Intermediate TB-burden Country Research Articles

Lack of latent tuberculosis (TB) screening and delay in anti-retroviral therapy initiation in HIV-TB co-infection: an 11-year study in an intermediate TB-burden country

Objectives: To examine the prevalence and characteristics of HIV-tuberculosis (TB) co-infected patients in Singapore, an intermediate TB-burden country.Methods: Retrospective data across 11 years was obtained from the National University Hospital (NUH), a quaternary hospital and the National Centre for Infectious Diseases (NCID), the national HIV center.Results: From December 2005 to December 2016, 4015 HIV-infected patients were managed at NUH and NCID, of whom, respectively, 48 and 272 were diagnosed with active TB disease. Only 2 patients (0.6%) were screened for latent TB infection on HIV diagnosis. Mean CD4 count at TB diagnosis was 125.0 ± 153.9 cells/mm3. More patients with HIV diagnosed ≥6 weeks before TB (41%) were associated with CD4 counts >200 cells/mm3 than patients with TB diagnosed ≥6 weeks before HIV (2%). Of 124 (38.6%) HIV-TB patients with CD4 count ≤50 cells/mm3, only 18 (14.2%) started anti-retroviral therapy (ART) in <2 weeks. Of patients with pulmonary TB, 33.5% had normal chest x-ray.Conclusions: Latent TB infection screening in HIV-infected patients is low, and ART initiation is delayed in HIV-TB patients with CD4 ≤50 cells/mm3. Pulmonary TB patients with HIV can be infectious despite normal chest x-ray. Clinical practices can be further improved to benefit HIV-TB patients.

Clinical and radiologic characteristics of radiologically missed miliary tuberculosis.

While chest CT provides important clue for diagnosis of miliary tuberculosis (TB), patients are occasionally missed on initial CT, which might delay the diagnosis. This study was to evaluate the clinical and radiological characteristics of radiologically missed miliary TB.Total 117 adult patients with microbiologically confirmed miliary TB in an intermediate TB-burden country were included. ‘Missed miliary TB’ were defined as the case in which miliary TB was not mentioned as a differential diagnosis in the initial CT reading. Clinical characteristics and radiologic findings including the predominant nodule size, demarcation of miliary nodules and disease extent on CT were retrospectively evaluated. Findings were compared between the missed and non-missed miliary TB groups. Multivariable analyses were performed to determine independent risk factors of missed miliary TB.Of 117 patients with miliary TB, 13 (11.1%) were classified as missed miliary TB; these patients were significantly older than those with non-missed miliary TB (median age, 71 vs 57 years, P = .024). There was a significant diagnostic delay in the missed miliary TB group (P < .001). On chest CT, patients with missed miliary TB had a higher prevalence of ill-defined nodules (84.6% vs 14.4%; P < .001), miliary nodule less than 2 mm showing granular appearance (69.2% vs 12.5%; P < .001), and subtle disease extent (less than 25% of whole lung field, 46.2% vs 8.7%; P < .001). Multivariable analysis revealed that only CT findings including ill-defined nodule (Odd ratios [OR], 15.64; P = .002) and miliary nodule less than 2 mm (OR, 10.08; P = .007) were independently associated with missed miliary TB.Approximately 10% of miliary TB could be missed on initial chest CT, resulting in a delayed diagnosis and treatment. Caution is required in patients with less typical CT findings showing ill-defined miliary nodules less than 2 mm showing granular appearance and follow-up CT might have a benefit.

Long-term performance of the IGRA to predict and prevent active tuberculosis development in HIV-infected patients.

