Development and evaluation of a multiplex serodiagnostic bead assay (BurkPx) for accurate melioidosis diagnosis.
Burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative soil bacterium well recognized in Southeast Asia and northern Australia. However, wider and expanding global distribution of B. pseudomallei has been elucidated. Early diagnosis is critical for commencing the specific...
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ftdoajarticles:oai:doaj.org/article:82f38f7fa29f4f5c99268ebfdcee035c 2023-05-15T15:15:08+02:00 Development and evaluation of a multiplex serodiagnostic bead assay (BurkPx) for accurate melioidosis diagnosis. Erik W Settles Derek Sonderegger Austin B Shannon Kimberly R Celona Rachel Lederer Jinhee Yi Courtney Seavey Kyle Headley Mimi Mbegbu Maxx Harvey Mitch Keener Chris Allender Heidie Hornstra Fernando P Monroy Celeste Woerle Vanessa Theobald Mark Mayo Bart J Currie Paul Keim 2023-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011072 https://doaj.org/article/82f38f7fa29f4f5c99268ebfdcee035c EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0011072 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011072 https://doaj.org/article/82f38f7fa29f4f5c99268ebfdcee035c PLoS Neglected Tropical Diseases, Vol 17, Iss 2, p e0011072 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011072 2023-03-05T01:33:15Z Burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative soil bacterium well recognized in Southeast Asia and northern Australia. However, wider and expanding global distribution of B. pseudomallei has been elucidated. Early diagnosis is critical for commencing the specific therapy required to optimize outcome. Serological testing using the indirect hemagglutination (IHA) antibody assay has long been used to augment diagnosis of melioidosis and to monitor progress. However, cross reactivity and prior exposure may complicate the diagnosis of current clinical disease (melioidosis). The goal of our study was to develop and initially evaluate a serology assay (BurkPx) that capitalized upon host response to multiple antigens. Antigens were selected from previous studies for expression/purification and conjugation to microspheres for multiantigen analysis. Selected serum samples from non-melioidosis controls and serial samples from culture-confirmed melioidosis patients were used to characterize the diagnostic power of individual and combined antigens at two times post admission. Multiple variable models were developed to evaluate multivariate antigen reactivity, identify important antigens, and determine sensitivity and specificity for the diagnosis of melioidosis. The final multiplex assay had a diagnostic sensitivity of 90% and specificity of 93%, which was superior to any single antigen in side-by-side comparisons. The sensitivity of the assay started at >85% for the initial serum sample after admission and increased to 94% 21 days later. Weighting antigen contribution to each model indicated that certain antigen contributed to diagnosis more than others, which suggests that the number of antigens in the assay can be decreased. In summation, the BurkPx assay can facilitate the diagnosis of melioidosis and potentially improve on currently available serology assays. Further evaluation is now required in both melioidosis-endemic and non-endemic settings. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 17 2 e0011072 |
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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 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Erik W Settles Derek Sonderegger Austin B Shannon Kimberly R Celona Rachel Lederer Jinhee Yi Courtney Seavey Kyle Headley Mimi Mbegbu Maxx Harvey Mitch Keener Chris Allender Heidie Hornstra Fernando P Monroy Celeste Woerle Vanessa Theobald Mark Mayo Bart J Currie Paul Keim Development and evaluation of a multiplex serodiagnostic bead assay (BurkPx) for accurate melioidosis diagnosis. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative soil bacterium well recognized in Southeast Asia and northern Australia. However, wider and expanding global distribution of B. pseudomallei has been elucidated. Early diagnosis is critical for commencing the specific therapy required to optimize outcome. Serological testing using the indirect hemagglutination (IHA) antibody assay has long been used to augment diagnosis of melioidosis and to monitor progress. However, cross reactivity and prior exposure may complicate the diagnosis of current clinical disease (melioidosis). The goal of our study was to develop and initially evaluate a serology assay (BurkPx) that capitalized upon host response to multiple antigens. Antigens were selected from previous studies for expression/purification and conjugation to microspheres for multiantigen analysis. Selected serum samples from non-melioidosis controls and serial samples from culture-confirmed melioidosis patients were used to characterize the diagnostic power of individual and combined antigens at two times post admission. Multiple variable models were developed to evaluate multivariate antigen reactivity, identify important antigens, and determine sensitivity and specificity for the diagnosis of melioidosis. The final multiplex assay had a diagnostic sensitivity of 90% and specificity of 93%, which was superior to any single antigen in side-by-side comparisons. The sensitivity of the assay started at >85% for the initial serum sample after admission and increased to 94% 21 days later. Weighting antigen contribution to each model indicated that certain antigen contributed to diagnosis more than others, which suggests that the number of antigens in the assay can be decreased. In summation, the BurkPx assay can facilitate the diagnosis of melioidosis and potentially improve on currently available serology assays. Further evaluation is now required in both melioidosis-endemic and non-endemic settings. |
format |
Article in Journal/Newspaper |
author |
Erik W Settles Derek Sonderegger Austin B Shannon Kimberly R Celona Rachel Lederer Jinhee Yi Courtney Seavey Kyle Headley Mimi Mbegbu Maxx Harvey Mitch Keener Chris Allender Heidie Hornstra Fernando P Monroy Celeste Woerle Vanessa Theobald Mark Mayo Bart J Currie Paul Keim |
author_facet |
Erik W Settles Derek Sonderegger Austin B Shannon Kimberly R Celona Rachel Lederer Jinhee Yi Courtney Seavey Kyle Headley Mimi Mbegbu Maxx Harvey Mitch Keener Chris Allender Heidie Hornstra Fernando P Monroy Celeste Woerle Vanessa Theobald Mark Mayo Bart J Currie Paul Keim |
author_sort |
Erik W Settles |
title |
Development and evaluation of a multiplex serodiagnostic bead assay (BurkPx) for accurate melioidosis diagnosis. |
title_short |
Development and evaluation of a multiplex serodiagnostic bead assay (BurkPx) for accurate melioidosis diagnosis. |
title_full |
Development and evaluation of a multiplex serodiagnostic bead assay (BurkPx) for accurate melioidosis diagnosis. |
title_fullStr |
Development and evaluation of a multiplex serodiagnostic bead assay (BurkPx) for accurate melioidosis diagnosis. |
title_full_unstemmed |
Development and evaluation of a multiplex serodiagnostic bead assay (BurkPx) for accurate melioidosis diagnosis. |
title_sort |
development and evaluation of a multiplex serodiagnostic bead assay (burkpx) for accurate melioidosis diagnosis. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doi.org/10.1371/journal.pntd.0011072 https://doaj.org/article/82f38f7fa29f4f5c99268ebfdcee035c |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 2, p e0011072 (2023) |
op_relation |
https://doi.org/10.1371/journal.pntd.0011072 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011072 https://doaj.org/article/82f38f7fa29f4f5c99268ebfdcee035c |
op_doi |
https://doi.org/10.1371/journal.pntd.0011072 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
17 |
container_issue |
2 |
container_start_page |
e0011072 |
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1766345517447512064 |