Cargando…

1030. Chasing the Long Tail of Infectious Diseases: Detecting Capnocytophaga canimorsus and Pasteurella multocida Infections with A Plasma-based Microbial Cell-Free DNA Next Generation Sequencing Test

BACKGROUND: Capnocytophaga canimorsus (Cc) and Pasteurella multocida (Pm) are gram negative bacterial commensal pathogens typically from dogs or cats that can cause severe infection in humans when spread through licks, scratches or bites. The diagnosis of these infections can be limited by: (1) thei...

Descripción completa

Detalles Bibliográficos
Autores principales: Degner, Nicholas R, Galvan-Castillo, Ricardo, Alexander, Jose, Arun, Aparna, de Vries, Christiaan R, Macintyre, Ann, Perkins, Bradley, Ahmed, Asim A, Smollin, Matthew
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643751/
http://dx.doi.org/10.1093/ofid/ofab466.1224
_version_ 1784609924863492096
author Degner, Nicholas R
Galvan-Castillo, Ricardo
Alexander, Jose
Arun, Aparna
de Vries, Christiaan R
Macintyre, Ann
Perkins, Bradley
Ahmed, Asim A
Smollin, Matthew
author_facet Degner, Nicholas R
Galvan-Castillo, Ricardo
Alexander, Jose
Arun, Aparna
de Vries, Christiaan R
Macintyre, Ann
Perkins, Bradley
Ahmed, Asim A
Smollin, Matthew
author_sort Degner, Nicholas R
collection PubMed
description BACKGROUND: Capnocytophaga canimorsus (Cc) and Pasteurella multocida (Pm) are gram negative bacterial commensal pathogens typically from dogs or cats that can cause severe infection in humans when spread through licks, scratches or bites. The diagnosis of these infections can be limited by: (1) their fastidious nature and difficulty to culture; (2) the nonspecific manifestations of the infections; and (3) the unreliability of dog or cat exposure history. Open-ended microbial cell free DNA (mcfDNA) next-generation sequencing (NGS) offers a potential solution to overcome these limitations. METHODS: The Karius Test(TM) (KT) developed and validated in Karius’s CLIA certified/CAP accredited lab in Redwood City, CA detects mcfDNA in plasma. After mcfDNA is extracted and NGS performed, human reads are removed, and remaining sequences are aligned to a curated database of > 1500 organisms. McfDNA from organisms present above a statistical threshold are reported and quantified in molecules/µL (MPM). KT detections of Cc and Pm were reviewed from August 2017 - present; clinical information was obtained with test requisition or consultation upon result reporting. RESULTS: KT detected 5 cases of Cc (25,039 MPM +/- 41,062) and 8 cases of Pm (33,264 MPM +/- 69,301) (Table 1). All detections of Cc were in adults (60% male) and included 2 cases of culture-negative endocarditis (one with known liver disease) and one case of sepsis with diffuse rash. Pm detections occurred in 6 adults and 2 children (75% male) and included 2 cases of culture-negative endocarditis, and single cases each of endovascular graft infection, pneumonia, fever of unknown origin, and a cranial dog bite complicated by an abscess. Two patients had immunocompromising conditions including neuroblastoma and aplastic anemia. [Image: see text] CONCLUSION: Unbiased, plasma-based mcfDNA NGS provides a rapid, non-invasive test to diagnose diverse clinical infections by Cc and Pm. These cases highlight the potential of the KT to diagnose infections caused by fastidious/unculturable pathogens with non-specific clinical manifestations and broad differential diagnoses. DISCLOSURES: Nicholas R. Degner, MD, MPH, MS, Karius Inc. (Employee, Shareholder) Ricardo Galvan-Castillo, MD, Karius Inc. (Employee, Shareholder) Jose Alexander, MD, D(ABMM), FCCM, CIC, SM, MB(ASCP), BCMAS, Karius (Employee) Aparna Arun, MD, Karius (Employee) Ann Macintyre, DO, Karius, Inc. (Employee) Bradley Perkins, MD, Karius, Inc. (Employee) Asim A. Ahmed, MD, Karius, Inc. (Employee) Matthew Smollin, PharmD, Karius, Inc. (Employee)