<sec id="st1"> <title>OBJECTIVE</title> To estimate the long-term performance of the interferon-gamma release assay (IGRA) in predicting active tuberculosis (ATB) development among human immunodeficiency virus (HIV) infected patients in an intermediate TB burden country. </sec> <sec id="st2"> <title>DESIGN</title> A retrospective cohort study was conducted. HIV-infected patients with 1 IGRA result but no current or previous ATB who had been retained in care for 1 year were enrolled and observed for ATB development from 2006 to 2016. </sec> <sec id="st3"> <title>RESULTS</title> Sixty-two IGRA-positive and 354 IGRA-negative patients were observed for a median period of 4.03 years. ATB incidence in IGRA-positive vs. negative patients was respectively 15.24/1000 person-years (py) (95%CI 4.15-39.02) vs. 0.67/1000 py (95%CI 0.01-3.68) (P = 0.001). The sensitivity, specificity and positive and negative predictive values of the IGRA were respectively 80.0% (28.4-99.5%), 85.9% (82.1-89.1%), 6.5% (4.0-10.2%) and 99.7% (98.4-99.9%). Among the 62 IGRA-positive patients, 25 were treated for latent tuberculous infection (LTBI) and 37 were not. Patients with LTBI treatment did not develop ATB, while four cases of ATB occurred among patients without LTBI treatment. Among the 257 IGRA-negative patients who received a follow-up IGRA, 34 (12.9%) patients converted to positive. No ATB developed in IGRA converters. </sec> <sec id="st4"> <title>CONCLUSION</title> Screening for LTBI using IGRAs and LTBI treatment can be useful to prevent ATB in an intermediate TB burden country. </sec>.

Combined IFN-γ and TNF-α release assay for differentiating active tuberculosis from latent tuberculosis infection

The IFN-γ-release assay (IGRA) cannot differentiate active tuberculosis (TB) from latent TB infection (LTBI). We hypothesized that the TNF-α-release assay (TARA) combined with IGRA might discriminate active TB from not active TB without LTBI. Adult patients with suspected TB, and with unrelated diseases such as herpes zoster as controls, were enrolled in an intermediate TB-burden country. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as those having not active TB with and without LTBI based on IGRA results. The IGRA and TARA by using ELISPOT assays were performed on peripheral mononuclear cells. Thirty six patients with active TB and 53 patients including 18 not active TB with LTBI and 35 not active TB without LTBI were finally included. The sensitivity and specificity of the IGRA for those patients found to have active TB were 94% (CI, 80-99) and 66% (CI 52-78), respectively. Combining the IGRA and the TARA substantially increased the specificity for active TB (93%, CI, 82-98; P = 0.001) compared with the IGRA only, without compromising sensitivity (89%, CI, 73-96; P = 0.67). Combining the IGRA and TARA appears to be useful for diagnosing active TB.

RISK FACTORS FOR DELAYED DIAGNOSIS OF PULMONARY TUBERCULOSIS IN INTERMEDIATE TB BURDEN COUNTRY

RespirologyVolume 22, Issue S3 p. 11-12 Tuberculosis 1 RISK FACTORS FOR DELAYED DIAGNOSIS OF PULMONARY TUBERCULOSIS IN INTERMEDIATE TB BURDEN COUNTRY First published: 20 November 2017 https://doi.org/10.1111/resp.13206_17Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume22, IssueS3Supplement: 22nd Congress of the Asian Pacific Society of Respirology, International Convention Centre, Sydney, Australia, 23–26 November 2017November 2017Pages 11-12 RelatedInformation

Poor predictability of QuantiFERON-TB assay in recipients and donors for tuberculosis development after kidney transplantation in an intermediate-TB-burden country

BackgroundTuberculosis (TB) is a common opportunistic infection after kidney transplantation (KT). The QuantiFERON-TB-Gold In-Tube test (QFT) is widely used for assessing latent TB; however, it is currently unclear whether the pre-KT QFT of the recipient and donor can predict post-KT TB.MethodsWe retrospectively reviewed patients who received KT between January 2009 and December 2015 at Seoul National University Hospital. The QFT was performed in 458 KT recipients and 239 paired living donors, and 138 KT recipients underwent both the QFT and tuberculin skin test (TST). After excluding 12 patients diagnosed as having clinically latent TB, we evaluated whether the QFT of the recipient and donor was predictive for new-onset active TB after KT.ResultsThe QFT was positive in 101 (22.1%) recipients and associated with clinically latent TB before KT (P < 0.05). However, agreement between the TST and QFT was poor (κ = 0.327). Post-KT TB occurred in 1 of 95 recipients with a positive QFT, and 2 cases of TB occurred among 351 patients with a negative or indeterminate QFT. The incidence of TB was 242 cases/100,000 person-years among 446 KT recipients with a median follow-up of 30.2 months. The QFT of recipients could not predict post-KT TB in Poisson regression analysis (relative risk [RR], 1.847; 95% confidence interval [CI], 0.168–20.373; P = 0.616). Of 234 living donor-recipient pairs, the QFT of the recipient (RR, 5.012; 95% CI, 0.301–83.430; P = 0.261) and QFT of the donor (RR, 1.758; 95% CI, 0.106–29.274; P = 0.694) could not predict post-KT TB.ConclusionThe QFT of recipients or living donors pre-KT cannot predict the short-term development of post-KT TB in an intermediate TB-burden country.

