Dataset Information

Whole blood interferon-? release assay is insufficient for the diagnosis of sputum smear negative pulmonary tuberculosis.

ABSTRACT:

Purpose

We investigated the value of an interferon-? release assay (IGRA) for the diagnosis of active pulmonary tuberculosis (PTB) among sputum smear negative PTB suspects in an environment with intermediate burden of PTB and high Bacillus Calmette-Guerin (BCG) vaccination rate.

Materials and methods

We retrospectively reviewed IGRA, medical records, chest PA and CT scan of PTB suspects seen at Gangnam Severance Hospital, Seoul, Korea from Oct. 2007 to Apr. 2013. "Active PTB" was diagnosed when 1) M. tuberculosis culture positive, 2) confirmation by pathologic examination; or 3) clinical findings compatible with TB.

Results

Of 224 sputum smear negative PTB suspects, 94 were confirmed as having active PTB. There were no statistically significant differences in the diagnostic yield of IGRA between immunocompromised and immunocompetent sputum smear negative PTB suspects. IGRA did show superior sensitivity [81.9%, 95% confidence interval (CI); 74.13-89.70%] in the diagnosis of sputum smear negative PTB when compared with chest high-resolution computed tomography (HRCT), tuberculin skin test (TST), and chest X-ray (p<0.001). Also, IGRA showed highest negative predictive value (82.7%, 95% CI; 75.16-90.15%) when compared with HRCT, TST and chest X-ray (p=0.023). However, combining the results of IGRA with those of HRCT, TST, or both did not increase any diagnostic parameters.

Conclusion

Failure to increase diagnostic yields by combination with other diagnostic modalities suggests that additional enforcement with IGRA may be insufficient to exclude other diagnoses in sputum smear negative PTB suspects and to screen active PTB in an environment with intermediate TB prevalence and a high BCG vaccination rate.

SUBMITTER: Park H

PROVIDER: S-EPMC3990062 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Whole blood interferon-γ release assay is insufficient for the diagnosis of sputum smear negative pulmonary tuberculosis.

Park HeeJin H Shin Jung Ar JA Kim Hyung Jung HJ Ahn Chul Min CM Chang Yoon Soo YS

Yonsei medical journal 20140401 3

<h4>Purpose</h4>We investigated the value of an interferon-γ release assay (IGRA) for the diagnosis of active pulmonary tuberculosis (PTB) among sputum smear negative PTB suspects in an environment with intermediate burden of PTB and high Bacillus Calmette-Guerin (BCG) vaccination rate.<h4>Materials and methods</h4>We retrospectively reviewed IGRA, medical records, chest PA and CT scan of PTB suspects seen at Gangnam Severance Hospital, Seoul, Korea from Oct. 2007 to Apr. 2013. "Active PTB" was ...[more]