format Online
Article
Text
id pubmed-8643751
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-86437512021-12-06 1030. Chasing the Long Tail of Infectious Diseases: Detecting Capnocytophaga canimorsus and Pasteurella multocida Infections with A Plasma-based Microbial Cell-Free DNA Next Generation Sequencing Test Degner, Nicholas R Galvan-Castillo, Ricardo Alexander, Jose Arun, Aparna de Vries, Christiaan R Macintyre, Ann Perkins, Bradley Ahmed, Asim A Smollin, Matthew Open Forum Infect Dis Poster Abstracts BACKGROUND: Capnocytophaga canimorsus (Cc) and Pasteurella multocida (Pm) are gram negative bacterial commensal pathogens typically from dogs or cats that can cause severe infection in humans when spread through licks, scratches or bites. The diagnosis of these infections can be limited by: (1) their fastidious nature and difficulty to culture; (2) the nonspecific manifestations of the infections; and (3) the unreliability of dog or cat exposure history. Open-ended microbial cell free DNA (mcfDNA) next-generation sequencing (NGS) offers a potential solution to overcome these limitations. METHODS: The Karius Test(TM) (KT) developed and validated in Karius’s CLIA certified/CAP accredited lab in Redwood City, CA detects mcfDNA in plasma. After mcfDNA is extracted and NGS performed, human reads are removed, and remaining sequences are aligned to a curated database of > 1500 organisms. McfDNA from organisms present above a statistical threshold are reported and quantified in molecules/µL (MPM). KT detections of Cc and Pm were reviewed from August 2017 - present; clinical information was obtained with test requisition or consultation upon result reporting. RESULTS: KT detected 5 cases of Cc (25,039 MPM +/- 41,062) and 8 cases of Pm (33,264 MPM +/- 69,301) (Table 1). All detections of Cc were in adults (60% male) and included 2 cases of culture-negative endocarditis (one with known liver disease) and one case of sepsis with diffuse rash. Pm detections occurred in 6 adults and 2 children (75% male) and included 2 cases of culture-negative endocarditis, and single cases each of endovascular graft infection, pneumonia, fever of unknown origin, and a cranial dog bite complicated by an abscess. Two patients had immunocompromising conditions including neuroblastoma and aplastic anemia. [Image: see text] CONCLUSION: Unbiased, plasma-based mcfDNA NGS provides a rapid, non-invasive test to diagnose diverse clinical infections by Cc and Pm. These cases highlight the potential of the KT to diagnose infections caused by fastidious/unculturable pathogens with non-specific clinical manifestations and broad differential diagnoses. DISCLOSURES: Nicholas R. Degner, MD, MPH, MS, Karius Inc. (Employee, Shareholder) Ricardo Galvan-Castillo, MD, Karius Inc. (Employee, Shareholder) Jose Alexander, MD, D(ABMM), FCCM, CIC, SM, MB(ASCP), BCMAS, Karius (Employee) Aparna Arun, MD, Karius (Employee) Ann Macintyre, DO, Karius, Inc. (Employee) Bradley Perkins, MD, Karius, Inc. (Employee) Asim A. Ahmed, MD, Karius, Inc. (Employee) Matthew Smollin, PharmD, Karius, Inc. (Employee) Oxford University Press 2021-12-04 /pmc/articles/PMC8643751/ http://dx.doi.org/10.1093/ofid/ofab466.1224 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Poster Abstracts
