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Next generation sequencing for diagnosis of central nervous system aspergillosis in liver transplant recipients
Fang Chen1,2, Yujing Zhao3, Chuan Shen1
1Department of Liver Surgery, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China.
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.
Insights
Next-generation sequencing (NGS) aids in the early detection of fungal infections like aspergillosis in liver transplant recipients. This advanced molecular tool shows promise for diagnosing central nervous system fungal infections, though outcomes remain challenging.
Area of Science:
- Medical Mycology
- Infectious Diseases
- Transplant Medicine
Background:
- Fungal encephalitis is a rare but serious complication in liver transplant (LT) recipients.
- Diagnosing central nervous system (CNS) fungal infections, particularly aspergillosis, is challenging with conventional cerebrospinal fluid (CSF) tests.
- Next-generation sequencing (NGS) offers a potential advancement for identifying CNS fungal pathogens.
Purpose of the Study:
- To evaluate the utility of NGS in the early diagnosis of CNS aspergillosis in liver transplant recipients.
- To assess the effectiveness of NGS in identifying fungal pathogens in CSF samples.
Main Methods:
- Shotgun metagenomic sequencing was employed to detect pathogens in the CSF of patients with suspected CNS infections.
- Sequencing was performed using the BGIseq-50 platform.
Main Results:
- NGS identified Aspergillus in the CSF of 5 patients with suspected CNS infections, despite varied clinical presentations.
- Sequence reads for Aspergillus ranged from 2 to 25, with genomic coverage between 0.0003% and 0.0036%.
- Early identification facilitated timely antifungal therapy, but 4 out of 5 patients ultimately succumbed to severe infections.
Conclusions:
- This study demonstrates the potential of NGS for the early diagnosis of CNS aspergillosis in liver transplant recipients.
- NGS represents a valuable new tool that could improve diagnostic capabilities for CNS aspergillosis.
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