Tuberculosis Research Unit, Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College London, London, UK.
Br Med Bull. 2010;93:69-84. doi: 10.1093/bmb/ldp039. Epub 2009 Nov 18.
Diagnosis and treatment of latent tuberculosis infection (LTBI) is a cornerstone of tuberculosis (TB) control in the developed world. In the last century, the tuberculin skin test (TST) was the only means of diagnosing LTBI. ELISpot and whole-blood ELISA, collectively known as interferon-gamma release assays (IGRAs), are promising new tools.
IGRAs are more specific than TST for diagnosis of LTBI as they are not confounded by previous bacille Calmette-Guerin (BCG) vaccination. Assessing IGRA sensitivity in the absence of a gold standard for LTBI is challenging. Studies have therefore used surrogate markers such as active TB and correlation with degree of TB exposure in contact investigations. These studies suggest that sensitivity of ELISpot is higher than TST while whole-blood ELISA has similar sensitivity to TST. Recent longitudinal studies demonstrating the prognostic power of these tests for development of active TB provide definitive evidence that positive IGRA results reflect infection with dormant yet viable bacilli.
Is the prognostic power of IGRAs greater than the TST? What are the false-negative rates in immunocompromised individuals with LTBI at high risk of progressing to active TB?
IGRAs have been incorporated into national guidelines, although their optimal deployment in diagnostic algorithms is evolving. The health economic benefits of utilizing IGRAs are increasingly recognized, partly because their high specificity avoids unnecessary chemoprophylaxis in BCG-vaccinated persons with false-positive TST results.
Current IGRAs are being improved and next-generation tests, with improved sensitivity, could enable the reliable exclusion of LTBI in immunocompromised individuals.
在发达国家，诊断和治疗潜伏性结核感染（LTBI）是结核病（TB）控制的基石。在上个世纪，结核菌素皮肤试验（TST）是诊断 LTBI 的唯一手段。酶联免疫斑点技术（ELISpot）和全血酶联免疫吸附试验（whole-blood ELISA），统称为干扰素-γ释放试验（IGRAs），是很有前途的新工具。
IGRAs 比 TST 更能准确地诊断 LTBI，因为它们不受卡介苗（BCG）接种的影响。在没有 LTBI 金标准的情况下，评估 IGRAs 的敏感性是具有挑战性的。因此，研究使用了替代标志物，如活动性结核病和接触者调查中与 TB 暴露程度的相关性。这些研究表明，ELISpot 的敏感性高于 TST，而全血 ELISA 的敏感性与 TST 相似。最近的纵向研究表明，这些试验对发展为活动性 TB 的预测能力提供了明确的证据，表明阳性 IGRA 结果反映了潜伏但有活力的细菌感染。
IGRAs 的预测能力是否大于 TST？在有 LTBI 且有进展为活动性 TB 高风险的免疫功能低下个体中，假阴性率是多少？
IGRAs 已被纳入国家指南，尽管其在诊断算法中的最佳应用仍在不断发展。IGRAs 的健康经济效益越来越受到认可，部分原因是其高特异性避免了在 TST 结果为假阳性的 BCG 接种者中不必要的化学预防。
目前的 IGRAs 正在得到改进，下一代测试具有更高的敏感性，能够可靠地排除免疫功能低下个体中的 LTBI。
