Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study.
Serial QuantiFERON testing and tuberculosis disease risk among young children: an observational cohort study.
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DOI：
10.1016/s2213-2600(17)30060-7
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
Hatherill M
中科院分区：
文献类型：
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作者：
Andrews JR;Nemes E;Tameris M;Landry BS;Mahomed H;McClain JB;Fletcher HA;Hanekom WA;Wood R;McShane H;Scriba TJ;Hatherill M
定量干扰素γ释放测定结果在预测结核分枝杆菌感染向活动性疾病进展方面的价值尚不清楚。我们分析了在南非报道的MVA85A疫苗有效性试验的数据。入选年龄在18-24周的未感染HIV的QuantiFERON-TB试管金（QFT）阴性婴儿。在中期研究访问（第336天）时，我们通过定量QFT结果（IFN-γ <0.35, 0.35 - 4.00, bbb4.00 IU/ml）对参与者进行分层，并确定在随后的6-24个月内进展为活动性结核病的风险。安慰剂组与MVA85A组间QFT无差异；因此，两组均纳入分析。研究临床医生并非对QFT值一无所知，但使用了严格的病例定义并排除了QFT结果。在第336天进行QFT测试的2,512名婴儿中，172名（6.8%）呈阳性。与QFT非转换者（疾病发病率为0.7 / 100人-年；95% CI: 0.4 - 1）相比，IFN-γ值在0.35 - 4.00 IU/ml之间的QFT转换儿童的疾病风险没有显著增加（2.5 / 100人-年；95% CI: 0.4 - 9.4； IRR为3.7;p= 0.23）。然而，与非转换者（IRR 42.5, p< 0.0001）相比，IFN-γ值为bb0.4.00 IU/ml时的QFT转换与疾病发病率显著增加相关（28.0 / 100人-年；95% CI: 14.9 - 45.7）；与IFN-γ值在0.35 - 4.00 IU/ml之间的儿童相比（IRR: 11.4; p= 0.00047）。在91个重复测试的QFT转换器中，53个（58.2%）从阳性转为阴性。QFT逆转风险与QFT转换时的IFN-γ值呈负相关，IFN-γ值< 4.00 IU/ml时风险最高（47/61;77.0%）。在幼儿中，结核病风险没有显著升高，QFT逆转是常见的，在IFN-γ值高达推荐测试阈值的10倍时QFT转换。相比之下，在非常高的IFN-γ值（bbbb4·00 IU/ml）时，QFT转换需要加强对极高结核病风险的诊断和预防干预。
The value of quantitative interferon-γ release assay results for predicting progression from Mycobacterium tuberculosis infection to active disease is unknown. We analysed data from a reported vaccine efficacy trial of MVA85A in South Africa. QuantiFERON-TB Gold In-Tube (QFT) negative, HIV uninfected infants aged 18–24 weeks were enrolled. We stratified participants by quantitative QFT result (IFN-γ <0.35, 0·35–4·00, >4·00 IU/ml) at the intermediate study visit (Day 336) and determined risk of progression to active tuberculosis disease over the subsequent 6–24 months. No QFT differences were observed between placebo and MVA85A groups; therefore, both groups were included in analyses. Study clinicians were not blinded to QFT values, but strict case definitions were used and excluded QFT results. Among 2,512 infants with QFT tests performed at Day 336, 172 (6·8%) were positive. Compared with QFT non-converters (disease incidence 0·7 per 100 person-years; 95% CI: 0·4–1·1), children with QFT conversion at IFN-γ values between 0·35–4·00 IU/ml did not have significantly increased risk of disease (2·5 per 100 person-years; 95% CI: 0·4–9·4; IRR 3·7; p=0·23). However, QFT conversion at IFN-γ values >4·00 IU/ml was associated with markedly increased disease incidence (28·0 per 100 person-years; 95% CI: 14·9–45·7) compared to nonconverters (IRR 42·5; p<0·0001); and compared to children with IFN-γ values between 0·35–4·00 IU/ml (IRR: 11·4; p=0·00047). Among 91 QFT converters with a repeat test, 53 (58·2%) reverted from positive to negative. QFT reversion risk was inversely associated with IFN-γ value at QFT conversion and was highest (47/61; 77·0%) with IFN-γ values <4·00 IU/ml. In young children, tuberculosis disease risk was not significantly elevated, and QFT reversion was common, following QFT conversion at IFN-γ values up to 10 times the recommended test threshold. By contrast, QFT conversion at very high IFN-γ values (>4·00 IU/ml) warrants intensified diagnostic and preventive intervention for extremely high risk of tuberculosis disease.