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...
Published in: | PLOS Neglected Tropical Diseases |
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Online Access: | https://doi.org/10.1371/journal.pntd.0011067 https://doaj.org/article/eeea63ae78c4475da089be4f17be7c0f |
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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 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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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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1766345517073170432 |