IFN-γ release assay versus tuberculin skin test for monitoring TB infection in healthcare workers

Figures & data

Table 1. Head-to-head comparison of the IFN-γ release assay and the tuberculin skin test in healthcare workers from different countries.

Study (year)	Country	Sample size	IGRA+; TST+	IGRA-; TST+	IGRA+; TST-	IGRA-; TST-	Ref.
		n	n (%)	n (%)	n (%)	n (%)
Hotta et al. (2007)	Japan	202	3 (1.5)	117 (57.9)	0	82 (40.6)	[67]
Mirtskhulava et al. (2008)	Georgia	265	133 (50.2)	44 (16.6)	26 (9.8)	62 (23.4)	[53]
Nienhaus et al. (2008)	Germany	261	15 (5.7)	48 (18.4)	10 (3.8)	188 (72.4)	[27]
Alvarez-León et al. (2009)	Spain	123	5 (4.1)	4 (3.3)	3 (2.4)	111 (90.2)	[55]
Casas et al. (2009)	Spain	145	42 (30.0)	59 (40.1)	1 (0.7)	43 (29.7)	[23]
Girardi et al. (2009)	Italy	115	25 (21.7)	36 (31.3)	4 (3.5)	50 (43.5)	[62]
Khanna et al. (2009)	UK	148	9 (6.1)	15 (10.1)	3 (2.0)	121 (81.8)	[25]
Torres Costa et al. (2009)	Portugal	1218	371 (30.5)	532 (43.7)	26 (2.1)	289 (23.7)	[13]
Tripodi et al. (2009)	France	148	23 (15.5)	74 (50.0)	5 (3.3)	46 (31.1)	[22]
Vinton et al. (2009)	Australia	341	16 (4.7)	98 (28.9)	5 (1.5)	222 (65.5)	[59]
Khoury et al. (2011)	USA	611	8 (1.3)	42 (6.9)	4 (0.7)	557 (91.1)	[50]
Total		3733	668 (17.9)	1103 (29.5)	101 (2.7)	1597 (42.8)

+: Positive; -: Negative; IGRA: IFN-γ release assay; TST: Tuberculin skin test.

Table 2. Characteristics and results of studies on serial testing using IFN-γ release assay.

Study (year)	Country	IGRA	Months between IGRA	n^†	Initially positive IGRA, n (%)	IGRA reversions, n (%)	IGRA conversions n/N^‡ (%)	Ref.
Studies in countries with a high incidence of TB (≥100 per 100,000 population and year)
Pai et al. (2006)	India	QFT	18	216	38 (17.6)	9 (23.7)	18/178 (10.1)	[79]
Studies in countries with an intermediate incidence of TB (≥ 20 and <100 per 100,000 population and year)
Chee et al. (2009)	Singapore	T-SPOT	12	182	–	–	9/182 (4.9)	[80]
Lee et al. (2009)	South Korea	QFT	12	169	23 (13.6)	–	21/146 (14.4)	[81]
Yoshiyama et al. (2009)	Japan	QFT	24–48	311	30 (8.7)	13 (43.3)	6/286 (2.1)	[82]
Torres Costa et al. (2011)	Portugal	QFT	12	670	208 (31.0)	46 (22.1)	51/462 (11.0)	[14]
Rafiza et al. (2012)	Malaysia	QFT	12	769	64 (8.3)	19 (29.7)	69/704 (9.8)	[83]
Studies in countries with a low incidence of TB (<20 per 100,000 population and year)
Pollock et al. (2008)	USA	QFT	1–7	43	–	–	2/43 (4.7)	[91]
Zwerling et al. (2009)	Canada	QFT	12	60	4 (6.7)	2 (50.0)	4/56 (7.1)	[84]
Belknap et al. (2010)	USA	QFT	6	1281	50 (3.9)	20 (40.0)	44/1169 (3.8)	[92]
		T-SPOT			68 (5.3)	36 (52.9)	44/1117 (3.9)
Gandra et al. (2010)	USA	QFT	1	164	–	95 (57.9)	–	[74]
Ringshausen et al. (2010)	Germany	QFT	5	182	18 (9.9)	6 (33.3)	3/162 (1.9)	[87]
Schablon et al. (2010)	Germany	QFT	12	287	42 (14.6)	13 (31.0)	15/245 (6.1)	[88]
Schablon et al. (2011)	Germany	QFT	12	154	2 (1.5)	1 (50.0)	1/152 (0.7)	[89]
Fong et al. (2012)	USA	QFT	12	1857	–	–	52/1857 (2.8)	[90]
Joshi et al. (2012)	USA	QFT	1	45	–	18 (40.0)	–	[86]

^†Number of subjects with IGRA test repeats in the course of the study.

