and isoniazid DST) was 10 (9–13) days for conventional MODS and 8.5 (7–11) for MODS Kit (p<0.01). Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples) and reference indirect DST (97.9% agreement, 687/702 evaluable samples). Conclusions MODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked), readily repurposed for second-line DST in the near future

A field evaluation of the Hardy TB MODS Kit™ for the rapid phenotypic diagnosis of tuberculosis and multi-drug resistant tuberculosis.

PubMed

Martin, Laura; Coronel, Jorge; Faulx, Dunia; Valdez, Melissa; Metzler, Mutsumi; Crudder, Chris; Castillo, Edith; Caviedes, Luz; Grandjean, Louis; Rodriguez, Mitzi; Friedland, Jon S; Gilman, Robert H; Moore, David A J

2014-01-01

Even though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory. 2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ), conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct) DST and proportion method (indirect) DST. 778 samples (31.8%) were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals) of the MODS Kit were 99.3% (98.3-99.8%), 98.3% (97.5-98.8%), 95.8% (94.0-97.1%), and 99.7% (99.3-99.9%). Median (interquartile ranges) time to culture-positivity (and rifampicin and isoniazid DST) was 10 (9-13) days for conventional MODS and 8.5 (7-11) for MODS Kit (p<0.01). Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples) and reference indirect DST (97.9% agreement, 687/702 evaluable samples). MODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked), readily repurposed for second-line DST in the near future, provides a fresh opportunity for improving equity of

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

PubMed

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

2014-05-16

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

Evaluation of a rapid culture method for tuberculosis diagnosis: a Latin American multi-center study.

PubMed

Robledo, J A; Mejía, G I; Morcillo, N; Chacón, L; Camacho, M; Luna, J; Zurita, J; Bodon, A; Velasco, M; Palomino, J C; Martin, A; Portaels, F

2006-06-01

Tuberculosis (TB) diagnostic laboratories in Latin America. Evaluation of thin-layer agar (TLA) compared to Löwenstein-Jensen (LJ) culture for the diagnosis of TB. Phase II prospective study in six laboratories. Samples included sputum and extra-pulmonary specimens from patients with a clinical diagnosis of TB. Respiratory samples were decontaminated using NaOH/ NALC; all samples were centrifuged, stained with Ziehl-Neelsen for acid-fast bacilli (AFB), cultured on LJ and TLA and identified according to recommended procedures. Sensitivity and likelihood ratios (LR), growth detection time and contamination rate were calculated for both media. A total of 1118 clinical specimens were studied. Cultures detected Mycobacterium tuberculosis in all AFB-positive samples, whereas for AFB-negative specimens LJ detected 3.2% and TLA 4.4%. Sensitivity was 92.6% (95%CI 87.9-95.9) and 84.7% (95%CI 78.8-89.0) for TLA and LJ, respectively. Positive and negative LRs were similar. Contamination was 5.1% for TLA and 3.0% for LJ. Median time to detection of a positive culture was 11.5 days (95%CI 9.3-15.0) for TLA and 30.5 days (95%CI 26.9-39.0) for LJ (P < 0.0001). Difference in the characteristics of the participating laboratories, the disease prevalence and the number and type of specimens processed did not affect the overall performance of TLA as compared to LJ, supporting the robustness of the method and its feasibility in different laboratory settings.

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

PubMed

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

2013-01-01

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

Rapid diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis using a molecular-based diagnostic algorithm.

PubMed

Simons, S O; van der Laan, T; Mulder, A; van Ingen, J; Rigouts, L; Dekhuijzen, P N R; Boeree, M J; van Soolingen, D

2014-10-01

There is an urgent need for rapid and accurate diagnosis of pyrazinamide-resistant multidrug-resistant tuberculosis (MDR-TB). No diagnostic algorithm has been validated in this population. We hypothesized that pncA sequencing added to rpoB mutation analysis can accurately identify patients with pyrazinamide-resistant MDR-TB. We identified from the Dutch national database (2007-11) patients with a positive Mycobacterium tuberculosis culture containing a mutation in the rpoB gene. In these cases, we prospectively sequenced the pncA gene. Results from the rpoB and pncA mutation analysis (pncA added to rpoB) were compared with phenotypic susceptibility testing results to rifampicin, isoniazid and pyrazinamide (reference standard) using the Mycobacterial Growth Indicator Tube 960 system. We included 83 clinical M. tuberculosis isolates containing rpoB mutations in the primary analysis. Rifampicin resistance was seen in 72 isolates (87%), isoniazid resistance in 73 isolates (88%) and MDR-TB in 65 isolates (78%). Phenotypic reference testing identified pyrazinamide-resistant MDR-TB in 31 isolates (48%). Sensitivity of pncA sequencing added to rpoB mutation analysis for detecting pyrazinamide-resistant MDR-TB was 96.8%, the specificity was 94.2%, the positive predictive value was 90.9%, the negative predictive value was 98.0%, the positive likelihood was 16.8 and the negative likelihood was 0.03. In conclusion, pyrazinamide-resistant MDR-TB can be accurately detected using pncA sequencing added to rpoB mutation analysis. We propose to include pncA sequencing in every isolate with an rpoB mutation, allowing for stratification of MDR-TB treatment according to pyrazinamide susceptibility. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

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

PubMed

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

2016-01-01

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

Mixing Enthalpies of TbBr3-MBr Liquid Mixtures

NASA Astrophysics Data System (ADS)

Rycerz, L.; Gaune-Escard, M.

2001-12-01

The molar enthalpies of mixing, Δmix Hm in the binary liquid systems TbBr3-MBr (M = Li, Na, K, Rb, Cs) have been m easured with a Calvet-type high-tem perature microcalorimeter over the entire composition range with an accuracy of about 6 %. Mixing of the two liquid components was achieved by using the "break-off am poule" technique. All the investigated systems show negative enthalpies of mixing with a minim um value of approxim ately -1.25, - 8 .3 , -17.0, - 2 0 . 0 and -22.5 kJ mol -1, for M = Li, Na, K, Rb and Cs, respectively. The mixing enthalpy in the TbBr3- LiBr system is positive in the TbBr3-rich region. For all the systems, the enthalpy minimum occurs at mole fraction xTbBr3 ≈ 0.3 - 0.4. The molar enthalpies of form ation Δ formHm (3MBr, TbBr3, 1) for M = Li, Na, K, Rb and Cs at 1113 K (arising from the reaction 3M Br(1) +TbBr3(1) = (3MBr, TbBr3) (1)) are found to be -4 .8 , -31.3, -63.3, -70.3 and -8 1 .2 kJ mol-1 , respectively. The leastsquares coefficients A, B, C, D and E in the equation λ (kJ mol-1) = A + B x + C x2 + Dx3 + Ex4, where A is an interaction param eter and x = xTbBr , are also reported.

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

PubMed Central

2014-01-01

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

'Multiple-test' approach to the laboratory diagnosis of tuberculosis -perception of medical doctors from Ujjain, India.

PubMed

Purohit, Manju Raj; Sharma, Megha; Rosales-Klintz, Senia; Lundborg, Cecilia Stålsby

2015-08-11

Delay in diagnosis is one of the most important factors for the control of tuberculosis (TB) in endemic countries like India. As laboratory diagnosis is the mainstay for identification of active disease, we aim to explore and understand the opinions of medical doctors about the laboratory diagnosis of TB in Ujjain, India. Sixteen qualified specialist medical doctors from Ujjain were purposefully selected for the study. Individual interviews with the doctors (13 men and 3 women), were conducted. As one interview could not be completed, data from 15 interviews were analyzed using manifest and latent content analysis. Based on perception of the doctors, the theme; 'challenges and need for the laboratory diagnosis of TB' emerged from the following subthemes: (i) Relationship between basic element of the TB diseases process such as 'Symptoms prior to diagnoses' and 'Clinical characteristics of TB', which were not specific enough to diagnose TB (ii) The prevailing conditions such as lack of explicit diagnostic tools, lead to the doctors using the 'multiple tests' or 'empiric treatment' approach (iii) The doctors proposed that there is a need for access to a rapid, single and simple diagnostic test, and a need for awareness and knowledge of the practitioners regarding specific TB investigations, and early referral to improve the situation at resource-limited settings. The medical specialists use a 'multiple test' or 'empiric treatment' approach to diagnose TB. According to the participants, there is a low dependence and uptake of the available laboratory TB investigations by medical practitioners. There is an urgent need to have a specific, simple and reliable test, and a protocol, to improve diagnosis of TB and to prevent development of resistant TB.

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.

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

PubMed

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

2015-01-01

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

Evaluation of Loopamp™MTBC detection kit for diagnosis of pulmonary tuberculosis at a peripheral laboratory in a high burden setting.

PubMed

Nguyen, Van Anh Thi; Nguyen, Hung Van; Dinh, Thuong Van; Du, Ha Hoang; Do, Chinh Nhu; Marks, Guy B; Nguyen, Nhung Viet

2018-03-01

The Loopamp™MTBC detection kit (TB-LAMP) was designed to replace the sputum smear microscopy for the diagnosis of pulmonary tuberculosis. We evaluated its performance at a peripheral laboratory in Vietnam. The sensitivity of TB-LAMP was 45.5% (28.1%-63.6%), which was equal to 3-sputum smear microscopy but lower than that of Xpert MTB/RIF (87.8% [71.8%-96.6%]). In patients with culture-confirmed TB, sensitivity was 80% (51.9%-95.7%) in smear-positive and 16.7% (3.5%-41.4%) in smear-negative cases. The specificity of TB-LAMP was 95.1% (92.7%-96.9%), which was lower than that of smear microscopy (98.9% [97.5%-99.7%]) and Xpert MTB/RIF (99.3% [98.1%-99.9%]) (P<0.05). The probability of TB detection by TB-LAMP was more influenced by sample quality and viscosity than were smear microscopy, Xpert MTB/RIF, and culture. The present data do not support the use of TB-LAMP as a replacement test for smear microscopy in peripheral laboratories. Copyright © 2017 Elsevier Inc. All rights reserved.

Tuberculin skin test and ELISPOT/T. SPOT.TB in children and adolescents with juvenile idiopathic arthritis

PubMed Central

2014-01-01

Background There are controversies regarding the accuracy of the tuberculin skin test (TST) and methods based on the production of interferon gamma by sensitized T cells for the diagnosis of latent tuberculosis infection (LTBI) in pediatrics and immunosuppressed patients. Our objectives are to study TST and ELISPOT/T. SPOT.TB in the diagnosis of LTBI in children and adolescents with JIA undergoing methotrexate, the correlation between both and the sensitivity and specificity of T. SPOT.TB. Methods This is an observational prospective longitudinal study in which children and adolescents with JIA undergoing methotrexate therapy were assessed for clinical and epidemiological data for LTBI, in addition to performing TST and T. SPOT.TB at baseline and after 3 and 12months. Results There were 24 patients. The prevalence of LTBI at inclusion was 20.8%, the incidence after initiation of immunosuppressions 26.3% and the prevalence at the end of the study 41.6%. Epidemiological history positive for TB showed a relative risk of 2.0 for the development of LTBI. Only 2 patients had positive T. SPOT.TB but only in one it was useful for detecting early LTBI. T. SPOT.TB presented a sensitivity of 10%, specificity of 92.8%, and low correlation with TST. No patient developed TB disease at a mean follow-up of 47months. Conclusions We found a high prevalence of ILTB that doubled with immunosuppression and that epidemiological history was an important relative risk. T. SPOT.TB showed low sensitivity and high specificity, and no superiority over TST. There was low agreement and little influence of immunosuppression on the results of both tests. PMID:24904240

When students become patients: TB disease among medical undergraduates in Cape Town, South Africa.

PubMed

Van der Westhuizen, Helene-Mari; Dramowski, Angela

2017-05-24

Medical students acquire latent tuberculosis (TB) infection at a rate of 23 cases/100 person-years. The frequency and impact of occupational TB disease in this population are unknown. A self-administered questionnaire was distributed via email and social media to current medical students and recently graduated doctors (2010 - 2015) at two medical schools in Cape Town. Individuals who had developed TB disease as undergraduate students were eligible to participate. Quantitative and qualitative data collected from the questionnaire and semi-structured interviews were analysed with descriptive statistics and a framework approach to identify emerging themes. Twelve individuals (10 female) reported a diagnosis of TB: pulmonary TB (n=6), pleural TB (n=3), TB lymphadenitis (n=2) and TB spine (n=1); 2/12 (17%) had drug-resistant disease (DR-TB). Mean diagnostic delay post consultation was 8.1 weeks, with only 42% of initial diagnoses being correct. Most consulted private healthcare providers (general practitioners (n=7); pulmonologists (n=4)), and nine underwent invasive procedures (bronchoscopy, pleural fluid aspiration and tissue biopsy). Substantial healthcare costs were incurred (mean ZAR25 000 for drug-sensitive TB, up to  ZAR104 000 for DR-TB). Students struggled to obtain treatment, incurred high transport costs and missed academic time. Students with DR-TB interrupted their studies and experienced severe side-effects (hepatotoxicity, depression and permanent ototoxicity). Most participants cited poor TB infection-control practices at their training hospitals as a major risk factor for occupational TB. Undergraduate medical students in Cape Town are at high risk of occupationally acquired TB, with an unmet need for comprehensive occupational health services and support.

Mycothiol acetyltransferase (Rv0819) of Mycobacterium tuberculosis is a potential biomarker for direct diagnosis of tuberculosis using patient serum specimens.

PubMed

Zeitoun, H; Bahey-El-Din, M; Kassem, M A; Aboushleib, H M

2017-12-01

Mycobacterium tuberculosis infection constitutes a global threat that results in significant morbidity and mortality worldwide. Efficient and early diagnosis of tuberculosis (TB) is of paramount importance for successful treatment. The aim of the current study is to investigate the mycobacterial mycothiol acetyltransferase Rv0819 as a potential novel biomarker for the diagnosis of active TB infection. The gene encoding Rv0819 was cloned and successfully expressed in Escherichia coli. The recombinant Rv0819 was purified using metal affinity chromatography and was used to raise murine polyclonal antibodies against Rv0819. The raised antibodies were employed for direct detection of Rv0819 in patient serum samples using dot blot assay and competitive enzyme-linked immunosorbent assay (ELISA). Serum samples were obtained from 68 confirmed new TB patients and 35 healthy volunteers as negative controls. The dot blot assay showed sensitivity of 64·7% and specificity of 100%, whereas the competitive ELISA assay showed lower sensitivity (54·4%) and specificity (88·57%). The overall sensitivity of the combined results of the two tests was found to be 89·7%. Overall, the mycobacterial Rv0819 is a potential TB serum biomarker that can be exploited, in combination with other TB biomarkers, for efficient and reliable diagnosis of active TB infection. The early and accurate diagnosis of tuberculosis infection is of paramount importance for initiating treatment and avoiding clinical complications. Most current diagnostic tests have poor sensitivity and/or specificity and in many cases they are too expensive for routine diagnostic testing in resource-limited settings. In the current study, we examined a novel mycobacterial serum biomarker, namely mycothiol acetyltransferase Rv0819. The antigen was detectable in serum specimens of a significant number of tuberculosis patients. This article proves the importance of Rv0819 and paves the way towards its future use as a useful

Evaluation of the Xpert® MTB/RIF assay and microscopy for the diagnosis of Mycobacterium tuberculosis in Namibia.

PubMed

Mavenyengwa, Rooyen T; Shaduka, Emma; Maposa, Innocent

2017-01-11

Tuberculosis (TB) kills approximately two million people and infects around nine million worldwide annually. Its proper management, especially in resource-limited settings, has been hindered by the lack of rapid and easy-to-use diagnostic tests. Sputum smear microscopy remains the cheapest, readily available diagnostic method but it only identifies less than half of the patients with a HIV/TB co-infection because the bacilli would have disseminated from the lungs to other areas of the body. The fully automated Xpert® MTB/RIF assay is a promising innovation for diagnosing TB and detecting resistance to rifampicin. This study aimed to evaluate the use of Xpert® MTB/RIF assay and microscopy in the diagnosis of Mycobacterium tuberculosis in Namibia, by determining the disease's epidemiology and calculating the proportion of cases infected just with TB and those with a resistance to rifampicin among the total suspected cases of TB in the country. This retrospective study analysed TB cases that were diagnosed using both the Xpert® MTB/RIF assay and microscopy. Data were collected from patient records from the Meditech laboratory information system of the Namibia Institute of Pathology for the time period of July 2012-April 2013. Data from 13 regions were collected. The total number of specimens collected from patients with symptoms of pulmonary TB was 1 842. Of these, 594 (32.20%) were found to be positive for MTB by Xpert® MTB/RIF assay, out of which 443 (24.05%) were also found to be positive by microscopy. The remainder was negative. The male patients were more resistant to rifampicin when compared to the female patients. Tuberculosis is widely distributed throughout Namibia, with slightly more males infected than females. Most TB patients are also co-infected with HIV. Both microscopy and Xpert® MTB/RIF assay are crucial for the diagnosis of TB in the country. Screening diagnostic efforts should focus on the sexually active HIV positive male population who could

Factors associated with patient, and diagnostic delays in Chinese TB patients: a systematic review and meta-analysis.

PubMed

Li, Ying; Ehiri, John; Tang, Shenglan; Li, Daikun; Bian, Yongqiao; Lin, Hui; Marshall, Caitlin; Cao, Jia

2013-07-02

Delay in seeking care is a major impediment to effective management of tuberculosis (TB) in China. To elucidate factors that underpin patient and diagnostic delays in TB management, we conducted a systematic review and meta-analysis of factors that are associated with delays in TB care-seeking and diagnosis in the country. This review was prepared following standard procedures of the Cochrane Collaboration and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and checklist. Relevant studies published up to November 2012 were identified from three major international and Chinese literature databases: Medline/PubMed, EMBASE and CNKI (China National Knowledge Infrastructure). We included 29 studies involving 38,947 patients from 17 provinces in China. Qualitative analysis showed that key individual level determinants of delays included socio-demographic and economic factors, mostly poverty, rural residence, lack of health insurance, lower educational attainment, stigma and poor knowledge of TB. Health facility determinants included limited availability of resources to perform prompt diagnosis, lack of qualified health workers and geographical barriers.Quantitative meta-analysis indicated that living in rural areas was a risk factor for patient delays (pooled odds ratio (OR) (95% confidence interval (CI)): 1.79 (1.62, 1.98)) and diagnostic delays (pooled OR (95% CI): 1.40 (1.23, 1.59)). Female patients had higher risk of patient delay (pooled OR (95% CI): 1.94 (1.13, 3.33)). Low educational attainment (primary school and below) was also a risk factor for patient delay (pooled OR (95% CI): 2.14 (1.03, 4.47)). The practice of seeking care first from Traditional Chinese Medicine (TMC) providers was also identified as a risk factor for diagnostic delay (pooled OR (95% CI): 5.75 (3.03, 10.94)). Patient and diagnostic delays in TB care are mediated by individual and health facility factors. Population-based interventions that seek to reduce TB

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 ...

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

PubMed

Zielonka, Tadeusz M

2015-01-01

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

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

PubMed Central

Shaik, Monisha; Danquah, Cynthia Amaning

2017-01-01

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

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

PubMed Central

2015-01-01

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

Comparative performance of Thin Layer Agar and Löwenstein-Jensen culture for diagnosis of tuberculosis.

PubMed

Battaglioli, T; Rintiswati, N; Martin, A; Palupi, K R; Bernaerts, G; Dwihardiani, B; Ahmad, R A; Matthys, F; Mahendradhata, Y; Van der Stuyft, P

2013-11-01

Sputum smear microscopy for the diagnosis of tuberculosis (TB) is cheap and simple but its sensitivity is low. Culture on Löwenstein-Jensen (LJ) is more sensitive but it takes a long time to yield results. Thin-Layer Agar (TLA) culture was suggested as an equally sensitive and faster alternative. We evaluated the performance of TLA for diagnosing TB in Jogjakarta, Indonesia. People with suspected TB presenting from July 2010 to July 2011 to two chest clinics of the National TB Control Programme network of Jogjakarta were eligible for inclusion. A sputum sample was sent to the Gadjah Mada University microbiology laboratory for concentration, smearing, Ziehl-Neelsen staining and culture on LJ and TLA. Sensitivity of cultures was evaluated against a composite reference standard (any positive culture). Time to detection of Mycobacteria was recorded. Out of 1414 samples, 164 (12%) were smear positive, 99 (7%) were scanty and 1151 (81%) were negative. On TLA and LJ respectively, 168 (12%) and 149 (11%) samples were positive, 72 (5%) and 32 (2%) were contaminated (κ = 0.64; 95% CI 0.59-0.69, p <0.01). Using the reference standard, 196 (14%) TB cases were identified. The sensitivity of TLA was 0.86 (95% CI 0.80-0.90), significantly higher (p 0.03) than for LJ (0.76; 95% CI 0.69-0.81). The median time to detection in days was significantly shorter (p <0.01) for TLA (12; 95% CI 11-13) than for LJ (44; 95% CI 43-45). TLA is a rapid and sensitive method for the diagnosis of TB. Implementation studies to evaluate the cost-effectiveness and impact of its introduction into programmatic settings are urgently needed. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

TB questions, East Kwaio answers: community-based participatory research in a remote area of Solomon Islands.

