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Host markers in QuantiFERON supernatants differentiate active TB from latent TB infection: preliminary report.

ABSTRACT: BACKGROUND: Interferon gamma release assays, including the QuantiFERON TB Gold In Tube (QFT) have been shown to be accurate in diagnosing Mycobacterium tuberculosis infection. These assays however, do not discriminate between latent TB infection (LTBI) and active TB disease. METHODS: We recruited twenty-three pulmonary TB patients and 34 household contacts from Cape Town, South Africa and performed the QFT test. To investigate the ability of new host markers to differentiate between LTBI and active TB, levels of 29 biomarkers in QFT supernatants were evaluated using a Luminex multiplex cytokine assay. RESULTS: Eight out of 29 biomarkers distinguished active TB from LTBI in a pilot study. Baseline levels of epidermal growth factor (EGF) soluble CD40 ligand (sCD40L), antigen stimulated levels of EGF, and the background corrected antigen stimulated levels of EGF and macrophage inflammatory protein (MIP)-1beta were the most informative single markers for differentiation between TB disease and LTBI, with AUCs of 0.88, 0.84, 0.87, 0.90 and 0.79 respectively. The combination of EGF and MIP-1beta predicted 96% of active TB cases and 92% of LTBIs. Combinations between EGF, sCD40L, VEGF, TGF-alpha and IL-1alpha also showed potential to differentiate between TB infection states. EGF, VEGF, TGF-alpha and sCD40L levels were higher in TB patients. CONCLUSION: These preliminary data suggest that active TB may be accurately differentiated from LTBI utilizing adaptations of the commercial QFT test that includes measurement of EGF, sCD40L, MIP-1beta, VEGF, TGF-alpha or IL-1alpha in supernatants from QFT assays. This approach holds promise for development as a rapid diagnostic test for active TB.

SUBMITTER: Chegou NN

PROVIDER: S-EPMC2696407 | biostudies-other | 2009

REPOSITORIES: biostudies-other

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Host markers in QuantiFERON supernatants differentiate active TB from latent TB infection: preliminary report.

Chegou Novel N NN Black Gillian F GF Kidd Martin M van Helden Paul D PD Walzl Gerhard G

BMC pulmonary medicine 20090516

<h4>Background</h4>Interferon gamma release assays, including the QuantiFERON TB Gold In Tube (QFT) have been shown to be accurate in diagnosing Mycobacterium tuberculosis infection. These assays however, do not discriminate between latent TB infection (LTBI) and active TB disease.<h4>Methods</h4>We recruited twenty-three pulmonary TB patients and 34 household contacts from Cape Town, South Africa and performed the QFT test. To investigate the ability of new host markers to differentiate between ...[more]

PMID: 19445695

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Project description:QuantiFERON®-TB Gold in-tube (QFT-GIT) supernatants may be important samples for use in assessment of anti-tuberculosis (TB) antibodies when only limited volumes of blood can be collected and when a combination of antibody and cytokine measurements are required. These analytes, when used together, may also have the potential to differentiate active pulmonary TB (APTB) from latent TB infection (LTBI). However, few studies have explored the use of QFT-GIT supernatants for investigations of antibody responses. This study determined the correlation and agreement between anti-CFP-10 and anti-ESAT-6 antibody concentrations in QFT-GIT nil supernatant and serum pairs from 68 TB household contacts. We also explored the ability of Mycobacterium tuberculosis (M.tb) specific antibodies, or ratios of antibody to interferon gamma (IFN-γ) in QFT-GIT supernatants, to differentiate 97 APTB cases from 58 individuals with LTBI. Sputum smear microscopy was used to define APTB, whereas the QFT-GIT and tuberculin skin test were used to define LTBI. There were strong and statistically significant correlations between anti-CFP-10 and anti-ESAT-6 antibodies in unstimulated QFT-GIT supernatants and sera (r = 0.89; p<0.0001 for both), and no significant differences in antibody concentration between them. Anti-CFP-10 & anti-ESAT-6 antibodies differentiated APTB from LTBI with sensitivities of 88.7% & 71.1% and specificities of 41.4% & 51.7% respectively. Anti-CFP-10 antibody/M.tb specific IFN-γ and anti-ESAT-6 antibody/M.tb specific IFN-γ ratios had sensitivities of 48.5% & 54.6% and specificities of 89.7% and 75.9% respectively. We conclude that QFT-GIT nil supernatants may be used in the place of sera when measuring antibody responses, reducing blood volumes needed for such investigations. Antibodies in QFT-GIT nil supernatants on their own discriminate APTB from LTBI with high sensitivity but have poor specificity, whereas the reverse is true when antibodies are used in combination with M.tb specific cytokines. Further antibody and antibody/cytokine combinations need to be explored to achieve better diagnostic accuracy.

