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Frontiers of Medicine

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CN 11-5983/R

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Front. Med.    2017, Vol. 11 Issue (4) : 528-535    https://doi.org/10.1007/s11684-017-0573-0
RESEARCH ARTICLE
Testing of tuberculosis infection among Chinese adolescents born after terminating the Bacillus Calmette--Guérin booster vaccination: subgroup analysis of a population-based cross-sectional study
Hengjing Li1, Henan Xin1, Shukun Qian2, Xiangwei Li1, Haoran Zhang1, Mufei Li1, Boxuan Feng1, Qi Jin1, Lei Gao1()
1. MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for Tuberculosis, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
2. Beijing Rehabilitation Hospital of Capital Medical University, Beijing 100043, China
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Abstract

The prevalence of tuberculosis infection among adolescents born after terminating the Bacillus Calmette–Guérin (BCG) booster vaccination in China was estimated using tuberculin skin testing (TST) and QuantiFERON-TB Gold assay (QFT) to investigate the influence of neonatal BCG vaccination on the performance of TST. Data analysis was conducted for 2831 eligible participants aged 5–15 years from the baseline survey of a population-based multi-center prospective study. The prevalence rates of TST (induration≥10 mm) and QFT positivity were 9.3% (264/2827) and 2.5% (71/2831), respectively. The rate of QFT indeterminate result was 2.2% (62/2831). The overall agreement between TST and QFT was low (concordance= 88.0%; κ coefficient= 0.125). Only TST was positively associated with BCG vaccination with an adjusted odds ratio of 1.71 [95% confidence interval, 1.26–2.31]. A history of close contact with patients of active TB was significantly associated with positivity for TST and QFT. Our results suggested that BCG neonatal vaccination still affects TST performance, and a two-step approach might be considered for TB infection testing among adolescents in China.
Keywords tuberculin skin test      interferon-γ release assays      adolescent      agreement     
Corresponding Author(s): Lei Gao   
Just Accepted Date: 06 September 2017   Online First Date: 03 November 2017    Issue Date: 04 December 2017
 Cite this article:   
Hengjing Li,Henan Xin,Shukun Qian, et al. Testing of tuberculosis infection among Chinese adolescents born after terminating the Bacillus Calmette--Guérin booster vaccination: subgroup analysis of a population-based cross-sectional study[J]. Front. Med., 2017, 11(4): 528-535.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-017-0573-0
https://academic.hep.com.cn/fmd/EN/Y2017/V11/I4/528
Total (N = 2831) Site A (N = 221) Site B (N = 963) Site C (N = 534) Site D (N = 1113) P for difference between the sites
n (%) n (%) n (%) n (%) n (%)
Gender 0.120
Male 1520 (53.7) 130 (58.8) 534 (55.4) 272 (50.9) 584 (52.5)
Female 1311 (46.3) 91 (41.2) 429 (44.6) 262 (49.1) 529 (47.5)
Age (year) <0.001
5?9 1459 (51.5) 90 (40.7) 620 (64.4) 232 (43.5) 517 (46.5)
10?15 1372 (48.5) 131 (59.3) 343 (35.6) 302 (56.5) 596 (53.5)
BMIa <0.001
Thinness 138 (4.9) 14 (6.3) 20 (2.1) 52 (9.7) 52 (4.7)
Normal 2263 (79.9) 113 (51.1) 774 (80.4) 411 (76.9) 965 (86.7)
Overweight 430 (15.2) 94 (42.6) 169 (17.5) 71 (13.4) 96 (8.6)
Household per capita income (RMB) <0.001
<6000 1855 (65.5) 43 (19.5) 756 (78.5) 254 (47.6) 802 (72.1)
≥6000 976 (34.5) 178 (80.5) 207 (21.5) 280 (52.4) 311 (27.9)
BCG scar <0.001
Absent 1014 (35.8) 7 (3.2) 199 (20.7) 140 (26.2) 668 (60.1)
