Detection of Mpox Virus Using Microbial Cell-free DNA: the Potential of Pathogen-Agnostic Sequencing for Rapid Identification of Emerging Pathogens.
HIV
metagenomic sequencing
microbial cell-free DNA
monkeypox
mpox
outbreak surveillance
Journal
The Journal of infectious diseases
ISSN: 1537-6613
Titre abrégé: J Infect Dis
Pays: United States
ID NLM: 0413675
Informations de publication
Date de publication:
12 Oct 2023
12 Oct 2023
Historique:
received:
31
07
2023
revised:
09
10
2023
accepted:
10
10
2023
medline:
12
10
2023
pubmed:
12
10
2023
entrez:
12
10
2023
Statut:
aheadofprint
Résumé
The 2022 global outbreak of mpox virus (MPXV) highlighted challenges with PCR 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. 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 imputed using publicly available sequences. MPXV mcfDNA was detected in 12 case-patients. Mpox was not suspected in 5, with one having documented resolution of mpox >6 months previously. Six had moderate to severe mpox, supported by high MPXV mcfDNA concentration; 4 died. In 7 case-patients, mcfDNA sequencing detected co-infections. Genotyping by mcfDNA sequencing identified 22 MPXV mutations at 10 genomic loci in 9 case-patients. Consistent with variation observed in the 2022 outbreak, 21/22 variants were G > A/C > T. Phylogenetic analyses imputed isolates to sublineages arising at different time points and from different geographic locations. We demonstrate the potential of plasma mcfDNA sequencing to detect, quantify, and, for acute infections with high sequencing coverage, subtype MPXV using a single non-invasive 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.
Sections du résumé
BACKGROUND
BACKGROUND
The 2022 global outbreak of mpox virus (MPXV) highlighted challenges with PCR 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
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 imputed using publicly available sequences.
RESULTS
RESULTS
MPXV mcfDNA was detected in 12 case-patients. Mpox was not suspected in 5, with one having documented resolution of mpox >6 months previously. Six had moderate to severe mpox, supported by high MPXV mcfDNA concentration; 4 died. In 7 case-patients, mcfDNA sequencing detected co-infections. Genotyping by mcfDNA sequencing identified 22 MPXV mutations at 10 genomic loci in 9 case-patients. Consistent with variation observed in the 2022 outbreak, 21/22 variants were G > A/C > T. Phylogenetic analyses imputed isolates to sublineages arising at different time points and from different geographic locations.
CONCLUSIONS
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 non-invasive 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.
Identifiants
pubmed: 37824825
pii: 7310835
doi: 10.1093/infdis/jiad452
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.