Diagnostic Usefulness of Bronchoalveolar Lavage Fluid Xpert MTB/RIF in Patients with Suspected Pauci-bacillary Pulmonary Tuberculosis

BackgroundRapid and accurate diagnosis of tuberculosis (TB) is important for appropriate treatment initiation and control of disease transmission. Xpert TB/RIF has been widely used for rapid diagnosis especially in sputum AFB smear-negative pulmonary TB. However, about one-third of patients with pauci-bacillary pulmonary TB still reveal negative Xpert TB/RIF results from sputum specimens. Theoretically, bronchoalveolar lavage (BAL) fluid can provide more sensitive specimen in those with sputum-scarce or AFB smear-negative pulmonary TB than sputum.However, there is limited data on the diagnostic performance of Xpert TB/RIF from BAL fluid in patients with pauci-bacillary pulmonary TB.MethodsAll patients with suspected pulmonary TB who underwent BAL due to sputum-scarcity or negative AFB smear results and underwent Xpert TB/RIF from BAL fluid were retrospectively reviewed at a tertiary hospital, Seoul, South Korea (an intermediate TB-burden country) between October 2014 and April 2017. Confirmed TB was defined to those with clinical specimens positive for M. tuberculosis by culture or PCR assays. Patients those with caseating granuloma in biopsy tissue and shows a good response to anti-tuberculous therapy were classified as having probable TB.ResultsA total of 113 patients were included in the analysis. Of these 113 patients, 30 (27%) were classified as confirmed TB, 7 (6%) as probable TB, and 76 (67%) as not TB. Of these 37 patients with confirmed or probable TB, 8 (22%) had miliary TB and 12 (32%) were immunocompromised. Only 15 (50%) of the 30 confirmed TB patients revealed positive Xpert TB/RIF results from BAL fluid. Overall sensitivity, specificity, positive predictive value, and negative predictive value of Xpert TB/RIF from BAL fluid for the diagnosis of TB were 41% (95% CI, 31%-41%), 100% (95% CI, 95%-100%), 100% (95% CI 77%-100%), and 78% (95% CI 74%-77%), respectivelyConclusionXpertTB/RIF from BAL fluid appears to be suboptimal to rule out pulmonary TB. The development of more sensitive and rapid test for pauci-bacillary pulmonary TB is needed.Disclosures All authors: No reported disclosures.

Diagnostic usefulness of T-cell based assays for tuberculous meningitis in HIV-uninfected patients

Early diagnosis and treatment of tuberculous meningitis (TBM) is essential for a positive outcome, but sensitive, specific, and rapid diagnostic tests for TBM are lacking. We evaluated the diagnostic utility of enzyme-linked immunosorbent spot (ELISPOT) assays in HIV-uninfected patients with suspected TBM. All HIV-uninfected patients with suspected TBM were prospectively enrolled at a tertiary care hospital in an intermediate TB-burden country, during a 6-year period. ELISPOT assays were performed on peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid-mononuclear cells (CSF-MC). Of the 276 evaluable patients, 90 (33%) were classified as having TBM (30 definite cases, 19 probable, and 41 possible), and 186 (67%) as having non-TBM. When comparing definite TBM versus non-TBM, the sensitivity and specificity of the PBMC ELISPOT assay (≥6 spots; manufacturer's recommended cut-off) for diagnosing TBM were 96% (95% CI, 82-100) and 58% (95% CI, 50-66), respectively. The CSF-MC ELISPOT assay (≥38 spots; receiver operating characteristic [ROC]-derived cut-off) was a useful rule-in test with specificity of 95% (96% CI, 90-98). Its sensitivity was 68% (95% CI, 45-86), which was superior those of AFB smear microscopy (14%; P < 0.001) and CSF Mycobacterium tuberculosis PCR (41%; P = 0.07). Combining this assay with M. tuberculosis PCR, clinical score, and both together increased sensitivity to 86%, 91%, and 95%, respectively, while retaining about 95% specificity. The CSF-MC ELISPOT assay appears to be a rapid and accurate rule-in test for the diagnosis of TBM and a useful adjunct for diagnosing TBM in HIV-uninfected patients.

Comparison of QuantiFERON-TB gold in tube test versus tuberculin skin test for screening of latent tuberculosis infection in Saudi Arabia: A population-based study.

OBJECTIVES:To compare QuantiFERON-TB gold in tube (QFT-GIT) test with tuberculin skin test (TST) in detecting latent tuberculosis infection (LTBI) among a general population in Saudi Arabia.METHODS:A population-based cross-sectional study was conducted between July 2010 and March 2013 among individuals randomly selected from the list of those receiving care at primary healthcare centers in three provinces of Saudi Arabia; Central, Western, and Eastern provinces. Those younger than 5 years, immunocompromised, had a current or previous history of active TB, LTBI, or who were receiving anti-TB medications were excluded. Informed consent was obtained before the study questionnaire was completed. Participants were then evaluated for LTBI using QFT-GIT test followed immediately by TST.RESULTS:Of the 1369 subjects included in the final analysis, QFT-GIT was positive in 124 (9.1%) and TST was positive in 127 (9.3%). Positive concordance was observed in 49 (3.6%) subjects while negative concordance was observed in 1167 (85.2%) subjects. The overall agreement between the two tests was 88.8% with a significant kappa (κ) test (κ = 0.332, P < 0.001). Concordance was significantly higher in younger age, female gender, single status, students, primary education, living in middle-sized families, and never smoked.CONCLUSIONS:The overall agreement of TST and QFT-GIT for the detection of LTBI among a Saudi general population was 88.8%. QFT-GIT is probably comparable to TST for detecting LTBI in an intermediate TB burden country with high at birth bacille calmette guerin vaccination coverage. Further prospective studies are needed to compare the ability of both tests to predict TB disease.

Accuracy of the Xpert® MTB/RIF assay for the diagnosis of extra-pulmonary tuberculosis in South Korea.

The Xpert(®) MTB/RIF assay has been endorsed by the World Health Organization for the detection of pulmonary and extra-pulmonary tuberculosis (EPTB). To determine the accuracy of the Xpert assay in diagnosing EPTB in South Korea, a country with an intermediate TB burden. We retrospectively reviewed the medical records of 1429 patients in whom the Xpert assay using EPTB specimens was requested between 1 January 2011 and 31 October 2013 in a tertiary referral hospital in South Korea. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for the diagnosis of EPTB and detection of rifampicin (RMP) resistance were calculated. Using culture as gold standard, the sensitivity, specificity, PPV and NPV of the assay were respectively 67.7%, 98.1%, 60% and 98.6%. Using a composite reference standard, the sensitivity, specificity, PPV and NPV were respectively 49.3%, 100%, 100% and 95.1%. The sensitivity, specificity, PPV and NPV for the detection of RMP resistance among specimens with positive results for Mycobacterium tuberculosis were respectively 80%, 100%, 100% and 97.7%. The Xpert assay showed acceptable sensitivity in certain groups and excellent specificity in diagnosing EPTB and detecting RMP resistance in an intermediate TB burden country.

Risk factors for false-negative results of T-SPOT.TB and tuberculin skin test in extrapulmonary tuberculosis

