Next generation sequencing for diagnosis of central nervous system aspergillosis in liver transplant recipients

Fang Chen; Yujing Zhao; Chuan Shen; Longzhi Han; Xiaosong Chen; Jianjun Zhang; Qiang Xia; Yongbing Qian

doi:10.21037/atm-21-92

Next generation sequencing for diagnosis of central nervous system aspergillosis in liver transplant recipients

Ann Transl Med. 2021 Jul;9(13):1071. doi: 10.21037/atm-21-92.

Authors

Fang Chen^{1

2}, Yujing Zhao³, Chuan Shen¹, Longzhi Han¹, Xiaosong Chen¹, Jianjun Zhang¹, Qiang Xia¹, Yongbing Qian¹

Affiliations

¹ Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
² Department of Pharmacy, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
³ Department of Anesthesiology, Second Xiangya Hospital, Central South University, Changsha, China.

Abstract

Background: Fungal encephalitis is uncommon and sometimes fatal in liver transplant (LT) recipients. Early diagnosis of central nervous system (CNS) fungal infections, especially aspergillosis, is difficult based on routine tests of cerebrospinal fluid (CSF) alone. Next-generation sequencing (NGS) as a new tool may help in this respect.

Methods: Shotgun metagenomics was used to detect pathogens in CSF of patients, who were clinically suspected of CNS infection. Sequencing was performed at BGIseq-50 platform (BGI, Shenzhen).

Results: NGS technique identified Aspergillus in CSF of 5 patients, who were suspected of CNS infection, although clinical symptoms of these patients varied dramatically. The resulting sequence reads corresponding to Aspergillus species ranged from 2 to 25, with genomic coverage ranging from 0.0003% to 0.0036%. Rapid identification of Aspergillus enabled early appropriate antifungal therapy, although 4 patients eventually died of severe infection.

Conclusions: This is the first study to highlight the utility of NGS in early diagnosis of CNS aspergillosis in LT recipients. This new tool may be helpful in improving the diagnosis of CNS aspergillosis.

Keywords: Aspergillus; central nervous system (CNS); cerebrospinal fluid; liver transplantation; next generation sequencing.