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ABSTRACT: Accurate and rapid detection of tuberculosis (TB) and drug resistance are critical for improving patient care and decreasing the spread of TB. Xpert® MTB/RIF assay (Xpert) is a rapid, automated test that can detect both TB and rifampicin resistance, within two hours after starting the test, with minimal hands-on technical time, but is more expensive than conventional sputum microscopy.
To assess the diagnostic accuracy of Xpert for pulmonary TB (TB detection), both where Xpert was used as an initial test replacing microscopy, and where Xpert was used as an add-on test following a negative smear microscopy result.To assess the diagnostic accuracy of Xpert for rifampicin resistance detection where Xpert was used as the initial test, replacing conventional culture-based drug susceptibility testing.The population of interest was adults suspected of having pulmonary TB or multidrug-resistant TB (MDR-TB), with or without HIV infection.
We performed a comprehensive search of the following databases: Cochrane Infectious Diseases Group Specialized Register; MEDLINE; EMBASE; ISI Web of Knowledge; MEDION; LILACS; BIOSIS; and SCOPUS. We also searched the metaRegister of Controlled Trials (mRCT) and the search portal of the WHO International Clinical Trials Registry Platform to identify ongoing trials. We performed searches on 25 September 2011 and we repeated them on 15 December 2011, without language restriction.
We included randomized controlled trials, cross-sectional, and cohort studies that used respiratory specimens to compare Xpert with culture for detecting TB and Xpert with conventional phenotypic drug susceptibility testing for detecting rifampicin resistance.
For each study, two review authors independently extracted a set of data using a standardized data extraction form. When possible, we extracted data for subgroups by smear and HIV status. We assessed the quality of studies using the QUADAS-2 tool. We carried out meta-analyses to estimate the pooled sensitivity and specificity of Xpert separately for TB detection and rifampicin resistance detection using a bivariate random-effects model. We estimated the median pooled sensitivity and specificity and their 95% credible intervals (CrI).
We identified 18 unique studies as eligible for this review, including two multicentre international studies, one with five and the other with six distinct study centres. The majority of studies (55.6%) were performed in low-income and middle-income countries. In 17 of the 18 studies, Xpert was performed by trained technicians in reference laboratories.When used as an initial test replacing smear microscopy (15 studies, 7517 participants), Xpert achieved a pooled sensitivity of 88% (95% CrI 83% to 92%) and pooled specificity of 98% (95% CrI 97% to 99%). As an add-on test following a negative smear microscopy result (14 studies, 5719 participants), Xpert yielded a pooled sensitivity of 67% (95% CrI 58% to 74%) and pooled specificity of 98% (95% CrI 97% to 99%). In clinical subgroups, we found the following accuracy estimates: the pooled sensitivity was 98% (95% CrI 97% to 99%) for smear-positive, culture-positive TB and 68% (95% CrI 59% to 75%) for smear-negative, culture-positive TB (15 studies); the pooled sensitivity was 80% (95% CrI 67% to 88%) in people living with HIV and 89% (95% CrI 81% to 94%) in people without HIV infection (four studies). For rifampicin resistance detection (11 studies, 2340 participants), Xpert achieved a pooled sensitivity of 94% (95% CrI 87% to 97%) and pooled specificity of 98% (95% CrI 97% to 99%). In a separate analysis, Xpert could distinguish between TB and nontuberculous mycobacteria (NTM) in clinical samples with high accuracy: among 139 specimens with NTM, Xpert was positive in only one specimen that grew NTM.In a hypothetical cohort of 1000 individuals suspected of having rifampicin resistance (a proxy for MDR-TB), where the prevalence of rifampicin resistance is 30%, we estimated that on average Xpert would wrongly identify 14 patients as being rifampicin resistant. In comparison, where the prevalence of rifampicin resistance is only 2%, we estimated that the number of individuals wrongly identified as rifampicin resistant would increase to 20, an increase of 43%.
