Metagenomic next generation sequencing of plasma RNA for diagnosis of unexplained, acute febrile illness in Uganda.

Autor: Kandathil AJ; Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America., Blair PW; Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.; Department of Pathology, Uniformed Services University, Bethesda, Maryland, United States of America., Lu J; Center for Computational Biology, Johns Hopkins University, Baltimore, Maryland, United States of America.; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America., Anantharam R; Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America., Kobba K; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Robinson ML; Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America., Alharthi S; Department of Pathology, Uniformed Services University, Bethesda, Maryland, United States of America., Ndawula EC; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Dumler JS; Department of Pathology, Uniformed Services University, Bethesda, Maryland, United States of America.; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America., Kakooza F; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Lamorde M; Infectious Diseases Institute, Makerere University, Kampala, Uganda., Thomas DL; Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America., Salzberg SL; Center for Computational Biology, Johns Hopkins University, Baltimore, Maryland, United States of America.; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.; Departments of Computer Science and Biostatistics, Johns Hopkins University, Baltimore, Maryland, United States of America., Manabe YC; Division of Infectious Diseases, Johns Hopkins School of Medicine, Baltimore, Maryland, United States of America.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2024 Sep 19; Vol. 18 (9), pp. e0012451. Date of Electronic Publication: 2024 Sep 19 (Print Publication: 2024).
DOI: 10.1371/journal.pntd.0012451
Abstrakt: Metagenomic next generation metagenomic sequencing (mNGS) has proven to be a useful tool in the diagnosis and identification of novel human pathogens and pathogens not identified on routine clinical microbiologic tests. In this study, we applied mNGS to characterize plasma RNA isolated from 42 study participants with unexplained acute febrile illness (AFI) admitted to tertiary referral hospitals in Mubende and Arua, Uganda. Study participants were selected based on clinical criteria suggestive of viral infection (i.e., thrombocytopenia, leukopenia). The study population had a median age of 28 years (IQR:24 to 38.5) and median platelet count of 114 x103 cells/mm3 (IQR:66,500 to 189,800). An average of 25 million 100 bp reads were generated per sample. We identified strong signals from diverse virus, bacteria, fungi, or parasites in 10 (23.8%) of the study participants. These included well recognized pathogens like Helicobacter pylori, human herpes virus-8, Plasmodium falciparum, Neisseria gonorrhoeae, and Rickettsia conorii. We further confirmed Rickettsia conorii infection, the cause of Mediterranean Spotted Fever (MSF), using PCR assays and Sanger sequencing. mNGS was a useful addition for detection of otherwise undetected pathogens and well-recognized non-pathogens. This is the first report to describe the molecular confirmation of a hospitalized case of MSF in sub-Saharan Africa (SSA). Further studies are needed to determine the utility of mNGS for disease surveillance in similar settings.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)
Databáze: MEDLINE
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