T-SPOT.TB, a recently developed T cell-based assay, has shown promise in diagnosing extrapulmonary tuberculosis (EPTB). However, a limited number of reports have compared the risk factors for false-negative results of tuberculin skin tests (TSTs) and T-SPOT.TB assays in patients with EPTB. We, thus, conducted a prospective, blinded, observational study to evaluate the risk factors for false-negative T-SPOT.TB and TST results in patients with EPTB. Between April 2008 and November 2011, all adult patients with suspected EPTB were prospectively enrolled at Asan Medical Center, Seoul, South Korea (an intermediate TB-burden country). Only patients with confirmed and probable EPTB who underwent TST and T-SPOT.TB were included in the final analysis. Of the 324 patients who underwent both TST and T-SPOT.TB testing, 128 patients with 96 (75%) culture- or polymerase chain reaction (PCR)-confirmed and 32 (25%) probable EPTB were finally analyzed. T-SPOT.TB assays were less likely to yield false-negative results than TSTs [17% (22/128) vs. 54% (69/128), p<0.001]. In a multivariate analysis, miliary TB was associated with false-negative TSTs [odds ratio (OR)=5.3; 95% confidence interval (CI) 1.7-16.1], while immunosuppression showed a trend toward false-negative TSTs (OR=2.5; 95% CI 0.9-6.8). Conversely, lymph node TB (OR=0.2; 95% CI 0.1-0.5) and skeletal TB (OR=0.2; 95% CI 0.1-0.5) were associated with true-positive TST results. The only risk factor for false-negative T-SPOT.TB results was TB meningitis (OR=2.6; 95% CI 1.0-6.6). Our findings suggest that T-SPOT.TB has a better sensitivity to diagnose EPTB than TST, especially in patients with immunosuppression or miliary TB.

Role of the Neutrophil-Lymphocyte Count Ratio in the Differential Diagnosis between Pulmonary Tuberculosis and Bacterial Community-Acquired Pneumonia

BackgroundDifferential diagnosis between pulmonary tuberculosis (TB) and bacterial community-acquired pneumonia (CAP) is often challenging. The neutrophil-lymphocyte count ratio (NLR), a convenient marker of inflammation, has been demonstrated to be a useful biomarker for predicting bacteremia. We investigated the usefulness of the NLR for discriminating pulmonary TB from bacterial CAP in an intermediate TB-burden country.MethodsWe retrospectively analyzed the clinical and laboratory characteristics of 206 patients suspected of having pulmonary TB or bacterial CAP from January 2009 to February 2011. The diagnostic ability of the NLR for differential diagnosis was evaluated and compared with that of C-reactive protein.ResultsSerum NLR levels were significantly lower in patients with pulmonary TB than in patients with bacterial CAP (3.67±2.12 vs. 14.64±9.72, P<0.001). A NLR <7 was an optimal cut-off value to discriminate patients with pulmonary TB from patients with bacterial CAP (sensitivity 91.1%, specificity 81.9%, positive predictive value 85.7%, negative predictive value 88.5%). The area under the curve for the NLR (0.95, 95% confidence interval [CI], 0.91-0.98) was significantly greater than that of C-reactive protein (0.83, 95% CI, 0.76-0.88; P=0.0015).ConclusionsThe NLR obtained at the initial diagnostic stage is a useful laboratory marker to discriminate patients with pulmonary TB from patients with bacterial CAP in an intermediate TB-burden country.

Diagnostic performance of T-SPOT. TB for extrapulmonary tuberculosis according to the site of infection

The clinical manifestations of extrapulmonary tuberculosis (E-TB) vary according to site of disease, so we tested the hypothesis that IFN-γ producing T-cell responses also vary in parallel. Therefore we conducted a prospective, blinded, observational study to evaluate the diagnostic performance of blood T-SPOT.TB according to the various sites of E-TB. From April 2008 to August 2010, all patients with suspected E-TB were enrolled at a tertiary hospital in an intermediate TB-burden country. Final diagnosis in patients with suspected E-TB was classified by clinical category. A total of 368 patients with suspected E-TB were enrolled; 196 (53%) were classified as having TB, including 119 (32%) with confirmed TB, 34 (9%) probable TB, and 43 (12%) possible TB; the remaining 172 (47%) were classified as not having TB. After excluding patients with possible TB, the T-SPOT.TB was more sensitive in patients with chronic forms of E-TB such as lymph node or osteoarticular TB (93%, 95% CI 83%-97%) than in patients with acute forms of E-TB such as TB meningitis or miliary TB (79%, 95% CI 66%-87%, P=0.03). The diagnostic performance of the blood T-SPOT.TB differs among patients with various clinical manifestations of E-TB.