This review shows that Xpert used as an initial diagnostic test for TB detection and rifampicin resistance detection in patients suspected of having TB, MDR-TB, or HIV-associated TB is sensitive and specific. Xpert may also be valuable as an add-on test following microscopy for patients who have previously been found to be smear-negative. An Xpert result that is positive for rifampicin resistance should be carefully interpreted and take into consideration the risk of MDR-TB in a given patient and the expected prevalence of MDR-TB in a given setting.Studies in this review mainly assessed sensitivity and specificity of the test when used in reference laboratories in research investigations. Most studies were performed in high TB burden countries. Ongoing use of Xpert in high TB burden countries will contribute to the evidence base on the diagnostic accuracy and clinical impact of Xpert in routine programmatic and peripheral health care settings, including settings where the test is performed at the point of care.
Cochrane database of systematic reviews (Online) 01/2013; 1:CD009593. · 5.72 Impact Factor
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ABSTRACT: Chest radiography for the diagnosis of active pulmonary tuberculosis (PTB) is limited by poor specificity and reader inconsistency. Scoring systems have been employed successfully for improving the performance of chest radiography for various pulmonary diseases. We conducted a systematic review to assess the diagnostic accuracy and reproducibility of scoring systems for PTB.We searched multiple databases for studies that evaluated the accuracy and reproducibility of chest radiograph scoring systems for PTB. We summarized results for specific radiographic features and scoring systems associated with PTB. Where appropriate, we estimated pooled performance of similar studies using a random effects model.Thirteen studies were included in the review, nine of which were in low TB burden settings. No scoring system was based solely on radiographic findings. All studies used systems with various combinations of clinical and radiologic features. Eleven studies involved scoring systems that were used for making decisions concerning hospital respiratory isolation. None of the included studies reported data on intra-reporter or inter-reporter reproducibility. Upper lobe infiltrates (pooled diagnostic odds ratio [DOR] 3.57, 95% CI 2.38 to 5.37, five studies) and cavities (DOR range, 1.97 to 25.66, 3 studies) were significantly associated with PTB. Sensitivities of the scoring systems were high (median 96%, IQR 93-98%), but specificities were low (median 46%, IQR 35-50%).Chest radiograph scoring systems appear useful in ruling-out PTB in hospitals, but their low specificity precludes ruling-in PTB. There is a need to develop accurate scoring systems for people living with HIV and for outpatient settings, especially in high TB burden settings.
European Respiratory Journal 12/2012; · 5.89 Impact Factor
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ABSTRACT: In an effort to update and clarify policies on tuberculosis drug susceptibility testing (DST), the World Health Organization (WHO) commissioned a systematic review evaluating WHO-endorsed diagnostic tests. We report the results of this systematic review and meta-analysis of the diagnostic accuracy and reproducibility of phenotypic DST for first-line and second-line anti-tuberculosis drugs. This review provides support for commercial broth-based systems recommended critical concentrations for isoniazid and rifampicin. Further studies are needed to evaluate critical concentrations for ethambutol and streptomycin that accurately detect susceptibility to these drugs. Evidence is limited on the performance of DST for pyrazinamide and second-line drugs.
