A 2-Biomarker Model Augments Clinical Prediction of Mortality in Melioidosis

Wright, Shelton W.; Kaewarpai, Taniya; Lovelace-Macon, Lara; Ducken, Deirdre; Hantrakun, Viriya; Rudd, Kristina E.; Teparrukkul, Prapit; Phunpang, Rungnapa; Ekchariyawat, Peeraya; Dulsuk, Adul; Moonmueangsan, B; Morakot, Chumpol; Thiansukhon, Ekkachai; Limmathurotsakul, Direk; Chantratita, Narisara; West, T. Eoin

doi:10.1093/cid/ciaa126

Cited by 9 publications

(9 citation statements)

References 46 publications

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“…Others have characterized plasma levels and/or mRNA expression of pro-and anti-inflammatory cytokines in melioidosis patients for similar purposes. For instance, levels of IFN-γ, IL-6, IL-8, IL-10, IL-23, and TNF-α were reported to be higher in melioidosis cases compared with healthy individuals (Kaewarpai et al, 2020 ; Sengyee et al, 2021 ; Wright et al, 2021 ). All of them except IFN-γ were associated with 28-day mortality.…”

Section: Discussionmentioning

confidence: 99%

“…All of them except IFN-γ were associated with 28-day mortality. IL-8 provided the best discrimination of mortality, and over time, non-survivors had increasing IL-6, IL-8, and IL-17A levels, in contrast to survivors (Kaewarpai et al, 2020 ; Wright et al, 2021 ). Similarly, Sengygee and coworkers correlated patient survival with high IFN-γ responses (Sengyee et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of two different vaccine platforms for immunization against melioidosis and glanders

et al. 2022

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Burkholderia pseudomallei and the closely related species, Burkholderia mallei, produce similar multifaceted diseases which range from rapidly fatal to protracted and chronic, and are a major cause of mortality in endemic regions. Besides causing natural infections, both microbes are Tier 1 potential biothreat agents. Antibiotic treatment is prolonged with variable results, hence effective vaccines are urgently needed. The purpose of our studies was to compare candidate vaccines that target both melioidosis and glanders to identify the most efficacious one(s) and define residual requirements for their transition to the non-human primate aerosol model. Studies were conducted in the C57BL/6 mouse model to evaluate the humoral and cell-mediated immune response and protective efficacy of three Burkholderia vaccine candidates against lethal aerosol challenges with B. pseudomallei K96243, B. pseudomallei MSHR5855, and B. mallei FMH. The recombinant vaccines generated significant immune responses to the vaccine antigens, and the live attenuated vaccine generated a greater immune response to OPS and the whole bacterial cells. Regardless of the candidate vaccine evaluated, the protection of mice was associated with a dampened cytokine response within the lungs after exposure to aerosolized bacteria. Despite being delivered by two different platforms and generating distinct immune responses, two experimental vaccines, a capsule conjugate + Hcp1 subunit vaccine and the live B. pseudomallei 668 ΔilvI strain, provided significant protection and were down-selected for further investigation and advanced development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evaluation of two different vaccine platforms for immunization against melioidosis and glanders

et al. 2022

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“…Twenty-three healthy individuals aged ≥ 18 years were recruited from Udon Thani Hospital and Mukdahan hospital as baseline controls for discovery and validation data sets. Inclusion and exclusion criteria for these controls were previously described [ 15 ].…”

Section: Methodsmentioning

confidence: 99%

Blood transcriptomics to characterize key biological pathways and identify biomarkers for predicting mortality in melioidosis

