Longitudinal assessment of an ELISPOT test for Mycobacterium tuberculosis infection.
Longitudinal assessment of an ELISPOT test for Mycobacterium tuberculosis infection.
复制标题
对结核分枝杆菌感染的ELISPOT测试的纵向评估。
DOI：
10.1371/journal.pmed.0040192
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发表时间：
2007-06
期刊：
影响因子：
15.8
通讯作者：
McAdam, Keith P.
中科院分区：
文献类型：
--
作者：
Hill, Philip C.;Brookes, Roger H.;Fox, Annette;Jackson-Sillah, Dolly;Jeffries, David J.;Lugos, Moses D.;Donkor, Simon A.;Adetifa, Ifedayo M.;de Jong, Bouke C.;Aiken, Alex M.;Adegbola, Richard A.;McAdam, Keith P.
关于基于 T 细胞的结核分枝杆菌感染检测性能的纵向信息非常少。为了解决这一缺陷，我们对酶联免疫吸附斑点试验（ELISPOT）与标准结核菌素皮肤试验（TST）进行了纵向评估。在结核病 (TB) 接触者中，我们在招募后 3 个月（n = 341）和 18 个月（n = 210）重复进行 ELISPOT 测试，并在 18 个月（n = 130）时进行 TST。我们评估了与转化和回复相关的因素，并调查了疑似结核病例。在 207 名 ELISPOT 阴性接触者中，51 名 (24.6%) 发生 3 个月 ELISPOT 转换，这与阳性招募 TST 相关（比值比 [OR] 2.2，95% 置信区间 [CI] 1.0–5.0，p = 0.048），与卡介苗 (BCG) 疫苗接种呈负相关（OR 0.5，95% CI） 0.2–1.0，p = 0.06）。在 134 名接触者中，54 名 (40.2%) 接受了 3 个月 ELISPOT 复归，这在 TST 复张阳性的患者中不太可能发生（OR 0.3，95% CI 0.1–0.8，p = 0.014）。 3 至 18 个月期间，35/132 (26.5%) 接触者接受了 ELISPOT 转换，28/78 (35.9%) 接受了 ELISPOT 回复。在具有完整结果的 210 名接触者中，73 名 (34.8%) 在所有三个时间点的 ELISPOT 均为阴性； 36 例 (17.1%) 在所有三个时间点均呈阳性。从招募到 18 个月，20 名联系人 (27%) 进行了 ELISPOT 转换； 37 人 (50%) 发生 TST 转换，这与 ELISPOT 阳性招募相关（OR 7.2，95% CI 1.4–37.1，p = 0.019）； 18 例（32.7%）接受了 ELISPOT 复查； 5 名（8.9%）接受了 TST 恢复。 13 名被诊断患有结核病的接触者的结果好坏参半，但表明 TST 敏感性较高。 ELISPOT 转换和回复均发生在结核分枝杆菌暴露后。快速 ELISPOT 逆转可能反映结核分枝杆菌清除或转变为休眠状态，并可能导致报道的 ELISPOT 转化率相对较低。因此，应谨慎解释结核分枝杆菌感染的 ELISPOT 检测阴性结果。 Philip Hill 及其同事报告称，ELISPOT 转换和回归都发生在 M 之后。结核病流行国家中的结核病暴露，并且 ELISPOT 结果与结核菌素皮试结果不一致。结核病是一种传染性细菌感染，通常发生在肺部。患有活动性结核病的人每当咳嗽或打喷嚏时就会通过空气飞沫传播致病细菌（结核分枝杆菌）。大多数以这种方式接触结核分枝杆菌的人都不会生病——他们的免疫系统成功地遏制了感染。然而，细菌在体内保持休眠状态，如果宿主免疫力因感染人类免疫缺陷病毒（HIV）等原因而下降，则可能在数年后引发疾病。因此，为了控制结核病的传播，与活动性结核病患者接触过的个人需要接受结核分枝杆菌感染检测，如果呈阳性则需要接受抗结核药物治疗。感染的标准测试是结核菌素皮肤测试（TST）。在此过程中，细菌抗原（免疫系统识别为外来的蛋白质）被注射到皮下。受感染个体的免疫系统攻击抗原并在注射部位产生硬肿胀。不幸的是，该测试不能检测所有结核分枝杆菌感染，并且最近开发了一种替代的基于实验室的测试。在结核分枝杆菌感染期间，称为 T 淋巴细胞的免疫系统细胞会产生干扰素 γ。这种蛋白质激活巨噬细胞，即杀死细菌的免疫系统细胞。 ELISPOT（酶联免疫吸附点）测试可测量 T 淋巴细胞产生的干扰素 γ。商业 ELISPOT 检测可用于诊断结核分枝杆菌感染，但人们对它们在个体重复检测中的表现以及 TST 或 ELISPOT 检测是否能更好地预测结核病的后期发展知之甚少。在这项研究中，研究人员通过对接触活动性结核病的冈比亚人进行 ELISPOT 测试的纵向评估来调查这些问题。研究人员招募了曾接触过活动性结核病的人，在招募时进行了 ELISPOT 测试和 TST，然后在三个月后重复进行 ELISPOT 测试，并在 18 个月后对一些参与者进行了这两项测试。他们分析了 ELISPOT 转换（从阴性结果变为阳性结果，表明出现主动免疫反应）和回复（从阳性结果变为阴性结果，反映细菌被清除或进入休眠状态）的频率，TST 结果是否反映了这些变化，以及参与者的哪些特征与转化或回复相关。四分之一最初 ELISPOT 结果为阴性的参与者在三个月后获得阳性结果，这一转变与招募时 TST 呈阳性相关。相比之下，三个月时的 ELISPOT 回归与最初的负 TST 相关，并且发生在近一半的参与者中。然而，大约三分之一的参与者在所有三个时间点的 ELISPOT 结果均为阴性，而五分之一的参与者在所有时间点的结果均为阳性。总体而言，在招募时和 18 个月时，这两项测试的同意率分别为 73% 和 60%。最后，在 13 名患有活动性结核病的接触者中，一些人最初在两项测试中均呈阳性，但其他人随后在一项、两项或两项测试中均呈阳性。这些发现表明，ELISPOT 转换和回复均发生在结核分枝杆菌感染初步筛查后。此外，他们认为，免疫系统对 TST 和 ELISPOT 检测检测到的结核分枝杆菌的反应发生在不同的时间尺度上，因此这两种检测在接触细菌后的不同时间检测结核分枝杆菌感染的能力可能有所不同。由于很少有接触者患上活动性结核病，因此研究结果并未表明哪种测试最能预测结核分枝杆菌感染后疾病的发展。需要进一步的研究来提供这些信息并揭示暴露于结核分枝杆菌后 ELISPOT 转换和回复的复杂性。然而，重要的是，本研究中出现的 ELISPOT 回复频率很高，表明 ELISPOT 结果阴性可能并不反映接触结核分枝杆菌后没有感染，因此必须谨慎解释。请通过此摘要的在线版本访问这些网站：http://dx.doi.org/10.1371/journal.pmed.0040192。美国疾病控制和预防中心提供消除结核病部门关于结核病、其检测和诊断及其治疗的情况说明书 MedlinePlus 百科全书包含有关结核病和结核菌素皮试的信息（英语和西班牙语） 美国肺脏协会提供有关结核病和结核菌素皮试的情况说明书