Journal of clinical microbiology 11/2012; · 4.16 Impact Factor
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ABSTRACT: BACKGROUND: Sputum smear microscopy is the most widely available diagnostic test for pulmonary tuberculosis in countries with a high burden of the disease. Improving its accuracy is crucial to achievement of case-detection targets established by the Millennium Development Goals. Unfortunately, many patients are unable to submit all of the specimens needed for examination or to return for treatment because standard sputum collection and reporting requires several clinic visits. To inform policy recommendations by a WHO-convened Expert Group, we aimed to assess the accuracy of sputum smear examination with strategies for obtaining sputum on 1 day compared with strategies for obtaining sputum over 2 days. METHODS: We did a systematic review and meta-analysis of research articles comparing the accuracy of front-loaded or same-day microscopy and standard sputum smear microscopy for diagnosis of culture-confirmed pulmonary tuberculosis. We searched Medline, Embase, Biosis, and Web of Science for articles published between Jan 1, 2005, and Feb 14, 2012. Two investigators identified eligible articles and extracted data for individual study sites. We generated pooled summary estimates (95% CIs) for sensitivity and specificity by use of random-effects meta-analysis when four or more studies were available. FINDINGS: We identified eight relevant studies from five articles enrolling 7771 patients with suspected tuberculosis in low-income countries. Compared with the standard approach of examination of two smears with Ziehl-Neelsen light microscopy over 2 days, examination of two smears taken on the same day had much the same sensitivity (64% [95% CI 60 to 69] for standard microscopy vs 63% [58 to 68] for same-day microscopy) and specificity (98% [97 to 99] vs 98% [97 to 99]). We noted similar results for studies employing light-emitting diode fluorescence microscopy and for studies examining three smears, whether they were compared with two-smear strategies or with one another. INTERPRETATION: Same-day sputum smear microscopy is as accurate as standard smear microscopy. Data from tuberculosis programmes are needed to document the changes required in the health system to successfully implement the strategy and understand its effects. FUNDING: WHO and US National Institutes of Health.
The Lancet Infectious Diseases 10/2012; · 17.39 Impact Factor
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ABSTRACT: Diagnostic tests for active tuberculosis (TB) based on the detection of antibodies (serological tests) have been commercially available for decades, although no international guidelines have recommended their use. An estimated 1.5 million serological TB tests, mainly enzyme-linked immunosorbent assays, are performed in India alone every year, mostly in the private sector. The cost of serological tests in India is conservatively estimated at US $15 million (`825 million) per year. Findings from systematic reviews on the diagnostic accuracy of serological tests for both pulmonary and extra-pulmonary TB suggest that these tests are inaccurate and imprecise. A cost-effectiveness modelling study suggests that, if used as a replacement test for sputum microscopy, serology would increase costs to the Indian TB control sector approximately 4-fold and result in fewer disability-adjusted life years averted and more false-positive diagnoses. After considering all available evidence, the World Health Organization issued a strong recommendation against the use of currently available commercial serological tests for the diagnosis of TB disease. The expanding evidence base continues to demonstrate that the harms/risks of serological tests far outweigh the benefits. Greater engagement of the private sector is needed to discontinue the use of serological tests and to replace these tests with WHO-endorsed new diagnostics in India. The recent ban on import or sale of TB serological tests by the Indian health ministry is a welcome step in the right direction.
The Indian journal of medical research 05/2012; 135(5):695-702. · 1.84 Impact Factor
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ABSTRACT: Undiagnosed and mismanaged tuberculosis (TB) continues to fuel the global TB epidemic. Rapid, accurate and early diagnosis of TB is therefore a priority to improve TB case detection and interrupt transmission. Although considerable improvements have been made in TB diagnostics, there are two major gaps in the existing diagnostics pipeline: (1) lack of a simple accurate point-of-care test that can be used for rapid diagnosis at the primary care level; (2) lack of a biomarker (or combination of biomarkers) that can be used to identify latently infected individuals who will benefit most from preventive therapy. Currently available commercial serological (antibody detection) tests are inaccurate and do not improve patient outcomes. Despite this evidence, dozens of serological tests are sold and used in countries (e.g. India) with weak regulatory systems, especially in the private sector. Recognizing the threat posed by these suboptimal tests, a World Health Organization (WHO) Expert Group has strongly recommended against the use of serological tests for the diagnosis of pulmonary and extra-pulmonary TB. Another WHO Expert Group has discouraged the use of interferon-γ release assays for active pulmonary TB diagnosis in low- and middle-income countries. All existing tests for latent TB infection appear to have only modest predictive value and further research is needed to identify highly predictive biomarkers.
Medical Principles and Practice 01/2012; 21(1):4-13. · 0.89 Impact Factor
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ABSTRACT: The diagnostic value of interferon-γ release assays (IGRAs) for active tuberculosis in low- and middle-income countries is unclear.
