What is the difference between Quantiferon and T-Spot test in the effectiveness of diagnosing TB?

Comment by InpharmD Researcher

Thank you for reopening your inquiry. We have added an additional primary literature section. Please let us know if there is any specific information you'd like detailed. We'd be delighted to assist! Thank you for using InpharmD, and please think of us again the next time you have a query. Studies suggest the T-spot test has a higher sensitivity than the Quantiferon test in diagnosing TB, but the difference is not deemed to be statistically significant. As such, guidelines do not recommend one test over the other. Studies do suggest there may be a greater variation in sensitivity/specificity in certain populations (e.g., HIV positive, <5 years old, >80 years old) with each test.

Background

Per consensus guidelines from the Centers for Disease Control and Prevention (CDC) and Infectious Diseases Society of America (IDSA), the sensitivity of interferon-gamma release assays (IGRAs) are consistently found to be equal (Quantiferon, 81-86%) or superior (T-spot, 90-95%) to the sensitivity of tuberculosis skin testing (71-82%). In patients who were vaccinated with BCG, IGRAs and tuberculosis skin tests appear to be similar. A meta-analysis found the specificity of Quantiferon to be >95% in patients vaccinated with BCG; however, data is more limited for the T-spot test in these patients. The sensitivity of IGRAs, both Quantiferon and T-spot, in persons with HIV is estimated to range from 65% to 100%. The guidelines do not recommend one test over another; instead, they discuss IGRA tests as a whole versus skin testing. [1]

A 2018 prospective comparative study (Table 1) assessed the diagnostic performance of the QuantiFERON-TB Gold In-Tube test and T-SPOT.TB assays in 746 patients with active tuberculosis (TB) and compared the concordance in routine clinical practice in a setting with high tuberculosis rates. Sensitivities for the T-spot assay were 88.6% (95% confidence interval [CI] 83.3 to 92.5) in the confirmed TB group and 83.1% (95% CI 78.4 to 87) in the group with probable TB. Sensitivities for the Quantiferon test were 88.4% (95% CI 82.9 to 92.3) in the confirmed TB group and 82.5% (95% CI 77.6 to 86.5%) in the group of patients with probable TB. T-spot had a specificity of 63.4% (95% CI 57.4 to 69) compared to 60.5% (95% CI 82.9 to 92.3) with Quantiferon in patients with no TB. Sensitivity and specificity values were higher for the T-spot, but none of these values were significantly different. The T-spot assay resulted in significantly fewer indeterminate test results (0.4%) compared to the Quantiferon (4.3%; p<0.001). There was a 92.3% agreement between the tests. The results show there may be small differences in the accurate diagnosis of tuberculosis with T-spot and Quantiferon, but the differences are unlikely to be significant. [2]

A retrospective analysis assessed the relevance of age on the sensitivity of interferon-gamma release assays (Quantiferon [N=192] or T-spot test [N=212]). The positivity of the test was compared to a true infection as defined by a positive culture or PCR. The overall sensitivity of the Quantiferon test was 80.2%, while the overall sensitivity of the T-spot test was 91.0%. The sensitivities of Quantiferon and T-spot, respectively, 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 tests (p = 0.039). However, only Quantiferon was significantly related to age in the multivariate analysis. The authors conclude Quantiferon, but not T-spot, was significantly affected by patient age. [3]

A 2006 prospective study enrolled 393 patients to compare the efficacy of two commercial blood assays, T-SPOT.TB and QuantiFERON-TB Gold, with the tuberculin skin test in patients with suspected latent or active tuberculosis. Overall, both tests had a similar agreement with the skin test; however, Quantiferon was associated with more indeterminate results than with T-spot (11% vs 3%; p <0.0001). Age ≤ 5 years was one of the identified factors related to indeterminate results with Quantiferon (p=0.003), but not with T-spot. Immunosuppressive treatments were also contributory to indeterminate results for both tests. Significantly higher rates of positive results were seen in T-spot than in Quantiferon (38% vs 26%; p <0.0001). Notably, individuals who had close contact with active tuberculosis were less likely to test positive with Quantiferon than with T-spot (p = 0.001). In conclusion, the authors emphasized that in routine clinical practice T-spot and Quantiferon might provide different results. [4]

References:

[1] Lewinsohn DM, Leonard MK, LoBue PA, et al. Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention clinical practice guidelines: diagnosis of tuberculosis in adults and children. Clinical Infectious Diseases. 2017;64(2):e1-e33. doi:10.1093/cid/ciw694
[2] Du F, Xie L, Zhang Y, et al. Prospective Comparison of QFT-GIT and T-SPOT.TB Assays for Diagnosis of Active Tuberculosis. Sci Rep. 2018;8(1):5882. Published 2018 Apr 12. doi:10.1038/s41598-018-24285-3
[3] Bae W, Park KU, Song EY, et al. Comparison of the Sensitivity of QuantiFERON-TB Gold In-Tube and T-SPOT.TB According to Patient Age. PLoS One. 2016;11(6):e0156917. Published 2016 Jun 3. doi:10.1371/journal.pone.0156917
[4] Ferrara G, Losi M, D'Amico R, et al. Use in routine clinical practice of two commercial blood tests for diagnosis of infection with Mycobacterium tuberculosis: a prospective study. Lancet. 2006;367(9519):1328-1334. doi:10.1016/S0140-6736(06)68579-6
Literature Review

A search of the published medical literature revealed 1 study investigating the researchable question:

What is the difference between Quantiferon and T-Spot test in the effectiveness of diagnosing TB?

Level of evidence

C - Multiple studies with limitations or conflicting results  Read more→


Please see Table 1 for your response.

