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Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection.

ABSTRACT: BACKGROUND:Accurate etiology diagnosis is crucial for central nervous system infections (CNS infections). The diagnostic value of metagenomic next-generation sequencing (mNGS), an emerging powerful platform, remains to be studied in CNS infections. METHODS:We conducted a single-center prospective cohort study to compare mNGS with conventional methods including culture, smear and etc. 248 suspected CNS infectious patients were enrolled and clinical data were recorded. RESULTS:mNGS reported a 90.00% (9/10) sensitivity in culture-positive patients without empirical treatment and 66.67% (6/9) in empirically-treated patients. Detected an extra of 48 bacteria and fungi in culture-negative patients, mNGS provided a higher detection rate compared to culture in patients with (34.45% vs. 7.56%, McNemar test, p??0.0083). Compared to conventional methods, positive percent agreement and negative percent agreement was 75.00% and 69.11% separately. mNGS detection rate was significantly higher in patients with cerebrospinal fluid (CSF) WBC?>?300?*?106/L, CSF protein?>?500 mg/L or glucose ratio???0.3. mNGS sequencing read is correlated with CSF WBC, glucose ratio levels and clinical disease progression. CONCLUSION:mNGS showed a satisfying diagnostic performance in CNS infections and had an overall superior detection rate to culture. mNGS may held diagnostic advantages especially in empirically treated patients. CSF laboratory results were statistically relevant to mNGS detection rate, and mNGS could dynamically monitor disease progression.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC7222471 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection.

Zhang Yi Y Cui Peng P Zhang Hao-Cheng HC Wu Hong-Long HL Ye Ming-Zhi MZ Zhu Yi-Min YM Ai Jing-Wen JW Zhang Wen-Hong WH

Journal of translational medicine 20200513 1

<h4>Background</h4>Accurate etiology diagnosis is crucial for central nervous system infections (CNS infections). The diagnostic value of metagenomic next-generation sequencing (mNGS), an emerging powerful platform, remains to be studied in CNS infections.<h4>Methods</h4>We conducted a single-center prospective cohort study to compare mNGS with conventional methods including culture, smear and etc. 248 suspected CNS infectious patients were enrolled and clinical data were recorded.<h4>Results</h ...[more]

PMID: 32404108

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Project description:ObjectiveTimely and precise etiology diagnosis is crucial for optimized medication regimens and better prognosis in central nervous system infections (CNS infections). We aimed to analyze the impact of mNGS tests on the management of patients with CNS infections.MethodsWe conducted a single-center retrospective cohort study to analyze the value of mNGS in clinical applications. Three hundred sixty-nine patients with a CNS infection diagnosis were enrolled, and their clinical data were collected. CDI and DDI were defined in our study to describe the intensity of drug use in different groups. We used LOH and mRS to evaluate if the application of mNGS can benefit CNS infected patients.ResultsmNGS reported a 91.67% sensitivity in culture-positive patients and an 88.24% specificity compared with the final diagnoses. Patients who participated with the mNGS test had less drug use, both total (58.77 vs. 81.18) and daily (22.6 vs. 28.12, P < 0.1, McNemar) intensity of drug use, and length of hospitalization (23.14 vs. 24.29). Patients with a consciousness grading 1 and 3 had a decrease in CDI (Grade 1, 86.49 vs. 173.37; Grade 3, 48.18 vs. 68.21), DDI (Grade 1, 1.52 vs. 2.72; Grade 3, 2.3 vs. 2.45), and LOH (Grade 1, 32 vs. 40; Grade 3, 21 vs. 23) with the application of mNGS. Patients infected with bacteria in the CNS had a reduced CDI, DDI, and LOH in the mNGS group. This was compared with the TraE group that had 49% of patients altered medication plans, and 24.7% of patients reduced drug intensity four days after mNGS reports. This was because of the reduction of drug types.ConclusionmNGS showed its high sensitivity and specificity characteristics. mNGS may assist clinicians with more rational medication regimens and reduce the drug intensity for patients. The primary way of achieving this is to reduce the variety of drugs, especially for severe patients and bacterial infections. mNGS has the ability of improving the prognosis of CNS infected patients.

