PT  - JOURNAL ARTICLE
AU  - Tran Tan Thanh
AU  - Climent Casals-Pascual
AU  - Nguyen Thi Han Ny
AU  - Nghiem My Ngoc
AU  - Ronald Geskus
AU  - Le Nguyen Truc Nhu
AU  - Nguyen Thi Thu Hong
AU  - Du Trong Duc
AU  - Do Dang Anh Thu
AU  - Phan Nha Uyen
AU  - Vuong Bao Ngoc
AU  - Le Thi My Chau
AU  - Van Xuan Quynh
AU  - Nguyen Ho Hong Hanh
AU  - Nguyen Thuy Thuong Thuong
AU  - Le Thi Diem
AU  - Bui Thi Bich Hanh
AU  - Vu Thi Ty Hang
AU  - Pham Kieu Nguyet Oanh
AU  - Roman Fischer
AU  - Nguyen Hoan Phu
AU  - Ho Dang Trung Nghia
AU  - Nguyen Van Vinh Chau
AU  - Ngo Thi Hoa
AU  - Benedikt M. Kessler
AU  - Guy Thwaites
AU  - Le Van Tan
TI  - Diagnostic Cerebrospinal Fluid Biomarker Discovery and Validation in Patients with Central Nervous System Infections
AID  - 10.1101/2020.01.13.899625
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.01.13.899625
4099  - http://biorxiv.org/content/early/2020/01/14/2020.01.13.899625.short
4100  - http://biorxiv.org/content/early/2020/01/14/2020.01.13.899625.full
AB  - Background Central nervous system (CNS) infections are common causes of morbidity and mortality worldwide. Rapid, accurate identification of the likely cause is essential for clinical management and the early initiation of antimicrobial therapy, which potentially improves clinical outcome.Methods We applied liquid chromatography tandem mass-spectrometry on 45 cerebrospinal fluid (CSF) samples from a cohort of adults with/without CNS infections to discover potential diagnostic protein biomarkers. We then validated the diagnostic performance of a selected biomarker candidate in an independent cohort of 364 consecutively treated adults with CNS infections admitted to a referral hospital in southern Vietnam.Results In the discovery cohort, we identified lipocalin 2 (LCN2) as a potential biomarker of bacterial meningitis. The analysis of the validation cohort showed that LCN2 could discriminate bacterial meningitis from other CNS infections, including tuberculous meningitis, cryptococcal meningitis and viral/antibody-mediated encephalitis (sensitivity: 0.88 (95% confident interval (CI): 0.77–0.94), specificity: 0.91 (95%CI: 0.88–0.94) and diagnostic odd ratio: 73.8 (95%CI: 31.8–171.4)). LCN2 outperformed other CSF markers (leukocytes, glucose, protein and lactate) commonly used in routine care worldwide. The combination of LCN2 and these four routine CSF markers resulted in the highest diagnostic performance for bacterial meningitis (area under receiver-operating-characteristic-curve 0.96; 95%CI: 0.93–0.99).Conclusions Our results suggest that LCN2 is a sensitive and specific biomarker for discriminating bacterial meningitis from a broad spectrum of CNS infections. A prospective study is needed to further assess the diagnostic utility of LCN2 in the diagnosis and management of CNS infections.