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Pathogen Detection Using Metagenomic Next-Generation Sequencing of Plasma Samples from Patients with Sepsis in Uganda

Grundy, Brian S., Parikh, Hardik, Jacob, Shevin ORCID:, Banura, Patrick, Moore, Chris C., Liu, Jie and Houpt, Eric R. (2023) 'Pathogen Detection Using Metagenomic Next-Generation Sequencing of Plasma Samples from Patients with Sepsis in Uganda'. Microbiology Spectrum, Vol 11, Issue 1, e0431222.

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Metagenomic sequencing is a promising new method for pathogen detection. We aimed to detect pathogens from archived plasma using metagenomic sequencing in a previously well-characterized cohort of 254 predominantly HIV-infected patients with sepsis in Uganda. We used Illumina sequencing and the Chan Zuckerberg ID metagenomics platform to sequence and identify pathogens. On average, each plasma sample yielded 3,404,737 ± 2,201,997 reads (mean ± standard deviation), of which 220,032 ± 416,691 (6.3% ± 8.6%) were identified as nonhuman reads. Using a background model filter, 414 genus-specific pathogen identifications were found in the 254 samples. Nineteen pathogens were previously detected positive by quantitative PCR (qPCR), compared to sequencing, which demonstrated 30.2% sensitivity and 99.5% specificity. Sensitivity was higher for viral pathogens than nonviral pathogens (37% versus 5%). For example, HIV viremia was detected in 69% of samples using qPCR, and sequencing revealed 70% sensitivity and 92% specificity. There were 75 genus-specific potential pathogens identified by sequencing in this cohort, including hepatitis B and Epstein-Barr virus (EBV), among several others. qPCR showed a prevalence of hepatitis B and EBV viremia of 17% and 45%, respectively. In-hospital mortality was associated with a lower qPCR threshold cycle value for EBV (adjusted odds ratio, 0.85; P < .001) but not for hepatitis B or HIV. In conclusion, a broad range of potential pathogens were identified by metagenomic sequencing in patients with sepsis in Uganda. Unexpectedly high rates of hepatitis B and EBV viremia were found. Whether these viral infections in HIV patients with sepsis are clinically important requires further study.

Item Type: Article
Subjects: QU Biochemistry > Genetics > QU 460 Genomics. Proteomics
WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 240 Bacteremia. Sepsis. Toxemias
WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 400 Fluid elements. Plasma. Serum. Blood proteins. Blood protein disorders
Faculty: Department: Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):
SWORD Depositor: JISC Pubrouter
Depositing User: JISC Pubrouter
Date Deposited: 07 Feb 2023 13:12
Last Modified: 23 Feb 2023 16:09


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