Very little longitudinal information is available regarding the performance of T cell-based tests for Mycobacterium tuberculosis infection. To address this deficiency, we conducted a longitudinal assessment of the enzyme-linked immunosorbent spot test (ELISPOT) test in comparison to the standard tuberculin skin test (TST). In tuberculosis (TB) contacts we repeated ELISPOT tests 3 mo (n = 341) and 18 mo (n = 210) after recruitment and TSTs at 18 mo (n = 130). We evaluated factors for association with conversion and reversion and investigated suspected cases of TB. Of 207 ELISPOT-negative contacts, 51 (24.6%) had 3-mo ELISPOT conversion, which was associated with a positive recruitment TST (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.0–5.0, p = 0.048) and negatively associated with bacillus Calmette-Guérin (BCG) vaccination (OR 0.5, 95% CI 0.2–1.0, p = 0.06). Of 134 contacts, 54 (40.2%) underwent 3-mo ELISPOT reversion, which was less likely in those with a positive recruitment TST (OR 0.3, 95% CI 0.1–0.8, p = 0.014). Between 3 and 18 mo, 35/132 (26.5%) contacts underwent ELISPOT conversion and 28/78 (35.9%) underwent ELISPOT reversion. Of the 210 contacts with complete results, 73 (34.8%) were ELISPOT negative at all three time points; 36 (17.1%) were positive at all three time points. Between recruitment and 18 mo, 20 (27%) contacts had ELISPOT conversion; 37 (50%) had TST conversion, which was associated with a positive recruitment ELISPOT (OR 7.2, 95% CI 1.4–37.1, p = 0.019); 18 (32.7%) underwent ELISPOT reversion; and five (8.9%) underwent TST reversion. Results in 13 contacts diagnosed as having TB were mixed, but suggested higher TST sensitivity. Both ELISPOT conversion and reversion occur after M. tuberculosis exposure. Rapid ELISPOT reversion may reflect M. tuberculosis clearance or transition into dormancy and may contribute to the relatively low reported ELISPOT conversion rate. Therefore, a negative ELISPOT test for M. tuberculosis infection should be interpreted with caution. Philip Hill and colleagues report that both ELISPOT conversion and reversion occur afterM. tuberculosis exposure in an endemic country and that the ELISPOT results agree poorly with results from the tuberculin skin test. Tuberculosis is a contagious bacterial infection, usually of the lungs. People with active tuberculosis spread the causative bacterium (Mycobacterium tuberculosis) in airborne droplets whenever they cough or sneeze. Most people exposed to M. tuberculosis in this way never become ill—their immune system successfully contains the infection. However, the bacteria remain dormant in the body and can cause disease years later if host immunity declines because of, for example, infection with the human immunodeficiency virus (HIV). Consequently, to control the spread of tuberculosis, individuals who have been in contact with people with active tuberculosis need to be tested for infection with M. tuberculosis and treated with antituberculosis drugs if positive. The standard test for infection is the tuberculin skin test (TST). In this, bacterial antigens (proteins that the immune system recognize as foreign) are injected under the skin. The immune system of infected individuals attacks the antigen and produces a hard swelling at the injection site. Unfortunately, this test does not detect all M. tuberculosis infections and an alternative, laboratory-based test has recently been developed. During M. tuberculosis infections, immune system cells called T lymphocytes produce interferon gamma. This protein activates macrophages, immune system cells that kill bacteria. The ELISPOT (enzyme-linked immunosorbent spot) test measures interferon gamma production by T lymphocytes. Commercial ELISPOT tests are available for the diagnosis of M. tuberculosis infection, but little is known about how they perform when used in repeat tests in individuals or whether the TST or