Rapid diagnosis of tuberculous peritonitis by T cell-based assays on peripheral blood and peritoneal fluid mononuclear cells

The utility of a newly-developed Mycobacterium tuberculosis-specific enzyme-linked immunosorbent spot (ELISPOT) assay for diagnosis of tuberculous peritonitis (TBP) has not been fully assessed. All patients with suspected TBP in a tertiary care hospital in an intermediate TB burden country were prospectively enrolled over a 30-month period. ELISPOT assays were performed on peripheral mononuclear cells (PBMC) and mononuclear cells from peritoneal fluid (PF-MC). Sixty-four patients with suspected TBP were enrolled. Of these, 30 (47%) were classified as having TBP (27 confirmed and 3 probable cases), and 25 (39%) were classified as not having active tuberculosis. The remaining 9 (14%) with possible TBP were excluded from the final analysis. Five (8%) of the total 64 patients gave indeterminate PBMC ELISPOT results and 7 (18%) of 39 patients who underwent PF-MC ELISPOT assay revealed indeterminate PF-MC ELISPOT results. The sensitivity and specificity, respectively, of the tested methods for diagnosing TBP were as follows: PBMC ELISPOT (≥ 6 spots), 86% and 67%; PF-MC ELISPOT (≥ 14 spots), 92% and 86%; PF-MC ELISPOT/PBMC ELISPOT ratio (≥ 2), 75% and 93%; and PF ADA levels (≥ 38 IU/L), 95% and 100%. The areas under the receiver operating characteristics curves were as follows: PF-MC ELISPOT, 0.96; PF ADA, 0.96; PBMC ELISPOT, 0.88; and PF-MC ELISPOT/PBMC ELISPOT ratio, 0.87, respectively. Although the ELISPOT assay does not outperform PF ADA, the ELISPOT assay using PBMC and PF-MC is a useful adjunct for diagnosing TBP, especially for a rule-in test when PF/MC/PBMC ELISPOT ratio (≥ 2) is used. However, the relatively high proportion of indeterminate results limits test utility, so further studies are needed to develop an optimized assay prototype.

Prevalence and risk factors of latent tuberculosis infection among health care workers in Malaysia

BackgroundHealth care workers are exposed to patients with tuberculosis and are at risk of nosocomial infection. The aim of this study was to determine the prevalence and factors associated with latent tuberculosis infection among health care workers in Malaysia and also to evaluate the agreement between Quantiferon TB Gold in tube test with Tuberculin Skin Test.MethodsA cross sectional study was conducted at four randomly selected hospitals in the Klang Valley from December 2008 to May 2009. Self administered questionnaire was used to obtain information on health care workers and possible risk factors. The response rate for this study was 90.8% with 954 respondents completed the questionnaire and were tested with Quantiferon TB Gold in tube for latent tuberculosis infection. Agreement between Quantiferon TB Gold in tube and Tuberculin Skin Test was assessed among 95 health care workers who consented to undergo both tests.ResultsThe overall prevalence of latent tuberculosis infection among health care workers was 10.6% (CI: 8.6%; 12.6%). Factors significantly associated with latent tuberculosis infection were aged 35 years and older [9.49 (CI: 2.22; 40.50)], history of living in the same house with close family members or friends who had active tuberculosis [8.69 (CI: 3.00; 25.18)], worked as a nurse [4.65 (CI: 1.10; 19.65)] and being male [3.70 (CI: 1.36; 10.02)]. Agreement between Quantiferon TB Gold in tube test and tuberculin skin test at cut-off points of 10 mm and 15 mm was 50.5% and 82.1% respectively. However, Kappa-agreement was poor for both cut-off points.ConclusionThe prevalence of latent tuberculosis infection in Malaysia was relatively low for an intermediate TB burden country. We could not comment on the occupational risk of latent tuberculosis infection among health care worker compared to the general population as there were no prevalence data available for latent tuberculosis infection in the general population. Kappa agreement between Quantiferon TB gold in-tube and tuberculin skin test was poor.

