NHP BurkPx: A multiplex serodiagnostic bead assay to monitor Burkholderia pseudomallei exposures in non-human primates.

Background Melioidosis is a disease caused by the bacterium Burkholderia pseudomallei, infecting humans and non-human primates (NHP) through contaminated soil or water. World-wide there are an estimated 165,000 human melioidosis cases each year, but recordings of NHP cases are sporadic. Clinical det...

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Published in:PLOS Neglected Tropical Diseases
Main Authors: Kimberly R Celona, Austin B Shannon, Derek Sonderegger, Jinhee Yi, Fernando P Monroy, Christopher Allender, Heidie Hornstra, Mary B Barnes, Elizabeth S Didier, Rudolf P Bohm, Kathrine Phillippi-Falkenstein, Daniel Sanford, Paul Keim, Erik W Settles
Format: Article in Journal/Newspaper
Language:English
Published: Public Library of Science (PLoS) 2023
Subjects:
Online Access:https://doi.org/10.1371/journal.pntd.0011067
https://doaj.org/article/eeea63ae78c4475da089be4f17be7c0f
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spelling ftdoajarticles:oai:doaj.org/article:eeea63ae78c4475da089be4f17be7c0f 2023-05-15T15:15:08+02:00 NHP BurkPx: A multiplex serodiagnostic bead assay to monitor Burkholderia pseudomallei exposures in non-human primates. Kimberly R Celona Austin B Shannon Derek Sonderegger Jinhee Yi Fernando P Monroy Christopher Allender Heidie Hornstra Mary B Barnes Elizabeth S Didier Rudolf P Bohm Kathrine Phillippi-Falkenstein Daniel Sanford Paul Keim Erik W Settles 2023-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011067 https://doaj.org/article/eeea63ae78c4475da089be4f17be7c0f EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0011067 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011067 https://doaj.org/article/eeea63ae78c4475da089be4f17be7c0f PLoS Neglected Tropical Diseases, Vol 17, Iss 2, p e0011067 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011067 2023-03-05T01:33:15Z Background Melioidosis is a disease caused by the bacterium Burkholderia pseudomallei, infecting humans and non-human primates (NHP) through contaminated soil or water. World-wide there are an estimated 165,000 human melioidosis cases each year, but recordings of NHP cases are sporadic. Clinical detection of melioidosis in humans is primarily by culturing B. pseudomallei, and there are no standardized detection protocols for NHP. NHP are an important animal model for melioidosis research including clinical trials and development of biodefense countermeasures. Methodology/principle findings We evaluated the diagnostic potential of the multiple antigen serological assay, BurkPx, in NHP using two sera sets: (i) 115 B. pseudomallei-challenged serum samples from 80 NHP collected each week post-exposure (n = 52) and at euthanasia (n = 47), and (ii) 126 B. pseudomallei-naïve/negative serum samples. We observed early IgM antibody responses to carbohydrate antigens followed by IgG antibody recognition to multiple B. pseudomallei protein antigens during the second week of infection. B. pseudomallei negative serum samples had low to intermediate antibody cross reactivity to the antigens in this assay. Infection time was predicted as the determining factor in the variation of antibody responses, with 77.67% of variation explained by the first component of the principal component analysis. A multiple antigen model generated a binary prediction metric ([Formula: see text]), which when applied to all data resulted in 100% specificity and 63.48% sensitivity. Removal of week 1 B. pseudomallei challenged serum samples increased the sensitivity of the model to 95%. Conclusion/significance We employed a previously standardized assay for humans, the BurkPx assay, and assessed its diagnostic potential for detection of B. pseudomallei exposure in NHP. The assay is expected to be useful for surveillance in NHP colonies, in investigations of suspected accidental releases or exposures, and for identifying vaccine correlates of protection. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 17 2 e0011067
institution Open Polar
collection Directory of Open Access Journals: DOAJ Articles
op_collection_id ftdoajarticles
language English
topic Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
spellingShingle Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
Kimberly R Celona
Austin B Shannon
Derek Sonderegger
Jinhee Yi
Fernando P Monroy
Christopher Allender
Heidie Hornstra
Mary B Barnes
Elizabeth S Didier
Rudolf P Bohm
Kathrine Phillippi-Falkenstein
Daniel Sanford
Paul Keim
Erik W Settles
NHP BurkPx: A multiplex serodiagnostic bead assay to monitor Burkholderia pseudomallei exposures in non-human primates.