PMID: 24719140

Similar Datasets

Project description:BackgroundSputum obtained either under instruction from a health-care worker or through induction can improve case detection of active tuberculosis. However, the best initial sputum sampling strategy for adults with suspected smear-negative or sputum-scarce tuberculosis in primary care is unclear. We compared these two methods of sample acquisition in such patients.MethodsIn this randomised controlled trial, we enrolled adults (age ≥18 years) with sputum-scarce or smear-negative suspected tuberculosis from three primary care clinics in Cape Town, South Africa. Patients were randomly assigned (1:1) to receive either health-care worker instruction or induction to obtain sputum samples. Neither patients nor investigators were masked to allocation. The primary outcome was the proportion of patients who had started treatment after 8 weeks in a modified intention-to-treat population. Secondary outcomes were proportions starting treatment within different time periods, proportion of patients producing sputum for diagnosis, adverse effects, sputum samples' quality, and case detection by diagnostic method. This study is registered with ClinicalTrials.gov, number NCT01545661.FindingsWe enrolled 481 patients, of whom 213 were assigned to health-care worker instruction versus 268 assigned to induction. The proportion of patients who started treatment in the 8 weeks after enrolment did not differ significantly between groups (53/213 [25%] vs 73/268 [27%]; OR 0·88, 95% CI 0·57-1·36; p=0·56). A higher proportion of instructed versus induced patients initiated empiric treatment based on clinical and radiography findings (32/53 [60%] vs 28/73 [38%]; p=0·015). An adequate sputum sample ≥1 mL was acquired in a lower proportion of instructed versus induced patients (164/213 [77%] vs 238/268 [89%]; p<0·0001), and culture-based diagnostic yield was lower in instructed versus induced patients (24/213 [11%] vs 51/268 [19%]; p=0·020). However, same-day tuberculosis case detection was similar in both groups using either smear microscopy (13/213 [6%] vs 22/268 [8%]; p=0·38) or Xpert-MTB/RIF assay (13/89 [15%] vs 20/138 [14%]; p=0·98). No serious adverse events occurred in either group; side-effects related to sample acquisition were reported in 32 of 268 (12%) patients who had sputum induction and none who had instruction. Cost per procedure was lower for instructed than for induced patients (US$2·14 vs US$7·88).InterpretationAlthough induction provides an adequate sample and a bacteriological diagnosis more frequently than instruction by a health-care worker, it is more costly, does not result in a higher proportion of same-day diagnoses, and-because of widespread empiric treatment-may not result in more patients starting treatment. Thus, health-care worker instruction might be the preferred strategy for initial collection of sputum samples in adults with suspected sputum-scarce or smear-negative tuberculosis in a high burden primary care setting.FundingSouth African National Research Foundation, European Commission, National Institutes of Health, European and Developing Countries Clinical Trials Partnership, Discovery Foundation.

Project description:Accurate diagnosis and subsequent treatment of latent tuberculosis infection (LTBI) is essential for TB elimination. However, the absence of a gold standard test for diagnosing LTBI makes assessment of the true prevalence of LTBI and the accuracy of diagnostic tests challenging. Bayesian latent class models can be used to make inferences about disease prevalence and the sensitivity and specificity of diagnostic tests using data on the concordance between tests. We performed the largest meta-analysis to date aiming to evaluate the performance of tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) for LTBI diagnosis in various patient populations using Bayesian latent class modelling.Systematic search of PubMeb, Embase and African Index Medicus was conducted without date and language restrictions on September 11, 2017 to identify studies that compared the performance of TST and IGRAs for LTBI diagnosis. Two IGRA methods were considered: QuantiFERON-TB Gold In Tube (QFT-GIT) and T-SPOT.TB. Studies were included if they reported 2x2 agreement data between TST and QFT-GIT or T-SPOT.TB. A Bayesian latent class model was developed to estimate the sensitivity and specificity of TST and IGRAs in various populations, including immune-competent adults, immune-compromised adults and children. A TST cut-off value of 10 mm was used for immune-competent subjects and 5 mm for immune-compromised individuals.A total of 157 studies were included in the analysis. In immune-competent adults, the sensitivity of TST and QFT-GIT were estimated to be 84% (95% credible interval [CrI] 82-85%) and 52% (50-53%), respectively. The specificity of QFT-GIT was 97% (96-97%) in non-BCG-vaccinated and 93% (92-94%) in BCG-vaccinated immune-competent adults. The estimated figures for TST were 100% (99-100%) and 79% (76-82%), respectively. T-SPOT.TB has comparable specificity (97% for both tests) and better sensitivity (68% versus 52%) than QFT-GIT in immune-competent adults. In immune-compromised adults, both TST and QFT-GIT display low sensitivity but high specificity. QFT-GIT and TST are equally specific (98% for both tests) in non-BCG-vaccinated children; however, QFT-GIT is more specific than TST (98% versus 82%) in BCG-vaccinated group. TST is more sensitive than QFT-GIT (82% versus 73%) in children.This study is the first to assess the utility of TST and IGRAs for LTBI diagnosis in different population groups using all available data with Bayesian latent class modelling. Our results challenge the current beliefs about the performance of LTBI screening tests, and have important implications for LTBI screening policy and practice. We estimated that the performance of IGRAs is not as reliable as previously measured in the general population. However, IGRAs are not or minimally affected by BCG and should be the preferred tests in this setting. Adoption of IGRAs in settings where BCG is widely administered will allow for a more accurate identification and treatment of LTBI.