结核菌素皮试和全血γ干扰素测定试验的儿童结核感染诊断应用研究

目的 评价结核菌素（PPD）皮试和全血γ干扰素（IFN-γ）测定试验诊断儿童结核病的准确性。方法 选择2006年7月至2010年4月首都医科大学附属北京儿童医院住院临床诊断结核和呼吸系统疾病的患儿为研究对象。根据患儿所暴露的结核感染危险因素分为5组：A组：无结核病密切接触史的非结核病的呼吸系统疾病患儿；B组：有活动性结核病患者密切接触史的非结核病的呼吸系统疾病患儿；C组：无结核病密切接触史的临床诊断结核病患儿；D组：有活动性结核病患者密切接触史的临床诊断结核病患儿；E组：病原学或病理学确诊的活动性结核病患儿。患儿于入院当日行PPD皮试，入院后1~7 d采集外周静脉血行全血IFN-γ测定。以敏感度、特异度、阴性预测值、阳性预测值和似然比评价PPD皮试和全血IFN-γ测定对结核病的诊断价值。结果 125例患儿进入分析。A组40例，B组11例，C组29例，D组27例，E组18例。①PPD皮试取硬结≥10 mm为阳性判断标准时，诊断结核病的敏感度为77.0%，特异度为70.6%；取硬结≥15 mm为阳性判断标准时，诊断结核病的敏感度为50.0%、特异度为80.2%；全血IFN-γ测定的敏感度为85.1%、特异度为94.1%。②PPD皮试取硬结≥10 mm为阳性判断标准诊断结核病时，<3岁患儿PPD皮试的敏感度和特异度均显著低于≥3岁患儿，城区和郊区患儿的敏感度和特异度接近；全血IFN-γ测定诊断结核病的敏感度和特异度在不同年龄、居住地间差异无统计学意义。③全血IFN-γ测定阳性率与结核感染暴露因素的相关性优于PPD皮试（取硬结≥10或15 mm为阳性判断标准时）。结论 潜伏结核感染筛查时以硬结≥15 mm作为PPD皮试阳性判断标准，可提高诊断的特异度；临床疑似结核病的诊断以硬结≥10 mm作为PPD皮试阳性判断标准，可提高诊断的敏感度。全血IFN-γ测定诊断结核病的敏感度和特异度均较好。

Evaluation of the tuberculin skin test and the whole blood interferon-γ assay for the diagnosis of tuberculosis infection in children

Objective To evaluate the results of PPD test influenced by different standards, and to compare PPD test and the whole-blood interferon-γ(IFN-γ) assay for the diagnosis of tuberculosis(TB) infection in children. Methods All the participants were grouped into 5 groups according to the risk of infection: Group 1, children with pulmonary disease, without identifiable risk of M.tuberculosis infection (n=40); Group 2, children with pulmonary disease ,with identifiable risk of M.tuberculosis infection(n=11); Group 3, children with TB diagnosed on the basis of clinical findings ,without identifiable risk of M.tuberculosis infection(n=29); Group 4, children with TB diagnosed on the basis of clinical findings, with identifiable risk of M.tuberculosis infection(n=27); Group 5, children with TB confirmed by pathogeny or pathology(n=18). The indexes of PPD test and IFN -γ assay, including sensitivity, specificity, likelihood ratio et al, was evaluated in all the subjects. The correlation of the two tests with the risk of tuberculosis infection was measured by estimating the coefficient of correlation. Results The sensitivity decreased significantly with positive standard increasing gradually. Especially when a 15-mm induration cutoff was used, we found a false-negative tuberculin skin test result. Of 74 TB patients, 15（15/74，20.3%）children had positive IFN-γ assay results and negative PPD test results, 16（16/74，21.6%）children had the PPD induration ranged from 10-14 mm. When a 10-mm induration cutoff was used in active TB patients which suggested that 10-mm was the best critical value of PPD test in patients. When the 10-mm induration cutoff was used in detection of latent tuberculosis infection, the specificity of PPD test decreased significantly. The sensitivity and specificity of PPD test(10-mm cutoff value) were 77.0% and 70.6%, respectively.We considered that the false-positive result was caused by BCG vaccination or nontuberculosis mycobacterial(NTM) infection. The result indicated that BCG vaccination was the influencing factor of PPD test. When the cutoff point was increased to 15mm, 12.5%(5/40) and 9.1%（1/11）children were diagnosed as tuberculosis infection in group A and B by PPD test, which was in accordance with the predicted prevalence of TB infection(9%). The sensitivity and specificity of IFN -γ assay were 85.1% and 94.1% respectively, which were significantly higher than PPD tests. The result suggested that IFN-γ assay was an important tool in the diagnosis of active TB and TB infection. Although both of the two tests were related to the exposure factors of tuberculosis infection, IFN -γ assay was better than PPD test. Conclusions When detection of latent tuberculosis infection, the 15-mm cutoff point could help to avoid the effect of BCG vaccination or NTM infection. In the diagnosis of active TB patients, the 10-mm cutoff point could help to increase the sensitivity of PPD test. The whole-blood IFN-γ assay could be used as a important assistant tool of the tuberculin test in the clinical diagnosis of pediatric tuberculosis infection.