Detection of Mpox Virus Using Microbial Cell-Free DNA: The Potential of Pathogen-Agnostic Sequencing for Rapid Identification of Emerging Pathogens.

Autor:	Park SY; Medical Affairs, Karius, Inc, Redwood City, California., Lindner MS; Analytics, Karius, Inc., Redwood City, California., Brick K; Analytics, Karius, Inc., Redwood City, California., Noll N; Analytics, Karius, Inc., Redwood City, California., Ounit R; Analytics, Karius, Inc., Redwood City, California., Noa LJ; Infectious Disease Section, AdventHealth Orlando, Florida., Sabzwari R; Infectious Diseases, Edward Hines Jr Veterans Affairs Hospital, Hines, Illinois., Trible R; Georgia Infectious Diseases, PC, Atlanta., Sniffen JC; Infectious Disease Section, AdventHealth Orlando, Florida., Roth P; Infectious Diseases, Prisma Health-Upstate, Greenville, South Carolina., Khan A; Infectious Diseases, Carle Foundation Hospital, Urbana, Illinois., Rodriguez A; Infectious Diseases, Orlando Health, Florida., Sahra S; Department of Infectious Diseases, Oklahoma University Medical Center, Oklahoma City., Davis MJ; Department of Infectious Diseases and International Medicine, University of Minnesota, Minneapolis, MN., Brar IS; Infectious Diseases, Baptist Memorial Health Care, Memphis, Tennessee., Balasundaram G; Medical Affairs, Karius, Inc, Redwood City, California., Nolte FS; Medical Affairs, Karius, Inc, Redwood City, California., Blauwkamp TA; Executive Team, Karius, Inc., Redwood City, California., Perkins BA; Executive Team, Karius, Inc., Redwood City, California., Bercovici S; Executive Team, Karius, Inc., Redwood City, California.
Jazyk:	angličtina
Zdroj:	The Journal of infectious diseases [J Infect Dis] 2024 Mar 26; Vol. 229 (Supplement_2), pp. S144-S155.
DOI:	10.1093/infdis/jiad452
Abstrakt:	Background: The 2022 global outbreak of Monkeypox virus (MPXV) highlighted challenges with polymerase chain reaction detection as divergent strains emerged and atypical presentations limited the applicability of swab sampling. Recommended testing in the United States requires a swab of lesions, which arise late in infection and may be unrecognized. We present MPXV detections using plasma microbial cell-free DNA (mcfDNA) sequencing. Methods: Fifteen plasma samples from 12 case-patients were characterized through mcfDNA sequencing. Assay performance was confirmed through in silico inclusivity and exclusivity assessments. MPXV isolates were genotyped using mcfDNA, and phylodynamic information was imputed using publicly available sequences. Results: MPXV mcfDNA was detected in 12 case-patients. Mpox was not suspected in 5, with 1 having documented resolution of mpox >6 months previously. Six had moderate to severe mpox, supported by high MPXV mcfDNA concentrations; 4 died. In 7 case-patients, mcfDNA sequencing detected coinfections. Genotyping by mcfDNA sequencing identified 22 MPXV mutations at 10 genomic loci in 9 case-patients. Consistent with variation observed in the 2022 outbreak, 21 of 22 variants were G > A/C > T. Phylogenetic analyses imputed isolates to sublineages arising at different time points and from different geographic locations. Conclusions: We demonstrate the potential of plasma mcfDNA sequencing to detect, quantify, and, for acute infections with high sequencing coverage, subtype MPXV using a single noninvasive test. Sequencing plasma mcfDNA may augment existing mpox testing in vulnerable patient populations or in patients with atypical symptoms or unrecognized mpox. Strain type information may supplement disease surveillance and facilitate tracking emerging pathogens. Competing Interests: Potential conflicts of interest. S. Y. P., M. S. L., K. B., N. N., G. B., T. A. B., F. S. N., B. A. P., and S. B. are employees of Karius, Inc. R. O. was an employee of Karius, Inc, at the time the project was conceived and executed. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu