Using ELISPOT to Expose False Positive Skin Test Conversion in Tuberculosis Contacts
Using ELISPOT to Expose False Positive Skin Test Conversion in Tuberculosis Contacts
复制标题
DOI：
10.1371/journal.pone.0000183
复制
发表时间：
2007-01-31
期刊：
影响因子：
3.7
通讯作者：
McAdam, Keith P.
中科院分区：
文献类型：
--
作者：
Hill, Philip C.;Jeffries, David J.;McAdam, Keith P.
背景重复结核菌素皮肤试验可能是假阳性，因为过去暴露于分枝杆菌的免疫力下降。我们评估了ELISPOT试验是否可以通过增强对非结核分枝杆菌暴露的免疫力来识别结核病（TB）接触者。方法/主要调查结果。我们对1665名结核病接触者进行了结核菌素和ELISPOT试验：799名结核菌素试验阴性，并在3个月后进行了重复试验。结核菌素试验转换的患者进行ELISPOT、胸部X线检查和痰液分析（如适用）。我们比较了转化者与非转化者，评估了两个时间点内ELISPOT结果的四种组合中每一种的概率，并估计了调整ELISPOT灵敏度和特异性的加强。704例（72%）接触者进行了重复结核菌素试验; 176例（25%）有试验转换，这随着接触病例（p = 0.002）、年龄增加（p = 0.0006）和BCG疤痕（p = 0.06）而增加。114例结核菌素试验转换者有ELISPOT结果：16例（14%）招募阳性/随访阳性，9例（8%）阳性/阴性，34例（30%）阴性/阳性，55例（48%）阴性/阴性。在皮肤试验转换者中，ELISPOT结果的年龄有显著的非线性效应（p = 0.038）。随着年龄的增长，皮肤测试转换者的估计增加范围为32%-41%。三名转换者被诊断为结核病，两名有ELISPOT结果：两者都是阳性的，包括一名在招募时。结论/意义。我们估计，冈比亚结核病病例接触者中结核菌素皮试转换的大约三分之一是由于对非结核分枝杆菌暴露的免疫力增强。需要进一步的纵向研究，以确认ELISPOT是否可以可靠地识别结核菌素试验转换，将受益于预防性治疗的病例接触。
Background. Repeat tuberculin skin tests may be false positive due to boosting of waned immunity to past mycobacterial exposure. We evaluated whether an ELISPOT test could identify tuberculosis (TB) contacts with boosting of immunity to non-tuberculous mycobacterial exposure. Methodology/Principal Findings. We conducted tuberculin and ELISPOT tests in 1665 TB contacts: 799 were tuberculin test negative and were offered a repeat test after three months. Those with tuberculin test conversion had an ELISPOT, chest X-ray and sputum analysis if appropriate. We compared converters with non-converters, assessed the probability of each of four combinations of ELISPOT results over the two time points and estimated boosting with adjustment for ELISPOT sensitivity and specificity. 704 (72%) contacts had a repeat tuberculin test; 176 (25%) had test conversion, which increased with exposure to a case (p = 0.002), increasing age (p = 0.0006) and BCG scar (p = 0.06). 114 tuberculin test converters had ELISPOT results: 16(14%) were recruitment positive/follow-up positive, 9 (8%) positive/negative, 34 (30%) negative/positive, and 55 (48%) were negative/negative. There was a significant non-linear effect of age for ELISPOT results in skin test converters (p = 0.038). Estimates of boosting ranged from 32%-41% of skin test converters with increasing age. Three converters were diagnosed with TB, two had ELISPOT results: both were positive, including one at recruitment. Conclusions/Significance. We estimate that approximately one third of tuberculin skin test conversion in Gambian TB case contacts is due to boosting of immunity to non-tuberculous mycobacterial exposure. Further longitudinal studies are required to confirm whether ELISPOT can reliably identify case contacts with tuberculin test conversion that would benefit most from prophylactic treatment.