We searched multiple databases for studies published through May 2010 that evaluated the diagnostic performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT) among adults with suspected active pulmonary tuberculosis or patients with confirmed cases in low- and middle-income countries. We summarized test performance characteristics with use of forest plots, hierarchical summary receiver operating characteristic (HSROC) curves, and bivariate random effects models.
Our search identified 789 citations, of which 27 observational studies (17 QFT-GIT and 10 T-SPOT) evaluating 590 human immunodeficiency virus (HIV)-uninfected and 844 HIV-infected individuals met inclusion criteria. Among HIV-infected patients, HSROC/bivariate pooled sensitivity estimates (highest quality data) were 76% (95% confidence interval [CI], 45%-92%) for T-SPOT and 60% (95% CI, 34%-82%) for QFT-GIT. HSROC/bivariate pooled specificity estimates were low for both IGRA platforms among all participants (T-SPOT, 61% [95% CI, 40%-79%]; QFT-GIT, 52% [95% CI, 41%-62%]) and among HIV-infected persons (T-SPOT, 52% [95% CI, 40%-63%]; QFT-GIT, 50% [95% CI, 35%-65%]). There was no consistent evidence that either IGRA was more sensitive than the tuberculin skin test for active tuberculosis diagnosis.
In low- and middle-income countries, neither the tuberculin skin test nor IGRAs have value for active tuberculosis diagnosis in adults, especially in the context of HIV coinfection.
The Journal of Infectious Diseases 11/2011; 204 Suppl 4:S1120-9. · 6.41 Impact Factor
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ABSTRACT: Serological (antibody detection) tests for tuberculosis (TB) are widely used in developing countries. As part of a World Health Organization policy process, we performed an updated systematic review to assess the diagnostic accuracy of commercial serological tests for pulmonary and extrapulmonary TB with a focus on the relevance of these tests in low- and middle-income countries.
We used methods recommended by the Cochrane Collaboration and GRADE approach for rating quality of evidence. In a previous review, we searched multiple databases for papers published from 1 January 1990 to 30 May 2006, and in this update, we add additional papers published from that period until 29 June 2010. We prespecified subgroups to address heterogeneity and summarized test performance using bivariate random effects meta-analysis. For pulmonary TB, we included 67 studies (48% from low- and middle-income countries) with 5,147 participants. For all tests, estimates were variable for sensitivity (0% to 100%) and specificity (31% to 100%). For anda-TB IgG, the only test with enough studies for meta-analysis, pooled sensitivity was 76% (95% CI 63%-87%) in smear-positive (seven studies) and 59% (95% CI 10%-96%) in smear-negative (four studies) patients; pooled specificities were 92% (95% CI 74%-98%) and 91% (95% CI 79%-96%), respectively. Compared with ELISA (pooled sensitivity 60% [95% CI 6%-65%]; pooled specificity 98% [95% CI 96%-99%]), immunochromatographic tests yielded lower pooled sensitivity (53%, 95% CI 42%-64%) and comparable pooled specificity (98%, 95% CI 94%-99%). For extrapulmonary TB, we included 25 studies (40% from low- and middle-income countries) with 1,809 participants. For all tests, estimates were variable for sensitivity (0% to 100%) and specificity (59% to 100%). Overall, quality of evidence was graded very low for studies of pulmonary and extrapulmonary TB.
Despite expansion of the literature since 2006, commercial serological tests continue to produce inconsistent and imprecise estimates of sensitivity and specificity. Quality of evidence remains very low. These data informed a recently published World Health Organization policy statement against serological tests. Please see later in the article for the Editors' Summary.
PLoS Medicine 08/2011; 8(8):e1001062. · 16.27 Impact Factor
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ABSTRACT: Undiagnosed and misdiagnosed tuberculosis (TB) drives the epidemic in India. Serological (antibody detection) TB tests are not recommended by any agency, but widely used in many countries, including the Indian private sector. The cost and impact of using serology compared with other diagnostic techniques is unknown.