topic_facet Arctic medicine. Tropical medicine
RC955-962
Public aspects of medicine
RA1-1270
description Background Melioidosis is a disease caused by the bacterium Burkholderia pseudomallei, infecting humans and non-human primates (NHP) through contaminated soil or water. World-wide there are an estimated 165,000 human melioidosis cases each year, but recordings of NHP cases are sporadic. Clinical detection of melioidosis in humans is primarily by culturing B. pseudomallei, and there are no standardized detection protocols for NHP. NHP are an important animal model for melioidosis research including clinical trials and development of biodefense countermeasures. Methodology/principle findings We evaluated the diagnostic potential of the multiple antigen serological assay, BurkPx, in NHP using two sera sets: (i) 115 B. pseudomallei-challenged serum samples from 80 NHP collected each week post-exposure (n = 52) and at euthanasia (n = 47), and (ii) 126 B. pseudomallei-naïve/negative serum samples. We observed early IgM antibody responses to carbohydrate antigens followed by IgG antibody recognition to multiple B. pseudomallei protein antigens during the second week of infection. B. pseudomallei negative serum samples had low to intermediate antibody cross reactivity to the antigens in this assay. Infection time was predicted as the determining factor in the variation of antibody responses, with 77.67% of variation explained by the first component of the principal component analysis. A multiple antigen model generated a binary prediction metric ([Formula: see text]), which when applied to all data resulted in 100% specificity and 63.48% sensitivity. Removal of week 1 B. pseudomallei challenged serum samples increased the sensitivity of the model to 95%. Conclusion/significance We employed a previously standardized assay for humans, the BurkPx assay, and assessed its diagnostic potential for detection of B. pseudomallei exposure in NHP. The assay is expected to be useful for surveillance in NHP colonies, in investigations of suspected accidental releases or exposures, and for identifying vaccine correlates of protection.
format Article in Journal/Newspaper
author Kimberly R Celona
Austin B Shannon
Derek Sonderegger
Jinhee Yi
Fernando P Monroy
Christopher Allender
Heidie Hornstra
Mary B Barnes
Elizabeth S Didier
Rudolf P Bohm
Kathrine Phillippi-Falkenstein
Daniel Sanford
Paul Keim
Erik W Settles
author_facet Kimberly R Celona
Austin B Shannon
Derek Sonderegger
Jinhee Yi
Fernando P Monroy
Christopher Allender
Heidie Hornstra
Mary B Barnes
Elizabeth S Didier
Rudolf P Bohm
Kathrine Phillippi-Falkenstein
Daniel Sanford
Paul Keim
Erik W Settles
author_sort Kimberly R Celona
title NHP BurkPx: A multiplex serodiagnostic bead assay to monitor Burkholderia pseudomallei exposures in non-human primates.
title_short NHP BurkPx: A multiplex serodiagnostic bead assay to monitor Burkholderia pseudomallei exposures in non-human primates.
title_full NHP BurkPx: A multiplex serodiagnostic bead assay to monitor Burkholderia pseudomallei exposures in non-human primates.
title_fullStr NHP BurkPx: A multiplex serodiagnostic bead assay to monitor Burkholderia pseudomallei exposures in non-human primates.
title_full_unstemmed NHP BurkPx: A multiplex serodiagnostic bead assay to monitor Burkholderia pseudomallei exposures in non-human primates.
title_sort nhp burkpx: a multiplex serodiagnostic bead assay to monitor burkholderia pseudomallei exposures in non-human primates.
publisher Public Library of Science (PLoS)
publishDate 2023
url https://doi.org/10.1371/journal.pntd.0011067
https://doaj.org/article/eeea63ae78c4475da089be4f17be7c0f
geographic Arctic
geographic_facet Arctic
genre Arctic
genre_facet Arctic
op_source PLoS Neglected Tropical Diseases, Vol 17, Iss 2, p e0011067 (2023)
op_relation https://doi.org/10.1371/journal.pntd.0011067
https://doaj.org/toc/1935-2727
https://doaj.org/toc/1935-2735
1935-2727
1935-2735
doi:10.1371/journal.pntd.0011067
https://doaj.org/article/eeea63ae78c4475da089be4f17be7c0f
op_doi https://doi.org/10.1371/journal.pntd.0011067
container_title PLOS Neglected Tropical Diseases
container_volume 17
container_issue 2
container_start_page e0011067
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