PubMed

Massey, P D; Wakageni, J; Kekeubata, E; Maena'adi, J; Laete'esafi, J; Waneagea, J; Fangaria, G; Jimuru, C; Houaimane, M; Talana, J; MacLaren, D; Speare, R

2012-01-01

East Kwaio is a remote region on the island of Malaita, Solomon Islands. Atoifi Adventist Hospital (the Hospital) is the only hospital and tuberculosis (TB) services provider in the region. If people come to the Hospital with TB, they are usually admitted for the two-month intensive phase of treatment as there are no community-based TB services. Most people walk or travel by canoe to the Hospital as there are no roads. East Kwaio is known to have high rates of TB; however, it has a low case detection rate and low treatment completion. The aims of this study were to explore why people with TB, especially from the mountain areas, present to the Hospital so late in their illness or do not present at all. The study was part of a larger project to strengthen the research capacity of local health workers and community leaders, supported by visiting researchers from Australia. Semi-structured interviews with TB patients, a focus group of key informants and direct interaction with a community with a history of TB were used to explore reasons why people present to the Hospital late in their TB illness. Four interviews and a focus group of 12 key informants were conducted and a mountain hamlet with a history of TB was visited. The results represent the data from the interviews and the focus group. The time delay in presenting to the Hospital from when participants first became unwell ranged between two and three years. In the mountain hamlet, two additional people with probable TB were seen who had not presented to the Hospital during illnesses of five and nine months. Reasons for delays included: seeking care from traditional healers; the challenge of accessing health services due to distance, cost and cultural issues different from the Hospital's worldview; social isolation when in hospital; and being old so not having long to live. Delays in diagnosis of people with TB will increase the risk of transmission to family and through hamlets and villages. This study has led to

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

PubMed

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

2014-01-01

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

Cellular immune response in MDR-TB patients to different protein expression of MDR and susceptible Mycobacterium tuberculosis: Rv0147, a novel MDR-TB biomarker.

PubMed

Hadizadeh Tasbiti, Alireza; Yari, Shamsi; Siadat, Seyed Davar; Tabarsi, Payam; Saeedfar, Kayvan; Yari, Fatemeh

2018-02-01

Tuberculosis (TB) is a crucial public health problem with prevalence of multidrug resistant (MDR) rising. An accurate TB biomarker is urgently needed to monitor the response to treatment in patients with MDR tuberculosis. To analyze interaction between selected MDR-TB purified protein and immune cells, dendritic cells from MDR-TB patients and healthy subjects were stimulated by 55KDa protein fractions (Rv0147). The purified proteins identified by proteomic techniques (two-dimensional gel electrophoresis, mass spectrometry) and peptide sequences are known to bind a MHC class I alleles which are extracted from the Immune Epitope Database and Analysis Resource database ( www.iedb.org ). T cells were isolated from PBMC by negative selection and cells were cultured in RPMI-1640 at 37 °C and 5% CO 2 . Cell culture was assayed for cytokine IL-10 and INF-γ by ELISA. We found that INF-γ production was significantly (335 ± 35.5 pg/ml, P ˂ 0.05) upregulated after protein candidate (Rv0147) stimulation by dendritic cells from MDR-TB patients, whereas IL-10 production was greatly reduced compared with production in healthy subjects (212 ± 9.94 pg/ml, P ˂ 0.05). In fact, the purified protein, Rv0147, stimulated dendritic cells from MDR-TB patients, failed to produce IL-10 and directly stimulates INF-γ production by T cells. These results suggest that the purified protein, Rv0147, may stimulate Th1 type protective cytokine response in MDR-TB patients but not in normal subjects. The production of INF-γ but not IL-10 in the presence of purified protein, Rv0147, may be shifted to Th1 responses in MDR-TB patients and supports its potential as protein vaccine candidates against TB.

Cost Analysis of a Nucleic Acid Amplification Test in the Diagnosis of Pulmonary Tuberculosis at an Urban Hospital with a High Prevalence of TB/HIV

PubMed Central

Wang, Yun F.; Leonard, Michael K.; White, Nancy; McFarland, Deborah A.; Blumberg, Henry M.

2014-01-01

Introduction The Centers for Disease Control and Prevention has recommended using a nucleic acid amplification test (NAAT) for diagnosing pulmonary tuberculosis (TB) but there is a lack of data on NAAT cost-effectiveness. Methods We conducted a prospective cohort study that included all patients with an AFB smear-positive respiratory specimen at Grady Memorial Hospital in Atlanta, GA, USA between January 2002 and June 2008. We determined the sensitivity, specificity, and positive and negative predictive value of a commercially available and FDA-approved NAAT (amplified MTD, Gen-Probe) compared to the gold standard of culture. A cost analysis was performed and included costs related to laboratory tests, hospital charges, anti-TB medications, and contact investigations. Average cost per patient was calculated under two conditions: (1) using a NAAT on all AFB smear-postive respiratory specimens and (2) not using a NAAT. One-way sensitivity analyses were conducted to determine sensitivity of cost difference to reasonable ranges of model inputs. Results During a 6 1/2 year study period, there were 1,009 patients with an AFB smear-positive respiratory specimen at our public urban hospital. We found the NAAT to be highly sensitive (99.6%) and specific (99.1%) on AFB smear-positive specimens compared to culture. Overall, the positive predictive value (PPV) of an AFB smear-positive respiratory specimen for culture-confirmed TB was 27%. The PPV of an AFB smear-positive respiratory specimen for culture-confirmed TB was significantly higher for HIV-uninfected persons compared to those who were HIV-seropositive (152/271 [56%] vs. 85/445 [19%]; RR = 2.94, 95% CI 2.36–3.65, p<0.001). The cost savings of using the NAAT was $2,003 per AFB smear-positive case. Conclusions Routine use of the NAAT on AFB smear-positive respiratory specimens was highly cost-saving in our setting at a U.S. urban public hospital with a high prevalence of TB and HIV because of the low PPV of an AFB

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

PubMed

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

2018-02-01

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

Tuberculosis Facts - Exposure to TB

MedlinePlus

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

Tuberculosis Facts - Testing for TB

MedlinePlus

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

Unwrapping the diagnosis of tuberculosis in primary care: a qualitative study.

PubMed

Metcalf, Elizabeth P; Davies, Joanne C; Wood, Fiona; Butler, Christopher C

2007-02-01

Although tuberculosis (TB) is relatively rare in the UK, its diagnosis is important because diagnostic delays can result in worse outcomes for patients and expose others to the risk of infection. Atypical presentations may be common, and patients' help-seeking behaviour may influence the diagnostic process in primary care. Little is known about the process of diagnosing TB in primary care in developed countries. To understand the process of diagnosing TB in UK primary care. Qualitative inductive study with paired semi-structured interviews. Communities and general practices in south-east Wales. Interviews were conducted with 17 patients diagnosed with TB in the previous 6 months and 16 GPs involved with their care. Data were analysed thematically. In response to expected classical features, GPs generally ordered specific tests. Both GPs and patients reported atypical presentations, and then the diagnostic and referral net was appropriately widened in most cases. Identified barriers to prompt diagnosis included atypical presentations and low clinical suspicion of TB, lack of continuity of care, workload demands that limit time with patients, and suboptimal clinician-patient communication. GPs recognised the growing problem of TB nationally and the need for improved education among health professionals. GPs' and patients' accounts about the process of diagnosing TB suggest that delays can occur, although they are not typical. Where diagnosis is clear, GPs generally test specifically and refer appropriately; where diagnosis is less clear, the diagnostic net is cast further. It is only when certain core values of general practice are not applied (including continuity of care, considering context appropriately, and eliciting and responding appropriately to patients' explanatory models) that clinicians and patients identify a suboptimal diagnostic process.

The value of auditing negative lower GI investigations preceding a final diagnosis of colorectal cancer.

PubMed

Somasekar, A; James, L; Stephenson, B M; Thompson, I W; Vellacott, K D; Allison, M C

2009-09-01

To review all preceding 'negative' large bowel investigations in patients with a final diagnosis of colorectal cancer, and to examine whether delayed diagnosis was associated with worse outcome. Details were gathered on all patients with a new diagnosis of colorectal adenocarcinoma presenting over 4.5 years. For each patient the hospital's clinical workstation and radiology and endoscopy databases were interrogated for all flexible sigmoidoscopies, colonoscopies and barium enemas during the 5 years prior to diagnosis. Among the 570 patients, 28 (5%) had undergone colonoscopy and/or flexible sigmoidoscopy that had not shown colorectal cancer during the 5 years preceding final diagnosis, and a further 28 (5%) had undergone 'negative' barium enemas. Polyp surveillance might have missed four lesions destined to become malignant. Correspondingly there were three patients undergoing IBD surveillance found to have CRC, having had a negative complete colonoscopy within the preceding 5 years. Among patients undergoing de novo colonoscopy for diagnosis the true miss rate was only one patient per year. At August 2007, 29 (58%) of those with delayed diagnosis were still alive, compared with 216 (42%) of those diagnosed during initial investigation (chi2 = 5.04, P < 0.05). Colonoscopic miss rates are in line with previous studies. The application of simple clinical ground rules will avoid most pitfalls. The methodology described herein may assist in auditing the quality assurance of lower gastrointestinal diagnostic services. Despite the delay, late diagnosis was found to be associated with improved survival and a lower likelihood of metastatic disease.

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

Advances in the diagnosis of tuberculous pleuritis

PubMed Central

2016-01-01

Pleural tuberculosis (TB) remains difficult to diagnose. In about two-thirds of the cases the diagnosis is reliant upon clinical suspicion along with consistent fluid biochemistries (i.e., lymphocytic predominant exudates) and exclusion of other potential causes for the effusion. Microbiological methods for a confirmatory diagnosis of pleural TB, which include acid-fast smears (Ziehl-Nelseen), cultures on solid media (Lowenstein-Jensen) and polymerase chain reaction tests from either pleural fluid or sputum samples, remain suboptimal since they are positive in only a minority of patients. Liquid media, however, significantly increase sensitivity while shortening culture positivity as compared with solid cultures. A number of pleural fluid biomarkers such as adenosine deaminase (ADA), interferon-Ƴ, interferon-Ƴ-induced protein of 10 KDa (IP-10) and interleukin-27 (IL-27), have shown promise for the rapid diagnosis of TB, but only ADA combines the accuracy and simplicity required to be considered a mainstay investigative tool for clinical decisions, particularly in areas with medium to high TB prevalence. In countries where ADA is not available, pleural biopsies to evaluate for caseating granulomas are a standard diagnostic approach. They are now frequently performed under ultrasound guidance to optimize yield and patient safety. PMID:27570776

Pre- and post-diagnosis costs of tuberculosis to patients on Directly Observed Treatment Short course in districts of southwestern Ethiopia: a longitudinal study.

PubMed

Asres, Abyot; Jerene, Degu; Deressa, Wakgari

2018-05-21

Financial burden on tuberculosis (TB) patients results in delayed treatment and poor compliance. We assessed pre- and post-diagnosis costs to TB patients. A longitudinal study among 735 new TB cases was conducted from January 2015 through June 2016 in 10 woredas (districts) of southwestern Ethiopia. Direct out-of-pocket, payments, and lost income (indirect cost) were solicited from patients during the first 2 months and at the end of treatment. Thus, we ascertained direct medical, nonmedical, and indirect costs incurred by patients during pre- and post-diagnosis periods. We categorized costs incurred from onset of illness until TB diagnosis as pre-diagnosis and that incurred after diagnosis through treatment completion as post-diagnosis. Pre- and post-diagnosis costs constitute total cost incurred by the patients. We fitted linear regression model to identify predictors of cost. Between onset of illness and anti-TB treatment course, patients incurred a median (inter-quartile range (IQR)) of US$201.48 (136.7-318.94). Of the total cost, the indirect and direct costs respectively constituted 70.6 and 29.4%. TB patients incurred a median (IQR) of US$97.62 (6.43-184.22) and US$93.75 (56.91-141.54) during the pre- and post-diagnosis periods, respectively. Thus, patients incurred 53.6% of the total cost during the pre-diagnosis period. Direct out-of-pocket expenses during the pre- and post-diagnosis periods respectively amount to median (IQR) of US$21.64 (10.23-48.31) and US$35.02 (0-70.04). Patient delay days (p < 0.001), provider delay days (p < 0.001), number of healthcare facilities visited until TB diagnosis (p < 0.001), and TB diagnosis at private facilities (p = 0.02) independently predicted increased pre-diagnosis cost. Similarly, rural residence (p < 0.001), hospitalization during anti-TB treatment (p < 0.001), patient delay days (p < 0.001), and provider delay days (p < 0.001) predicted increased post-diagnosis costs. TB patients

The Significance of Sensitive Interferon Gamma Release Assays for Diagnosis of Latent Tuberculosis Infection in Patients Receiving Tumor Necrosis Factor-α Antagonist Therapy.

PubMed

Jung, Yu Jung; Woo, Hye In; Jeon, Kyeongman; Koh, Won-Jung; Jang, Dong Kyoung; Cha, Hoon Suk; Koh, Eun Mi; Lee, Nam Yong; Kang, Eun-Suk

2015-01-01

We compared two interferon gamma release assays (IGRAs), QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB, for diagnosis of latent tuberculosis infection (LTBI) in patients before and while receiving tumor necrosis factor (TNF)-α antagonist therapy. This study evaluated the significance of sensitive IGRAs for LTBI screening and monitoring. Before starting TNF-α antagonist therapy, 156 consecutive patients with rheumatic diseases were screened for LTBI using QFT-GIT and T-SPOT.TB tests. According to our study protocol, QFT-GIT-positive patients received LTBI treatment. Patients positive by any IGRAs were subjected to follow-up IGRA tests after completing LTBI-treatment and/or during TNF-α antagonist therapy. At the initial LTBI screening, 45 (28.9%) and 70 (44.9%) patients were positive by QFT-GIT and T-SPOT.TB, respectively. The agreement rate between IGRA results was 78.8% (k = 0.56; 95% confidence interval [95% CI] = 0.43 to 0.68). Of 29 patients who were positive only by T-SPOT.TB in the initial screening, 83% (19/23) were persistently positive by T-SPOT.TB, while QFT-GIT testing showed that 36% (9/25) had conversion during TNF-α antagonist therapy. By the end of the follow-up period (218 to 1,264 days), four patients (4/137, 2.9%) developed active tuberculosis (TB) diseases during receiving TNF-α antagonist therapy. Among them, one was Q-T+, one was Q+T-, and the remaining two were Q-T- at the initial screening (Q, QuantiFERON-TB Gold In-Tube; T, T-SPOT.TB; +, positive; -, negative). Two (2/4, 50%) patients with TB reactivation had at least one prior risk factor consistent with previous TB infection. This study demonstrated the need to capitalize on sensitive IGRAs to monitor for LTBI in at-risk patients for a more sensitive diagnosis in countries with an intermediate TB burden.

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

PubMed

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

2016-04-01

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

Pathway to care for drug resistant tuberculosis cases identified during a retrospective study conducted in high TB burden wards in Mumbai.

PubMed

Lobo, Eunice; Shah, Shimoni; Rangan, Sheela; Dholakia, Yatin; Mistry, Nerges

2018-05-10

Background: Mumbai is witnessing a rising incidence of all forms of drug resistant tuberculosis (DR-TB). Methods: A population-based, retrospective study was conducted between April and July 2014, in 15 high TB burden wards in Mumbai, to capture the patient pathways to TB care. A total of 23 DR-TB patients were identified and their pathways to access DR-TB care were recorded using semi-structured interviews. Results: The total DR-TB pathway time of new patients (who did not report any past episode of TB) (180 days; IQR 123,346) was found to be more than twice that of retreatment patients (who reported a past episode of TB) (69 days; IQR 42,128). Conclusions: The unacceptable delay for diagnosis and treatment of DR-TB in Mumbai advocates for consistent implementation of early screening of patients using rapid gene-based technologies.

Optimal triage test characteristics to improve the cost-effectiveness of the Xpert MTB/RIF assay for TB diagnosis: a decision analysis.

PubMed

van't Hoog, Anna H; Cobelens, Frank; Vassall, Anna; van Kampen, Sanne; Dorman, Susan E; Alland, David; Ellner, Jerrold

2013-01-01

High costs are a limitation to scaling up the Xpert MTB/RIF assay (Xpert) for the diagnosis of tuberculosis in resource-constrained settings. A triaging strategy in which a sensitive but not necessarily highly specific rapid test is used to select patients for Xpert may result in a more affordable diagnostic algorithm. To inform the selection and development of particular diagnostics as a triage test we explored combinations of sensitivity, specificity and cost at which a hypothetical triage test will improve affordability of the Xpert assay. In a decision analytical model parameterized for Uganda, India and South Africa, we compared a diagnostic algorithm in which a cohort of patients with presumptive TB received Xpert to a triage algorithm whereby only those with a positive triage test were tested by Xpert. A triage test with sensitivity equal to Xpert, 75% specificity, and costs of US$5 per patient tested reduced total diagnostic costs by 42% in the Uganda setting, and by 34% and 39% respectively in the India and South Africa settings. When exploring triage algorithms with lower sensitivity, the use of an example triage test with 95% sensitivity relative to Xpert, 75% specificity and test costs $5 resulted in similar cost reduction, and was cost-effective by the WHO willingness-to-pay threshold compared to Xpert for all in Uganda, but not in India and South Africa. The gain in affordability of the examined triage algorithms increased with decreasing prevalence of tuberculosis among the cohort. A triage test strategy could potentially improve the affordability of Xpert for TB diagnosis, particularly in low-income countries and with enhanced case-finding. Tests and markers with lower accuracy than desired of a diagnostic test may fall within the ranges of sensitivity, specificity and cost required for triage tests and be developed as such.

High Resolution Chest Computerized Tomography in the Diagnosis of Ocular Sarcoidosis in a High TB Endemic Population.

PubMed

Babu, Kalpana; Shukla, Sai Bhakti; Philips, Mariamma

2017-04-01

To review the role of high resolution chest computed tomography (HRCT) in ocular sarcoidosis in a high TB endemic population. This was a retrospective study. Out of 140 cases, 54 had ocular sarcoidosis, while 86 cases had ocular tuberculosis. Abnormal HRCT findings was noted in 52 cases (96.3%) of ocular sarcoidosis compared with 55 cases (64.7%) of ocular tuberculosis (p = 0.001). Mediastinal lymphadenopathy was the most common finding in both groups (p = 0.544). Hilar lymphadenopathy and fissural nodules were significantly seen in ocular sarcoidosis (p = 0.001). Necrosis was seen in three cases of ocular sarcoidosis. In nearly half of the cases, it was not possible to differentiate between sarcoidosis and tuberculosis on HRCT. HRCT is a useful diagnostic tool in ocular sarcoidosis. Bilateral hilar lymphadenopathy and fissural nodules are significant findings in ocular sarcoidosis. A confident diagnosis of ocular sarcoidosis is made by the amalgamation of results of clinical, radiologic, and other laboratory investigations.

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

PubMed

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

2013-09-01

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

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

PubMed

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

2013-07-01

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

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.

Evaluation of cytokine responses against novel Mtb antigens as diagnostic markers for TB disease.

PubMed

Awoniyi, Dolapo O; Teuchert, Andrea; Sutherland, Jayne S; Mayanja-Kizza, Harriet; Howe, Rawleigh; Mihret, Adane; Loxton, Andre G; Sheehama, Jacob; Kassa, Desta; Crampin, Amelia C; Dockrell, Hazel M; Kidd, Martin; Rosenkrands, Ida; Geluk, Annemieke; Ottenhoff, Tom H M; Corstjens, P L A M; Chegou, Novel N; Walzl, Gerhard

2016-09-01

We investigated the accuracy of host markers detected in Mtb antigen-stimulated whole blood culture supernatant in the diagnosis of TB. Prospectively, blood from 322 individuals with presumed TB disease from six African sites was stimulated with four different Mtb antigens (Rv0081, Rv1284, ESAT-6/CFP-10, and Rv2034) in a 24 h whole blood stimulation assay (WBA). The concentrations of 42 host markers in the supernatants were measured using the Luminex multiplex platform. Diagnostic biosignatures were investigated through the use of multivariate analysis techniques. 17% of the participants were HIV infected, 106 had active TB disease and in 216 TB was excluded. Unstimulated concentrations of CRP, SAA, ferritin and IP-10 had better discriminating ability than markers from stimulated samples. Accuracy of marker combinations by general discriminant analysis (GDA) identified a six analyte model with 77% accuracy for TB cases and 84% for non TB cases, with a better performance in HIV uninfected patients. A biosignature of 6 cytokines obtained after stimulation with four Mtb antigens has moderate potential as a diagnostic tool for pulmonary TB disease individuals and stimulated marker expression had no added value to unstimulated marker performance. Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Tuberculosis Facts - TB Can Be Treated

MedlinePlus

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

Tuberculosis Facts - You Can Prevent TB

MedlinePlus

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

Diagnosis of Concurrent Pulmonary Tuberculosis and Tuberculous Otitis Media Confirmed by Xpert MTB/RIF in the United States.

PubMed

Tompkins, Kathleen M; Reimers, Melissa A; White, Becky L; Herce, Michael E

2016-05-01

Tuberculosis (TB) remains an important cause of infectious morbidity in the United States (US), necessitating timely and accurate diagnosis. We report a case of concurrent pulmonary and extrapulmonary TB presenting as tuberculous otitis media in a hospitalized US patient admitted with cough, night sweats, and unilateral purulent otorrhea. Diagnosis was made by smear microscopy and rapidly confirmed by Xpert MTB/RIF-a novel, automated nucleic acid amplification test for the rapid detection of drug-susceptible and drug-resistant TB. This case adds to the growing body of evidence validating Xpert MTB/RIF as an effective tool for the rapid diagnosis of extrapulmonary TB, even in low TB-prevalence settings such as the US, when testing is performed on non-respiratory specimens.

Diagnosis of Concurrent Pulmonary Tuberculosis and Tuberculous Otitis Media Confirmed by Xpert MTB/RIF in the United States

PubMed Central

Tompkins, Kathleen M.; Reimers, Melissa A.; White, Becky L.; Herce, Michael E.