Project description:BackgroundRecently, with the rapid progress of metagenomic next-generation sequencing (mNGS), inconsistency between mNGS results and clinical diagnoses has become more common. There is currently no reasonable explanation for this, and the interpretation of mNGS reports still needs to be standardised.MethodsA retrospective analysis was conducted on 47 inpatients with suspected central nervous system (CNS) infections, and clinical data were recorded. The final diagnosis was determined by an expert group based on the patient's clinical manifestation, laboratory examination, and response to treatment. mNGS results were compared with the final diagnosis, and any inconsistencies that occurred were investigated. Finally, the credibility of mNGS results was evaluated using the integral approach, which consists of three parts: typical clinical features, positive results with the traditional method, and cerebrospinal fluid cells ≥ 100 (× 106/L) or protein ≥ 500 mg/L, with one point for each item.ResultsForty-one patients with suspected CNS infection were assigned to infected (ID, 31/41, 75.61%) and non-infected groups (NID, 10/41, 24.39%) after assessment by a panel of experts according to the composite diagnostic criteria. For mNGS-positive results, 20 of the 24 pathogens were regarded as contaminants when the final score was ≤ 1. The remaining 11 pathogens detected by mNGS were all true positives, which was consistent with the clinical diagnosis when the score was ≥ 2. For mNGS negative results, when the score was ≥ 2, the likelihood of infection may be greater than when the score is ≤ 1.ConclusionThe integral method is effective for evaluating mNGS results. Regardless of whether the mNGS result was positive or negative, the possibility of infection was greater when the score was ≥ 2. A negative mNGS result does not necessarily indicate that the patient was not clinically infected, and, therefore, clinical features are more important.

Project description:BackgroundsThe incidence of angiostrongyliasis is increasing in recent decades due to the expanding endemic areas all over the world. Clinicians face tremendous challenge of diagnosing angiostrongyliasis because of the lack of awareness of the disease and less effective definitive laboratory tests.Case presentationA 27-year-old man initially manifested skin itching, emesis, myalgia and quadriparesis. With progressive weakness of four limbs and elevated protein in the cerebrospinal fluid (CSF), he was diagnosed as Guillain-Barré syndrome and treated with intravenous methylprednisolone and immunoglobulin. However, the patient deteriorated with hyperpyrexia, headache and then persistent coma. The routine tests for Angiostrongylus cantonensis (A. cantonensis) with both the CSF and the serum were all negative. In contrast, the metagenomic next-generation sequencing (mNGS) was applied with the serum sample and the CSF sample in the middle phase. The central nervous system (CNS) angiostrongyliasis was diagnosed by mNGS with the mid-phase CSF, but not the mid-phase serum. At the same time, the CSF analysis revealed eosinophils ratio up to 67%. The discovery of A. cantonensis was confirmed by PCR with CSF later. Unfortunately, the patient died of severe angiostrongyliasis. During his hospitalization, mNGS was carried out repeatedly after definitive diagnosis and targeted treatment. The DNA strictly map reads number of A. cantonensis detected by mNGS was positively correlated with the CSF opening pressure and clinical manifestations.ConclusionsThe case of A. cantonensis infection highlights the benefit of mNGS as a target-free identification in disclosing the rare CNS angiostrongyliasis in the unusual season, while solid evidence from routine clinical testing was absent. The appropriate sample of mNGS should be chosen according to the life cycle of A. cantonensis. Besides, given the fact that the DNA reads number of A. cantonensis fluctuated with CSF opening pressure and clinical manifestations, whether mNGS could be applied as a marker of effectiveness of treatment is worth further exploration.

Dataset Information

Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection.

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Clinical application and evaluation of metagenomic next-generation sequencing in suspected adult central nervous system infection.

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