Metagenomic next-generation sequencing for the diagnosis of neurobrucellosis

Abstract

Objective: This study investigates the application of metagenomic next-generation sequencing (mNGS) in the diagnosis of neurobrucellosis (NB). Methods: We retrospectively analyzed patients diagnosed with NB who underwent cerebrospinal fluid (CSF) mNGS testing in Xijing Hospital from 2015 to 2021. Results: Among the 20 individuals included in the study, the serum rose bengal test was positive in 11 out of 16 cases, serum agglutination test was positive in 13 out of 16 cases, CSF culture was positive in 6 out of 11 cases, and CSF mNGS tests were positive in 18 out of 20 cases. Conclusion: CSF mNGS demonstrates superior sensitivity; therefore, it is recommended to collect CSF for mNGS testing prior to antibiotic therapy when NB is suspected.

Plain language summary

Neurobrucellosis (NB) is a disease of the nervous system caused by a type of bacteria called Brucella. It is rare, serious and manifests inconsistently, making it hard to diagnose. Metagenomic next-generation sequencing (mNGS) is a new way to detect disease-causing bacteria by looking at their genetic material. mNGS is fast, accurate and covers a wide range of disease-causing bacteria. We looked back at patients diagnosed with NB at Xijing Hospital between 2015 and 2021 and tested samples of the fluid surrounding the brain and the spinal cord, called cerebrospinal fluid (CSF), by mNGS. A total of 20 patients were included in the study. Compared with the traditional methods, mNGS of CSF samples showed advantages in diagnosing NB. However, antibiotics may affect the results.

Tweetable abstract

Neurobrucellosis (NB) is a rare and severe disease with atypical manifestations, which makes diagnosis very difficult. This article showed that CSF metagenomic next-generation sequencing has a superior sensitivity for the diagnosis of NB compared with traditional tests.

Summary points

• Neurobrucellosis (NB) is a rare and severe disease with atypical manifestations, which makes diagnosis very difficult.

• To our knowledge, this study includes the largest sample size of NB confirmed by metagenomic next-generation sequencing (mNGS).

• Cerebrospinal fluid (CSF) mNGS has superior sensitivity for the diagnosis of NB. A CSF mNGS test can be performed in the early period to identify Brucella in clinical practice.

• We recommend performing the CSF mNGS test prior to initiating antibiotic therapy in order to identify Brucella during the early period.

Keywords: :

• CSF
• diagnosis
• metagenomic next-generation sequencing
• neurobrucellosis

Author contributions

W Jiang and X Liu conceived the project and designed the paper. W Li and Y Li drafted the manuscript. Y He analyzed and synthesized study data. W Li performed the analysis of sequencing data and revised the manuscript. All authors involved in the clinical care and management of the patients. X Li, T Bian and T Liu collected the clinical data. W Li, Y He and Y Li contributed equally to this work. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Financial disclosure

This work was supported by the Discipline Promotion Project of Xijing Hospital (XJZT19MJ21). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study involving human participants was reviewed and approved by the Ethical Review Committee of Xijing Hospital (approval no. KY20151103-2). The participants provided their written informed consent to participate in this study.

Acknowledgments

The authors are grateful to staff at Hugobiotech Co., Ltd. (Beijing, China) for sequencing.

Additional information

Funding

This work was supported by the Discipline Promotion Project of Xijing Hospital (XJZT19MJ21).