Yimthin

Cliff

Phunpang

et al. 2021

Emerging Microbes & Infections

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Melioidosis is a tropical infectious disease caused by the Gram-negative bacillus, Burkholderia pseudomallei that is often lethal in many endemic areas. The objective of this study was to characterize the transcriptome in melioidosis patients and identify genes associated with outcome. RNA-seq was performed on whole blood RNA in a discovery set of 29 melioidosis patients and 3 healthy controls using Ion AmpliSeq Transcriptome. Transcriptomic profiles of patients who did not survive to 28 days were compared with patients who survived and healthy controls. RT-qPCR of 28 differentially expressed genes was performed in a validation set of 60 melioidosis patients and 20 healthy controls. In RNAseq analysis, 65 genes were significantly up-regulated and 218 were down-regulated in nonsurvivors compared to survivors. Up-regulated genes were involved in myeloid leukocyte activation, Toll-like receptor cascades and reactive oxygen species metabolic processes. Down-regulated genes were hematopoietic cell lineage, adaptive immune system and lymphocyte activation pathways. RT-qPCR in the validation set of patients confirmed differential expression of a subset of genes. IL1R2, GAS7, S100A9, IRAK3, and NFKBIA were significantly higher in non-survivors compared with survivors (P < 0.005) and healthy controls (P < 0.0001). The AUROCC of these genes for mortality discrimination ranged from 0.80-0.88. In survivors, expression of IL1R2, S100A9 and IRAK3 genes decreased significantly over 28 days (P < 0.05). Whole blood transcriptomics characterizes the host response in melioidosis. Expression levels of specific genes are potential biomarkers to predict outcomes. These findings augment our understanding of this severe infection.

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“…Our prognostic signature indicates that lower glutamate levels are associated with fatal melioidosis, a finding that is consistent with previous reports of reduced glutamate levels in nonsurvivors of severe sepsis and its potential utility as an early biomarker for death in septic shock ( 46 ). Although promising, this prognostic signature requires further investigation in an independent cohort of patients with melioidosis and comparison to other predictive biomarkers and clinical tools ( 9 , 15 , 47 – 49 ).…”

Section: Discussionmentioning

confidence: 99%

“…Subjects at least 18 years of age admitted to Sunpasitthiprasong Hospital in Ubon Ratchathani, Thailand with suspected community-acquired infection were sequentially and prospectively enrolled within 24 hours of admission into the Ubon-Sepsis parent study from 2013 through 2017. This cohort has been described previously ( 9 – 15 ). Plasma samples were obtained from all participants at the time of enrollment.…”

Section: Methodsmentioning

confidence: 99%

Plasma Metabolomics Reveals Distinct Biological and Diagnostic Signatures for Melioidosis

Xia,

Hantrakun,

Teparrukkul

et al. 2024

Am J Respir Crit Care Med

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Rationale The global burden of sepsis is greatest in low-resource settings. Melioidosis, infection with the gram-negative bacterium Burkholderia pseudomallei , is a frequent cause of fatal sepsis in endemic tropical regions such as Southeast Asia. Objectives To investigate whether plasma metabolomics would identify biological pathways specific to melioidosis and yield clinically meaningful biomarkers. Methods Using a comprehensive approach, differential enrichment of plasma metabolites and pathways was systematically evaluated in individuals selected from a prospective cohort of patients hospitalized in rural Thailand with infection. Statistical and bioinformatics methods were used to distinguish metabolomic features and processes specific to patients with melioidosis and between fatal and nonfatal cases. Measurements and Main Results Metabolomic profiling and pathway enrichment analysis of plasma samples from patients with melioidosis ( n = 175) and nonmelioidosis infections ( n = 75) revealed a distinct immuno-metabolic state among patients with melioidosis, as suggested by excessive tryptophan catabolism in the kynurenine pathway and significantly increased levels of sphingomyelins and ceramide species. We derived a 12-metabolite classifier to distinguish melioidosis from other infections, yielding an area under the receiver operating characteristic curve of 0.87 in a second validation set of patients. Melioidosis nonsurvivors ( n = 94) had a significantly disturbed metabolome compared with survivors ( n = 81), with increased leucine, isoleucine, and valine metabolism, and elevated circulating free fatty acids and acylcarnitines. A limited eight-metabolite panel showed promise as an early prognosticator of mortality in melioidosis. Conclusions Melioidosis induces a distinct metabolomic state that can be examined to distinguish underlying pathophysiological mechanisms associated with death. A 12-metabolite signature accurately differentiates melioidosis from other infections and may have diagnostic applications.

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A 2-Biomarker Model Augments Clinical Prediction of Mortality in Melioidosis

Cited by 9 publications

References 46 publications

Evaluation of two different vaccine platforms for immunization against melioidosis and glanders

Evaluation of two different vaccine platforms for immunization against melioidosis and glanders

Blood transcriptomics to characterize key biological pathways and identify biomarkers for predicting mortality in melioidosis

Plasma Metabolomics Reveals Distinct Biological and Diagnostic Signatures for Melioidosis

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