2015-01-01

Tuberculosis (TB) remains an important cause of infectious morbidity in the United States (US), necessitating timely and accurate diagnosis. We report a case of concurrent pulmonary and extrapulmonary TB presenting as tuberculous otitis media in a hospitalized US patient admitted with cough, night sweats, and unilateral purulent otorrhea. Diagnosis was made by smear microscopy and rapidly confirmed by Xpert MTB/RIF—a novel, automated nucleic acid amplification test for the rapid detection of drug-susceptible and drug-resistant TB. This case adds to the growing body of evidence validating Xpert MTB/RIF as an effective tool for the rapid diagnosis of extrapulmonary TB, even in low TB-prevalence settings such as the US, when testing is performed on non-respiratory specimens. PMID:27346926

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

PubMed

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

2014-06-01

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

Pathway to care for drug resistant tuberculosis cases identified during a retrospective study conducted in high TB burden wards in Mumbai

PubMed Central

Lobo, Eunice; Shah, Shimoni; Rangan, Sheela; Dholakia, Yatin; Mistry, Nerges

2018-01-01

Background: Mumbai is witnessing a rising incidence of all forms of drug resistant tuberculosis (DR-TB). Methods: A population-based, retrospective study was conducted between April and July 2014, in 15 high TB burden wards in Mumbai, to capture the patient pathways to TB care. A total of 23 DR-TB patients were identified and their pathways to access DR-TB care were recorded using semi-structured interviews. Results: The total DR-TB pathway time of new patients (who did not report any past episode of TB) (180 days; IQR 123,346) was found to be more than twice that of retreatment patients (who reported a past episode of TB) (69 days; IQR 42,128). Conclusions: The unacceptable delay for diagnosis and treatment of DR-TB in Mumbai advocates for consistent implementation of early screening of patients using rapid gene-based technologies. PMID:29863175

Distinct trajectories of positive and negative affect after colorectal cancer diagnosis.

PubMed

Ciere, Yvette; Janse, Moniek; Almansa, Josué; Visser, Annemieke; Sanderman, Robbert; Sprangers, Mirjam A G; Ranchor, Adelita V; Fleer, Joke

2017-06-01

Insight into trajectories of positive affect (PA) and negative affect (NA) across the cancer continuum may improve understanding of the nature of adjustment problems. The primary aim of this study was to identify subgroups of patients with distinct trajectories of PA and NA following diagnosis of colorectal cancer (CRC). Secondary to this aim, the co-occurrence between trajectories and their association with goal-related processes was explored. CRC patients (n = 186) completed questionnaires within 1 month, 7 months, and 18 months after diagnosis. Multilevel models were used to study the trajectory of PA and NA, as measured with the Positive and Negative Affect Schedule (PANAS). Four classes with distinct PA trajectories were identified: low (18.8%), increasing (6.7%), moderate (68.2%), and high (6.3%); 2 trajectories of NA emerged: low (36.3%) and moderate (63.7%). There was no significant association between PA and NA trajectory class probabilities. The average trajectory of PA covaried with levels of goal disturbance and goal reengagement over time, while the average NA trajectory covaried with goal disturbance and goal disengagement. Compared with the general population, our sample of cancer patients suffered from a lack of positive emotions, but not a high presence of negative emotions. About one fifth of patients reported low PA up to 18 months after diagnosis and may benefit from supportive care. Furthermore, the trajectory of PA was independent of that of NA and related with a distinct goal adjustment process (i.e., goal disengagement vs. goal reengagement). This finding indicates the need to tailor psychological care to the nature of the adjustment problem. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Laboratory diagnosis of tuberculosis: Advances in technology and drug susceptibility testing.

PubMed

Oommen, Seema; Banaji, Nandita

2017-01-01

There have been rapid technological advances in the detection of Mycobacterium tuberculosis and its drug susceptibility in clinical samples. These include advances in microscopic examination, in vitro culture and application of molecular techniques. The World Health Organization (WHO) has played a large role in evaluating these technologies for their efficacy and feasibility, especially in the developing countries. Amongst these, the Revised National Tuberculosis Control Programme (RNTCP), through its national network of designated microscopy centres and intermediate reference laboratories, has adopted certain technologies that are currently implemented in India. Advances in microscopy technology include fluorescent microscopy using light-emitting diode source, sodium hypochlorite microscopy and vital fluorescent staining of sputum smears. Automation of in vitro culture has markedly reduced the turnaround time (TAT), even in smear-negative samples, and permits simultaneous detection of resistant mutants. Molecular detection of drug resistance has further reduced the TAT, and the cartridge-based nucleic acid amplification test with its performance convenience and rapid results, appears poised to become the future of tuberculosis (TB) diagnosis in all settings, provided the cost of testing is reduced especially for use in private diagnostic settings. This article reviews technologies currently available for the diagnosis of TB, keeping in mind the WHO recommendations and the RNTCP practices. This is a thematic synthesis of data available on diagnosis in literature, preserving the conclusions of the primary studies.

Questions and Answers about TB

MedlinePlus

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

Quality control in QuantiFERON-TB gold in-tube for screening latent tuberculosis infection in health care workers.

PubMed

Igari, Hidetoshi; Watanabe, Akira; Ichimura, Yasunori; Sakurai, Takayuki; Taniguchi, Toshibumi; Ishiwada, Naruhiko

2017-04-01

QuantiFERON-TB gold in-tube has been used for screening latent tuberculosis infection in newly employed health care workers in Japan. There have been a few studies concerning quality control. We retrospectively analysed QuantiFERON-TB gold in-tube results in a hospital in Japan. Interferon-γ values in three blood collection tubes for QuantiFERON-TB gold in-tube were analysed in association with the positivity rate. The data set consisted of health care workers aged 20-29 years during the 7 years between 2010 and 2016. The yearly QuantiFERON-TB gold in-tube positivity rate was 0.9%, 16.4%, 3.0%, 39.3%, 2.8%, 0.9% and 1.5%, and was extremely high in 2011 and 2013. The interferon-γ values in the tuberculosis antigen tube were elevated in these two years, as indicated by higher median and wider interquartile range. The interferon-γ value in the negative control tube was also higher in 2011. The higher interferon-γ values in collection tubes (tuberculosis antigen tube and/or negative control tube) resulted in higher QuantiFERON-TB gold in-tube positivity rate. The distribution of interferon-γ in tuberculosis antigen tube and negative control tube, as evaluated by median and interquartile range, proved to be an effective index for the quality control of QuantiFERON-TB gold in-tube. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

HIV and Tuberculosis (TB)

MedlinePlus

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

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.

Prevalence of latent TB infection and TB disease among adolescents in high TB burden countries in Africa: a systematic review protocol.

PubMed

Bunyasi, Erick Wekesa; Schmidt, Bey-Marrie; Abdullahi, Leila Hussein; Mulenga, Humphrey; Tameris, Michele; Luabeya, Angelique; Shenje, Justin; Scriba, Thomas; Geldenhuys, Hennie; Wood, Robin; Hatherill, Mark

2017-03-10

Almost a third of the world population has latent tuberculosis (TB) infection (LTBI), ∼10 million of whom develop TB disease annually, despite existence of effective, but lengthy, preventive and curative drug regimens. Although adolescents appear to have a very high force of LTBI, their reported incidence of TB disease is less than that of their corresponding general population. The few available studies on adolescent TB infection and disease prevalence are not sufficient to address the apparent discordance between rates of infection and disease in high TB burden countries in Africa. Therefore, we aim to perform a systematic review to examine the relationship between adolescent LTBI and TB disease, benchmarked against national TB disease burden data. A comprehensive literature search will be performed for cross-sectional studies and screening data in cohort studies to determine the prevalence of LTBI and TB disease among adolescents in high TB burden countries in Africa in the following databases: PubMed , Scopus , Cochrane library , Web of Science , Africa Wide , CINAHL and the Africa Index Medicus . This will be supplemented by a search of reference lists of selected articles for potentially relevant articles. We will restrict our search to articles published in the English language between 1990 and 2016 among adolescents in order to obtain estimates reflective of the mature HIV epidemic in most high TB burden countries in Africa that occurred over this critical period. Primary end points are: prevalence of LTBI and TB disease. We will use the random-effects or fixed-effects modelling for our meta-analysis based on heterogeneity estimates. No ethics approval is required given that this is a systematic review. Findings will be disseminated in a peer-reviewed journal in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). CRD42015023495. Published by the BMJ Publishing Group Limited. For permission to use (where not already

Evaluation of host Hsp(s) as potential biomarkers for the diagnosis of tuberculous meningitis.

PubMed

Shekhawat, Seema D; Purohit, Hemant J; Taori, Girdhar M; Daginawala, Hatim F; Kashyap, Rajpal S

2016-01-01

Diagnosis of tuberculosis meningitis (TBM) remains challenging in tuberculosis (TB) endemic countries. The need for TB biomarkers arises, in part, from the difficulty of accurately diagnosing TBM with the available methods. To explore the potential of host Hsps (Hsp 25, Hsp 60, Hsp 70 and Hsp 90) as an alternative marker in TBM diagnosis, we evaluated cerebrospinal fluid (CSF) sample of TBM (n=49), Pyogenic Meningitis (PM) (n=20), Viral Meningitis (VM) (n=09), Fungal Meningitis (FM) (n=04) and non infectious control (n=79) patients using indirect ELISA. Out of four Hsps, Hsp 70 and Hsp 90 yields 89% & 88% sensitivity and 82% & 89% specificity, respectively. The positive (PPV) and negative (NPV) predictive values yielded in TBM group for Hsp 70 was 86.27% (73.74-94.27) and 93.51% (85.48-97.83), respectively. For Hsp 90 the obtained PPV was 89.36% (76.88-96.41) and NPV was 91.36% (82.99-96.44). In 86% of TBM patients all the four Hsps were found to be positive and none of the patient was found to be negative for all Hsps in the same group. The data presented in the study indicate that host Hsp 70 and Hsp 90 shows good sensitivity and specificity and have potential in the diagnosis of TBM disease. The combined use of all Hsps (Hsp 25, Hsp 60, Hsp 70 and Hsp 90) effectively distinguishes patients with TBM from other disease controls. Copyright © 2015 Elsevier B.V. All rights reserved.

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

PubMed

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

2014-01-01

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

Performance assessment of the Capilia TB assay and the BD ProbeTec ET system for rapid culture confirmation of Mycobacterium tuberculosis.

PubMed

Wang, Jann-Yuan; Lee, Li-Na; Lai, Hsin-Chih; Hsu, Hsiao-Leng; Jan, I-Shiow; Yu, Chong-Jen; Hsueh, Po-Ren; Yang, Pan-Chyr

2007-12-01

Because of the increasing numbers of nontuberculous mycobacterial isolates from clinical specimens, rapid and accurate methods for culture confirmation of Mycobacterium tuberculosis are urgently needed. The study evaluated the performance of the Capilia TB immunochromatographic assay (TAUNS, Numazu, Japan) for culture confirmation of M. tuberculosis using 242 culture-positive liquid media in 2 mycobacterial laboratories from November 2005 to February 2006. Among the 242 samples, 183 were also tested with the BD ProbeTec ET (CTB) assay (Becton Dickinson, Sparks, MD). The results of both assays were compared to the culture results and to each other. The overall sensitivity and specificity of the Capilia TB assay were 98.6% and 97.9%, respectively, and for the CTB assay were 97.3% and 97.1%, respectively. The positive and negative predictive values for the Capilia TB assay were 98.6% and 97.9%, respectively, and for the CTB assay were 98.2% and 95.8%, respectively. Among the 183 samples tested with both assays, 8 had discrepant results, including Capilia-TB-false-positive in 2, CTB-false-positive in another 2, CTB-false-negative in 2, Capilia TB-false-negative in 1, and both assays with false-negative results in the remaining one. This study demonstrated that the Capilia TB assay has a similar diagnostic value with the CTB assay. In addition, with the immunochromatographic method, it is less time-consuming and does not require other laboratory equipment.

What is the cost of diagnosis and management of drug resistant tuberculosis in South Africa?

PubMed

Pooran, Anil; Pieterson, Elize; Davids, Malika; Theron, Grant; Dheda, Keertan

2013-01-01

Drug-resistant tuberculosis (DR-TB) is undermining TB control in South Africa. However, there are hardly any data about the cost of treating DR-TB in high burden settings despite such information being quintessential for the rational planning and allocation of resources by policy-makers, and to inform future cost-effectiveness analyses. We analysed the comparative 2011 United States dollar ($) cost of diagnosis and treatment of drug sensitive TB (DS-TB), MDR-TB and XDR-TB, based on National South African TB guidelines, from the perspective of the National TB Program using published clinical outcome data. Assuming adherence to national DR-TB management guidelines, the per patient cost of XDR-TB was $26,392, four times greater than MDR-TB ($6772), and 103 times greater than drug-sensitive TB ($257). Despite DR-TB comprising only 2.2% of the case burden, it consumed ~32% of the total estimated 2011 national TB budget of US $218 million. 45% and 25% of the DR-TB costs were attributed to anti-TB drugs and hospitalization, respectively. XDR-TB consumed 28% of the total DR-TB diagnosis and treatment costs. Laboratory testing and anti-TB drugs comprised the majority (71%) of MDR-TB costs while hospitalization and anti-TB drug costs comprised the majority (92%) of XDR-TB costs. A decentralized XDR-TB treatment programme could potentially reduce costs by $6930 (26%) per case and reduce the total amount spent on DR-TB by ~7%. Although DR-TB forms a very small proportion of the total case burden it consumes a disproportionate and substantial amount of South Africa's total annual TB budget. These data inform rational resource allocation and selection of management strategies for DR-TB in high burden settings.

Difference Between Latent TB Infection and Active TB Disease

MedlinePlus

... chest x-ray, or positive sputum smear or culture • • Has active TB bacteria in his/her body • • Usually feels sick and may have symptoms such as coughing, fever, and weight loss • • May spread TB bacteria to others • • Needs treatment ...

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

PubMed Central

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

2014-01-01

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

Microscopic observation drug-susceptibility assay vs. Xpert® MTB/RIF for the diagnosis of tuberculosis in a rural African setting: a cost-utility analysis.

PubMed

Wikman-Jorgensen, Philip E; Llenas-García, Jara; Pérez-Porcuna, Tomàs M; Hobbins, Michael; Ehmer, Jochen; Mussa, Manuel A; Ascaso, Carlos

2017-06-01

To compare the cost-utility of microscopic observation drug-susceptibility assay (MODS) and Xpert ® MTB/RIF implementation for tuberculosis (TB) diagnosis in rural northern Mozambique. Stochastic transmission compartmental TB model from the healthcare provider perspective with parameter input from direct measurements, systematic literature reviews and expert opinion. MODS and Xpert ® MTB/RIF were evaluated as replacement test of smear microscopy (SM) or as an add-on test after a negative SM. Costs were calculated in 2013 USD, effects in disability-adjusted life years (DALY). Willingness to pay threshold (WPT) was established at once the per capita Gross National Income of Mozambique. MODS as an add-on test to negative SM produced an incremental cost-effectiveness ratio (ICER) of 5647.89USD/DALY averted. MODS as a substitute for SM yielded an ICER of 5374.58USD/DALY averted. Xpert ® MTB/RIF as an add-on test to negative SM yielded ICER of 345.71USD/DALY averted. Xpert ® MTB/RIF as a substitute for SM obtained an ICER of 122.13USD/DALY averted. TB prevalence and risk of infection were the main factors impacting MODS and Xpert ® MTB/RIF ICER in the one-way sensitivity analysis. In the probabilistic sensitivity analysis, Xpert ® MTB/RIF was most likely to have an ICER below the WPT, whereas MODS was not. Our cost-utility analysis favours the implementation of Xpert ® MTB/RIF as a replacement of SM for all TB suspects in this rural high TB/HIV prevalence African setting. © 2017 John Wiley & Sons Ltd.

Lessons learnt from TB screening in closed immigration centres in Italy

PubMed Central

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

2016-01-01

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

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

PubMed Central

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

2013-01-01

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

In-house PCR with DNA extracted directly from positive slides to confirm or exclude the diagnosis of tuberculosis: focus on biosafety.

PubMed

de Almeida, Isabela Neves; Aleixo, Agdemir Valéria; Carvalho, Wânia da Silva; de Miranda, Silvana Spindola

2015-01-01

The possibility to obtain DNA from smears is a valuable alternative to remedy the lack of samples when they are totally used for bacilloscopy; this technique solves the biosafety problem related to a possible accident with the transportation of flasks containing potentially transmissible clinical samples. Hence, the purpose of this study was to utilize the insertion sequence IS6110 for amplification of DNA from a smear-positive sample for tuberculosis (TB) diagnosis. Among the 52 positive bacilloscopies, sensitivity, specificity, positive predictive value and negative predictive value were 52.3%, 100%, 100% and 89.7%, respectively whereas accuracy was 90.7%. The IS6110-based PCR for TB diagnosis developed in DNA extracted from a positive smear is a fast, simple, specific, and safe method. Copyright © 2014 Asociación Argentina de Microbiología. Publicado por Elsevier España, S.L.U. All rights reserved.

Staying on Track with TB Medicine

MedlinePlus

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

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

High levels of vulnerability and anticipated stigma reduce the impetus for tuberculosis diagnosis in Cape Town, South Africa.

PubMed

Murray, Emma J; Bond, Virginia A; Marais, Ben J; Godfrey-Faussett, Peter; Ayles, Helen M; Beyers, Nulda

2013-07-01

Prolonged diagnostic and treatment delays, particularly in settings experiencing concomitant human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics, undermine global TB control efforts. Current TB control policy in South Africa, as organized through the National TB Control Programme (NTP), relies on the voluntary presentation of TB suspects to local clinics for diagnosis, i.e. passive case finding (PCF). In 2005 a participatory study suggested that popular interpretation and perception of TB within eight South African township sites in and around Cape Town, all carrying a high burden of HIV and undiagnosed TB, undermine PCF. Both people's association of TB with dirt and squalor, and the anticipation of HIV-related stigma, combine to impede TB diagnosis. Respondents conveyed TB as unavoidable; this perception is expressed in the context of vulnerability where so much-including dirt-is largely beyond the control of local residents. The lack of control has a disempowering effect, reducing the drive for seeking treatment. In addition, low confidence in patient confidentiality and anticipated HIV-related stigma act as direct deterrents to TB diagnosis and treatment. In conclusion, we wish to draw attention to high levels of disease stigma and vulnerability, and how these undermine PCF. Public health interventions that wish to improve case detection should aim to: (1) emphasize how early treatment improves outcome and can curb ongoing transmission; (2) combat a sense of communal vulnerability to TB; (3) address anticipated HIV-TB stigma; and (4) improve the quality of care provided at local diagnostic services, addressing low levels of patient confidentiality.

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

PubMed

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

2018-04-05

Targeted testing and treatment of latent TB infection (LTBI) are priorities on the global health agenda, but LTBI management remains challenging. We aimed to evaluate the prognostic value of the QuantiFERON TB-Gold (QFT) test for incident TB, focusing on the interferon (IFN)-γ level, when applied in routine practice in a low TB incidence setting. In this large population-based prospective cohort, we linked QFT results in Norway (1 January 2009-30 June 2014) with national registry data (Norwegian Surveillance System for Infectious Diseases, Norwegian Prescription Database, Norwegian Patient Registry and Statistics Norway) to assess the prognostic value of QFT for incident TB. Participants were followed until 30 June 2016. We used restricted cubic splines to model non-linear relationships between IFN-γ levels and TB, and applied these findings to a competing risk model. The prospective analyses included 50 389 QFT results from 44 875 individuals, of whom 257 developed TB. Overall, 22% (n=9878) of QFT results were positive. TB risk increased with the IFN-γ level until a plateau level, above which further increase was not associated with additional prognostic information. The HRs for TB were 8.8 (95% CI 4.7 to 16.5), 19.2 (95% CI 11.6 to 31.6) and 31.3 (95% CI 19.8 to 49.5) times higher with IFN-γ levels of 0.35 to <1.00, 1.00 to <4.00 and >4.00 IU/mL, respectively, compared with negative tests (<0.35 IU/mL). Consistently, QFT demonstrates increased risk of incident TB with rising IFN-γ concentrations, indicating that IFN-γ levels may be used to guide targeted treatment of LTBI. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Role of Gist and PHOG Features in Computer-Aided Diagnosis of Tuberculosis without Segmentation

PubMed Central

Chauhan, Arun; Chauhan, Devesh; Rout, Chittaranjan

2014-01-01

Purpose Effective diagnosis of tuberculosis (TB) relies on accurate interpretation of radiological patterns found in a chest radiograph (CXR). Lack of skilled radiologists and other resources, especially in developing countries, hinders its efficient diagnosis. Computer-aided diagnosis (CAD) methods provide second opinion to the radiologists for their findings and thereby assist in better diagnosis of cancer and other diseases including TB. However, existing CAD methods for TB are based on the extraction of textural features from manually or semi-automatically segmented CXRs. These methods are prone to errors and cannot be implemented in X-ray machines for automated classification. Methods Gabor, Gist, histogram of oriented gradients (HOG), and pyramid histogram of oriented gradients (PHOG) features extracted from the whole image can be implemented into existing X-ray machines to discriminate between TB and non-TB CXRs in an automated manner. Localized features were extracted for the above methods using various parameters, such as frequency range, blocks and region of interest. The performance of these features was evaluated against textural features. Two digital CXR image datasets (8-bit DA and 14-bit DB) were used for evaluating the performance of these features. Results Gist (accuracy 94.2% for DA, 86.0% for DB) and PHOG (accuracy 92.3% for DA, 92.0% for DB) features provided better results for both the datasets. These features were implemented to develop a MATLAB toolbox, TB-Xpredict, which is freely available for academic use at http://sourceforge.net/projects/tbxpredict/. This toolbox provides both automated training and prediction modules and does not require expertise in image processing for operation. Conclusion Since the features used in TB-Xpredict do not require segmentation, the toolbox can easily be implemented in X-ray machines. This toolbox can effectively be used for the mass screening of TB in high-burden areas with improved efficiency. PMID

The additional role of Xpert MTB/RIF in the diagnosis of intrathoracic tuberculous lymphadenitis.