 

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

Design

Multicenter, prospective, comparison study 

N= 746

Objective

To assess the diagnostic performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB assays in patients with active tuberculosis (TB), and compare the concordance between the two diagnostic assays in routine clinical practice in a high TB setting

Study Groups

Confirmed TB (n= 185)

Probable TB (n= 298)

Non-TB (n= 263)

Inclusion Criteria

Clinically suspected pulmonary TB based on the clinical symptoms, signs, or radiographic evidence with final diagnosis and negative HIV test results 

Exclusion Criteria

Lack of data and no final diagnosis after a follow-up of at least 3 months; history of previous TB or TB contact and previous anti-TB therapy before enrollment 

Methods

Subjects from four hospitals in China with a definite diagnosis based on medical history, physical exam, blood test, microbial cultures, radiographic exam, and lung biopsy after a three-month follow-up were further categorized by confirmed TB, probable TB, and Non-TB to receive T-SPOT.TB and QFT-GIT analyses. 

Confirmed TB was defined as microbiologically confirmed pulmonary TB with three positives results in sputum smears or culture analyses; probable TB was defined as having clinical symptoms and radiological findings without microbiological evidence of M. tuberculosis infection; Non-TB was defined as the presence of other differential diagnoses and non-responsiveness to anti-TB therapy during the follow-up period. 

Duration

Study enrollment: between June 2012 and November 2013

Follow-up: 3 months 

Outcome Measures

Study outcomes: sensitivity and specificity of the T-SPOT.TB and QFT-GIT assays in determining patients with active TB; concordance between the T-SPOT.TB and QFT-GIT assays; risk factors associated with indeterminate interferon-γ release assays (IGRA) results

Baseline Characteristics

  

Confirmed TB (n= 185)

Probable TB (n= 298)

 Non-TB (n= 263)

Mean age, years (range)

 45 (19 to 79) 47 (23 to 81)

51 (26 to 84) 

Male 

 126 179 161

Mean duration of symptoms, days (range)

 60 (30 to 150) 

60 (30 to 180)

 65 (30 to 100)

BCG vaccinated 

127 (68.6%)

 211 (70.8%)

195 (74.1%)

Underlying disease 

Diabetes mellitus 

COPD

Connective tissue disease 

Solid tumor 

Virus hepatitis or cirrhosis 

Intestinal obstruction 

 

41

23

3

4

6

2

 

29

24

2

3

7

5

 

27

20

5

0

4

0

In the non-TB group (n= 263), 168 had lung carcinomas, 53 had bacterial pneumonia or a lung abscess, 13 had bronchiectasis, and 29 had other lung diseases. 

Results

Sensitivity, specificity, and concordance

Confirmed TB (n= 185)

Probable TB (n= 298)

Non-TB (n= 263)

 

T-SPOT.TB

(n= 185)

QFT-GIT

(n= 181)

T-SPOT.TB

(n= 296)

QFT-GIT

(n= 280)

T-SPOT.TB 

(n= 262)

QFT-GIT

(n= 253)

Sensitivity (95% CI)

88.6 %

(83.3 to 92.5)

88.4%

(82.9 to 92.3)

83.1%

(78.4 to 87)

82.5%

(77.6 to 86.5)

 -- --

Specificity (95% CI)

 -- -- -- --

63.4%

(57.4 to 69)

60.5%

(54.3 to 66.3)

Agreement between the two tests (95% CI), Kappa

n= 181

93.4% (86.6 to 100), 0.66

n= 280

90% (83.2 to 98.8), 0.65

n= 253

93.7% (86.9 to 100), 0.87

Risk factors of indeterminate results 

Indeterminate 

(n= 32)

Determinate

(n= 714)

p-value, odds ratio (95% CI)

Age ≥ median aged 47 years

21 (65.2%)

303 (42.4%)

 0.01, 2.841 (1.339 to 6.024)

Underlying disease

 18 (56.3%)

208 (29.1%)

 0.002, 3.401 (1.645 to 6.993)

The overall sensitivity (95% CI) was 85.2% (82 to 88.3) for T-SPOT.TB and 84.8% (81.2 to 87.8) for QFT-G IT; The overall specifity (95% CI) was 63.4% (57.4 to 69) for T-SPOT.TB and 60.5% (54.3 to 66.3) for QFT-G IT (no statistically significant, all p-value > 0.05). 

The T-spot assay resulted in significantly fewer indeterminate test results (0.4%) compared to the Quantiferon (4.3%; p<0.001).

Other tested risk factors, such as microbiological findings, laboratory findings, other disease states, sex, and duration of symptoms (days), were not significantly associated with indeterminate results. 

*CI = confidence interval

Adverse Events

 Not applicable in this study 

Study Author Conclusions

In conclusion, while there were some differences in the performance of the T-SPOT.TB and QFT-GIT assays, the two commercialized IGRAs, have similar sensitivities to diagnose active TB. When combined, the two assays may be of complementary diagnostic value for probable TB. However, the high false-positive rates of these tests limit their usefulness in routine clinical practice in China, where the prevalence of latent tuberculosis infection is high. Therefore, these assays should not be used alone to rule out or rule in active TB cases, and further modification is needed to improve their accuracy. 

InpharmD Researcher Critique

Given the multicenter study design, the variations in diagnostic/confirmatory criteria might lead to inconsistent definite diagnoses, potentially affecting the overall sensitivity and specificity of the two tests. Additionally, since the study was conducted in China, the results might not be readily generalized to US populations with different TB prevalence. 



References:

Du F, Xie L, Zhang Y, et al. Prospective Comparison of QFT-GIT and T-SPOT.TB Assays for Diagnosis of Active Tuberculosis. Sci Rep. 2018;8(1):5882. Published 2018 Apr 12. doi:10.1038/s41598-018-24285-3