Degner, Nicholas R
Galvan-Castillo, Ricardo
Alexander, Jose
Arun, Aparna
de Vries, Christiaan R
Macintyre, Ann
Perkins, Bradley
Ahmed, Asim A
Smollin, Matthew
1030. Chasing the Long Tail of Infectious Diseases: Detecting Capnocytophaga canimorsus and Pasteurella multocida Infections with A Plasma-based Microbial Cell-Free DNA Next Generation Sequencing Test
title 1030. Chasing the Long Tail of Infectious Diseases: Detecting Capnocytophaga canimorsus and Pasteurella multocida Infections with A Plasma-based Microbial Cell-Free DNA Next Generation Sequencing Test
title_full 1030. Chasing the Long Tail of Infectious Diseases: Detecting Capnocytophaga canimorsus and Pasteurella multocida Infections with A Plasma-based Microbial Cell-Free DNA Next Generation Sequencing Test
title_fullStr 1030. Chasing the Long Tail of Infectious Diseases: Detecting Capnocytophaga canimorsus and Pasteurella multocida Infections with A Plasma-based Microbial Cell-Free DNA Next Generation Sequencing Test
title_full_unstemmed 1030. Chasing the Long Tail of Infectious Diseases: Detecting Capnocytophaga canimorsus and Pasteurella multocida Infections with A Plasma-based Microbial Cell-Free DNA Next Generation Sequencing Test
title_short 1030. Chasing the Long Tail of Infectious Diseases: Detecting Capnocytophaga canimorsus and Pasteurella multocida Infections with A Plasma-based Microbial Cell-Free DNA Next Generation Sequencing Test
title_sort 1030. chasing the long tail of infectious diseases: detecting capnocytophaga canimorsus and pasteurella multocida infections with a plasma-based microbial cell-free dna next generation sequencing test
topic Poster Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8643751/
http://dx.doi.org/10.1093/ofid/ofab466.1224
work_keys_str_mv AT degnernicholasr 1030chasingthelongtailofinfectiousdiseasesdetectingcapnocytophagacanimorsusandpasteurellamultocidainfectionswithaplasmabasedmicrobialcellfreednanextgenerationsequencingtest
AT galvancastilloricardo 1030chasingthelongtailofinfectiousdiseasesdetectingcapnocytophagacanimorsusandpasteurellamultocidainfectionswithaplasmabasedmicrobialcellfreednanextgenerationsequencingtest
AT alexanderjose 1030chasingthelongtailofinfectiousdiseasesdetectingcapnocytophagacanimorsusandpasteurellamultocidainfectionswithaplasmabasedmicrobialcellfreednanextgenerationsequencingtest
AT arunaparna 1030chasingthelongtailofinfectiousdiseasesdetectingcapnocytophagacanimorsusandpasteurellamultocidainfectionswithaplasmabasedmicrobialcellfreednanextgenerationsequencingtest
AT devrieschristiaanr 1030chasingthelongtailofinfectiousdiseasesdetectingcapnocytophagacanimorsusandpasteurellamultocidainfectionswithaplasmabasedmicrobialcellfreednanextgenerationsequencingtest
AT macintyreann 1030chasingthelongtailofinfectiousdiseasesdetectingcapnocytophagacanimorsusandpasteurellamultocidainfectionswithaplasmabasedmicrobialcellfreednanextgenerationsequencingtest
AT perkinsbradley 1030chasingthelongtailofinfectiousdiseasesdetectingcapnocytophagacanimorsusandpasteurellamultocidainfectionswithaplasmabasedmicrobialcellfreednanextgenerationsequencingtest
AT ahmedasima 1030chasingthelongtailofinfectiousdiseasesdetectingcapnocytophagacanimorsusandpasteurellamultocidainfectionswithaplasmabasedmicrobialcellfreednanextgenerationsequencingtest
AT smollinmatthew 1030chasingthelongtailofinfectiousdiseasesdetectingcapnocytophagacanimorsusandpasteurellamultocidainfectionswithaplasmabasedmicrobialcellfreednanextgenerationsequencingtest