PubMed

Lee, Jinwoo; Choi, Sun Mi; Lee, Chang-Hoon; Lee, Sang-Min; Yim, Jae-Joon; Yoo, Chul-Gyu; Kim, Young Whan; Han, Sung Koo; Park, Young Sik

2017-06-01

Diagnosis of intrathoracic tuberculosis (TB) lymphadenitis remains a challenge because of difficulties in obtaining adequate tissue and the lack of a sensitive test. Recently, Xpert MTB/RIF assay is being used for rapid diagnosis of pulmonary TB, but it has not yet been widely validated in intrathoracic TB lymphadenitis. The aim of this study was to assess the additional role of Xpert MTB/RIF in diagnosing intrathoracic TB lymphadenitis using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) specimen. Consecutive patients who underwent Xpert MTB/RIF assay using EBUS-TBNA specimen from January 2012 and November 2013 at a tertiary referral hospital were recruited. Among them, the cases with malignant lymph nodes were excluded. Among 73 patients, 13 (17.8%) cases were diagnosed with intrathoracic TB lymphadenitis. In detail, 10 patients were diagnosed using conventional methods only (histology or AFB culture) and 3 patients were additionally diagnosed when adding Xpert MTB/RIF assay. The median time to diagnosis using Xpert MTB/RIF (1 day) was shorter than conventional methods (3 days for histology, 14 days for AFB culture). Rifampin resistance was not detected in any patients. In patients with enlarged intrathoracic lymph nodes and low suspicion of malignancy, combination of conventional diagnostic methods with Xpert MTB/RIF could lead to additional and rapid diagnosis of intrathoracic TB lymphadenitis. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

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

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

PubMed

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

2018-05-01

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

Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity.

PubMed

Paris, Luisa; Magni, Ruben; Zaidi, Fatima; Araujo, Robyn; Saini, Neal; Harpole, Michael; Coronel, Jorge; Kirwan, Daniela E; Steinberg, Hannah; Gilman, Robert H; Petricoin, Emanuel F; Nisini, Roberto; Luchini, Alessandra; Liotta, Lance

2017-12-13

An accurate urine test for pulmonary tuberculosis (TB), affecting 9.6 million patients worldwide, is critically needed for surveillance and treatment management. Past attempts failed to reliably detect the mycobacterial glycan antigen lipoarabinomannan (LAM), a marker of active TB, in HIV-negative, pulmonary TB-infected patients' urine (85% of 9.6 million patients). We apply a copper complex dye within a hydrogel nanocage that captures LAM with very high affinity, displacing interfering urine proteins. The technology was applied to study pretreatment urine from 48 Peruvian patients, all negative for HIV, with microbiologically confirmed active pulmonary TB. LAM was quantitatively measured in the urine with a sensitivity of >95% and a specificity of >80% ( n = 101) in a concentration range of 14 to 2000 picograms per milliliter, as compared to non-TB, healthy and diseased, age-matched controls (evaluated by receiver operating characteristic analysis; area under the curve, 0.95; 95% confidence interval, 0.9005 to 0.9957). Urinary LAM was elevated in patients with a higher mycobacterial burden ( n = 42), a higher proportion of weight loss ( n = 37), or cough ( n = 50). The technology can be configured in a variety of formats to detect a panel of previously undetectable very-low-abundance TB urinary analytes. Eight of nine patients who were smear-negative and culture-positive for TB tested positive for urinary LAM. This technology has broad implications for pulmonary TB screening, transmission control, and treatment management for HIV-negative patients. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

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

PubMed

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

2018-01-01

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

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

Automatic detection of mycobacterium tuberculosis using artificial intelligence.

PubMed

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

2018-03-01

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. 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. Examined against the double confirmed diagnosis by pathologists both via microscopes and digital slides, TB-AI achieved 97.94% sensitivity and 83.65% specificity. 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.

Latent TB infection and pulmonary TB disease among patients with diabetes mellitus in Bandung, Indonesia.

PubMed

Koesoemadinata, Raspati C; McAllister, Susan M; Soetedjo, Nanny N M; Febni Ratnaningsih, Dwi; Ruslami, Rovina; Kerry, Sarah; Verrall, Ayesha J; Apriani, Lika; van Crevel, Reinout; Alisjahbana, Bachti; Hill, Philip C

2017-02-01

Screening and treatment of latent TB infection (LTBI) and TB disease could reduce diabetes mellitus (DM)-associated TB. We aimed to describe the prevalence of LTBI and pulmonary TB among patients with DM in a TB-endemic setting. Patients with DM attending a hospital and community centres in Bandung, Indonesia, underwent LTBI screening using interferon gamma release assay (IGRA). TB was investigated by sputum smear, culture and x-ray. TB contacts from a parallel study were age- and sex-matched to patients with DM to compare LTBI and TB disease prevalence. Of 682 patients with DM screened, 651 (95.5%) were eligible. Among 'TB disease-free' patients, LTBI prevalence was 38.9% (206/530; 95% CI 34.7-43.2). Patients with DM were less likely to be IGRA positive than TB contacts (38.6%, 54/140; 95% CI 30.5-46.6 vs 68.6%, 96/140; 95% CI 60.9-72.3: p<0.001); but had a higher disease prevalence (4.9%, 8/164; 95% CI 1.6-8.2 vs 1.2%, 2/164; 95% CI -0.5 to 2.9: p=0.054). Patients with DM in crowded households had increased risk of LTBI (AOR 1.71; 95% CI 1.19-2.45). LTBI prevalence in patients with DM was lower than in household contacts, but patients with DM were more likely to have TB disease. Further studies should explore possible benefits of LTBI screening and preventive therapy in patients with DM in TB-endemic settings. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

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

NASA Astrophysics Data System (ADS)

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

2018-02-01

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

Snapshot of Quantiferon TB gold testing in Northern Mexico.

PubMed

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

2011-12-01

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

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

PubMed

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

2014-09-01

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

A first insight into high prevalence of undiagnosed smear-negative pulmonary tuberculosis in Northern Ethiopian prisons: implications for greater investment and quality control.

PubMed

Biadglegne, Fantahun; Rodloff, Arne C; Sack, Ulrich

2014-01-01

Tuberculosis (TB) transmission in prisons poses significant risks to inmates as well as the general population. Currently, there are no data on smear-negative pulmonary TB cases in prisons and by extension no data on the impact such cases have on TB incidence. This study was designed to obtain initial data on the prevalence of smear-negative cases of TB in prisons as well as preliminary risk factor analysis for such TB cases. This cross-sectional survey was conducted in November 2013 at eight main prisons located in the state of Amhara, Ethiopia. Interviews using a structured and pretested questionnaire were done first to identify symptomatic prisoners. Three consecutive sputum samples were collected and examined using acid fast bacilli (AFB) microscopy at the point of care. All smear-negative sputum samples were taken for culture and Xpert testing. Descriptive and multivariate analysis was done using SPSS version 16. Overall the prevalence of smear-negative pulmonary TB cases in the study prisons was 8% (16/200). Using multivariate analysis, a contact history to TB patients in prison, educational level, cough and night sweating were found to be predictors of TB positivity among smear-negative pulmonary TB cases (p ≤ 0.05). In the studied prisons, high prevalence of undiagnosed TB cases using AFB microscopy was documented, which is an important public health concern that urgently needs to be addressed. Furthermore, patients with night sweating, non-productive cough, a contact history with TB patients and who are illiterate merit special attention, larger studies are warranted in the future to assess the associations more precisely. Further studies are also needed to examine TB transmission dynamics by patients with smear-negative pulmonary TB in a prison setting.

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

PubMed

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

2016-09-01

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

Barriers and outcomes: TB patients co-infected with HIV accessing antiretroviral therapy in rural Zambia.

PubMed

Chileshe, Muatale; Bond, Virginia Anne

2010-01-01

The vulnerabilities that underlie barriers faced by the rural poor whilst trying to access and adhere to "free" antiretroviral treatment (ART) demand more attention. This paper highlights barriers that poor rural Zambians co-infected with tuberculosis (TB) and HIV and their households faced in accessing ART between September 2006 and July 2007, and accounts for patient outcomes by the end of TB treatment and (more sporadically) beyond October 2009. The analysis draws on findings from wider anthropological fieldwork on the converging impact of TB, HIV and food insecurity, focusing for the purpose of this paper on ethnographic case-studies of seven newly diagnosed TB patients co-infected with HIV and their six households (one household had two TB patients). Economic barriers included being pushed into deeper poverty by managing TB, rural location, absence of any external assistance, and mustering time and extended funds for transport and "special food" during and beyond the end of TB. In the case of death, funeral costs were astronomical. Social barriers included translocation, broken marriages, a sub-ordinate household position, gender relations, denial, TB/HIV stigma and the difficulty of disclosure. Health facility barriers involved understaffing, many steps, lengthy procedures and inefficiencies (lost blood samples, electricity cuts). By the end of TB treatment, outcomes were mixed; two co-infected patients had died, three had started ART and two had yet to start ART. The three on ART underwent a striking transformation in the short term. By October 2009, two more had died and three were doing well. The study advocates nutritional support and other material support (especially transport funds) for co-infected TB patients until ART is accessed and livelihood regained. More prompt diagnosis of TB and reducing steps and increasing the reach of the ART programme in rural areas are also recommended.

Pre-treatment loss to follow-up among smear-positive TB patients in tertiary hospitals, Quetta, Pakistan.

PubMed

Wali, A; Kumar, A M V; Hinderaker, S G; Heldal, E; Qadeer, E; Fatima, R; Ullah, A; Safdar, N; Yaqoob, A; Anwar, K; Ul Haq, M

2017-03-21

Setting: Three public sector tertiary care hospitals in Quetta, Balochistan, Pakistan, with anecdotal evidence of gaps between the diagnosis and treatment of patients with tuberculosis (TB). Objectives: To assess the proportion of pre-treatment loss to follow-up (LTFU), defined as no documented evidence of treatment initiation or referral in TB registers, among smear-positive pulmonary TB patients diagnosed in 2015, and the associated sociodemographic factors. Design: A retrospective cohort study involving the review of laboratory and TB registers. Results: Of 1110 smear-positive TB patients diagnosed (58% female, median age 40 years, 5% from outside the province or the country), 235 (21.2%) were lost to follow-up before starting treatment. Pre-treatment LTFU was higher among males; in patients residing far away, in rural areas, outside the province or the country; and in those without a mobile phone number. Conclusion: About one fifth of the smear-positive TB patients were lost to follow-up before starting treatment. Strengthening the referral and feedback mechanisms and using information technology to improve the tracing of patients is urgently required. Further qualitative research is needed to understand the reasons for pre-treatment LTFU from the patient's perspective.

Pre-treatment loss to follow-up among smear-positive TB patients in tertiary hospitals, Quetta, Pakistan

PubMed Central

Kumar, A. M. V.; Hinderaker, S. G.; Heldal, E.; Qadeer, E.; Fatima, R.; Ullah, A.; Safdar, N.; Yaqoob, A.; Anwar, K.; Ul Haq, M.

2017-01-01

Setting: Three public sector tertiary care hospitals in Quetta, Balochistan, Pakistan, with anecdotal evidence of gaps between the diagnosis and treatment of patients with tuberculosis (TB). Objectives: To assess the proportion of pre-treatment loss to follow-up (LTFU), defined as no documented evidence of treatment initiation or referral in TB registers, among smear-positive pulmonary TB patients diagnosed in 2015, and the associated sociodemographic factors. Design: A retrospective cohort study involving the review of laboratory and TB registers. Results: Of 1110 smear-positive TB patients diagnosed (58% female, median age 40 years, 5% from outside the province or the country), 235 (21.2%) were lost to follow-up before starting treatment. Pre-treatment LTFU was higher among males; in patients residing far away, in rural areas, outside the province or the country; and in those without a mobile phone number. Conclusion: About one fifth of the smear-positive TB patients were lost to follow-up before starting treatment. Strengthening the referral and feedback mechanisms and using information technology to improve the tracing of patients is urgently required. Further qualitative research is needed to understand the reasons for pre-treatment LTFU from the patient's perspective. PMID:28775939

Tuberculosis in HIV-infected South African children with complicated severe acute malnutrition.

PubMed

Adler, H; Archary, M; Mahabeer, P; LaRussa, P; Bobat, R A

2017-04-01

Academic tertiary referral hospital in Durban, South Africa. To describe the incidence and diagnostic challenges of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children with severe acute malnutrition (SAM). Post-hoc analysis of a randomised controlled trial that enrolled antiretroviral therapy naïve, HIV-infected children with SAM. Trial records and hospital laboratory results were explored for clinical diagnoses and bacteriologically confirmed cases of TB. Negative binomial regression was used to explore associations with confirmed cases of TB, excluding cases where the clinical diagnosis was not supported by microbiological confirmation. Of 82 children enrolled in the study, 21 (25.6%) were diagnosed with TB, with bacteriological confirmation in 8 cases. Sputum sampling (as opposed to gastric washings) was associated with an increased risk of subsequent diagnosis of TB (adjusted relative risk [aRR] 1.134, 95%CI 1.02-1.26). Culture-proven bacterial infection during admission was associated with a reduced risk of TB (aRR 0.856, 95%CI 0.748-0.979), which may reflect false-negative microbiological tests secondary to empiric broad-spectrum antibiotics. TB is common in HIV-infected children with SAM. While microbiological confirmation of the diagnosis is feasible, empiric treatment remains common, possibly influenced by suboptimal testing and false-negative TB diagnostics. Rigorous microbiological TB investigation should be integrated into the programmatic management of HIV and SAM.

Delay in initiation of treatment after diagnosis of pulmonary tuberculosis in primary health care setting: eight year cohort analysis from district Faridabad, Haryana, North India.

PubMed

Kant, Shashi; Singh, Arvind K; Parmeshwaran, Giridara G; Haldar, Partha; Malhotra, Sumit; Kaur, Ravneet

2017-01-01

Delay in initiation of tuberculosis (TB) treatment may have a tremendous impact on disease transmission, development of drug resistance, poor outcome and overall survival of TB patients. The delay can occur at various levels. Delay in initiation of treatment after diagnosis is mostly due to health system failure and has immense programmatic implications. It has not been studied extensively in the Indian setting. The authors did a cohort analysis of all TB patients initiated on treatment from two primary health centres (PHCs) at Ballabgarh Health and Demographic Surveillance System between January 2007 and December 2014. Diagnosis and treatment of TB in the study area was done as per the protocol envisaged in the national program. Information related to demography, details of diagnosis and treatment of TB and outcome of treatment were extracted from the TB register. Delay in initiation of treatment after diagnosis was considered if the gap between diagnosis and treatment was greater than 7 days. Bivariate and multivariate analyses were done to find the association of various factors with delay in initiation of treatment after diagnosis. Out of 885 patients, 662 patients started treatment for pulmonary TB. Mean time interval between diagnosis and initiation of treatment was 8.95 days. Only 57.7% of pulmonary TB patients were started on treatment within 7 days of diagnosis, and an additional 24.5% were started on treatment 8-14 days after diagnosis. Patients on retreatment regimens and those residing in villages without a PHC were more likely to have delayed initiation of treatment (odds ratio (OR)=1.82 (1.3-2.7, p=0.001) and OR=1.62 (1.1-2.5, p=0.01) respectively). Delay in initiation of treatment was also associated with unfavourable treatment outcome such as default, failure or death. There is a need to have healthcare changes related to TB care to enable initiation of treatment as early as possible. Pretreatment counselling especially for retreatment

The role of ancestry in TB susceptibility of an admixed South African population.

PubMed

Daya, Michelle; van der Merwe, Lize; van Helden, Paul D; Möller, Marlo; Hoal, Eileen G

2014-07-01

Genetic susceptibility to tuberculosis (TB) has been well established and this, taken together with variation in susceptibility observed between different geographic and ethnic populations, implies that susceptibility to TB may in part be affected by ethnicity. In a previous genome-wide TB case-control study (642 cases and 91 controls) of the admixed South African Coloured (SAC) population, we found a positive correlation between African San ancestry and TB susceptibility, and negative correlations with European and Asian ancestries. Since genome-wide data was available for only a small number of controls in the previous study, we endeavored to validate this finding by genotyping a panel of ancestry informative markers (AIMs) in additional individuals, yielding a data set of 918 cases and 507 controls. Ancestry proportions were estimated using the AIMs for each of the source populations of the SAC (African San, African non-San, European, South Asian and East Asian). Using logistic regression models to test for association between TB and ancestry, we confirmed the substantial effect of ancestry on TB susceptibility. We also investigated the effect of adjusting for ancestry in candidate gene TB association studies of the SAC. We report a polymorphism that is no longer significantly associated with TB after adjustment for ancestry, a polymorphism that is significantly associated with TB only after adjustment for ancestry, and a polymorphism where the association significance remains unchanged. By comparing the allele frequencies of these polymorphisms in the source populations of the SAC, we demonstrate that association results are likely to be affected by adjustment for ancestry if allele frequencies differ markedly in the source populations of the SAC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Integration and task shifting for TB/HIV care and treatment in highly resource-scarce settings: one size may not fit all.

PubMed

Van Rie, Annelies; Patel, Monita R; Nana, Mbonze; Vanden Driessche, Koen; Tabala, Martine; Yotebieng, Marcel; Behets, Frieda

2014-03-01

A crucial question in managing HIV-infected patients with tuberculosis (TB) concerns when and how to initiate antiretroviral therapy (ART). The effectiveness of CD4-stratified ART initiation in a nurse-centered, integrated TB/HIV program at primary care in Kinshasa, Democratic Republic of Congo, was assessed. Prospective cohort study was conducted to assess the effect of CD4-stratified ART initiation by primary care nurses (513 TB patients, August 2007 to November 2009). ART was to be initiated at 1 month of TB treatment if CD4 count is <100 cells per cubic millimeter, at 2 months if CD4 count is 100-350 cells per cubic millimeter, and at the end of TB treatment after CD4 count reassessment if CD4 count is >350 cells per cubic millimeter. ART uptake and mortality were compared with a historical prospective cohort of 373 HIV-infected TB patients referred for ART to a centralized facility and 3577 HIV-negative TB patients (January 2006 to May 2007). ART uptake increased (17%-69%, P < 0.0001) and mortality during TB treatment decreased (20.1% vs 9.8%, P < 0.0003) after decentralized, nurse-initiated, CD4-stratified ART. Mortality among TB patients with CD4 count >100 cells per cubic millimeter was similar to that of HIV-negative TB patients (5.6% vs 6.3%, P = 0.65), but mortality among those with CD4 count <100 cells per cubic millimeter remained high (18.8%). Nurse-centered, CD4-stratified ART initiation at primary care level was effective in increasing timely ART uptake and reducing mortality among TB patients but may not be adequate to prevent mortality among those presenting with severe immunosuppression. Further research is needed to determine the optimal management at primary care level of TB patients with CD4 counts <100 cells per cubic millimeter.

The Impact of a Line Probe Assay Based Diagnostic Algorithm on Time to Treatment Initiation and Treatment Outcomes for Multidrug Resistant TB Patients in Arkhangelsk Region, Russia.

PubMed

Eliseev, Platon; Balantcev, Grigory; Nikishova, Elena; Gaida, Anastasia; Bogdanova, Elena; Enarson, Donald; Ornstein, Tara; Detjen, Anne; Dacombe, Russell; Gospodarevskaya, Elena; Phillips, Patrick P J; Mann, Gillian; Squire, Stephen Bertel; Mariandyshev, Andrei

2016-01-01

In the Arkhangelsk region of Northern Russia, multidrug-resistant (MDR) tuberculosis (TB) rates in new cases are amongst the highest in the world. In 2014, MDR-TB rates reached 31.7% among new cases and 56.9% among retreatment cases. The development of new diagnostic tools allows for faster detection of both TB and MDR-TB and should lead to reduced transmission by earlier initiation of anti-TB therapy. The PROVE-IT (Policy Relevant Outcomes from Validating Evidence on Impact) Russia study aimed to assess the impact of the implementation of line probe assay (LPA) as part of an LPA-based diagnostic algorithm for patients with presumptive MDR-TB focusing on time to treatment initiation with time from first-care seeking visit to the initiation of MDR-TB treatment rather than diagnostic accuracy as the primary outcome, and to assess treatment outcomes. We hypothesized that the implementation of LPA would result in faster time to treatment initiation and better treatment outcomes. A culture-based diagnostic algorithm used prior to LPA implementation was compared to an LPA-based algorithm that replaced BacTAlert and Löwenstein Jensen (LJ) for drug sensitivity testing. A total of 295 MDR-TB patients were included in the study, 163 diagnosed with the culture-based algorithm, 132 with the LPA-based algorithm. Among smear positive patients, the implementation of the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 50 and 66 days compared to the culture-based algorithm (BacTAlert and LJ respectively, p<0.001). In smear negative patients, the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 78 days when compared to the culture-based algorithm (LJ, p<0.001). However, several weeks were still needed for treatment initiation in LPA-based algorithm, 24 days in smear positive, and 62 days in smear negative patients. Overall treatment outcomes were better in LPA-based algorithm

The yield and feasibility of integrated screening for TB, diabetes and HIV in four public hospitals in Ethiopia.