Validity of interferon-γ-release assays for the diagnosis of latent tuberculosis in haemodialysis patients

Haemodialysis patients are at higher risk of developing active tuberculosis (TB) infection. However, tuberculin skin tests (TST) have limitations and the diagnostic usefulness of interferon-γ-release assays (IG-RAs) remains unclear in immunocompromised hosts including haemodialysis patients. Haemodialysis patients were enrolled from a dialysis centre in Korea, an intermediate TB-burden country with a high bacille Calmette–Guérin (BCG) vaccination rate. The QuantiFERON-Gold TB In tube test® (QFT) and the T-SPOT TB test® (T-SPOT) were performed, along with the TST. We stratified patients to low- and high-risk groups, according to the risk factors for latent TB. Association between each of the three diagnostic tests and the risk of latent TB was analysed. One hundred and sixty-seven patients were enrolled. The positive rates for the TST, the QFT and T-SPOT were 23.5, 45.9 and 60.4%, respectively. Previous BCG vaccination increased the TST-positive rate in the low-risk group (OR 4.438), whereas it affected neither QFT nor T-SPOT. The positive QFT rates were 41.2 and 62.5% in the low- and high-risk groups, respectively. The QFT was associated with the high-risk group (OR 2.578), whereas the TST was not. The positive T-SPOT rates were 58.9 and 65.7% in the low- and high-risk groups, respectively. The frequency of indeterminate results was higher for the QFT (12.6%) compared with the T-SPOT (4.8%). In conclusion, the IG-RAs can be useful for the diagnosis of latent TB infection in haemodialysis patients.

Performance of the tuberculin skin test and interferon-γ release assay for detection of tuberculosis infection in immunocompromised patients in a BCG-vaccinated population

BackgroundInterferon-γ release assay (IGRA) may improve diagnostic accuracy for latent tuberculosis infection (LTBI). This study compared the performance of the tuberculin skin test (TST) with that of IGRA for the diagnosis of LTBI in immunocompromised patients in an intermediate TB burden country where BCG vaccination is mandatory.MethodsWe conducted a retrospective observational study of patients given the TST and an IGRA, the QuantiFERON-TB Gold In-Tube (QFT-IT), at Severance Hospital, a tertiary hospital in South Korea, from December 2006 to May 2009.ResultsOf 211 patients who underwent TST and QFT-IT testing, 117 (55%) were classified as immunocompromised. Significantly fewer immunocompromised than immunocompetent patients had positive TST results (10.3% vs. 27.7%, p 0.001), whereas the percentage of positive QFT-IT results was comparable for both groups (21.4% vs. 25.5%). However, indeterminate QFT-IT results were more frequent in immunocompromised than immunocompetent patients (21.4% vs. 9.6%, p 0.021). Agreement between the TST and QFT-IT was fair for the immunocompromised group (κ = 0.38), but moderate agreement was observed for the immunocompetent group (κ = 0.57). Indeterminate QFT-IT results were associated with anaemia, lymphocytopenia, hypoproteinemia, and hypoalbuminemia.ConclusionIn immunocompromised patients, the QFT-IT may be more sensitive than the TST for detection of LTBI, but it resulted in a considerable proportion of indeterminate results. Therefore, both tests may maximise the efficacy of screening for LTBI in immunocompromised patients.

Comparison of two commercial interferon- assays for diagnosing Mycobacterium tuberculosis infection

The clinical usefulness of ex vivo interferon-gamma assays may largely depend on the assay format and epidemiological status of tuberculosis (TB) in the region studied. From July 2004 to June 2005 a prospective comparison study was undertaken at a tertiary referral hospital in South Korea. The results of tuberculin skin tests (TST) and the commercially available QuantiFERON-TB Gold (QFT-G) and T SPOT-TB (SPOT) assays were compared in an intermediate TB-burden country. Of the 224 participants studied, results from all three tests (TST, QFT-G, and SPOT) were available in 218; 87 with active TB and 131 at a low risk for TB. Using 10 mm as a cut-off for TST, SPOT sensitivity (96.6%) was significantly higher than that seen for TST (66.7%) and QFT-G (70.1%). QFT-G showed superior specificity over TST (91.6 versus 78.6%). Although the specificity of QFT-G was higher than that of SPOT (91.6 versus 84.7%), the difference was not statistically significant. Whilst some differences were found in the performance of the two commercialised interferon-gamma assays, they seemed to be superior in their detection of Mycobacterium tuberculosis infection compared with tuberculin skin tests. The most appropriate choice of interferon-gamma assay to use may depend on the clinical setting.