^‡Number of subjects with initially negative IGRA.

IGRA: IFN-γ release assay; QFT: QuantiFERON-TB Gold or Gold In-Tube; TB: Tuberculosis; T-SPOT: T-SPOT.TB.

Table 3. Rates of divergent IFN-γ release assay results depending on the IFN-γ concentration in the first IFN-γ release assay (n = 1787).

First IGRA	Second IGRA-positive		Total
	n	Row (%)	n	Col (%)
<0.1 IU/ml	76	6.9	1095	80.8
0.1 to <0.2 IU/ml	30	20.5	146	10.8
0.2 to <0.35 IU/ml	43	37.7	114	8.4
Negative	149	11.0	1355	100/75.8^†
First IGRA	Second IGRA-negative		Total
	n	Row (%)	n	Col (%)
0.35 to <0.7 IU/ml	63	52.5	120	27.8
0.7 to <1.0 IU/ml	9	20.5	44	10.2
1.0 to <2.0 IU/ml	18	29.5	61	14.1
2.0 to <3.0 IU/ml	9	20.0	45	10.4
3.0 to <4.0 IU/ml	8	27.6	29	6.7
4.0 to <5.0 IU/ml	3	14.3	21	4.9
≥5.0 IU/ml	9	8.0	112	25.9
Positive	119	27.5	432	100/24.2^†

^†Of the total sample (n = 1787).

Hotta K, Ogura T, Nishii K et al. Whole blood interferon-gamma assay for baseline tuberculosis screening among Japanese healthcare students. PLoS ONE 2(8), e803 (2007).

 Google Scholar

Mirtskhulava V, Kempker R, Shields KL et al. Prevalence and risk factors for latent tuberculosis infection among health care workers in Georgia. Int. J. Tuberc. Lung Dis. 12(5), 513–519 (2008).

 PubMed Web of Science ®Google Scholar

Nienhaus A, Schablon A, Bâcle CL, Siano B, Diel R. Evaluation of the interferon-γ release assay in healthcare workers. Int. Arch. Occup. Environ. Health 81(3), 295–300 (2008).

 PubMedGoogle Scholar

Alvarez-León EE, Espinosa-Vega E, Santana-Rodríguez E et al. Screening for tuberculosis infection in spanish healthcare workers: comparison of the QuantiFERON-TB gold in-tube test with the tuberculin skin test. Infect. Control Hosp. Epidemiol. 30(9), 876–883 (2009).

 PubMedGoogle Scholar

Casas I, Latorre I, Esteve M et al. Evaluation of interferon-γ release assays in the diagnosis of recent tuberculosis infection in health care workers. PLoS ONE 4(8), e6686 (2009).

 Web of Science ®Google Scholar

Girardi E, Angeletti C, Puro V et al. Estimating diagnostic accuracy of tests for latent tuberculosis infection without a gold standard among healthcare workers. Euro Surveill. 14(43), (2009).

 PubMedGoogle Scholar

Khanna P, Nikolayevskyy V, Warburton F, Dobson E, Drobniewski F. Rate of latent tuberculosis infection detected by occupational health screening of nurses new to a London teaching hospital. Infect. Control Hosp. Epidemiol. 30(6), 581–584 (2009).

 PubMedGoogle Scholar

Torres Costa J, Sá R, Cardoso MJ et al. Tuberculosis screening in Portuguese healthcare workers using the tuberculin skin test and the interferon-γ release assay. Eur. Respir. J. 34(6), 1423–1428 (2009).

 PubMedGoogle Scholar

Tripodi D, Brunet-Courtois B, Nael V et al. Evaluation of the tuberculin skin test and the interferon-γ release assay for TB screening in French healthcare workers. J. Occup. Med. Toxicol. 4, 30 (2009).

 PubMedGoogle Scholar

Vinton P, Mihrshahi S, Johnson P, Jenkin GA, Jolley D, Biggs BA. Comparison of QuantiFERON-TB Gold In-Tube Test and tuberculin skin test for identification of latent Mycobacterium tuberculosis infection in healthcare staff and association between positive test results and known risk factors for infection. Infect. Control Hosp. Epidemiol. 30(3), 215–221 (2009).