PubMed

Jerene, Degu; Hiruy, Nebiyu; Jemal, Ilili; Gebrekiros, Wondimu; Anteneh, Tadesse; Habte, Dereje; Melese, Muluken; Suarez, Pedro; Sangiwa, Gloria

2017-03-01

Our objective was to demonstrate the feasibility of integrated care for TB, HIV and diabetes mellitus (DM) in a pilot project in Ethiopia. Healthcare workers in four hospitals screened patients with TB for HIV and DM; patients with HIV for DM and TB; and patients with DM for TB. Fasting and random plasma glucose (RPG) tests were used to confirm the diagnosis of DM. We used screening checklists for TB and DM, and additional risk scoring criteria to identify patients at risk of DM. Of 3439 study participants, 888 were patients with DM, 439 patients with TB and 2112 from HIV clinics. Six of the patients with DM had TB of whom five were already on treatment; and 141 (32.4%) patients with TB had DM, of whom only five were previously diagnosed with DM. Symptomatic patients and those with a risk score of 5 or more were about three times more likely to have abnormal blood glucose level. Of 2075 HIV patients with RPG determined, only 31 (1.5%) had abnormal RPG. Tri-directional screening was feasible for detecting and managing previously undiagnosed TB and DM. More work is needed to better understand the interaction between HIV and DM. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Impact of Introducing the Line Probe Assay on Time to Treatment Initiation of MDR-TB in Delhi, India

PubMed Central

Singla, Neeta; Satyanarayana, Srinath; Sachdeva, Kuldeep Singh; Van den Bergh, Rafael; Reid, Tony; Tayler-Smith, Katherine; Myneedu, V. P.; Ali, Engy; Enarson, Donald A.; Behera, Digamber; Sarin, Rohit

2014-01-01

Setting National Institute of Tuberculosis and Respiratory Diseases (erstwhile Lala Ram Sarup Institute) in Delhi, India. Objectives To evaluate before and after the introduction of the line Probe Assay (LPA) a) the overall time to MDR-TB diagnosis and treatment initiation; b) the step-by-step time lapse at each stage of patient management; and c) the lost to follow-up rates. Methods A retrospective cohort analysis was done using data on MDR-TB patients diagnosed during 2009–2012 under Revised National Tuberculosis Control Programme at the institute. Results Following the introduction of the LPA in 2011, the overall median time from identification of patients suspected for MDR-TB to the initiation of treatment was reduced from 157 days (IQR 127–200) to 38 days (IQR 30–79). This reduction was attributed mainly to a lower diagnosis time at the laboratory. Lost to follow-up rates were also significantly reduced after introduction of the LPA (12% versus 39% pre-PLA). Conclusion Introduction of the LPA was associated with a major reduction in the delay between identification of patients suspected for MDR-TB and initiation of treatment, attributed mainly to a reduction in diagnostic time in the laboratory. PMID:25058124

Automatic diagnosis of tuberculosis disease based on Plasmonic ELISA and color-based image classification.

PubMed

AbuHassan, Kamal J; Bakhori, Noremylia M; Kusnin, Norzila; Azmi, Umi Z M; Tania, Marzia H; Evans, Benjamin A; Yusof, Nor A; Hossain, M A

2017-07-01

Tuberculosis (TB) remains one of the most devastating infectious diseases and its treatment efficiency is majorly influenced by the stage at which infection with the TB bacterium is diagnosed. The available methods for TB diagnosis are either time consuming, costly or not efficient. This study employs a signal generation mechanism for biosensing, known as Plasmonic ELISA, and computational intelligence to facilitate automatic diagnosis of TB. Plasmonic ELISA enables the detection of a few molecules of analyte by the incorporation of smart nanomaterials for better sensitivity of the developed detection system. The computational system uses k-means clustering and thresholding for image segmentation. This paper presents the results of the classification performance of the Plasmonic ELISA imaging data by using various types of classifiers. The five-fold cross-validation results show high accuracy rate (>97%) in classifying TB images using the entire data set. Future work will focus on developing an intelligent mobile-enabled expert system to diagnose TB in real-time. The intelligent system will be clinically validated and tested in collaboration with healthcare providers in Malaysia.

Local level epidemiological analysis of TB in people from a high incidence country of birth.

PubMed

Massey, Peter D; Durrheim, David N; Stephens, Nicola; Christensen, Amanda

2013-01-22

The setting for this analysis is the low tuberculosis (TB) incidence state of New South Wales (NSW), Australia. Local level analysis of TB epidemiology in people from high incidence countries-of-birth (HIC) in a low incidence setting has not been conducted in Australia and has not been widely reported. Local level analysis could inform measures such as active case finding and targeted earlier diagnosis. The aim of this study was to use a novel approach to identify local areas in an Australian state that have higher TB rates given the local areas' country of birth profiles. TB notification data for the three year period 2006-2008 were analysed by grouping the population into those from a high-incidence country-of-birth and the remainder. During the study period there were 1401 notified TB cases in the state of NSW. Of these TB cases 76.5% were born in a high-incidence country. The annualised TB notification rate for the high-incidence country-of-birth group was 61.2/100,000 population and for the remainder of the population was 1.8/100,000. Of the 152 Local Government Areas (LGA) in NSW, nine had higher and four had lower TB notification rates in their high-incidence country-of-birth populations when compared with the high-incidence country-of-birth population for the rest of NSW. The nine areas had a higher proportion of the population with a country of birth where TB notification rates are >100/100,000. Those notified with TB in the nine areas also had a shorter length of stay in Australia than the rest of the state. The areas with higher TB notification rates were all in the capital city, Sydney. Among LGAs with higher TB notification rates, four had higher rates in both people with a high-incidence country of birth and people not born in a high-incidence country. The age distribution of the HIC population was similar across all areas, and the highest differential in TB rates across areas was in the 5-19 years age group. Analysing local area TB rates and possible

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

PubMed

Fujiki, Akiko; Kato, Seiya

2008-06-01

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

Negative symptoms: History of the concept and their position in diagnosis of schizophrenia.

PubMed

Dollfus, Sonia; Lyne, John

2017-08-01

Current conceptualizations of schizophrenia have been introduced over centuries and continue to progress in recent decades. Symptoms have been divided into several domains, contrasting negative and positive symptoms which are different in their nature, onset, progression and response to treatment. An account of the different historical changes of the concept – essentially nosographic – has led to models attempting to integrate findings for each dimension of the disorder. This paper reviews the history of negative symptoms in diagnosis and how different approaches have been utilised to consider negative symptoms in the concept of schizophrenia. The paper also bridges various international classifications which have evolved and modified the role of negative symptoms in their diagnostic criteria for schizophrenia, which highlights the challenge of defining this disease.

Delayed diagnosis of endobronchial mucoepidermoid carcinoma in a 29-year-old male

PubMed Central

Jain, Akanksha; Madan, Neha Kawatra; Arava, Sudheer; Pandey, Durgatosh; Madan, Karan

2016-01-01

Mucoepidermoid carcinoma (MEC) is an uncommon primary lung tumor. It usually involves large airways and presents clinically and radiologically with nonspecific features. Because of nonspecific presentation diagnosis is frequently delayed. We report the case of a 29-year-old male patient wherein a clinico-radiological consideration of tuberculosis (TB) led to a prolonged treatment with anti-TB medications without response. Flexible bronchoscopic biopsy confirmed the diagnosis of MEC following that the patient underwent curative surgical resection. PMID:27186000

TB Is Back.

ERIC Educational Resources Information Center

Natale, Jo Anna

1992-01-01

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

Xpert MTB/RIF assay for diagnosis of pulmonary tuberculosis in sputum specimens in remote health care facility.

PubMed

Geleta, Dereje Assefa; Megerssa, Yoseph Cherinet; Gudeta, Adugna Negussie; Akalu, Gizachew Taddesse; Debele, Melaku Tesfaye; Tulu, Kassu Desta

2015-10-19

Xpert MTB/RIF assay is considered as a great advance over conventional smear and culture in the diagnosis of TB and MDR-TB by simultaneously detecting M.tuberculosis and rifampicin resistance bacilli. However, very little information regarding the performance characteristics of Xpert MTB/RIF assay is available in Ethiopia. Therefore, the purpose of this study was to evaluate the performance of Xpert MTB/RIF assay compared to conventional sputum smear and culture methods for the diagnosis of pulmonary tuberculosis in remote health care facility. A paired expectorated sputum samples were obtained from 227 consecutively recruited patients with signs and symptoms suggestive of tuberculosis at Karamara hospital during December 2013 to May 2014. One of the sputum specimen was tested directly by Ziehl-Neelsen staining and Xpert MTB/RIF assay without NALC-NaOH decontamination. The other of pair of sputa specimen was cultured for isolation of TB bacilli by conventional methods. Diagnostic performance of Xpert MTB/RIF assay and AFB smear microscopy were calculated against culture as the gold standard. Overall 25.5% (58/227) samples were positive for Mycobacterium tuberculosis complex (MTBC) by MGIT and/or LJ media of which 36.2% (21/58) and 65.5% (35/58) were positive by AFB smear microscopy and Xpert MTB/RIF respectively. The sensitivity, specificity, as well as the positive and negative predictive value of Xpert MTB/RIF assay were 65.5% (95% CI: 53.3-77.7%), 96.3% (95% CI: 93.4-99.2%), 86.4% (95% CI: 76.2-96.5%), and 88.6% (95% CI: 83.9-93.3%) respectively. Eighteen of 58 (31%) cases that were smear microscopy negative, were positive by Xpert MTB/RIF assay. Although Xpert MTB/RIF assay demonstrated high sensitivity in detecting MTBC in sputum specimens compared with conventional AFB smear microscopy, it demonstrated suboptimal sensitivity in smear negative patients compared to conventional culture.

Temporal trends in TB notification rates during ART scale-up in Cape Town: an ecological analysis.

PubMed

Hermans, Sabine; Boulle, Andrew; Caldwell, Judy; Pienaar, David; Wood, Robin

2015-01-01

Although antiretroviral therapy (ART) reduces individual tuberculosis (TB) risk by two-thirds, the population-level impact remains uncertain. Cape Town reports high TB notification rates associated with endemic HIV. We examined population trends in TB notification rates during a 10-year period of expanding ART. Annual Cape Town TB notifications were used as numerators and mid-year Cape Town populations as denominators. HIV-stratified population was calculated using overall HIV prevalence estimates from the Actuarial Society of South Africa AIDS and Demographic model. ART provision numbers from Western Cape government reports were used to calculate overall ART coverage. We calculated rates per 100,000 population over time, overall and stratified by HIV status. Rates per 100,000 total population were also calculated by ART use at treatment initiation. Absolute numbers of notifications were compared by age and sub-district. Changes over time were described related to ART provision in the city as a whole (ART coverage) and by sub-district (numbers on ART). From 2003 to 2013, Cape Town's population grew from 3.1 to 3.7 million inhabitants, and estimated HIV prevalence increased from 3.6 to 5.2%. ART coverage increased from 0 to 63% in 2013. TB notification rates declined by 16% (95% confidence interval (CI), 14-17%) from a 2008 peak (851/100,000) to a 2013 nadir (713/100,000). Decreases were higher among the HIV-positive (21% (95% CI, 19-23%)) than the HIV-negative (9% (95% CI, 7-11%)) population. The number of HIV-positive TB notifications decreased mainly among 0- to 4- and 20- to 34-year-olds. Total population rates on ART at TB treatment initiation increased over time but levelled off in 2013. Overall median CD4 counts increased from 146 cells/µl (interquartile range (IQR), 66, 264) to 178 cells/µl (IQR 75, 330; p<0.001). Sub-district antenatal HIV seroprevalence differed (10-33%) as did numbers on ART (9-29 thousand). Across sub-districts, infant HIV-positive TB

Incremental Yield of Including Determine-TB LAM Assay in Diagnostic Algorithms for Hospitalized and Ambulatory HIV-Positive Patients in Kenya.

PubMed

Huerga, Helena; Ferlazzo, Gabriella; Bevilacqua, Paolo; Kirubi, Beatrice; Ardizzoni, Elisa; Wanjala, Stephen; Sitienei, Joseph; Bonnet, Maryline

2017-01-01

Determine-TB LAM assay is a urine point-of-care test useful for TB diagnosis in HIV-positive patients. We assessed the incremental diagnostic yield of adding LAM to algorithms based on clinical signs, sputum smear-microscopy, chest X-ray and Xpert MTB/RIF in HIV-positive patients with symptoms of pulmonary TB (PTB). Prospective observational cohort of ambulatory (either severely ill or CD4<200cells/μl or with Body Mass Index<17Kg/m2) and hospitalized symptomatic HIV-positive adults in Kenya. Incremental diagnostic yield of adding LAM was the difference in the proportion of confirmed TB patients (positive Xpert or MTB culture) diagnosed by the algorithm with LAM compared to the algorithm without LAM. The multivariable mortality model was adjusted for age, sex, clinical severity, BMI, CD4, ART initiation, LAM result and TB confirmation. Among 474 patients included, 44.1% were severely ill, 69.6% had CD4<200cells/μl, 59.9% had initiated ART, 23.2% could not produce sputum. LAM, smear-microscopy, Xpert and culture in sputum were positive in 39.0% (185/474), 21.6% (76/352), 29.1% (102/350) and 39.7% (92/232) of the patients tested, respectively. Of 156 patients with confirmed TB, 65.4% were LAM positive. Of those classified as non-TB, 84.0% were LAM negative. Adding LAM increased the diagnostic yield of the algorithms by 36.6%, from 47.4% (95%CI:39.4-55.6) to 84.0% (95%CI:77.3-89.4%), when using clinical signs and X-ray; by 19.9%, from 62.2% (95%CI:54.1-69.8) to 82.1% (95%CI:75.1-87.7), when using clinical signs and microscopy; and by 13.4%, from 74.4% (95%CI:66.8-81.0) to 87.8% (95%CI:81.6-92.5), when using clinical signs and Xpert. LAM positive patients had an increased risk of 2-months mortality (aOR:2.7; 95%CI:1.5-4.9). LAM should be included in TB diagnostic algorithms in parallel to microscopy or Xpert request for HIV-positive patients either ambulatory (severely ill or CD4<200cells/μl) or hospitalized. LAM allows same day treatment initiation in patients at

Why India should become a global leader in high-quality, affordable TB diagnostics

PubMed Central

Small, Peter

2012-01-01

The scale up of DOTS in India is one of the greatest public health accomplishments, and yet undiagnosed and poorly managed TB continues to fuel the epidemic such that India continues to have the highest number of TB cases in the world. Recognizing these challenges, the Government of India has set an ambitious goal of providing universal access to quality diagnosis and treatment for all TB patients in the country. Innovative tools and delivery systems in both the public and private sectors are essential for reaching this goal. Fortunately, India has the potential to solve its TB problem with “home-grown” solutions. Just as Indian pharmaceutical companies revolutionized access to high-quality, affordable AIDS drugs through generic production, Indian diagnostic companies could also become the world's hub for high-quality generic diagnostics. In the long term, India has the potential to lead the world in developing innovative TB diagnostics. For this to happen, Indian industry must move from the import and imitation approach to genuine innovation in both product development as well as delivery. This must be supported by permissive policies and enhanced funding by the Indian government and the private sector. Strict regulation of diagnostics, increased attention to quality assurance in laboratories, and greater engagement of the private health care providers are also needed to effectively deliver innovative products and approaches. PMID:22771602

Prevalence and Factors Associated with Tuberculosis Treatment Success among TB/HIV Co-Infection in North-East Malaysia.

PubMed

Jalal, Tengku Mardhiah Tengku; Abdullah, Sarimah; Wahab, Farhanah Abd; Dir, Sharina; Naing, Nyi Nyi

2017-12-01

One of the six strategies developed by WHO, in order to stop Tuberculosis (TB) is addressing TB/HIV high-risk groups. This study aimed to determine the prevalence of successful TB treatment and factors associated with TB treatment success among TB/HIV co-infection patients in North-East Malaysia. A cross-sectional study was carried out in the a-year period from 2003 to 2012 by reviewing TB/HIV records in all hospitals and health clinics. The outcome of interest was treatment success as defined by Ministry of Health (MOH) when the patients was cured or completed TB treatment. Out of 1510 total TB/HIV co-infection cases, 27.9% (95% CI: 25.2, 30.6) of the patients were having treatment success. A majority of TB/HIV co-infection cases were male (91.1%). Fifty-eight percent the patients were drug addicts and 6% were having positive tuberculin tests. The multiple logistic regression revealed that male (OR: 0.39, 95% CI: 0.22, 0.71) and positive tuberculin test result (OR: 2.61, 95% CI: 1.63, 4.19) were significantly associated with the treatment success of TB/HIV co-infection patients. Other factors such as age, comorbid, sputum smear and x-ray findings were not significantly factors in this study. Female patients and those with negative tuberculin test should be emphasised for successful tuberculosis treatment.

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

PubMed

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

2018-03-20

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

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

PubMed

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

2018-01-01

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

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

PubMed

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

2016-01-01

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

Predicting treatment failure, death and drug resistance using a computed risk score among newly diagnosed TB patients in Tamaulipas, Mexico.

PubMed

Abdelbary, B E; Garcia-Viveros, M; Ramirez-Oropesa, H; Rahbar, M H; Restrepo, B I

2017-10-01

The purpose of this study was to develop a method for identifying newly diagnosed tuberculosis (TB) patients at risk for TB adverse events in Tamaulipas, Mexico. Surveillance data between 2006 and 2013 (8431 subjects) was used to develop risk scores based on predictive modelling. The final models revealed that TB patients failing their treatment regimen were more likely to have at most a primary school education, multi-drug resistance (MDR)-TB, and few to moderate bacilli on acid-fast bacilli smear. TB patients who died were more likely to be older males with MDR-TB, HIV, malnutrition, and reporting excessive alcohol use. Modified risk scores were developed with strong predictability for treatment failure and death (c-statistic 0·65 and 0·70, respectively), and moderate predictability for drug resistance (c-statistic 0·57). Among TB patients with diabetes, risk scores showed moderate predictability for death (c-statistic 0·68). Our findings suggest that in the clinical setting, the use of our risk scores for TB treatment failure or death will help identify these individuals for tailored management to prevent these adverse events. In contrast, the available variables in the TB surveillance dataset are not robust predictors of drug resistance, indicating the need for prompt testing at time of diagnosis.

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

PubMed

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

2015-09-01

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

Diagnosis and management of tuberculosis by private practitioners in Manila, Philippines.

PubMed

Auer, Christian; Lagahid, Jaime Y; Tanner, Marcel; Weiss, Mitchell G

2006-07-01

Private for-profit health care providers are prominent in the health system of the Philippines. To examine the practices of the private practitioners in Malabon, Metropolitan Manila, Philippines, concerning diagnosis and treatment of tuberculosis (TB). Forty-five private practitioners of Malabon who treat adult TB patients were interviewed. For diagnosis, most private practitioners relied on the clinical presentation and result of an X-ray. Only 13% of the respondents routinely also asked for sputum examination. Ninety-six percent used X-ray as a tool to monitor treatment. Sixty percent of the respondents prescribed a regimen consisting of isoniazid, rifampicin, pyrazinamide, and ethambutol. Except for rifampicin, over-dosage was common. For re-treatment cases, none prescribed the WHO-recommended re-treatment regimen. The private practitioners perceived the main reasons for patient non-adherence to be the patients' lack of finances to buy drugs and patients' perceived well being after a certain period of treatment. Patients' lack of money was seen as the main obstacle to compliance. The only case holding mechanism mentioned was occasional clinic appointments of the TB patients. Private practices for diagnosis and treatment of TB typically deviate from guidelines. The quality of care among private practitioners needs improvement. Innovative strategies are required.

[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.

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

PubMed Central

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

2015-01-01

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

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.

Characteristics of patients with delayed diagnosis of infectious pulmonary tuberculosis.

PubMed

Phoa, Lee-Lan; Teleman, Monica D; Wang, Yee-Tang; Chee, Cynthia B E

2005-03-01

The aim of this study was to identify patient and disease characteristics associated with delayed diagnosis of infectious pulmonary tuberculosis (TB). A retrospective analysis of 375 adult patients with culture-positive pulmonary TB and cough, treated at the Singapore Tuberculosis Control Unit (TBCU) in 2000, was carried out using data extracted from the TB notification registry and clinical records of the TBCU. Demographic, social, clinical and disease characteristics of patients with reported cough of duration less than, and exceeding, the median duration for the study population were compared. The median duration of cough reported at TB notification was 4 weeks (range, 1-156 weeks). By multivariate analysis, patients with cough > 4 weeks were more likely to be < 65 years old (adjusted odds ratio (OR), 1.8; 95% CI, 1.1-2.9; P = 0.02), of Chinese ethnicity (adjusted OR, 2.0; 95% CI, 1.2-3; P = 0.004), more likely to be sputum acid-fast bacilli smear-positive (adjusted OR, 1.7; 95% CI, 1.1-2.7; P = 0.016), and to have weight loss (adjusted OR, 2.6; 95% CI, 1.7-4; P < 0.01). Further studies are needed to identify the possible reasons for delayed diagnosis of TB among those < 65 years old, in the Chinese population in Singapore.

Public Relations Manager Involvement in Strategic Issue Diagnosis.

ERIC Educational Resources Information Center

Lauzen, Martha M.

1995-01-01

Reports on an exploratory study that seeks to build theoretical understanding of how public relations practitioner involvement in one type of strategic organizational decision making--strategic issue diagnosis--is related to shared values with top management, diagnosis accuracy, strategy pursued, and the power of the public relations function. (TB)

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

PubMed

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

2016-03-24

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

Referral of tuberculosis symptomatic clients from private pharmacies to public sector clinics for diagnosis and treatment in Cambodia.

PubMed

Bell, Carolyn A; Ilomäki, Jenni; Pichenda, Koeut; Duncan, Gregory J; Saini, Bandana

2015-04-01

Cambodia is one of the 22 countries with a high burden of tuberculosis (TB). People often first seek treatment for cough and other TB symptoms through private pharmacies. The National Tuberculosis Programme trained willing private sector pharmacies to refer TB symptomatic clients to their closest public sector clinic for diagnosis and treatment. The study objective was to investigate factors associated with referral of TB symptomatic clients from pharmacies to public sector clinics in Phnom Penh, Cambodia. Face-to-face structured interviews were conducted with staff from a stratified random sample of 180 private pharmacies in Phnom Penh in 2012. Trained interviewers were Khmer speakers. Logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for factors associated with self-reported referral during the previous 3 months. Fifty (29.6%) pharmacies reported that they had referred 125 clients (range 1-10) to public sector clinics during the previous 3 months. In total, 164 (96.5%) pharmacies reported that they always referred all TB symptomatic clients to DOTS (directly observed treatment, short course) clinics. More than 6-year participation in the programme (OR 5.23, 95% CI 1.93-14.18) and willingness to always continue referring (OR 12.24, 95% CI 11.61-93.10) were associated with referral of one or more clients in the previous 3 months. Referral to the client's closest clinic was negatively associated with referral (OR 0.45, 95% CI 0.23-0.99). Pharmacies' ongoing commitment to the Referral Programme was strongly associated with referral. Increased advocacy among the high number of non-referring pharmacies may improve programme performance. Factors negatively associated with referral may need investigation. © 2015 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons, Ltd.

