Grupo de Epidemiología, Universidad de Antioquia, Medellín, Colombia.
PLoS One. 2009 Dec 14;4(12):e8257. doi: 10.1371/journal.pone.0008257.
OBJECTIVES: Household contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNgamma produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNgamma levels in HHCs correlate with tuberculosis development. METHODS: A cohort of 2060 HHCs was followed for 2-3 years after exposure to a tuberculosis case. Besides TST, IFNgamma responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination. RESULTS: Using TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNgamma response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNgamma responders to CFP-10 (HR 1.82 95% CI 0.79-4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNgamma producers was observed (trend Log rank p = 0.007). DISCUSSION: CFP-10-induced IFNgamma production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprophylaxis to child contacts regardless of BCG vaccination.
目的：肺结核患者的家庭接触者（HHC）感染结核分枝杆菌和早期发病的风险很高。识别结核病发病风险的个体是结核病控制的理想目标。使用特定结核分枝杆菌抗原的干扰素-γ释放测定（IGRAs）为感染检测提供了结核菌素皮肤试验（TST）的替代方法。此外，这些抗原刺激产生的 IFN-γ水平可能具有预后价值。我们估计了 HHC 和其来源人群（SP）中结核分枝杆菌感染的 IGRAs 和 TST 患病率，并评估了 HHC 中的 IFNγ水平是否与结核病发病有关。 方法：对接触肺结核病例后的 2060 名 HHC 进行了 2-3 年的随访。除了 TST 外，还在 7 天全血培养中评估了对分枝杆菌抗原 CFP、CFP-10、HspX 和 Ag85A 的 IFNγ反应，并与哥伦比亚麦德林的 766 名 SP 个体进行了比较。由于哥伦比亚的结核病法规仅考虑对 5 岁以下、BCG 接种阳性且 TST 阳性的儿童进行异烟肼预防，因此未向儿童接触者提供异烟肼预防。 结果：使用 TST，65.9%的 HHC 和 42.7%的 SP 个体呈阳性（OR 2.60，p<0.0001）。IFNγ对 CFP-10 的反应呈阳性，CFP-10 是结核分枝杆菌感染的生物标志物，66.3%的 HHC 和 24.3%的 SP 呈阳性（OR=6.07，p<0.0001）。结核病发病率为 7.0/1000 人年。5 岁以下儿童占发病病例的 21.6%。CFP-10 阳性和阴性 IFNγ反应者之间未见显著差异（HR 1.82 95%CI 0.79-4.20 p=0.16）。然而，在高 HHC IFNγ产生者中观察到结核病发病的显著趋势（趋势 Log 秩 p=0.007）。 讨论：CFP-10 诱导的 IFNγ产生可用于确定 HHC 中的结核感染患病率，并确定发病风险最高的人群。儿童中较高的结核病发病率支持对儿童接触者进行化学预防，而不论其 BCG 接种情况如何。
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