ELISPOT test is better at predicting later development of tuberculosis. In this study, the researchers investigated these questions in a longitudinal assessment of the ELISPOT test in Gambians exposed to active tuberculosis. The researchers recruited people who had been in contact with active tuberculosis, did ELISPOT tests and TSTs at recruitment, then repeated the ELISPOT test after three months and both tests in some participants after 18 months. They analyzed how often ELISPOT conversion (a change from a negative to a positive result indicating the development of an active immune response) and reversion (a change from a positive to a negative result reflecting clearance of the bacteria or its entry into a dormant state) occurred, whether the TST results mirrored these changes, and which characteristics of the participants were associated with conversion or reversion. A quarter of participants who initially had a negative ELISPOT result had a positive result at three months, a conversion that was associated with a positive TST at recruitment. ELISPOT reversion at three months, by contrast, was associated with an initially negative TST and occurred in nearly half the participants. However, about a third of the participants had negative ELISPOT results at all three time points and a fifth had positive results at all times. Overall, the two tests agreed in 73% and 60% of the participants at recruitment and at 18 months, respectively. Finally, among the 13 contacts who developed active tuberculosis, some were initially positive in both tests but others showed subsequent conversion in one, both or neither test. These findings indicate that both ELISPOT conversion and reversion occur after initial screening for M. tuberculosis infection. In addition, they suggest that the immune system responses to M. tuberculosis detected by TST and the ELISPOT test occur over different time scales and so the two tests might differ in their ability to detect M. tuberculosis infections at different times after exposure to the bacteria. Because very few contacts developed active tuberculosis, the findings do not indicate which test best predicts disease development after M. tuberculosis infection. Further studies are needed to provide this information and to unravel the complexities of ELISPOT conversion and reversion after exposure to M. tuberculosis. Importantly, however, the high frequency of ELISPOT reversion seen in this study suggests that a negative ELISPOT result may not reflect a lack of infection after exposure to M. tuberculosis and must, therefore, be interpreted with caution. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040192. The US Centers for Disease Control and Prevention provide fact sheets from the Division of Tuberculosis Elimination about tuberculosis, its testing and diagnosis, and its treatment MedlinePlus Encyclopedia contains information on tuberculosis and the tuberculin skin test (in English and Spanish) The American Lung Association offers fact sheets on tuberculosis and on the tuberculin skin test
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影响因子：
3.7
作者：
Aiken AM;Hill PC;Fox A;McAdam KP;Jackson-Sillah D;Lugos MD;Donkor SA;Adegbola RA;Brookes RH
通讯作者：
Brookes RH
影响因子：
9.4
作者：
Kamerbeek, J;Schouls, L;vanEmbden, J
通讯作者：
vanEmbden, J
DOI：
10.1164/ajrccm.159.1.9801120
发表时间：
1999-01-01
影响因子：
24.7
作者：
Menzies, D
通讯作者：
Menzies, D
影响因子：
6.4
作者：
Wilkinson, KA;Kon, OM;Wilkinson, RJ
通讯作者：
Wilkinson, RJ
影响因子：
168.9
作者：
Ewer, K;Deeks, J;Lalvani, A
通讯作者：
Lalvani, A