[Diagnosis delay of pleural and pulmonary tuberculosis].

PubMed

Cherif, J; Mjid, M; Ladhar, A; Toujani, S; Mokadem, S; Louzir, B; Mehiri, N; Béji, M

2014-08-01

Tuberculosis (TB) is still being endemic in our country. Time until management determines both evolution and prognosis of this condition. The aim of this work is to evaluate the delay in diagnosis of TB in a respiratory unit from a university hospital series. The authors conducted a cross-sectional study including patients with pulmonary TBC and/or pleural. An evaluation of time management was conducted from the beginning of symptoms and various consultations with reference to the date of hospitalization and treatment set up. One hundred patients were included (pulmonary TB: 68 cases, pleural TB 23 cases, miliary pulmonary TB: 4 cases, pulmonary TB associated with other extrathoracic locations: 5 cases). The mean time of patient delay and total delay institution were respectively 43.6, 25.7 and 69.3 days. Variables responsible for long delays were: number of consultations more than 3 before hospitalization, empirical antibiotic therapy, of a regional hospital first consultation and the presence of extra-respiratory impairment. The patient delay was considered long. A reorganization of the TB control program, in particular by partial decentralization of care and health education is imperative in order to improve the quality of tuberculosis management in our country. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

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

PubMed

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

2015-01-31

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

The Collaborative Ocular Tuberculosis Study (COTS)-1 Report 3: Polymerase Chain Reaction in the Diagnosis and Management of Tubercular Uveitis: Global Trends.

PubMed

Agarwal, Aniruddha; Agrawal, Rupesh; Gunasekaran, Dinesh Visva; Raje, Dhananjay; Gupta, Bhaskar; Aggarwal, Kanika; Murthy, Somasheila L; Westcott, Mark; Chee, Soon Phaik; Mccluskey, Peter; Su Ling, Ho; Teoh, Stephen; Cimino, Luca; Biswas, Jyotirmay; Narain, Shishir; Agarwal, Manisha; Mahendradas, Padmamalini; Khairallah, Moncef; Jones, Nicholas; Tugal-Tutkun, Ilknur; Babu, Kalpana; Basu, Soumayava; Carreño, Ester; Lee, Richard; Al-Dhibi, Hassan; Bodaghi, Bahram; Invernizzi, Alessandro; Goldstein, Debra A; Herbort, Carl P; Barisani-Asenbauer, Talin; González-López, Julio J; Androudi, Sofia; Bansal, Reema; Moharana, Bruttendu; Mahajan, Sarakshi; Esposti, Simona; Tasiopoulou, Anastasia; Nadarajah, Sengal; Agarwal, Mamta; Abraham, Sharanya; Vala, Ruchi; Singh, Ramandeep; Sharma, Aman; Sharma, Kusum; Zierhut, Manfred; Kon, Onn Min; Cunningham, Emmett; Nguyen, Quan Dong; Pavesio, Carlos; Gupta, Vishali

2017-12-20

To analyze the role of polymerase chain reaction (PCR) of ocular fluids in management of tubercular (TB) anterior, intermediate, posterior, and panuveitis. In Collaborative Ocular Tuberculosis Study (COTS)-1 (25 centers, n = 962), patients with TB-related uveitis were included. 59 patients undergoing PCR of intraocular fluids (18 females; 53 Asian Indians) were included. 59 (6.13%) of COTS-1 underwent PCR analysis. PCR was positive for Mycobacterium TB in 33 patients (23 males; all Asian Indians). 26 patients were PCR negative (18 males). Eight patients with negative PCR had systemic TB. Anti-TB therapy was given in 18 negative and 31 PCR cases. At 1-year follow-up, five patients with positive PCR (15.15%) and three with negative PCR (11.54%) had persistence/worsening of inflammation. Data from COTS-1 suggest that PCR is not commonly done for diagnosing intraocular TB and positive/negative results may not influence management or treatment outcomes in the real world scenario.

Utility of the T-SPOT®.TB test's borderline category to increase test resolution for results around the cut-off point.

PubMed

Rego, Karen; Pereira, Kristen; MacDougall, James; Cruikshank, William

2018-01-01

Accurate identification of individuals with TB infection, is required to achieve the WHO's End TB Strategy goals. While there is general acceptance that the T-SPOT.TB test borderline category provides an opportunity to increase test resolution of results around the test cut-off point, this has not been investigated. 645,947 tests were analyzed to determine frequency of borderline results, effect of age and time between tests and associations between subjects' clinical risk factors and retest results. 645,947 tests produced 93.5% negatives, 4% positives, 0.6% invalids, and 1.8% borderlines. Within the borderline results, 5044 were repeated, with 59.2%, 20.0% and 20.2% resolving to negative, positive and borderline, respectively. Age of subject did not affect retest results; however, time between tests indicated that retest resolution occurred with greatest frequency after 90 days. TB risk factors were provided for 2640 subjects and 17% of low risk subjects with a high initial borderline resolved to negative while 27.6% of subjects with high risk and an initial low borderline resolved to positive, suggesting that these subjects could have been inappropriately classified if using a single cut-off point test with no borderline category. This study demonstrates the utility of the T-SPOT.TB test's borderline category to increase test resolution around the test cut-off point. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

TB in Children in the United States

MedlinePlus

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

TB control: challenges and opportunities for India.

PubMed

Pai, Madhukar; Daftary, Amrita; Satyanarayana, Srinath

2016-03-01

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

Effects of acculturation and psychosocial factors in Latino adolescents' TB-related behaviors.

PubMed

Salabarría-Peña, Y; Trout, P T; Gill, J K; Morisky, D E; Muralles, A A; Ebin, V J

2001-01-01

To determine the effect of acculturation and psychosocial factors (self-esteem, social support, mastery, and self-efficacy of medication taking) on Latino adolescents' adherence (completion of treatment, percent of appointments kept, number of treatment weeks, and number of days missed medication in past week) to tuberculosis (TB) treatment. Participants (N = 618) were recruited from two clinics located in Los Angeles, California, after receiving a positive diagnosis for Class II TB. Adolescents with high linguistic acculturation and ethnic identification had high mastery, self-esteem and self-efficacy. Teens with high ethnic identification perceived more support from parents. Almost 81% of participants completed treatment and the percentage of appointments kept was 76.3%. A high proportion of those completing the treatment regimen had their parents helping them to remember to take the medication. Older teens were less acculturated, less likely to complete treatment, and had a lower rate of appointment keeping. Age and difficulty in getting to the clinics were predictors of adherence. This study highlights the importance of parental support and sociocultural factors in adherence to TB treatment in this population.

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

PubMed

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

2018-04-01

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

Understanding social context on TB cases

NASA Astrophysics Data System (ADS)

Ariyanto, Y.; Wati, D. M.

2017-01-01

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

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

PubMed

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

2017-05-18

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

TB control programmes: the challenges for Africa.

PubMed

Harries, T

1996-11-01

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

Better care provided to patients with tuberculosis at county designated TB hospitals (CTD) compared to non-CTDs in rural China.

PubMed

Yuan, Li; Zhang, Hui; Zhou, Changming; Jiang, Weili; Zhao, Qi; Biao, Xu

2017-01-13

The primary unit of tuberculosis (TB) medical care in China is the county TB dispensary or county designated hospital (CTD), where patients can receive free diagnosis and treatment. However, a substantial number of patients seek their anti-TB treatment from general health facilities (Non-CTDs). This study aimed to investigate the first anti-TB treatment experience and choice of health facilities of retreated TB patients and their determinants. A cross-sectional study was conducted in Jiangsu, Shandong and Sichuan provinces. All registered re-treated TB patients were investigated using a structured questionnaire covering information on demographics, socio-economic characteristics, and previous anti-TB treatment experiences. Totally, 75.3% of 544 patients visited CTD directly for initial treatment. Patients who were female (OR:1.71, 95% CI: 1.01-2.87), over 40 years of age (OR:2.80, 95% CI: 1.24-6.33), from Jiangsu (OR:3.07, 95% CI: 1.57-6.01) and Sichuan (OR:4.47, 95% CI: 2.29-8.73) and those diagnosed before 2005 (OR:6.87, 95% CI: 4.24-11.13) had a significant higher risk receiving their initial treatment at a non-CTD. Patients were more likely to have standardized diagnosis and treatment regimens in CTD (89.8%) than in non-CTDs (65.9%). Patients treated in non-CTDs versus in CTD had a lower possibility to complete their treatment course during first TB episode (χ 2  = 3.926, P = 0.048), but there was no significant difference in the cure rate between different facilities (CTD 60.8%, Non-CTDs 59.1%). Patients in non-CTDs incurred higher costs (1,360 CNY) than those treated in CTD (920CNY). CTD play a key role in the National Tuberculosis Control Program. Patients should be guided to seek health care in county designated hospital, where they are more likely to receive appropriate examinations, treatment regimens and rigorous supervision, and to bear a lighter economic burden.

Unusual regioversatility of acetyltransferase Eis, a cause of drug resistance in XDR-TB

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

Chen, Wenjing; Biswas, Tapan; Porter, Vanessa R.

2011-09-06

The emergence of multidrug-resistant and extensively drug-resistant (XDR) tuberculosis (TB) is a serious global threat. Aminoglycoside antibiotics are used as a last resort to treat XDR-TB. Resistance to the aminoglycoside kanamycin is a hallmark of XDR-TB. Here, we reveal the function and structure of the mycobacterial protein Eis responsible for resistance to kanamycin in a significant fraction of kanamycin-resistant Mycobacterium tuberculosis clinical isolates. We demonstrate that Eis has an unprecedented ability to acetylate multiple amines of many aminoglycosides. Structural and mutagenesis studies of Eis indicate that its acetylation mechanism is enabled by a complex tripartite fold that includes two generalmore » control non-derepressible 5 (GCN5)-related N-acetyltransferase regions. An intricate negatively charged substrate-binding pocket of Eis is a potential target of new antitubercular drugs expected to overcome aminoglycoside resistance.« less

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

PubMed

Alcaide, Fernando; Coll, Pere

2011-03-01

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

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

PubMed

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

2013-09-04

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

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

PubMed Central

2013-01-01

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

[Characteristics of the diagnosis and treatment of pulmonary tuberculosis in patients with and without diabetes mellitus type 2].

PubMed

Carrión-Torres, Omar; Cazorla-Saravia, Patrick; Torres Sales, José William; Yhuri Carreazo, Nilton; De La Cruz Armijo, Frank Enrique

2015-10-01

To determine whether there are demographic, clinical and radiological differences among patients with pulmonary tuberculosis (TB) and patients with TB and type 2 diabetes mellitus (DM2 + TB). Observational retrospective cohort study. We compared the clinical characteristics of patients according to sex, age, time to sputum conversion to negative, presence of cavitation and the cure rate, duration of treatment and the proportion of change of treatment regimen, in patients with and without DM2 served by the Tuberculosis Control Program from 2010 to 2012 in the Rebagliati Healthcare Network of Lima, Peru. 31 patients with TB+DM2 and 144 patients with TB were included. Differences (p<0.05) in the diagnostic method, the average of symptoms and the resistance pattern of TB among patients with and without DM2 were found. The presence of cavitation was more frequent in patients with TB + DM2. Having TB + DM2 delayed the time to sputum smear conversion to negative (RRa 4.16, 95% CI: 1.1-1.6) in the adjusted Cox regression analysis. There are differences in demographic, clinical and radiological characteristics in TB patients with and without DM2.The time to sputum conversion to negative is greater in patients with DM2.

The pros and cons of the QuantiFERON test for the diagnosis of tuberculosis, prediction of disease progression, and treatment monitoring.

PubMed

Ndzi, Elvis Ndukong; Nkenfou, Celine Nguefeu; Gwom, Luc Christian; Fainguem, Nadine; Fokam, Joseph; Pefura, Yone

2016-06-01

Tuberculosis (TB) is a re-emerging disease with the advent of human immunodeficiency virus/AIDS infections. Discovered in 1959, diagnosed by various approaches and treated with antibiotics, the treatment of TB infection still poses public health concerns. Many cases of resistance and cross-resistance are observed. Diagnosis by culture, which is considered as the standard method, takes too long (20-30days) and is not suitable for extrapulmonary TB. QuantiFERON test, which is an indirect immunoassay based on blood, was developed. Much hope was placed in this new approach because it is based on blood, and many research teams have used it. We discuss the results of these different research groups who have used QuantiFERON for diagnosis, prediction of disease progression, or monitoring patients during the treatment of TB. Articles published in PubMed and documents published on Google were searched with the keywords: diagnosis and TB and QuantiFERON; TB and QuantiFERON and therapeutic monitoring; interferon-γ release assay; disease progression. These articles were read and analyzed. The results were controversial with regards to using the QuantiFERON test for the diagnosis of TB according to the study population (ethnic group, bacillus Calmette-Guérin vaccine use) and according to the state of the immune system of the people studied (human immunodeficiency virus immunosuppression in cancer medication, hypertension). Also, research findings were controversial with regards to using QuantiFERON for monitoring TB patients on anti-TB medications. Also, the predictive positive value for the progression to TB among immigrant close contacts of both interferon-γ release assays was not better than that of the tuberculin skin test. The QuantiFERON has advantages and limitations depending on the type of population studied. Recommendations are made to improve the sensitivity and specificity and to differentiate between latent and active TB by adding other specific proteins in the

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

PubMed

Denegetu, Amenu Wesen; Dolamo, Bethabile Lovely

2014-01-01

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

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

Effect of prolonged incubation time on results of the QuantiFERON TB gold in-tube assay for diagnosis of latent tuberculosis infection.

PubMed

Min, Joo-Won; Lee, Ha-Youn; Lee, Ji Sun; Lee, Jinwoo; Chung, Jae Ho; Han, Sung Koo; Yim, Jae-Joon

2013-09-01

Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results.

Effect of Prolonged Incubation Time on Results of the QuantiFERON TB Gold In-Tube Assay for Diagnosis of Latent Tuberculosis Infection

PubMed Central

Min, Joo-Won; Lee, Ha-Youn; Lee, Ji Sun; Lee, Jinwoo; Chung, Jae Ho; Han, Sung Koo

2013-01-01

Previous reports have shown that the sensitivity of the 6-day lymphocyte stimulation test is much higher than those of commercially available gamma interferon release assays (IGRAs). The aim of this study was to elucidate the effect of prolonged incubation on the results of the QuantiFERON TB Gold in-tube (QFT-GIT) assay. Patients aged >20 years with suspected tuberculosis (TB) were recruited prospectively from 1 May 2009 to 31 December 2010. In addition, healthy volunteers with no history of TB treatment were included as controls. For each participant, three sets of the QFT-GIT assay were performed using 24-, 48-, and 72-h incubation tests, and the results were compared. Thirty-seven patients with suspected pulmonary TB and 33 healthy controls were enrolled in the study. Of the 37 patients with suspected TB, the QFT-GIT assay results were positive for 28 (75.7%) after a 24-h incubation period. After prolonged incubation, the results differed in four (10.8%) of the 37 patients suspected of having TB. Among 27 patients with culture-confirmed TB, the sensitivities of the QFT-GIT assay after the 24-, 48-, and 72-h incubation tests were 85.2%, 81.5%, and 81.5%, respectively. Among the 33 healthy controls, the QFT-GIT assay results were positive in two (6.1%) after a 24-h incubation period. The results changed for two (6.1%) of the 33 healthy controls after prolonged incubation. The specificities of the QFT-GIT assay after 24, 48, and 72 h of incubation were 93.9%, 87.9%, and 90.9%, respectively. Prolonging the incubation time did not increase the sensitivity of the QFT-GIT assay. The manufacturer-recommended incubation time of 16 to 24 h should be respected because prolonged incubation can cause indeterminate or false-positive results. PMID:23825190

Integration of TB-HIV services at an ANC facility in Frances Baard District, Northern Cape, South Africa.

PubMed

Peters, J A; Heunis, C; Kigozi, G; Osoba, T; van der Walt, M

2015-03-21

Integrated tuberculosis-human immunodeficiency virus (TB-HIV) service delivery as part of maternal health services, including antenatal care (ANC), is widely recommended. This study assessed the implementation of collaborative TB-HIV service delivery at a hospital-based ANC service unit. A record review of a random sample of 308 pregnant women attending the ANC service between April 2011 and February 2012 was conducted. Data were extracted from registers and patient case notes. Outcomes included the proportion of women who underwent HIV counselling and testing (HCT), CD4 count testing, antiretroviral treatment (ART), cotrimoxazole preventive treatment (CPT), TB screening and isoniazid preventive treatment (IPT). Analysis measured variations in patient characteristics associated with service delivery. All women underwent HCT; 80% of those who tested HIV-positive were screened for TB. Most (85.9%) of the HIV-positive women received a CD4 count. However, only 12.9% of eligible women received ART prophylaxis onsite, only 35.7% were referred for initiation of ART, only 42.3% commenced IPT and none received CPT or further investigations for TB. HIV-negative women had 2.6 higher odds (95%CI 1.3-5.3) of receiving TB screening than their HIV-positive counterparts. Although the identification of HIV-positive women and TB suspects was adequate, implementation of other TB-HIV collaborative activities was sub-optimal.

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

Evaluation of Microscopic Observation Drug Susceptibility (MODS) and the string test for rapid diagnosis of pulmonary tuberculosis in HIV/AIDS patients in Bolivia.

PubMed

Lora, Meredith H; Reimer-McAtee, Melissa J; Gilman, Robert H; Lozano, Daniel; Saravia, Ruth; Pajuelo, Monica; Bern, Caryn; Castro, Rosario; Espinoza, Magaly; Vallejo, Maya; Solano, Marco; Challapa, Roxana; Torrico, Faustino

2015-06-06

Tuberculosis (TB) is the most common opportunistic infection and the leading cause of death in HIV-positive people worldwide. Diagnosing TB is difficult, and is more challenging in resource-scarce settings where culture-based diagnostic methods rely on poorly sensitive smear microscopy by Ziehl-Neelsen stain (ZN). We performed a cross-sectional study examining the diagnostic utility of Microscopic Observation Drug Susceptibility liquid culture (MODS) versus traditional Ziehl-Neelsen staining (ZN) and Lowenstein Jensen culture (LJ) of pulmonary tuberculosis (TB) and multidrug-resistant tuberculosis (MDRTB) in HIV-infected patients in Bolivia. For sputum scarce individuals we assessed the value of the string test and induced sputum for TB diagnosis. The presence of Mycobacterium tuberculosis (Mtb) in the sputum of 107 HIV-positive patients was evaluated by ZN, LJ, and MODS. Gastric secretion samples obtained by the string test were evaluated by MODS in 102 patients. The TB-HIV co-infection rate of HIV patients with respiratory symptoms by sputum sample was 45 % (48/107); 46/48 (96 %) were positive by MODS, 38/48 (79 %) by LJ, and 30/48 (63 %) by ZN. The rate of MDRTB was 9 % (4/48). Median time to positive culture was 10 days by MODS versus 34 days by LJ (p < 0.0001). In smear-negative patients, MODS detected TB in 17/18 patients, compared to 11/18 by LJ (94.4 % vs 61.0 %, p = 0.03 %). In patients unable to produce a sputum sample without induction, the string test cultured by MODS yielded Mtb in of 9/11 (82 %) TB positive patients compared to 11/11 (100 %) with induced sputum. Of the 10 patients unable to produce a sputum sample, 4 were TB-positive by string test. MODS was faster and had a higher Mtb detection yield compared to LJ, with a greater difference in yield between the two in smear-negative patients. The string test is a valuable diagnostic technique for HIV sputum-scarce or sputum-absent patients, and should be considered as an alternative test to induced

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

PubMed

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

2017-02-01

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

Multidrug-Resistant TB

PubMed Central

Cox, Helen; Coomans, Fons

2016-01-01

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

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.

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

PubMed

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

2018-04-26

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

Risk Factors Associated with MDR-TB at the Onset of Therapy among New Cases Registered with the RNTCP in Mumbai, India

PubMed Central

Atre, Sachin R.; D’Souza, Desiree T. B.; Vira, Tina S.; Chatterjee, Anirvan; Mistry, Nerges F.

2014-01-01

Background Multidrug-resistant TB (MDR-TB) has emerged as a major threat to global TB control efforts in recent years. Facilities for its diagnosis and treatment are limited in many high-burden countries, including India. In hyper-endemic areas like Mumbai, screening for newly diagnosed cases at a higher risk of acquiring MDR-TB is necessary, for initiating appropriate and timely treatment, to prevent its further spread. Objective To assess risk factors associated with MDR-TB among Category I, new sputum smear-positive cases, at the onset of therapy. Materials and Methods The study applied an unmatched case-control design for 514 patients (106 cases with MDR-TB strains and 408 controls with non-MDR-TB strains). The patients were registered with the Revised National Tuberculosis Control Program (RNTCP) in four selected wards of Mumbai during April 2004-January 2007. Data were collected through semi-structured interviews and drug susceptibility test results. Results Multivariate analysis indicated that infection with the Beijing strain (OR = 3.06; 95% C.I. = 1.12-8.38; P = 0.029) and female gender (OR = 1.68; 95% C.I. = 1.02-2.87; P = 0.042) were significant predictors of MDR-TB at the onset of therapy. Conclusion The study provides a starting point to further examine the usefulness of these risk factors as screening tools in identifying individuals with MDR-TB, in settings where diagnostic and treatment facilities for MDR-TB are limited. PMID:21727675

One of the possible mechanisms for the inhibition effect of Tb(III) on peroxidase activity in horseradish (Armoracia rusticana) treated with Tb(III).