Taking a patient cohort conservatively equal to the annual number of serological tests done in India (1.5 million adults suspected of having active TB), we used decision analysis to estimate costs and effectiveness of sputum smear microscopy (US$3.62 for two smears), microscopy plus automated liquid culture (mycobacterium growth indicator tube [MGIT], US$20/test), and serological testing (anda-tb ELISA, US$20/test). Data on test accuracy and costs were obtained from published literature. We adopted the perspective of the Indian TB control sector and an analysis frame of 1 year. Our primary outcome was the incremental cost per disability-adjusted life year (DALY) averted. We performed one-way sensitivity analysis on all model parameters, with multiway sensitivity analysis on variables to which the model was most sensitive. If used instead of sputum microscopy, serology generated an estimated 14,000 more TB diagnoses, but also 121,000 more false-positive diagnoses, 102,000 fewer DALYs averted, and 32,000 more secondary TB cases than microscopy, at approximately four times the incremental cost (US$47.5 million versus US$11.9 million). When added to high-quality sputum smears, MGIT culture was estimated to avert 130,000 incremental DALYs at an incremental cost of US$213 per DALY averted. Serology was dominated by (i.e., more costly and less effective than) MGIT culture and remained less economically favorable than sputum smear or TB culture in one-way and multiway sensitivity analyses.
In India, sputum smear microscopy remains the most cost-effective diagnostic test available for active TB; efforts to increase access to quality-assured microscopy should take priority. In areas where high-quality microscopy exists and resources are sufficient, MGIT culture is more cost-effective than serology as an additional diagnostic test for TB. These data informed a recently published World Health Organization policy statement against serological tests.
PLoS Medicine 08/2011; 8(8):e1001074. · 16.27 Impact Factor
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ABSTRACT: David Dowdy and colleagues discuss the complexities of costing new TB diagnostic tests, including GeneXpert, and argue that flexible analytic tools are needed for decision-makers to adapt large-sample cost-effectiveness data to local conditions.
PLoS Medicine 07/2011; 8(7):e1001063. · 16.27 Impact Factor
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ABSTRACT: To provide a narrative synthesis of evidence on interferon-gamma release assays (IGRAs) for the diagnosis of latent tuberculosis infection (LTBI) in individuals with immune-mediated inflammatory disorders (IMIDs).
Only a few studies have evaluated IGRAs in IMIDs, and most were small and varied considerably with respect to the use of immunosuppressive medications and types of IMIDs. Current evidence does not clearly suggest that IGRAs are better than tuberculin skin test (TST) in identifying individuals with IMID who could benefit from LTBI treatment. To date, no studies have been done on the predictive value of IGRAs in IMID patients. Important questions remain unanswered as to the impact of immunosuppressive medications and the impact of type of IMID on IGRA performance.
Despite the lack of clear evidence, there is an increasing tendency for guidelines to prefer IGRA over TST in IMIDs or to recommend both TST and IGRA to enhance sensitivity. We believe the use of either test is acceptable for LTBI screening. Clinicians could consider starting with IGRAs in individuals with a history of Bacille Calmette-Guérin (BCG) vaccination after infancy or with repeated BCG vaccinations. When the index of suspicion for LTBI is high, both IGRA and TST could be performed, especially prior to initiating TNF-α inhibitor therapy. Regardless of the test used, it is important to remember that in the face of immune-suppression, both IGRA and TST can be falsely negative and are thus only diagnostic aids - they will need to be interpreted with other clinical and risk factor data.
Current opinion in rheumatology 07/2011; 23(4):377-84. · 4.60 Impact Factor
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The Lancet Infectious Diseases 03/2011; 11(3):160-1. · 17.39 Impact Factor
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ABSTRACT: Childhood TB is difficult to diagnose, since disease tends to be paucibacillary and sputum specimens are not easy to obtain in children. Thus, blood-based immune assays are an attractive option. Systematic reviews of serological assays suggest that these tests produce highly inconsistent estimates of sensitivity and specificity, but much of the serology literature is based on adults. In children, there is insufficient evidence to recommend the use of serological tests for active TB diagnosis. Interferon-gamma release assays (IGRA) do not offer substantial improvements in sensitivity over the TST for the diagnosis of active disease. For latent TB infection, the IGRA correlates well with the exposure gradient and seems to have utility in reducing the number of children who undergo preventive therapy due to false-positive TST. Although IGRAs can be used as evidence of TB infection in children, appropriate specimen collection and microbiological confirmation of TB disease should remain a priority.
