脑脊液二代测序对中枢神经系统感染病原体的诊断效能

Diagnostic efficacy of cerebrospinal fluid next-generation sequencing for etiology of central nervous system infection

  • 摘要:
    目的 探讨宏基因组二代测序(mNGS)对中枢神经系统(CNS)感染病原学诊断效能。
    方法 连续纳入温州市中心医院2022年6月-2025年1月间收治、怀疑有中枢神经系统(CNS)感染的73例住院患者,采集脑脊液同时做mNGS及传统培养,以CNS感染临床诊断为依据,比较两种方法的灵敏度、特异度、阳性预测值、阴性预测值及Youden指数,采用受试者工作特征(ROC)曲线比较mNGS、传统培养的诊断效能。
    结果 最终临床确诊CNS感染患者41例,mNGS(DNA)检出阳性36例,包括单纯细菌感染且种类仅为1种的11例,单纯病毒(DNA)感染且种类仅为1种的4例,2种及以上病原体混合感染21例,混合感染模式及例数分别为:单纯细菌感染种类2种及以上4例、单纯病毒(DNA)感染种类2种及以上6例、细菌及病毒(DNA)混合感染4例、细菌及真菌混合感染1例、病毒(DNA)及真菌混合感染5例、细菌病毒(DNA)真菌混合感染1例;传统培养检出阳性8例,包含细菌感染6例、真菌感染2例。mNGS的灵敏度、特异度、阳性预测值、阴性预测值、约登指数分别为0.878、0.719、0.800、0.821、0.597;传统培养的灵敏度、特异度、阳性预测值、阴性预测值、约登指数分别为0.195、0.969、0.888、0.484、0.164。mNGS的阳性率高于传统培养(χ2=29.000,P<0.001),阳性检出率高于传统培养(χ2=4.690,P=0.030)。ROC曲线显示mNGS诊断CNS感染的曲线下面积(AUC)为0.790,传统培养则为0.573。
    结论 脑脊液mNGS可有效提升CNS感染病原体检出,诊断效能优于传统培养,可作为传统诊断技术的必要补充。

     

    Abstract:
    OBJECTIVE To explore the diagnostic efficacy of metagenomic next-generation sequencing (mNGS) in the etiology of central nervous system (CNS) infection.
    METHODS A total of 73 inpatients admitted to Wenzhou Central Hospital between Jun. 2022 and Jan. 2025 with suspected CNS infection were consecutively included. Cerebrospinal fluid was collected and tested for both mNGS and traditional culture. Based on the clinical diagnosis of CNS infection, the sensitivity, specificity, positive predictive value, negative predictive value and Youden′s index of the two methods were compared. The diagnostic efficacy of mNGS and traditional culture was evaluated with the receiver operating characteristic (ROC) curves.
    RESULTS Ultimately, 41 patients were clinically confirmed with CNS infection. mNGS (DNA) yielded positive results in 36 cases, there were 11 cases of simple bacterial infection with only 1 species, 4 cases of simple viral (DNA) infection with only 1 species, and 21 cases of mixed infections with no less than 2 species of pathogens. The types of mixed infections and the number of cases were as follows: 4 cases of simple bacterial infections with more than 2 species, 6 cases of simple viral (DNA) infections with more than 2 types, 4 cases of mixed infections with bacteria and viruses (DNA), 1 case of mixed infections with bacterial and fungi, 5 cases of mixed infections with viruses and fungi, and 1 case of mixed infection with bacteria, viruses (DNA) and fungi. Traditional culture detected positive results in 8 cases, including 6 cases of bacterial infection and 2 cases of fungal infection. The sensitivity, specificity, positive predictive value, negative predictive value and Youden′s index of mNGS were 0.878, 0.719, 0.800, 0.821 and 0.597, respectively. The sensitivity, specificity, positive predictive value, negative predictive value and Youden′s index of traditional culture were 0.195, 0.969, 0.888, 0.484 and 0.164, respectively. The positive rate of mNGS was higher than that of traditional culture (χ2=29.000, P < 0.001), and the positive detection rate was also higher (χ2=4.690, P=0.030). The ROC curve showed that the area under the curve (AUC) for mNGS in diagnosing CNS infection was 0.790, whereas it was 0.573 for traditional culture.
    CONCLUSION Cerebrospinal fluid mNGS can effectively improve the detection of pathogens causing CNS infection, with diagnostic efficacy superior to traditional culture, and can serve as a necessary supplement to traditional diagnostic techniques.

     

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