PubMed

Guo, Shaofen; Cao, Rui; Lu, Aihua; Zhou, Qing; Lu, Tianhong; Ding, Xiaolan; Li, Chaojun; Huang, Xiaohua

2008-05-01

One of the possible mechanisms for the inhibition effect of Tb(III) on peroxidase activity in horseradish (Armoracia rusticana) treated with Tb(III) was investigated using some biophysical and biochemical methods. Firstly, it was found that a large amount of Tb(III) can be distributed on the cell wall, that some Tb(III) can enter into the horseradish cell, indicating that peroxidase was mainly distributed on cell wall, and thus that Tb(III) would interact with horseradish peroxidase (HRP) in the plant. In addition, peroxidase bioactivity was decreased in the presence of Tb(III). Secondly, a new peroxidase-containing Tb(III) complex (Tb-HRP) was obtained from horseradish after treatment with Tb(III); the molecular mass of Tb-HRP is near 44 kDa and the pI is about 8.80. Thirdly, the electrocatalytic activity of Tb-HRP is much lower than that of HRP obtained from horseradish without treatment with Tb(III). The decrease in the activity of Tb-HRP is due to the destruction (unfolding) of the conformation in Tb-HRP. The planarity of the heme active center in the Tb-HRP molecule was increased and the extent of exposure of Fe(III) in heme was decreased, leading to inhibition of the electron transfer. The microstructure change in Tb-HRP might be the result of the inhibition effect of Tb(III) on peroxidase activity in horseradish.

Tuberculin skin test for the diagnosis of latent tuberculosis during renal replacement therapy in an endemic area: A single center study

PubMed Central

Agarwal, S. K.; Gupta, S.; Bhowmik, D.; Mahajan, S.

2010-01-01

Patients on renal replacement therapy (RRT) are at-risk for developing tuberculosis (TB). There is limited information on tuberculin skin test (TST) and its predictability for development of TB. In this prospective cohort study, patients taken for RRT were included. Patients with active TB were excluded. TST was done with 5-tuberculin unit. In addition to TST, age, sex, diabetes as basic disease, number of dialysis and blood transfusion (BT), pre-transplant TB, hepatitis B and C infections and type of immunosuppression were correlated with the development of TB. Of the 200 patients included, TST was positive in 21 and negative in 179. In TST negative group, 20 (11.1%) and in TST positive group 5 (23.8%) patients developed TB. TB free survival in two groups was similar (P = 0.08). On multivariate Cox regression analysis, hazard of development of TB by TST was 2.7 [P = 0.11, confidence interval (CI) 0.78-9.7]. There was no difference between TST non-responsive and TST negative patients (P = 0.18). Sensitivity and specificity of TST for predicting TB was only 20 and 9%, respectively. Our study shows that TST in patients on dialysis is an insensitive and nonspecific test to predict development of active TB. PMID:21072152

Serological Analysis of Tuberculosis in Goats by Use of the Enferplex Caprine TB Multiplex Test

PubMed Central

O'Brien, Amanda; Whelan, Clare; Clarke, John B.; Hayton, Alastair; Watt, Neil J.

2016-01-01

ABSTRACT Tuberculosis in goats is usually diagnosed clinically, at postmortem, or by a positive skin test. However, none of these approaches detects all infected animals. Serology offers an additional tool to identify infected animals missed by current tests. We describe the use of the Enferplex Caprine TB serology test to aid the management of a large dairy goat herd undergoing a tuberculosis breakdown. Initial skin and serology testing showed that IgG antibodies were present in both serum and milk from 100% of skin test-positive animals and in serum and milk from 77.8 and 95.4% of skin test-negative animals, respectively. A good correlation was observed between serum and milk antibody levels. The herd had been vaccinated against Mycobacterium avium subsp. paratuberculosis, but no direct serological cross-reactions were found. Subsequent skin testing revealed 13.7% positive animals, 64.9% of which were antibody positive, while 42.1% of skin test-negative animals were seropositive. Antibody responses remained high 1 month later (57.1% positive), and the herd was slaughtered. Postmortem analysis of 20 skin test-negative goats revealed visible lesions in 6 animals, all of which had antibodies to six Mycobacterium bovis antigens. The results provide indirect evidence that serology testing with serum or milk could be a useful tool in the diagnosis and management of tuberculosis in goats. PMID:27974399

Serological Analysis of Tuberculosis in Goats by Use of the Enferplex Caprine TB Multiplex Test.

PubMed

O'Brien, Amanda; Whelan, Clare; Clarke, John B; Hayton, Alastair; Watt, Neil J; Harkiss, Gordon D

2017-02-01

Tuberculosis in goats is usually diagnosed clinically, at postmortem, or by a positive skin test. However, none of these approaches detects all infected animals. Serology offers an additional tool to identify infected animals missed by current tests. We describe the use of the Enferplex Caprine TB serology test to aid the management of a large dairy goat herd undergoing a tuberculosis breakdown. Initial skin and serology testing showed that IgG antibodies were present in both serum and milk from 100% of skin test-positive animals and in serum and milk from 77.8 and 95.4% of skin test-negative animals, respectively. A good correlation was observed between serum and milk antibody levels. The herd had been vaccinated against Mycobacterium avium subsp. paratuberculosis, but no direct serological cross-reactions were found. Subsequent skin testing revealed 13.7% positive animals, 64.9% of which were antibody positive, while 42.1% of skin test-negative animals were seropositive. Antibody responses remained high 1 month later (57.1% positive), and the herd was slaughtered. Postmortem analysis of 20 skin test-negative goats revealed visible lesions in 6 animals, all of which had antibodies to six Mycobacterium bovis antigens. The results provide indirect evidence that serology testing with serum or milk could be a useful tool in the diagnosis and management of tuberculosis in goats. Copyright © 2017 American Society for Microbiology.

Lack of consensus in the diagnosis and treatment for ocular tuberculosis among uveitis specialists.

PubMed

Lou, Susan M; Larkin, Kelly L; Winthrop, Kevin; Rosenbaum, James T

2015-02-01

To assess the approach of specialists to ocular tuberculosis (TB). The American Uveitis Society (AUS) Listserv was surveyed using two clinical cases and general questions. Of 196 members, 87 responded (44.4%), of whom 64 were affiliated with practices in North America, while 23 were outside of North America. The survey provided normative data on how physicians evaluate patients with uveitis as well as opinions about ocular TB. Responses varied widely on such issues as (1) the pretest probability that a patient with granulomatous panuveitis had TB uveitis (range 1-75%) or that a patient with a risk factor for TB had ocular TB (range 0-90%); (2) the optimal duration of anti-TB therapy; and (3) whether therapy should be discontinued after 2 months in nonresponders. Consensus is lacking among uveitis specialists for the diagnosis or management of ocular TB.

Increased detection of smear-negative pulmonary tuberculosis by GeneXpert MTB/RIF® assay after bleach concentration.

PubMed

Tadesse, Mulualem; Aragaw, Dossegnaw; Rigouts, Leen; Abebe, Gemeda

2016-06-01

The GeneXpert MTB/RIF assay (Xpert) was endorsed as the initial diagnostic tool in people suspected of human immunodeficiency virus-associated or drug-resistant tuberculosis (TB). However, information regarding the performance of Xpert for diagnosing smear-negative TB in high burden settings remains limited. We evaluated the diagnostic accuracy of Xpert and the impact of bleach concentration on the performance of Xpert using smear-negative sputum samples from human immunodeficiency virus-negative patients. One spot and one morning smear-negative sputum samples per patient were examined using Xpert and culture at the Mycobacteriology Research Center of Jimma University, Ethiopia. The sputum culture on both Löwenstein-Jensen and/or Mycobacteria Growth Indicator Tube was the gold-standard. Of 185 smear-negative presumptive pulmonary TB cases, 19 (10.3%) had culture-proven TB. The sensitivity of Xpert on spot and morning sputum was similar (63.2%). Testing two specimens per patient insignificantly increased the sensitivity of Xpert. Bleach concentration and pelleting improved the sensitivity of Xpert over unprocessed sputum in paired samples (73.8% vs. 63.2%) without affecting the specificity (95%). Bleach concentration and pelleting allowed an additional seven cases of TB (missed on the first and second direct Xperts) to be detected, five of which were from culture-negative cases. Testing of a single sputum sample by Xpert can reach reasonable sensitivity and results would be available on the same day, avoiding loss of patients and treatment delay. The sensitivity of Xpert was improved after bleach concentration and pelleting, although its added value needs further study on a larger scale. Copyright © 2016 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.

Giant magnetoelectric effect in negative magnetostrictive/piezoelectric/positive magnetostrictive semiring structure

NASA Astrophysics Data System (ADS)

Zeng, Lingyu; Zhou, Minhong; Bi, Ke; Lei, Ming

2016-01-01

Magnetoelectric (ME) Ni/PZT/TbFe2 and TbFe2/PZT composites with two semiring structures are prepared. The dependence between ME coupling and magnetostrictive property of the composite is discussed. Because Ni possesses negative magnetostrictive property and TbFe2 shows positive magnetostrictive property, the ME voltage coefficient of Ni/PZT/TbFe2 semiring structure is much larger than that of TbFe2/PZT. In these composites, the ME voltage coefficient increases and the resonance frequency gradually decreases with the increase of the semiring radius, showing that structural parameters are key factors to the composite properties. Due to the strong ME coupling effect, a giant ME voltage coefficient αE = 44.8 V cm-1 Oe-1 is obtained. This approach opens a way for the design of ME composites with giant ME voltage coefficient.

HIV and TB co-infection in Indian context.

PubMed

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

2013-01-01

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

Assessment of the QuantiFERON-TB Gold In-Tube test for the detection of Mycobacterium tuberculosis infection in United States Navy recruits.

PubMed

Lempp, Jason M; Zajdowicz, Margan J; Hankinson, Arlene L; Toney, Sean R; Keep, Lisa W; Mancuso, James D; Mazurek, Gerald H

2017-01-01

Immunologic tests such as the tuberculin skin test (TST) and QuantiFERON®-TB Gold In-Tube test (QFT-GIT) are designed to detect Mycobacterium tuberculosis infection, both latent M. tuberculosis infection (LTBI) and infection manifesting as active tuberculosis disease (TB). These tests need high specificity to minimize unnecessary treatment and high sensitivity to allow maximum detection and prevention of TB. Estimate QFT-GIT specificity, compare QFT-GIT and TST results, and assess factor associations with test discordance among U.S. Navy recruits. Among 792 subjects with completed TST and QFT-GIT, 42(5.3%) had TST indurations ≥10mm, 23(2.9%) had indurations ≥15mm, 14(1.8%) had positive QFT-GIT results, and 5(0.6%) had indeterminate QFT-GITs. Of 787 subjects with completed TST and determinate QFT-GIT, 510(64.8%) were at low-risk for infection, 277(35.2%) were at increased risk, and none had TB. Among 510 subjects at low-risk (presumed not infected), estimated TST specificity using a 15mm cutoff, 99.0% (95%CI: 98.2-99.9%), and QFT-GIT specificity, 98.8% (95%CI: 97.9-99.8%), were not significantly different (p>0.99). Most discordance was among recruits at increased risk of infection, and most was TST-positive but QFT-GIT-negative discordance. Of 18 recruits with TST ≥15mm but QFT-GIT negative discordance, 14(78%) were at increased risk. TB prevalence in country of birth was the strongest predictor of positive TST results, positive QFT-GIT results, and TST-positive but QFT-GIT-negative discordance. Reactivity to M. avium purified protein derivative (PPD) was associated with positive TST results and with TST-positive but QFT-GIT-negative discordance using a 10 mm cutoff, but not using a 15 mm cutoff or with QFT-GIT results. M. tuberculosis infection prevalence was low, with the vast majority of infection occurring in recruits with recognizable risks. QFT-GIT and TST specificities were high and not significantly different. Negative QFT-GIT results among subjects

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

PubMed

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

2018-03-01

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

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

PubMed

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

2009-08-01

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

Discordance in CD4+T-Cell Levels and Viral Loads with Co-Occurrence of Elevated Peripheral TNF-α and IL-4 in Newly Diagnosed HIV-TB Co-Infected Cases

PubMed Central

Benjamin, Ronald; Banerjee, Atoshi; Sunder, Sharada Ramaseri; Gaddam, Sumanlatha; Valluri, Vijaya Lakshmi; Banerjee, Sharmistha

2013-01-01

Background Cytokines are the hallmark of immune response to different pathogens and often dictate the disease outcome. HIV infection and tuberculosis (TB) are more destructive when confronted together than either alone. Clinical data related to the immune status of HIV-TB patients before the initiation of any drug therapy is not well documented. This study aimed to collect the baseline information pertaining to the immune status of HIV-TB co-infected patients and correlate the same with CD4+T cell levels and viral loads at the time of diagnosis prior to any drug therapy. Methodology/Principal Findings We analyzed the cytokines, CD4+T cell levels and viral loads to determine the immune environment in HIV-TB co-infection. The study involved four categories namely, Healthy controls (n = 57), TB infected (n = 57), HIV infected (n = 59) and HIV-TB co-infected (n = 57) patients. The multi-partite comparison and correlation between cytokines, CD4+T-cell levels and viral loads prior to drug therapy, showed an altered TH1 and TH2 response, as indicated by the cytokine profiles and skewed IFN-γ/IL-10 ratio. Inadequate CD4+T cell counts in HIV-TB patients did not correlate with high viral loads and vice-versa. When compared to HIV category, 34% of HIV-TB patients had concurrent high plasma levels of IL-4 and TNF-α at the time of diagnosis. TB relapse was observed in 5 of these HIV-TB co-infected patients who also displayed high IFN-γ/IL-10 ratio. Conclusion/Significance With these studies, we infer (i) CD4+T-cell levels as baseline criteria to report the disease progression in terms of viral load in HIV-TB co-infected patients can be misleading and (ii) co-occurrence of high TNF-α and IL-4 levels along with a high ratio of IFN-γ/IL-10, prior to drug therapy, may increase the susceptibility of HIV-TB co-infected patients to hyper-inflammation and TB relapse. PMID:23936398

Extensively Drug-Resistant Tuberculosis: Principles of Resistance, Diagnosis, and Management.

PubMed

Wilson, John W; Tsukayama, Dean T

2016-04-01

Extensively drug-resistant (XDR) tuberculosis (TB) is an unfortunate by-product of mankind's medical and pharmaceutical ingenuity during the past 60 years. Although new drug developments have enabled TB to be more readily curable, inappropriate TB management has led to the emergence of drug-resistant disease. Extensively drug-resistant TB describes Mycobacterium tuberculosis that is collectively resistant to isoniazid, rifampin, a fluoroquinolone, and an injectable agent. It proliferates when established case management and infection control procedures are not followed. Optimized treatment outcomes necessitate time-sensitive diagnoses, along with expanded combinations and prolonged durations of antimicrobial drug therapy. The challenges to public health institutions are immense and most noteworthy in underresourced communities and in patients coinfected with human immunodeficiency virus. A comprehensive and multidisciplinary case management approach is required to optimize outcomes. We review the principles of TB drug resistance and the risk factors, diagnosis, and managerial approaches for extensively drug-resistant TB. Treatment outcomes, cost, and unresolved medical issues are also discussed. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Risk factors associated with default among new pulmonary TB patients and social support in six Russian regions.

PubMed

Jakubowiak, W M; Bogorodskaya, E M; Borisov, S E; Borisov, E S; Danilova, I D; Danilova, D I; Kourbatova, E V; Kourbatova, E K

2007-01-01

Tuberculosis (TB) services in six Russian regions in which social support programmes for TB patients were implemented. To identify risk factors for default and to evaluate possible impact of social support. Retrospective study of new pulmonary smear-positive and smear-negative TB patients registered during the second and third quarters of the 2003. Data were analysed in a case-control study including default patients as cases and successfully treated patients as controls, using multivariate logistic regression modelling. A total of 1805 cases of pulmonary TB were enrolled. Default rates in the regions were 2.3-6.3%. On multivariate analysis, risk factors independently associated with default outcome included: unemployment (OR 4.44; 95%CI 2.23-8.86), alcohol abuse (OR 1.99; 95%CI 1.04-3.81), and homelessness (OR 3.49; 95%CI 1.25-9.77). Social support reduced the default outcome (OR 0.13; 95%CI 0.06-0.28), controlling for age, sex, region, residence and acid-fast bacilli (AFB) smear of sputum. Unemployment, alcohol abuse and homelessness were associated with increased default outcome among new TB patients, while social support for TB patients reduced default. Further prospective randomised studies are necessary to evaluate the impact and to determine the most cost-effective social support for improving treatment outcomes of TB in patients in Russia, especially among populations at risk of default.

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

NASA Astrophysics Data System (ADS)

Cho, Myung D.; Okamoto, Yoshiyuki

1995-05-01

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

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

PubMed

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

2015-12-15

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

Helicobacter-negative gastritis: polymerase chain reaction for Helicobacter DNA is a valuable tool to elucidate the diagnosis.

PubMed

Kiss, S; Zsikla, V; Frank, A; Willi, N; Cathomas, G

2016-04-01

Helicobacter-negative gastritis has been increasingly reported. Molecular techniques as the polymerase chain reaction (PCR) may detect bacterial DNA in histologically negative gastritis. To evaluate of Helicobacter PCR in gastric biopsies for the daily diagnostics of Helicobacter-negative gastritis. Over a 5-year period, routine biopsies with chronic gastritis reminiscent of Helicobacter infection, but negative by histology, were tested by using a H. pylori specific PCR. Subsequently, PCR-negative samples were re-evaluated using PCR for other Helicobacter species. Of the 9184 gastric biopsies, 339 (3.7%) with histological-negative gastritis and adequate material were forwarded to PCR analysis for H. pylori and 146 (43.1%) revealed a positive result. In 193 H. pylori DNA-negative biopsies, re-analysis using PCR primers for other Helicobacter species, revealed further 23 (11.9%) positive biopsies, including 4 (2.1%) biopsies with H. heilmannii sensu lato. PCR-positive biopsies showed a higher overall inflammatory score, more lymphoid follicles/aggregates and neutrophils (P < 0.05). No Helicobacter DNA was found in control biopsies of 48 patients with neither primer set (P < 0.0001). In 274 patients with an endoscopic description, detection of H. pylori DNA was associated with ulcers and erosions (P < 0.01). Over all, in 339 histologically-negative gastric biopsies, Helicobacter DNA was detected in 169 (49.9%) samples with at least one primer set. Molecular testing offers a sensitive and specific diagnosis to a selected group of patients, in whom adequate searches for bacteria by conventional histology have resulted in the unsatisfactory diagnosis of H. pylori-negative gastritis. © 2016 John Wiley & Sons Ltd.

The strategic framework of tuberculosis control and prevention in the elderly: a scoping review towards End TB targets.

PubMed

Li, Jun; Chung, Pui-Hong; Leung, Cyrus L K; Nishikiori, Nobuyuki; Chan, Emily Y Y; Yeoh, Eng-Kiong

2017-06-01

With the rapid pace of population ageing, tuberculosis (TB) in the elderly increasingly becomes a public health challenge. Despite the increasing burden and high risks for TB in the elderly, targeted strategy has not been well understood and evaluated. We undertook a scoping review to identify current TB strategies, research and policy gaps in the elderly and summarized the results within a strategic framework towards End TB targets. Databases of Embase, MEDLINE, Global health and EBM reviews were searched for original studies, review articles, and policy papers published in English between January 1990 and December 2015. Articles examining TB strategy, program, guideline or intervention in the elderly from public health perspective were included.Nineteen articles met the inclusion criteria. Most of them were qualitative studies, issued in high- and middle-income countries and after 2000. To break the chain of TB transmission and reactivation in the elderly, infection control, interventions of avoiding delay in diagnosis and containment are essential for preventing transmission, especially in elderly institutions and aged immigrants; screening of latent TB infection and preventive therapy had effective impacts on reducing the risk of reactivation and should be used less reluctantly in older people; optimizing early case-finding with a high index of suspicion, systematic screening for prioritized high-risk groups, initial empirical and adequate follow-up treatment with close monitoring and evaluation, as well as enhanced programmatic management are fundamental pillars for active TB elimination. Evaluation of TB epidemiology, risk factors, impacts and cost-effectiveness of interventions, adopting accurate and rapid diagnostic tools, shorter and less toxic preventive therapy, are critical issues for developing strategy in the elderly towards End TB targets.TB control strategies in the elderly were comprehensively mapped in a causal link pathway. The framework and

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

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

PubMed

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

2012-01-01

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

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

PubMed

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

2018-05-31

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

The effect of the Xpert MTB/RIF test on the time to MDR-TB treatment initiation in a rural setting: a cohort study in South Africa's Eastern Cape Province.

PubMed

Iruedo, Joshua; O'Mahony, Don; Mabunda, Sikhumbuzo; Wright, Graham; Cawe, Busisiwe

2017-01-21

There are significant delays in initiation of multidrug-resistant tuberculosis (MDR -TB) treatment. The Xpert MTB/RIF test has been shown to reduce the time to diagnosis and treatment of MDR-TB predominantly in urban centres. This study describes the time to treatment of MDR-TB and the effect of Xpert MTB/RIF on time to treatment in a deprived rural area in South Africa. This was a retrospective cohort study analysing the medical records of patients diagnosed with MDR-TB in King Sabata Dalindyebo Sub-District between 2009 and 2014. Numerical data were reported using the Kruskal-Wallis and Wilcoxon sum rank tests and categorical data compared using the two-sample test of proportions. Of the 342 patients with MDR-TB identified, 285 were eligible for analysis, of whom 145 (61.4%) were HIV positive. The median time from sputum collection to MDR-TB diagnosis was 27 days (IQR: 2-45) and differed significantly between diagnostic modalities: Xpert MTB/RIF, 1 day (IQR: 1-4; n = 114: p < 0.0001); Line Probe Assay 12 days (IQR: 8-21; n = 28; p < 0.0001); and culture/phenotypic drug sensitivity testing 45 days (IQR: 39-59; n = 143: p < 0.0001). The time from diagnosis to treatment initiation was 14 days (IQR: 8-27) and did not differ significantly between diagnostic modality. The median time from sputum collection to treatment initiation was 49 days (IQR: 20-69) but differed significantly between diagnostic modalities: Xpert MTB/RIF, 18 days (IQR: 11-27; n = 114; p < 0.0001); Line Probe Assay 29 days (IQR: 14.5-53; n = 28; p < 0.0001); and culture/phenotypic drug sensitivity, 64 days (IQR: 50-103; n = 143: P < 0.0001). Age, sex and HIV status did not influence the time intervals. Xpert MTB/RIF significantly reduced the time to MDR-TB treatment in a deprived rural setting as a result of a reduced time to diagnosis. However, the national target of five days was not achieved. Further research is needed to explore and

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

PubMed

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

2018-05-01

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

Depressive symptoms and hazardous/harmful alcohol use are prevalent and correlate with stigma among TB-HIV patients in Lesotho.