Paediatric Respiratory Reviews 03/2011; 12(1):9-15. · 2.77 Impact Factor
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ABSTRACT: To determine whether interferon-gamma release assays (IGRAs) improve the identification of HIV-infected individuals who could benefit from latent tuberculosis infection therapy.
Systematic review and meta-analysis.
We searched multiple databases through May 2010 for studies evaluating the performance of the newest commercial IGRAs (QuantiFERON-TB Gold In-Tube [QFT-GIT] and T-SPOT.TB [TSPOT]) in HIV-infected individuals. We assessed the quality of all studies included in the review, summarized results in prespecified subgroups using forest plots, and where appropriate, calculated pooled estimates using random effects models.
The search identified 37 studies that included 5736 HIV-infected individuals. In three longitudinal studies, the risk of active tuberculosis was higher in HIV-infected individuals with positive versus negative IGRA results. However, the risk difference was not statistically significant in the two studies that reported IGRA results according to manufacturer-recommended criteria. In persons with active tuberculosis (a surrogate reference standard for latent tuberculosis infection), pooled sensitivity estimates were heterogeneous but higher for TSPOT (72%; 95% confidence interval [CI], 62-81%) than for QFT-GIT (61%; 95% CI, 47-75%) in low-/middle-income countries. However, neither IGRA was consistently more sensitive than the tuberculin skin test in head-to-head comparisons. Although TSPOT appeared to be less affected by immunosuppression than QFT-GIT and the tuberculin skin test, overall, differences among the three tests were small or inconclusive.
Current evidence suggests that IGRAs perform similarly to the tuberculin skin test at identifying HIV-infected individuals with latent tuberculosis infection. Given that both tests have modest predictive value and suboptimal sensitivity, the decision to use either test should be based on country guidelines and resource and logistic considerations.
JAIDS Journal of Acquired Immune Deficiency Syndromes 03/2011; 56(3):230-8. · 4.43 Impact Factor
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Medical Principles and Practice. 01/2011;
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The international journal of tuberculosis and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 12/2010; 14(12):1506-7. · 2.73 Impact Factor
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ABSTRACT: WHO has previously recommended sputum-smear examination at the end of the second month of treatment in patients with recently diagnosed pulmonary tuberculosis, and, if positive, extension of the intensive therapy phase. We did a systematic review and meta-analysis to assess the accuracy of a positive sputum smear or culture during treatment for predicting failure or relapse in pulmonary tuberculosis. We searched PubMed, Embase, and the Cochrane Library for studies published in English through December, 2009. We included randomised controlled trials, cohort, and case-control studies of previously untreated pulmonary tuberculosis patients who had received a standardised regimen with rifampicin in the initial phase. Accuracy results were summarised in forest plots and pooled by use of a hierarchical regression approach. 15 papers (28 studies) met the inclusion criteria. The pooled sensitivities for both 2-month smear (24% [95% CI 12-42%], six studies) and culture (40% [95% CI 25-56%], four studies) to predict relapse were low. Corresponding specificities (85% [95% CI 72-90%] and 85% [95% CI 77-91%]) were higher, but modest. For failure, 2-month smear (seven studies) had low sensitivity (57% [95% CI 41-73%]) and higher, although modest, specificity (81% [95% CI 72-87%]). Both sputum-smear microscopy and mycobacterial culture during tuberculosis treatment have low sensitivity and modest specificity for predicting failure and relapse. Although we pooled a diverse group of patients, the individual studies had similar performance characteristics. Better predictive markers are needed.