Project description:BackgroundWorld Health Organization (WHO) recommends systematic screening of high-risk populations, including household contacts (HHCs) of adult pulmonary tuberculosis (TB) patients, as a key strategy for elimination of TB. QuantiFERON-TB Gold In-Tube (QFT-GIT) assay and tuberculin skin test (TST) are two commonly used tools for the detection of latent tuberculosis infection (LTBI) but may yield differential results, affecting eligibility for TB preventive therapy.Materials and methodsA prospective cohort study of adult pulmonary TB patients and their HHCs were recruited in 2 cities of India, Pune and Chennai. HHCs underwent QFT-GIT (QIAGEN) and TST (PPD SPAN 2TU/5TU). A positive QFT-GIT was defined as value ?0.35 IU/ml and a positive TST as an induration of ?5 mm. A secondary outcome of TST induration ?10mm was explored. Proportion positive by either or both assays, discordant positives and negatives were calculated; test concordance was assessed using percentage agreement and kappa statistics; and risk factors for concordance and discordance including age categories were assessed using logistic regression. Sensitivity and specificity was estimated by latent class model.ResultsOf 1048 HHCs enrolled, 869 [median (IQR) age: 27 years (15-40)] had both TST and QFT-GIT results available and prevalence of LTBI by QFT-GIT was 54% [95% CI (51, 57)], by TST was 55% [95% CI (52, 58)], by either test was 74% [95% CI (71, 77) and by both tests was 35% [95% CI (31, 38)]. Discordance of TST+/QFT-GIT- was 21% while TST-/QFT-GIT+ was 26%. Poor to fair agreement occurred with TST 5mm or 10mm cutoff (60 and 61% agreement with kappa value of 0.20 and 0.25 respectively). Test agreement varied by age, TST strength and induration cut-off. In multivariate analysis, span PPD was a risk factor for QFT-GIT+ and TST- while absence of BCG scar was for TST+ and QFT-GIT-. Being employed and exposure to TB case outside the household case were associated with positivity by both the tests. Sensitivity of TST and QFT-GIT to diagnose LTBI was 77% and 69%. Probability of having LTBI was >90% when both tests were positive irrespective of exposure gradient.ConclusionPrevalence of LTBI among HHCs of adult pulmonary TB patients in India is very high and varies by test type, age, and exposure gradient. In our high TB burden setting, a strategy to treat all HHCs or a targeted strategy whereby an exposure index is used should be assessed in future preventive therapy and vaccine studies as HHCs have several factors that place them at high risk for progression to TB disease.

Project description:BackgroundTuberculosis (TB) in prisons usually occurs at higher rates than in the general population, especially in developing countries. TB has been reported as the most common cause of death among prisoners. Studies have shown limitations for early detection of TB in prisons that seem to result from mistaken concepts about TB, delayed diagnosis mainly due to the naturalization of lack of healthcare for this population METHODS: A scoping review was performed using the methodology of the Joanna Briggs Institute to assess "What are the scientific evidences on the epidemiology of TB in the prison system?". Then, a meta-analysis was performed to assess the prevalence of TB (active and latent) TB in prisoners. The results are presented as prevalence, in percentage, through random effects models, with a confidence interval of 95%.ResultsRegarding active TB, the results of the metanalysis showed that countries with a high burden of TB had a prevalence of 3.54% [2.71; 4.63], countries not considered to be high burden TB countries had a prevalence of 1.43% [0.86; 2.37]. Latent TB had a prevalence of 51.61% [39.46; 63.58] in high TB burden countries and a prevalence of 40.24% [23.51; 59.61] in countries with low TB burden. In terms of development, in low- and lower-middle-income countries, the prevalence of active TB was 3.13% [1.84; 5.29] and in high- and upper-middle income countries the prevalence was 2.25% [1.70; 2.99]. The prevalence of latent TB in high- and middle-income countries was 43.77% [28.61; 60.18] and of 49.42% [45.91; 52.94] in low and lower middle-income countries.ConclusionOur analysis suggests that TB, and probably other infectious diseases, find fertile ground in prisons where previous acquire social disadvantages seem to thrive-therefore, TB in prisons is a global public health problem and effective strategies are needed to control the disease are needed targeting the prison environment, including rapid health assessments to understand each context and to implement tailored and precision interventions.

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Host markers in QuantiFERON supernatants differentiate active TB from latent TB infection: preliminary report.

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Host markers in QuantiFERON supernatants differentiate active TB from latent TB infection: preliminary report.

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