 PubMed Web of Science ®Google Scholar

Khoury NZ, Binnicker MJ, Wengenack NL, Aksamit TR, Buchta WG, Molella RG. Preemployment screening for tuberculosis in a large health care setting: comparison of the tuberculin skin test and a whole-blood interferon-γ release assay. J. Occup. Environ. Med. 53(3), 290–293 (2011).

 PubMed Web of Science ®Google Scholar

Pai M, Joshi R, Dogra S et al. Serial testing of health care workers for tuberculosis using interferon-γ assay. Am. J. Respir. Crit. Care Med. 174(3), 349–355 (2006).

 PubMed Web of Science ®Google Scholar

Chee CB, Lim LK, Barkham TM et al. Use of a T cell interferon-γ release assay to evaluate tuberculosis risk in newly qualified physicians in Singapore healthcare institutions. Infect. Control Hosp. Epidemiol. 30(9), 870–875 (2009).

 PubMedGoogle Scholar

Lee K, Han MK, Choi HR et al. Annual incidence of latent tuberculosis infection among newly employed nurses at a tertiary care university hospital. Infect. Control Hosp. Epidemiol. 30(12), 1218–1222 (2009).

 PubMed Web of Science ®Google Scholar

Yoshiyama T, Harada N, Higuchi K, Nakajima Y, Ogata H. Estimation of incidence of tuberculosis infection in health-care workers using repeated interferon-γ assays. Epidemiol. Infect. 137(12), 1691–1698 (2009).

 PubMedGoogle Scholar

Torres Costa J, Silva R, Sá R, Cardoso MJ, Nienhaus A. Serial testing with the interferon-γ? Release assay in Portuguese healthcare workers. Int. Arch. Occup. Environ. Health 84(4), 461–469 (2011).

 PubMedGoogle Scholar

Rafiza S, Rampal KG. Serial testing of Malaysian health care workers with QuantiFERON®-TB Gold In-Tube. Int. J. Tuberc. Lung Dis. 16(2), 163–168 (2012).

 PubMedGoogle Scholar

Pollock NR, Campos-Neto A, Kashino S et al. Discordant QuantiFERON-TB Gold test results among US healthcare workers with increased risk of latent tuberculosis infection: a problem or solution? Infect. Control Hosp. Epidemiol. 29(9), 878–886 (2008).

 PubMed Web of Science ®Google Scholar

Zwerling AA, Cloutier Ladurantaye J, Pietrangelo F et al. Conversions and reversions in health care workers in Montreal, Canada using QuantiFERON-TB-gold in-tube. Am. J. Respir. Crit. Care Med. 179, Abstract A1012 (2009).

 Google Scholar

Belknap R, Wall K, Teeter L et al. Interferon-γ Release Assays (IGRAs) in serial testing for latent tuberculosis infection In US health care workers. Am. J. Respir. Crit. Care Med. 181, Abstract A2263 (2010).

 Google Scholar

Gandra S, Scott WS, Somaraju V, Wang H, Wilton S, Feigenbaum M. Questionable effectiveness of the QuantiFERON-TB Gold Test (Cellestis) as a screening tool in healthcare workers. Infect. Control Hosp. Epidemiol. 31(12), 1279–1285 (2010).

 PubMedGoogle Scholar

Ringshausen FC, Nienhaus A, Schablon A, Schlösser S, Schultze-Werninghaus G, Rohde G. Predictors of persistently positive Mycobacterium-tuberculosis-specific interferon-γ responses in the serial testing of health care workers. BMC Infect. Dis. 10, 220 (2010).

 PubMed Web of Science ®Google Scholar

Schablon A, Harling M, Diel R, Ringshausen FC, Torres Costa J, Nienhaus A. Serial testing with an interferon-γ release assay in German healthcare workers. GMS Krankenhhyg. Interdiszip. 5(2), Doc05 (2010).

 PubMedGoogle Scholar

Schablon A, Diel R, Diner G et al. Specificity of a whole blood IGRA in German nursing students. BMC Infect. Dis. 11, 245 (2011).

 PubMedGoogle Scholar

Fong KS, Tomford JW, Teixeira L et al. Challenges of interferon-γ release assay conversions in serial testing of health-care workers in a TB control program. Chest 142(1), 55–62 (2012).

 PubMed Web of Science ®Google Scholar

Joshi M, Monson TP, Woods GL. Use of interferon-γ release assays in a health care worker screening program: experience from a tertiary care centre in the United States. Can. Respir. J. 19(2), 84–88 (2012).

 PubMedGoogle Scholar