The Lancet Infectious Diseases 06/2010; 10(6):387-94. · 17.39 Impact Factor
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ABSTRACT: Serological antibody detection tests for tuberculosis may offer the potential to improve diagnosis. Recent meta-analyses have shown that commercially available tests have variable accuracies and a limited clinical role. We reviewed the immunodiagnostic potential of antigens evaluated in research laboratories (in-house) for the serodiagnosis of pulmonary tuberculosis and conducted a meta-analysis to evaluate the performance of comparable antigens. Selection criteria included the participation of at least 25 pulmonary tuberculosis patients and the use of purified antigens. Studies evaluating 38 kDa, MPT51, malate synthase, culture filtrate protein 10, TbF6, antigen 85B, alpha-crystallin, 2,3-diacyltrehalose, 2,3,6-triacyltrehalose, 2,3,6,6'-tetraacyltrehalose 2'-sulfate, cord factor, and TbF6 plus DPEP (multiple antigen) were included in the meta-analysis. The results demonstrated that (i) in sputum smear-positive patients, sensitivities significantly >or=50% were provided for recombinant malate synthase (73%; 95% confidence interval [CI], 58 to 85) and TbF6 plus DPEP (75%; 95% CI, 50 to 91); (ii) protein antigens achieved high specificities; (iii) among the lipid antigens, cord factor had the best overall performance (sensitivity, 69% [95% CI, 28 to 94]; specificity, 91% [95% CI, 78 to 97]); (iv) compared with the sensitivities achieved with single antigens (median sensitivity, 53%; range, 2% to 100%), multiple antigens yielded higher sensitivities (median sensitivity, 76%; range, 16% to 96%); (v) in human immunodeficiency virus (HIV)-infected patients who are sputum smear positive, antibodies to several single and multiple antigens were detected; and (vi) data on seroreactivity to antigens in sputum smear-negative or pediatric patients were insufficient. Potential candidate antigens for an antibody detection test for pulmonary tuberculosis in HIV-infected and -uninfected patients have been identified, although no antigen achieves sufficient sensitivity to replace sputum smear microscopy. Combinations of select antigens provide higher sensitivities than single antigens. The use of a case-control design with healthy controls for the majority of studies was a limitation of the review. Efforts are needed to improve the methodological quality of tuberculosis diagnostic studies.
Clinical and vaccine immunology: CVI 01/2009; 16(2):260-76. · 2.37 Impact Factor
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ABSTRACT: Conventional diagnostic tests for tuberculosis have several limitations and are often unhelpful in establishing the diagnosis of extrapulmonary tuberculosis. Although commercial serological antibody based tests are available, their usefulness in the diagnosis of extrapulmonary tuberculosis is unknown. A systematic review was conducted to assess the accuracy of commercial serological antibody detection tests for the diagnosis of extrapulmonary tuberculosis. In a comprehensive search, 21 studies that reported data on sensitivity and specificity for extrapulmonary tuberculosis were identified. These studies evaluated seven different commercial tests, with Anda-TB IgG accounting for 48% of the studies. The results showed that (1) all commercial tests provided highly variable estimates of sensitivity (range 0.00-1.00) and specificity (range 0.59-1.00) for all extrapulmonary sites combined; (2) the Anda-TB IgG kit showed highly variable sensitivity (range 0.26-1.00) and specificity (range 0.59-1.00) for all extrapulmonary sites combined; (3) for all tests combined, sensitivity estimates for both lymph node tuberculosis (range 0.23-1.00) and pleural tuberculosis (range 0.26-0.59) were poor and inconsistent; and (4) there were no data to determine the accuracy of the tests in children or in patients with HIV infection, the two groups for which the test would be most useful. At present, commercial antibody detection tests for extrapulmonary tuberculosis have no role in clinical care or case detection.
Postgraduate medical journal 12/2007; 83(985):705-12. · 1.38 Impact Factor
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Future Microbiology 09/2007; 2(4):355-9. · 3.82 Impact Factor
