NDLI: Nanopore targeted sequencing-based diagnosis of central nervous system infections in HIV-infected patients

Content Provider	Springer Nature : BioMed Central
Author	Yang, Xihong Zhou, Shuilian Chang, Ziwei Xi, Xiaotong Li, Jiahui Miao, Mengjiao Chen, Yaling Chen, Wei Zhang, Hongying Ding, Ran Hu, Zhiliang
Abstract	Background Early and accurate etiological diagnosis is very important for improving the prognosis of central nervous system (CNS) infections in human immunodeficiency virus (HIV)-infected patients. The goal is not easily achieved by conventional microbiological tests. We developed a nanopore targeted sequencing (NTS) platform and evaluated the diagnostic performance for CNS infections in HIV-infected patients, with special focus on cryptococcal meningitis (CM). We compared the CM diagnostic performance of NTS with conventional methods and cryptococcal polymerase chain reaction (PCR). Methods This study included 57 hospitalized HIV-infected patients with suspected CNS infections from September 2018 to March 2022. The diagnosis established during hospitalization includes 27 cases of CM, 13 CNS tuberculosis, 5 toxoplasma encephalitis, 2 cytomegalovirus (CMV) encephalitis and 1 Varicella-zoster virus (VZV) encephalitis. The 2 cases of CMV encephalitis also have co-existing CM. Target-specific PCR amplification was used to enrich pathogen sequences before nanopore sequencing. NTS was performed on stored cerebrospinal fluid (CSF) samples and the results were compared with the diagnosis during hospitalization. Results 53 (93.0%) of the patients were male. The median CD4 cell count was 25.0 (IQR: 14.0–63.0) cells/uL. The sensitivities of CSF culture, India ink staining, cryptococcal PCR and NTS for CM were 70.4% (95%CI: 51.5 − 84.1%), 76.0% (95%CI: 56.6 − 88.5%), 77.8% (59.2 − 89.4%) and 85.2% (95%CI: 67.5 − 94.1%), respectively. All those methods had 100% specificity for CM. Our NTS platform could identify Cryptococcus at species level. Moreover, NTS was also able to identify all the 5 cases of toxoplasma encephalitis, 2 cases of CMV encephalitis and 1 VZV encephalitis. However, only 1 of 13 CNS tuberculosis cases was diagnosed by NTS, and so did Xpert MTB/RIF assay. Conclusions NTS has a good diagnostic performance for CM in HIV-infected patients and may have the ability of simultaneously detecting other pathogens, including mixed infections. With continuing improving of the NTS platform, it may be a promising alterative microbiological test for assisting with the diagnosis of CNS infections.
Related Links	https://ann-clinmicrob.biomedcentral.com/counter/pdf/10.1186/s12941-024-00682-7.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	14760711
DOI	10.1186/s12941-024-00682-7
Journal	Annals of Clinical Microbiology and Antimicrobials
Issue Number	1
Volume Number	23
Language	English
Publisher	BioMed Central
Publisher Date	2024-02-29
Access Restriction	Open
Subject Keyword	Medical Microbiology Infectious Diseases Drug Resistance Microbial Genetics and Genomics Biochemistry Parasitology Nanopore targeted sequencing Central nervous system (CNS) infections HIV Cryptococcal meningitis
Content Type	Text
Resource Type	Article
Subject	Microbiology (medical) Infectious Diseases
Journal Impact Factor	4.6/2023
5-Year Journal Impact Factor	5.3/2023

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