Randall Philippa, Mutsvangwa Junior, Nliwasa Marriott, Wilson Lindsay, Makamure Beauty, Makambwa Edson, Meldau Richard, Dheda Keertan, Munyati Shungu, Siddiqi Omar, Corbett Elizabeth, Esmail Ali
Centre for Lung Infection and Immunity, Department of Medicine, University of Cape Town and Division of Pulmonology, University of Cape Town Lung Institute, Observatory, Cape Town, South Africa.
Antrum Biotech (Pty) Ltd, Cape Town, South Africa.
Open Forum Infect Dis. 2024 Aug 29;11(9):ofae496. doi: 10.1093/ofid/ofae496. eCollection 2024 Sep.
Tuberculous meningitis (TBM) mortality is high and current diagnostics perform suboptimally. We evaluated the diagnostic performance of a DNA-based assay (GeneXpert Ultra) against a new same-day immunodiagnostic assay that detects unstimulated interferon-gamma (IRISA-TB).
In a stage 1 evaluation, IRISA-TB was evaluated in biobanked samples from Zambia (n = 82; tuberculosis [TB] and non-TBM), and specificity in a South African biobank (n = 291; non-TBM only). Given encouraging results, a stage 2 evaluation was performed in suspected TBM patients from Zimbabwe and Malawi (n = 668). Patients were classified as having definite, probable or possible TBM, or non-TBM based on their microbiological results, cerebrospinal fluid (CSF) chemistry, and whether they received treatment.
In the stage 1 evaluation, sensitivity and specificity of IRISA-TB were 75% and 87% in the Zambian samples, and specificity was 100% in the South African samples. In the stage 2 validation, IRISA-TB sensitivity (95% confidence interval [CI]) was significantly higher than Xpert Ultra (76.2% [55.0%-89.4%] vs 25% [8.9%-53.3%]; = .0048) when trace readouts were considered negative. Specificity (95% CI) was similar for both assays (91.4% [88.8%-93.4%] vs 86.9% [83.4%-89.8%]). When the Xpert Ultra polymerase chain reaction product was verified by sequencing, the positive predictive value of trace readouts in CSF was 27.8%. Sensitivity of IRISA-TB was higher in human immunodeficiency virus (HIV)-infected versus uninfected participants (85.8% vs 66.7%).
As a same-day rule-in test, IRISA-TB had significantly better sensitivity than Xpert Ultra in a TB/HIV-endemic setting. An immunodiagnostic approach to TBM is promising, and further studies are warranted.
结核性脑膜炎（TBM）死亡率高，目前的诊断方法效果欠佳。我们评估了一种基于DNA的检测方法（GeneXpert Ultra）与一种新的同日免疫诊断方法（检测未刺激的干扰素-γ的IRISA-TB）的诊断性能。
在第1阶段评估中，在赞比亚的生物样本库样本（n = 82；结核病[TB]和非TBM）中评估IRISA-TB，并在南非生物样本库（n = 291；仅非TBM）中评估其特异性。鉴于结果令人鼓舞，在来自津巴布韦和马拉维的疑似TBM患者（n = 668）中进行了第2阶段评估。根据患者的微生物学结果、脑脊液（CSF）化学指标以及是否接受治疗，将患者分类为确诊、可能或疑似TBM，或非TBM。
在第1阶段评估中，赞比亚样本中IRISA-TB的敏感性和特异性分别为75%和87%，南非样本中的特异性为100%。在第2阶段验证中，当微量读数被视为阴性时，IRISA-TB的敏感性（95%置信区间[CI]）显著高于Xpert Ultra（76.2%[55.0%-89.4%]对25%[8.9%-53.3%]；P = 0.0048）。两种检测方法的特异性（95%CI）相似（91.4%[88.8%-93.4%]对86.9%[83.4%-89.8%]）。当通过测序验证Xpert Ultra聚合酶链反应产物时，CSF中微量读数的阳性预测值为27.8%。在人类免疫缺陷病毒（HIV）感染的参与者中，IRISA-TB的敏感性高于未感染的参与者（85.8%对66.7%）。
作为同日确诊检测，在TB/HIV流行地区，IRISA-TB的敏感性显著优于Xpert Ultra。TBM的免疫诊断方法前景广阔，值得进一步研究。