Present 1817 (64.2) 214 (96.8) 764 (79.3) 394 (73.8) 445 (39.9)
History of close contact with active TB patientsb <0.001
No 2693 (97.8) 218 (99.5) 947 (98.8) 480 (91.4) 1048 (99.6)
Yes 61 (2.2) 1 (0.5) 11 (1.2) 45 (8.6) 4 (0.4)
TST indurationb <0.001
<5 mm 2310 (81.7) 163 (73.8) 752 (78.1) 454 (85.5) 941 (84.7)
5?9 mm 253 (9.0) 12 (5.4) 142 (14.7) 37 (6.9) 62 (5.5)
10?14 mm 153 (5.4) 28 (12.7) 50 (5.2) 14 (2.6) 61 (5.5)
15?19 mm 63 (2.2) 6 (2.7) 15 (1.6) 10 (1.8) 32 (2.9)
≥20 mm 48 (1.7) 12 (5.4) 4 (0.4) 17 (3.2) 15 (1.4)
QFT test <0.001
Negative 2698 (95.3) 216 (97.7) 939 (97.5) 503 (94.2) 1040 (93.4)
Positive 71 (2.5) 3 (1.4) 18 (1.9) 21 (3.9) 29 (2.6)
Indeterminate 62 (2.2) 2 (0.9) 6 (0.6) 10 (1.9) 44 (4.0)
Tab.1  Characteristics of the study population
TST (≥10 mm)a QFT positivity
n/N (%) P for c 2 test Adjusted OR (95% CI) n/N (%) P for c 2 test Adjusted OR (95% CI)
Sex 0.360 0.977
Male 149/1520 (9.8) 38/1520 (2.5)
Female 115/1307 (8.8) 33/1311 (2.5)
Age (year) 0.361 0.123
5?9 129/1457 (8.9) 43/1459 (3.0)
10?15 135/1370 (9.9) 28/1372 (2.0)
Household per capita income (RMB) 0.219 0.700
<6000 164/1853 (8.9) 45/1855 (2.4)
≥6000 100/974 (10.3) 26/976 (2.7)
BCG scar 0.001 0.519
Absent 70/1012 (6.9) Reference 28/1014 (2.8)
Present 194/1815 (10.7) 1.71 (1.26?2.31) 43/1817 (2.4)
History of close contact with active TB patients 0.005 <0.001
No 243/2689 (9.0) Reference 63/2693 (2.3) Reference
Yes 12/61 (19.7) 3.24 (1.71?6.14) 7/61 (11.5) 5.41 (2.37?12.36)
BMIb 0.026 0.796
Thinness 11/137 (8.0) Reference 3/138 (2.2)
Normal 198/2261(8.8) 1.23 (0.65?2.30) 59/2263 (2.6)
Overweight 55/429 (12.8) 1.56 (0.79?3.05) 9/430 (2.1)
Study site <0.001 0.064
Site A 46/221 (20.8) Reference 3/221 (1.4)
Site B 69/962 (7.2) 0.33 (0.22?0.49) 18/963 (1.9)
Site C 41/531 (7.7) 0.32 (0.20?0.51) 21/534 (3.9)
Site D 108/1113 (9.7) 0.57 (0.38?0.85) 29/1113 (2.6)
Tab.2  Univariate and multivariate analyses of TST and QFT positivity
Fig.1  Agreement between QFT and TST results according to various cut-off values of TST. BCG, Bacillus Calmette–Guerin; QFT, QuantiFERON-TB Gold In-Tube; TST, tuberculin skin test.
Total
(N = 2827)		 TST?/QFT?
(N = 2466)		 TST+ /QFT+
(N = 26)		 TST?/QFT+
(N = 44)		 TST+ /QFT?
(N = 229)		 TST+ /QFT± a
(N= 9)		 TST?/QFT± a
(N= 53)
n n (%) n (%) n (%) n (%) n (%) n (%)
Gender Male 1520 1324 (87.1) 12 (0.8) 26 (1.7) 136 (8.9) 1 (0.1) 21 (1.4)
Female 1307 1142 (87.4) 14 (1.1) 18 (1.4) 93 (7.1) 8 (0.6) 32 (2.4)
Age (year) 5?9 1457 1270 (87.2) 11 (0.8) 32 (2.2) 116 (7.9) 2 (0.1) 26 (1.8)
10?15 1370 1196 (87.3) 15 (1.0) 12 (0.9) 113 (8.3) 7 (0.5) 27 (2.0)
BCG scar Absent 1012 898 (88.8) 10 (1.0) 17 (1.7) 57 (5.6) 3 (0.3) 27 (2.6)
Present 1815 1568 (86.4) 16 (0.9) 27 (1.5) 172 (9.5) 6 (0.3) 26 (1.4)
History of close contact with active TB patientsb No 2689 2351 (87.4) 18 (0.7) 44 (1.7) 216 (8.0) 9 (0.3) 51 (1.9)
Yes 61 49 (80.3) 7 (11.5) 0 (0) 5 (8.2) 0 (0) 0 (0)
Tab.3  Concordance and discordance between QFT and TST (≥10 mm)
TST results QFT positive (N = 71)
n		 Median of the TB antigen minus Nil control (IU/mL)a P value
Total ≥5 mm 33 2.19 <0.001
<5 mm 38 0.47
≥10 mm 27 2.48 <0.001
<10 mm 44 0.48
≥15 mm 24 2.49 <0.001
<15 mm 47 0.49
≥20 mm 20 2.49 0.002
<20 mm 51 0.51
TST results QFT positive (N = 7)
n		 Median of the TB antigen minus Nil control (IU/mL)a P value
Participants with a history of close contact with active TB patients ≥5 mm 7 2.34 –
<5 mm 0 –
≥10 mm 7 2.34 –
<10 mm 0 –
≥15 mm 6 2.19 0.716
<15 mm 1 2.48 –
≥20 mm 6 2.19 0.716
<20 mm 1 2.48 –
Tab.4  Distribution of QFT positives with regard to TST results
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