Adu Gyamfi Clement Gascua, Seeger Abigail, Mulengwa Durbbin, Vasiliu Anca, Carratala-Castro Lucia, Mtafya Bariki, Maphalala Nontobeko, Munguambe Shilzia, Saavedra Belen, Ness Tara, Maphalala Gugu, Acacio Sozinho, Mambuque Edson, Ehrlich Joanna, Mejia Rojelio, Ziyane Mangaliso, Kirchner H Lester, Lange Christoph, Kay Alexander, Garcia-Basteiro Alberto L, Mandalakas Anna, DiNardo Andrew R
Global Tuberculosis Program, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Department of Global Tuberculosis Program, Baylor Colloge of Medcine Foundation Eswatini, Mbabane, Eswatini.
Open Forum Infect Dis. 2025 Jun 24;12(8):ofaf345. doi: 10.1093/ofid/ofaf345. eCollection 2025 Aug.
Tuberculosis (TB) treatment monitoring is hindered by the lack of a rapidly measured biomarker that accurately predicts clinically relevant outcomes. Symptom screening poorly correlates with bacillary burden. Although culture is a direct measure of viable bacillary burden, the long turnaround time makes it clinically irrelevant.
The TB treatment monitoring potential of stool-based, quantitative polymerase chain reaction (qPCR) was prospectively assessed among 231 participants of all ages from Eswatini, Tanzania, and Mozambique with microbiologically confirmed TB. Stool qPCR results were compared to sputum culture, persistent symptoms, drug resistance, and World Health Organization TB outcomes.
Quantitative bacillary burden measured by stool qPCR strongly correlated with sputum culture at baseline (Spearman correlation = 0.79; < .001). Stool was successfully collected at >90% of all timepoints, while sputum collection decreased to <50% at the end of therapy. Participants with isoniazid or rifampin resistance demonstrated decreased bacillary clearance by sputum culture and stool qPCR during the first 2 weeks of treatment. Participants who remained culture positive at 2 months had a slower decrease in bacillary burden measured by stool qPCR compared to those who were culture negative by 2 months. The odds of a participant being culture positive at 2 months was associated with a lower initial qPCR cycle threshold (odds ratio [OR], 0.792; = .004), and a smaller absolute difference between the qPCR cycle threshold measured at 2 weeks and baseline (OR, 0.72; = .0006). Neither sputum culture, sputum Xpert Ultra, or stool qPCR was associated with resolution of symptoms or in-treatment death.
Stool-based TB treatment monitoring correlates with sputum culture but provides results faster, leverages a more accessible specimen, and identifies patients with TB who are at risk for drug resistance and persistent 2-month culture positivity. None of the quantitative tests of bacillary burden singularly could predict symptom resolution or death.
由于缺乏能快速检测且准确预测临床相关结果的生物标志物，结核病（TB）治疗监测受到阻碍。症状筛查与细菌负荷的相关性较差。虽然培养是对活菌负荷的直接测量，但周转时间长使其在临床上不适用。
在来自斯威士兰、坦桑尼亚和莫桑比克的231名各年龄段经微生物学确诊为结核病的参与者中，前瞻性评估基于粪便的定量聚合酶链反应（qPCR）用于结核病治疗监测的潜力。将粪便qPCR结果与痰培养、持续症状、耐药性及世界卫生组织的结核病治疗结果进行比较。
通过粪便qPCR测量的定量细菌负荷在基线时与痰培养密切相关（斯皮尔曼相关性 = 0.79；P <.001）。在所有时间点，超过90%的样本成功采集到粪便，而在治疗结束时痰样本采集率降至低于50%。对异烟肼或利福平耐药的参与者在治疗的前2周，痰培养和粪便qPCR显示细菌清除率降低。在2个月时仍培养阳性的参与者，与2个月时培养阴性的参与者相比，通过粪便qPCR测量的细菌负荷下降较慢。参与者在2个月时培养阳性的几率与较低的初始qPCR循环阈值相关（比值比[OR]，0.792；P =.004），以及在2周时测量的qPCR循环阈值与基线之间较小的绝对差值相关（OR，0.72；P =.0006）。痰培养、痰Xpert Ultra或粪便qPCR均与症状缓解或治疗期间死亡无关。
基于粪便的结核病治疗监测与痰培养相关，但能更快提供结果，利用更易获取的样本，并识别出有耐药风险和持续2个月培养阳性的结核病患者。单一的细菌负荷定量检测均无法预测症状缓解或死亡。
