一项用于对儿童结核病严重程度进行分类的三基因宿主反应特征的前瞻性评估。
A Prospective Evaluation of a Three-Gene Host Response Signature to Classify Tuberculosis Severity in Children.
作者信息
Sweetser Brittney, Nkereuwem Esin, Nakafeero Jascent, Gomez Marie, Wambi Peter, Nsereko Moses, Andama Alfred, Ernst Joel D, Cattamanchi Adithya, Kampmann Beate, Jaganath Devan, Wobudeya Eric
机构信息
Division of Pulmonary Diseases & Critical Care Medicine, University of California, Irvine, Orange, United States.
Center for Tuberculosis, Institute for Global Health Sciences, University of California, San Francisco, San Francisco, United States.
出版信息
J Pediatric Infect Dis Soc. 2025 May 13;14(5). doi: 10.1093/jpids/piaf041.
BACKGROUND
Children with non-severe TB may benefit from short-course treatment, but point-of-care tools are needed to stratify disease severity. We prospectively evaluated the Cepheid Xpert MTB-Host Response (HR) prototype cartridge for distinguishing TB severity in children with pulmonary TB (PTB) in The Gambia and Uganda.
METHODS
We included children <15 with microbiologically confirmed or clinically diagnosed unconfirmed PTB. Severity was defined using the World Health Organization (WHO) guidelines for a four-month, drug-susceptible regimen. Capillary or venous blood was tested with the HR cartridge for PCR-based detection of 3 mRNA genes and calculation of a TB score from cycle thresholds. We generated receiver operating characteristic curves with the TB score to classify severe TB and assessed if Xpert-HR could achieve the WHO target accuracy for treatment optimization (≥90% sensitivity, ≥70% specificity).
RESULTS
Among 106 children, the median age was 4 years (IQR 1-7), 56.6% were female, and 13.2% were living with HIV. In all children with PTB, Xpert-HR achieved an AUC of 0.67 (95% CI 0.55-0.78), with 89.3% sensitivity (95% CI 71.8-97.7) and 29.5% specificity (95% CI 19.7-40.9, cutoff ≤ -0.60). By confirmation status, Xpert-HR approached the target accuracy in children with Confirmed TB, with 62.5% specificity (95% CI 24.5-91.5) at 91.7% sensitivity (95% CI 61.5-99.8, cut-off ≤ -1.349). Among children with Unconfirmed TB, specificity was lower (24.3%, 95% CI 14.8-36.0) at 93.8% sensitivity (95% CI 69.8-99.8, cutoff ≤ -0.450). Target accuracy was almost achieved in children 5-9 regardless of confirmation status (100% sensitivity [95% CI 71.5-100], 66.7% specificity [95% CI 43.0-85.4], cutoff ≤ -1.35), but specificity (28.2%, 95% CI 18.6-39.5) was lower for children < 5 (92.9% sensitivity, 95% CI 76.5-99.1, cutoff ≤ -0.550).
CONCLUSIONS
Xpert-HR approached the target accuracy to stratify PTB severity in older children and those with Confirmed TB but had lower specificity in children with Unconfirmed TB. Child-specific signatures may be needed to improve performance in younger children with paucibacillary disease.
背景
非重症结核病患儿可能从短程治疗中获益，但需要即时检验工具来对疾病严重程度进行分层。我们前瞻性评估了赛沛Xpert MTB-Host Response（HR）原型检测卡，以区分冈比亚和乌干达肺结核（PTB）患儿的结核病严重程度。
方法
我们纳入了年龄小于15岁、经微生物学确诊或临床诊断为未确诊PTB的儿童。根据世界卫生组织（WHO）针对为期4个月的药物敏感方案的指南定义严重程度。使用HR检测卡对毛细血管血或静脉血进行检测，以基于PCR法检测3种mRNA基因，并根据循环阈值计算结核病评分。我们利用结核病评分生成受试者工作特征曲线，以对重症结核病进行分类，并评估Xpert-HR是否能够达到WHO用于治疗优化的目标准确性（敏感性≥90%，特异性≥70%）。
结果
在106名儿童中，中位年龄为4岁（四分位间距1 - 7岁），56.6%为女性，13.2%感染了HIV。在所有PTB患儿中，Xpert-HR的曲线下面积（AUC）为0.67（95%置信区间0.55 - 0.78），敏感性为89.3%（95%置信区间71.8 - 97.7），特异性为29.5%（95%置信区间19.7 - 40.9，临界值≤ -0.60）。根据确诊状态，Xpert-HR在确诊结核病患儿中接近目标准确性，敏感性为91.7%（95%置信区间61.5 - 99.8，临界值≤ -1.349）时，特异性为62.5%（95%置信区间24.5 - 91.5）。在未确诊结核病患儿中，敏感性为93.8%（95%置信区间69.8 - 99.8，临界值≤ -0.450）时，特异性较低（24.3%，95%置信区间14.8 - 36.0）。无论确诊状态如何，5 - 9岁儿童几乎达到了目标准确性（敏感性100% [95%置信区间71.5 - 100]，特异性66.7% [95%置信区间43.0 - 85.4]，临界值≤ -1.35），但小于5岁儿童的特异性较低（28.2%，95%置信区间18.6 - 39.5）（敏感性92.9%，95%置信区间76.5 - 99.1，临界值≤ -0.550）。
结论
Xpert-HR在年龄较大儿童和确诊结核病患儿中接近对PTB严重程度进行分层的目标准确性，但在未确诊结核病患儿中特异性较低。可能需要针对儿童的特征来提高患有少菌型疾病的年幼儿童的检测性能。
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