PubMed

Hayes-Larson, E; Hirsch-Moverman, Y; Saito, S; Frederix, K; Pitt, B; Maama-Maime, L; Howard, A A

2017-11-01

Limited data exist on the prevalence and correlates, including stigma, of mental health conditions, including depressive symptoms and alcohol use, among patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) in sub-Saharan Africa, despite their negative impact on health outcomes. To assess the prevalence and correlates of depressive symptoms and hazardous/harmful alcohol use among TB-HIV patients in the Start TB patients on ART and Retain on Treatment (START) study. START, a mixed-methods cluster-randomized trial, evaluated a combination intervention package vs. standard of care (SOC) to improve treatment outcomes in TB-HIV co-infected patients in Lesotho. Moderate/severe depressive symptoms and hazardous/harmful alcohol use were measured using baseline questionnaire data collected from April 2013 to March 2015. Demographic, psychosocial, and TB- and HIV-related knowledge and attitudes, including stigma, were assessed for association with both conditions using generalized linear mixed models. Among 371 participants, 29.8% reported moderate/severe depressive symptoms, and 24.7% reported hazardous/harmful alcohol use; 7% reported both. Depressive symptoms were significantly associated with less education, more difficulty understanding written medical information, non-disclosure of TB, greater TB stigma, and the SOC study arm. Hazardous/harmful alcohol use was significantly associated with male sex, as well as greater TB and external HIV stigma. Prevalence of depressive symptoms and hazardous/harmful alcohol use were high, suggesting a need for routine screening for, and treatment of, mental health disorders in TB-HIV patients.

Diagnosis and Treatment of Childhood Pulmonary Tuberculosis: A Cross-Sectional Study of Practices among Paediatricians in Private Sector, Mumbai

PubMed Central

Tauro, Carolyn Kavita; Gawde, Nilesh Chandrakant

2015-01-01

Majority of children with tuberculosis are treated in private sector in India with no available data on management practices. The study assessed diagnostic and treatment practices related to childhood pulmonary tuberculosis among paediatricians in Mumbai's private sector in comparison with International Standards for Tuberculosis Care (ISTC) 2009. In this cross-sectional study, 64 paediatricians from private sector filled self-administered questionnaires. Cough was reported as a symptom of childhood TB by 77.8% of respondents. 38.1% request sputum smear or culture for diagnosis and fewer (32.8%) use it for patients positive on chest radiographs and 32.8% induce sputum for those unable to produce it. Sputum negative TB suspect is always tested with X-ray or tuberculin skin test. 61.4% prescribe regimen as recommended in ISTC and all monitor progress to treatment clinically. Drug-resistance at beginning of treatment is suspected for child in contact with a drug-resistant patient (67.7%) and with prior history of antitubercular treatment (12.9%). About half of them (48%) request drug-resistance test for rifampicin in case of nonresponse after two to three months of therapy and regimen prescribed by 41.7% for multidrug-resistant TB was as per ISTC. The study highlights inappropriate diagnostic and treatment practices for managing childhood pulmonary TB among paediatricians in private sector. PMID:26379705

Diagnosis and Treatment of Childhood Pulmonary Tuberculosis: A Cross-Sectional Study of Practices among Paediatricians in Private Sector, Mumbai.

PubMed

Tauro, Carolyn Kavita; Gawde, Nilesh Chandrakant

2015-01-01

Majority of children with tuberculosis are treated in private sector in India with no available data on management practices. The study assessed diagnostic and treatment practices related to childhood pulmonary tuberculosis among paediatricians in Mumbai's private sector in comparison with International Standards for Tuberculosis Care (ISTC) 2009. In this cross-sectional study, 64 paediatricians from private sector filled self-administered questionnaires. Cough was reported as a symptom of childhood TB by 77.8% of respondents. 38.1% request sputum smear or culture for diagnosis and fewer (32.8%) use it for patients positive on chest radiographs and 32.8% induce sputum for those unable to produce it. Sputum negative TB suspect is always tested with X-ray or tuberculin skin test. 61.4% prescribe regimen as recommended in ISTC and all monitor progress to treatment clinically. Drug-resistance at beginning of treatment is suspected for child in contact with a drug-resistant patient (67.7%) and with prior history of antitubercular treatment (12.9%). About half of them (48%) request drug-resistance test for rifampicin in case of nonresponse after two to three months of therapy and regimen prescribed by 41.7% for multidrug-resistant TB was as per ISTC. The study highlights inappropriate diagnostic and treatment practices for managing childhood pulmonary TB among paediatricians in private sector.

Spatial distribution of extensively drug-resistant tuberculosis (XDR TB) patients in KwaZulu-Natal, South Africa

PubMed Central

Kapwata, Thandi; Morris, Natashia; Campbell, Angela; Mthiyane, Thuli; Mpangase, Primrose; Nelson, Kristin N.; Allana, Salim; Brust, James C. M.; Moodley, Pravi; Mlisana, Koleka

2017-01-01

Background KwaZulu-Natal province, South Africa, has among the highest burden of XDR TB worldwide with the majority of cases occurring due to transmission. Poor access to health facilities can be a barrier to timely diagnosis and treatment of TB, which can contribute to ongoing transmission. We sought to determine the geographic distribution of XDR TB patients and proximity to health facilities in KwaZulu-Natal. Methods We recruited adults and children with XDR TB diagnosed in KwaZulu-Natal. We calculated distance and time from participants’ home to the closest hospital or clinic, as well as to the actual facility that diagnosed XDR TB, using tools within ArcGIS Network analyst. Speed of travel was assigned to road classes based on Department of Transport regulations. Results were compared to guidelines for the provision of social facilities in South Africa: 5km to a clinic and 30km to a hospital. Results During 2011–2014, 1027 new XDR TB cases were diagnosed throughout all 11 districts of KwaZulu-Natal, of whom 404 (39%) were enrolled and had geospatial data collected. Participants would have had to travel a mean distance of 2.9 km (CI 95%: 1.8–4.1) to the nearest clinic and 17.6 km (CI 95%: 11.4–23.8) to the nearest hospital. Actual distances that participants travelled to the health facility that diagnosed XDR TB ranged from <10 km (n = 143, 36%) to >50 km (n = 109, 27%), with a mean of 69 km. The majority (77%) of participants travelled farther than the recommended distance to a clinic (5 km) and 39% travelled farther than the recommended distance to a hospital (30 km). Nearly half (46%) of participants were diagnosed at a health facility in eThekwini district, of whom, 36% resided outside the Durban metropolitan area. Conclusions XDR TB cases are widely distributed throughout KwaZulu-Natal province with a denser focus in eThekwini district. Patients travelled long distances to the health facility where they were diagnosed with XDR TB, suggesting a

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

PubMed Central

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

2018-01-01

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

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

PubMed

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

2018-06-27

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

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

PubMed Central

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

2013-01-01

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

Prospective Clinical Evaluation of the Serologic Tuberculous Glycolipid Test in Combination with the Nucleic Acid Amplification Test

PubMed Central

Maekura, Ryoji; Kohno, Hiroaki; Hirotani, Atsushi; Okuda, Yoshinari; Ito, Masami; Ogura, Takeshi; Yano, Ikuya

2003-01-01

We have conducted a prospective controlled multicenter study to evaluate differences in the levels of clinical utility of the tuberculous glycolipid (TBGL) serodiagnostic test and the nucleic acid amplification test in patients with smear-negative active pulmonary tuberculosis (TB). The TBGL test and the PCR test were individually not so useful for the rapid diagnosis of smear-negative active pulmonary TB. However, clinical utility was considerably improved by using the TBGL test and the PCR test in combination, especially in patients with smear-negative and culture-negative active pulmonary TB and in patients with minimally advanced lesions. PMID:12624077

Gender difference in delays to diagnosis and health care seeking behaviour in a rural area of Nepal.

PubMed

Yamasaki-Nakagawa, M; Ozasa, K; Yamada, N; Osuga, K; Shimouchi, A; Ishikawa, N; Bam, D S; Mori, T

2001-01-01

Directly observed treatment for tuberculosis using a short-course regimen (DOTS) was introduced in a rural area of Nepal. All new patients assigned to DOTS from mid-December 1997 to mid-June 1999 were eligible for the study. To examine delays in tuberculosis (TB) diagnosis and compare health care seeking behaviour between men and women. A cross-sectional analysis of patient interviews. Women were found to have a significantly longer total delay before diagnosis of tuberculosis (median 2.3 months for men, 3.3 months for women). When they visited traditional healers first, women had a significantly longer delay than men from the first visit to health care providers to diagnosis (median 1.5 months for men, 3.0 months for women). More women (35%) visited traditional healers before diagnosis than men (18%), and were more likely to receive more complicated charms from traditional healers. Men tended to visit the government medical establishment first if they knew that free TB treatment was available, but women did not. Women were more likely to visit and to believe in traditional healers; this might lead to the longer delays experienced before TB diagnosis.

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

PubMed Central

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

2015-01-01

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

Interpretation Criteria for Comparative Intradermal Tuberculin Test for Diagnosis of Bovine Tuberculosis in Cattle in Maroua Area of Cameroon

PubMed Central

Temwa, J.; Mouiche, M. M.; Iyawa, D.; Zoli, P. A.

2016-01-01

Intradermal tuberculin test (TST) is the choice method for diagnosis of bovine tuberculosis (Tb) in live animals. This work was done to assess the performance of single intradermal comparative cervical tuberculin (SICCT) test in randomly selected cattle in Maroua, Cameroon, against detection of Tb lesions and detection of Tb lesions plus acid fast bacilli in lesions. While 22.28% of slaughtered cattle presented Tb lesions at meat inspection, detection rates of anti-bovine-Tb antibody, Tb lesions, and Tb lesions plus acid fast bacilli were 68.57%, 32.95%, and 22.35%, respectively. SICCT-bovine-Tb positive cattle were 35.29%, 29.41%, 25.88%, 24.7%, and 21.18% at ≥2 mm, ≥2.5 mm, ≥3 mm, ≥3.5 mm, and ≥4 mm cut-offs, respectively. Higher sensitivity and predictive values were obtained at severe interpretations. The best performance was at ≥3 mm and ≥3.5 mm cut-offs. Against detection of Tb lesions, ≥3 mm and ≥3.5 mm showed sensitivity of 67.8% and specificity of 94.7% and 96.5%, respectively. For detection of Tb lesions accompanied with acid fast bacilli in lesions, ≥3 mm and ≥3.5 mm showed sensitivity of 89.4% and specificity of 92.4% and 93.9%, respectively. These findings revealed that interpretations of SICCT-bovine-Tb should be at ≥3 mm and/or ≥3.5 mm cut-offs. Severe interpretation of TST is essential for optimal diagnosis of bovine Tb in cattle in Maroua, Cameroon. PMID:27563481

Litigation as TB Rights Advocacy

PubMed Central

2016-01-01

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

Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB

PubMed Central

Chegou, Novel N.; Kriel, Belinda; Jacobs, Ruschca; Kidd, Martin; Loxton, Andre G.; Kaempfer, Susanne; Singh, Mahavir; Walzl, Gerhard

2017-01-01

Immunoglobulin G (IgG) based tests for the diagnosis of active tuberculosis (TB) disease often show a lack of specificity in TB endemic regions, which is mainly due to a high background prevalence of LTBI. Here, we investigated the combined performance of the responses of different Ig classes to selected mycobacterial antigens in primary healthcare clinic attendees with signs and symptoms suggestive of TB. The sensitivity and specificity of IgA, IgG and/or IgM to LAM and 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16kDa and 19kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 63 individuals who underwent diagnostic work-up for TB after presenting with symptoms and signs compatible with possible active TB were evaluated. Active TB was excluded in 42 individuals of whom 21 has LTBI whereas active TB was confirmed in 21 patients of whom 19 had a follow-up blood draw at the end of 6-month anti-TB treatment. The leading single serodiagnostic markers to differentiate between the presence or absence of active TB were anti-16 kDa IgA, anti-MPT64 IgA with sensitivity and specificity of 90%/90% and 95%/90%, respectively. The combined use of 3 or 4 antibodies further improved this performance to accuracies above 95%. After successful completion of anti-TB treatment at month 6, the levels of 16 kDa IgA and 16 kDa IgM dropped significantly whereas LAM IgG and TB-LTBI IgG increased. These results show the potential of extending investigation of anti-tuberculous IgG responses to include IgM and IgA responses against selected protein and non-protein antigens in differentiating active TB from other respiratory diseases in TB endemic settings. PMID:28415587

Detection of a combination of serum IgG and IgA antibodies against selected mycobacterial targets provides promising diagnostic signatures for active TB.

PubMed

Awoniyi, Dolapo O; Baumann, Ralf; Chegou, Novel N; Kriel, Belinda; Jacobs, Ruschca; Kidd, Martin; Loxton, Andre G; Kaempfer, Susanne; Singh, Mahavir; Walzl, Gerhard

2017-06-06

Immunoglobulin G (IgG) based tests for the diagnosis of active tuberculosis (TB) disease often show a lack of specificity in TB endemic regions, which is mainly due to a high background prevalence of LTBI. Here, we investigated the combined performance of the responses of different Ig classes to selected mycobacterial antigens in primary healthcare clinic attendees with signs and symptoms suggestive of TB. The sensitivity and specificity of IgA, IgG and/or IgM to LAM and 7 mycobacterial protein antigens (ESAT-6, Tpx, PstS1, AlaDH, MPT64, 16kDa and 19kDa) and 2 antigen combinations (TUB, TB-LTBI) in the plasma of 63 individuals who underwent diagnostic work-up for TB after presenting with symptoms and signs compatible with possible active TB were evaluated. Active TB was excluded in 42 individuals of whom 21 has LTBI whereas active TB was confirmed in 21 patients of whom 19 had a follow-up blood draw at the end of 6-month anti-TB treatment. The leading single serodiagnostic markers to differentiate between the presence or absence of active TB were anti-16 kDa IgA, anti-MPT64 IgA with sensitivity and specificity of 90%/90% and 95%/90%, respectively. The combined use of 3 or 4 antibodies further improved this performance to accuracies above 95%. After successful completion of anti-TB treatment at month 6, the levels of 16 kDa IgA and 16 kDa IgM dropped significantly whereas LAM IgG and TB-LTBI IgG increased. These results show the potential of extending investigation of anti-tuberculous IgG responses to include IgM and IgA responses against selected protein and non-protein antigens in differentiating active TB from other respiratory diseases in TB endemic settings.

Safety and efficacy of the C-Tb skin test to diagnose Mycobacterium tuberculosis infection, compared with an interferon γ release assay and the tuberculin skin test: a phase 3, double-blind, randomised, controlled trial.

PubMed

Ruhwald, Morten; Aggerbeck, Henrik; Gallardo, Rafael Vázquez; Hoff, Søren T; Villate, José I; Borregaard, Bettine; Martinez, José A; Kromann, Ingrid; Penas, Antón; Anibarro, Luis L; de Souza-Galvão, Maria Luiza; Sánchez, Francisca; Rodrigo-Pendás, Jose Ángel; Noguera-Julian, Antoni; Martínez-Lacasa, Xavier; Tuñez, Maria Victoria; Fernández, Virginia Leiro; Millet, Joan P; Moreno, Antonio; Cobos, Nazaret; Miró, José M; Roldan, Llanos; Orcau, Angels; Andersen, Peter; Caylá, Joan A

2017-04-01

Targeted screening and treatment of Mycobacterium tuberculosis infection substantially reduces the risk of developing active tuberculosis. C-Tb (Statens Serum Institute, Copenhagen, Denmark) is a novel specific skin test based on ESAT-6 and CFP10 antigens. We investigated the safety and diagnostic potential of C-Tb compared with established tests in the contact-tracing setting. Negative controls, close contacts, occasional contacts, and patients with active pulmonary tuberculosis were enrolled at 13 centres in Spain. We compared C-Tb with the QuantiFERON-TB Gold In-Tube ([QFT] Qiagen, Hilden, Germany) interferon γ release assay (IGRA) and the purified protein derivative (PPD) RT 23 tuberculin skin test ([TST] Statens Serum Institute). All participants older than 5 years were tested with QFT. Some participants in the negative control group received C-Tb without the TST to test for potential interactions between C-Tb and PPD RT 23. The rest were randomly assigned in blocks of ten and tested with both C-Tb and TST, with five in each block receiving injection of C-Tb in the right arm and the TST in the left arm and five vice versa. The primary and safety analyses were done in all participants randomly assigned to a group who received any test. This trial is registered with ClinicalTrials.gov, number NCT01631266, and with EudraCT, number 2011-005617-36. From July 24, 2012, to Oct 2, 2014, 979 participants were enrolled, of whom 263 were negative controls, 299 were occasional contacts, 316 were close contacts, and 101 were patients with tuberculosis. 970 (99%) participants completed the trial. Induration sizes were similar for C-Tb and TST, but TST positivity was affected by BCG vaccination status. We found a strong positive trend towards C-Tb test positivity with increasing risk of infection, from 3% in negative controls to 16% in occasional contacts, to 43% in close contacts. C-Tb and QFT results were concordant in 785 (94%) of 834 participants aged 5 years and older

Exploring workplace TB interventions with foreign-born Latino workers.

PubMed

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

2018-05-15

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

Vitamin D status among pulmonary TB patients and non-TB controls: a cross-sectional study from Mwanza, Tanzania.

PubMed

Friis, Henrik; Range, Nyagosya; Changalucha, John; Praygod, George; Jeremiah, Kidola; Faurholt-Jepsen, Daniel; Krarup, Henrik; Mølgaard, Christian; Andersen, Åse Bengaard

2013-01-01

Little is known about vitamin D status in low-income populations burdened with infectious diseases. Hence, there is a need for data on correlates of serum 25-hydroxy vitamin D (S-25(OH)D) and its validity during infections. To assess the role of pulmonary TB (PTB) and HIV as correlates of S-25(OH)D. Age-sex-matched cross-sectional study among PTB patients and non-TB controls. PTB patients were categorized as sputum negative (PTB-) and positive (PTB+) by culture. Non-TB controls were randomly selected among age-sex-matched neighbours to PTB+ patients. Height, weight, arm circumference and triceps skinfold were measured, and body mass index (BMI), arm fat (AFA) and muscle area (AMA) computed. HIV status, and S-25(OH)D, C-reactive protein (S-CRP) and α1-acid glycoprotein (S-AGP) were determined. Linear regression analysis with controls and PTB patients combined was used to identify correlates of S-25(OH)D. S-25(OH)D data were available on 97.8% (1570) of 1605 participants. Mean (SD) S-25(OH)D was 84.4 (25.6) nmol/L with 39.6% <75 nmol/L among 347 non-TB controls. Time of recruitment, sex, PTB and HIV, and elevated S-AGP were correlates of S-25(OH)D. S-25(OH)D was 24.8 (95% CI 18.6;30.9) nmol/L higher in PTB compared to controls among females, but only 9.8 (95% CI:4.5;15.2) nmol/L among males (interaction p<0.0001). Females had 13.8 (95% CI:8.2;21.9) nmol/L lower S-25(OH)D than males, and HIV infected individuals had 8.5 (95% CI:4.9;12.1) higher S-25(OH)D compared to uninfected. Elevated S-AGP was a positive correlate of S-25(OH)D. Low BMI was associated with S-25(OH)D, but not with infections or S-AGP in the model. While S-25(OH)D may decline transiently during a mild acute phase response, it may increase if the acute phase response leads to loss of fat. The validity of S-25(OH)D as a marker of vitamin D status may be affected by infections.

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

PubMed

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

2018-04-19

Tuberculosis (TB) in children is frequently paucibacillary and non-severe forms of pulmonary TB are common. Evidence for tuberculosis treatment in children is largely extrapolated from adult studies. Trials in adults with smear-negative tuberculosis suggest that treatment can be effectively shortened from 6 to 4 months. New paediatric, fixed-dose combination anti-tuberculosis treatments have recently been introduced in many countries, making the implementation of World Health Organisation (WHO)-revised dosing recommendations feasible. The safety and efficacy of these higher drug doses has not been systematically assessed in large studies in children, and the pharmacokinetics across children representing the range of weights and ages should be confirmed. SHINE is a multicentre, open-label, parallel-group, non-inferiority, randomised controlled, two-arm trial comparing a 4-month vs the standard 6-month regimen using revised WHO paediatric anti-tuberculosis drug doses. We aim to recruit 1200 African and Indian children aged below 16 years with non-severe TB, with or without HIV infection. The primary efficacy and safety endpoints are TB disease-free survival 72 weeks post randomisation and grade 3 or 4 adverse events. Nested pharmacokinetic studies will evaluate anti-tuberculosis drug concentrations, providing model-based predictions for optimal dosing, and measure antiretroviral exposures in order to describe the drug-drug interactions in a subset of HIV-infected children. Socioeconomic analyses will evaluate the cost-effectiveness of the intervention and social science studies will further explore the acceptability and palatability of these new paediatric drug formulations. Although recent trials of TB treatment-shortening in adults with sputum-positivity have not been successful, the question has never been addressed in children, who have mainly paucibacillary, non-severe smear-negative disease. SHINE should inform whether treatment-shortening of drug