The mechanism for low yield of blood culture in invasive aspergillosis; the clinical importance of antigen detection tests revisited

Kami, Masahiro; Murashige, Naoko; Fujihara, Tetsuaki; Sakagami, Nobutada; Tanaka, Yuji

doi:10.1038/sj.bmt.1704997

Cited by 12 publications

(9 citation statements)

References 6 publications

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“…Genome ontology enrichment analysis showed significant overrepresentation of complement cascade (5-fold enrichment, p < 1.55 X 10 −2 ). Consistent with the lack of circulating organisms in patients with acute IPA [ 10 ], no high confidence protein matches were obtained by searching peptide fingerprints within multiple Aspergillus databases ( Materials and Methods ). From these data we concluded that complement and coagulation cascades were components of the host response to IPA, and that active post-translational modification of these proteins were produced, perhaps through their consumption or proteolysis as a consequence of angio-invasion.…”

Section: Resultsmentioning

confidence: 99%

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Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens

et al. 2015

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Invasive pulmonary aspergillosis (IPA) is an opportunistic fungal infection in patients undergoing chemotherapy for hematological malignancy, hematopoietic stem cell transplant, or other forms of immunosuppression. In this group, Aspergillus infections account for the majority of deaths due to mold pathogens. Although early detection is associated with improved outcomes, current diagnostic regimens lack sensitivity and specificity. Patients undergoing chemotherapy, stem cell transplantation and lung transplantation were enrolled in a multi-site prospective observational trial. Proven and probable IPA cases and matched controls were subjected to discovery proteomics analyses using a biofluid analysis platform, fractionating plasma into reproducible protein and peptide pools. From 556 spots identified by 2D gel electrophoresis, 66 differentially expressed post-translationally modified plasma proteins were identified in the leukemic subgroup only. This protein group was rich in complement components, acute-phase reactants and coagulation factors. Low molecular weight peptides corresponding to abundant plasma proteins were identified. A candidate marker panel of host response (9 plasma proteins, 4 peptides), fungal polysaccharides (galactomannan), and cell wall components (β-D glucan) were selected by statistical filtering for patients with leukemia as a primary underlying diagnosis. Quantitative measurements were developed to qualify the differential expression of the candidate host response proteins using selective reaction monitoring mass spectrometry assays, and then applied to a separate cohort of 57 patients with leukemia. In this verification cohort, a machine learning ensemble-based algorithm, generalized pathseeker (GPS) produced a greater case classification accuracy than galactomannan (GM) or host proteins alone. In conclusion, Integration of host response proteins with GM improves the diagnostic detection of probable IPA in patients undergoing treatment for hematologic malignancy. Upon further validation, early detection of probable IPA in leukemia treatment will provide opportunities for earlier interventions and interventional clinical trials.

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Section: Resultsmentioning

confidence: 99%

“…Clinically, diagnosis of IPA is established on the basis of radiographic, culture, and fungal antigen detection in high-risk patients [ 6 , 9 ]. Despite hematogenous dissemination, fungal blood cultures are rarely positive [ 10 ]. The development of fungal antigen assays has added to the available diagnostic tools.…”

Section: Introductionmentioning

confidence: 99%

Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens

et al. 2015

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“…Conventional diagnostic methods for BSIs require several days to complete, and both false positive [15,16] and false negative results [17,18] have been reported. Delayed diagnosis correlates strongly with the high mortality of BSIs [19,20].…”

Section: Discussionmentioning

confidence: 99%

Identification of the most common pathogenic bacteria in patients with suspected sepsis by multiplex PCR

Arabestani

Fazzeli

Esfahani

2014

J Infect Dev Ctries

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Introduction: Staphylococcus aureus, coagulase-negative staphylococci, Enterococcus spp., Enterobacteriaceae, Pseudomonas aeruginosa, and Acinetobacter baumanii have been found to be the most prevalent bacteremia-causing bacteria in patients with septicemia. Early detection of bloodstream infection (BSI) is crucial in the clinical setting. A multiplex PCR method for identification of these agents in clinical samples has been developed in parallel by conventional microbiological methods. Methodology: The target genes selected for each of the organisms were very specific for designing primers. Design of primers was done using Mega4, Allel ID6, Oligo6, and Oligo analyzer software. The test comprises a universal PCR from the 16S rDNA gene and multiplex PCR from the rpoB, gyrA, sss, and chromosome X (as an internal control). Results: The sensitivity and specificity for universal PCR and multiplex PCR in comparison with BC were 83.87% and 91.58%, and 74.19% and 91.58%, respectively. The positive predictive value (PPV) and the negative predictive value (NPV) for these two PCRs were 76.47% and 94.57%, and 74.19% and 91.58%, respectively. PCR failed to identify bacteria which were found conventionally in only 3.96% and 6.34% of the cases by universal and multiplex PCR (mostly bacteria not included in the PCR cassette). In 6.34% of the cases, multiplex PCR afforded identification of bacteria, but BC showed no bacteria in the sample. Conclusions: The multiplex PCR approach facilitates the detection of bacteremia in blood samples within a few hours. Rapid detection of bacteria by multiplex PCR appears to be a valuable tool, allowing earlier pathogen-adopted antimicrobial therapy in critically ill patients.

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“…However, human aspergillosis typically starts as an infection of the respiratory tract. Culturing of Aspergillus from the blood of aspergillosis patients is usually not successful, hinting at a limited systemic component of the disease (26).…”

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confidence: 99%

CD4⁺T Cells Mediate the Protective Effect of the Recombinant Asp f3-Based Anti-Aspergillosis Vaccine

et al. 2011

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The mortality and morbidity caused by invasive aspergillosis present a major obstacle to the successful treatment of blood cancers with hematopoietic cell transplants. Patients who receive hematopoietic cell transplants are usually immunosuppressed for extended periods, and infection with the ubiquitous mold Aspergillus fumigatus is responsible for most cases of aspergillosis. Previously, we demonstrated that vaccination with recombinant forms of the A. fumigatus protein Asp f3 protected cortisone acetate-immunosuppressed mice from experimentally induced pulmonary aspergillosis. Here, we investigated the vaccine's protective mechanism and evaluated in particular the roles of antibodies and T cells. After vaccination, Asp f3-specific preinfection IgG titers did not significantly differ between surviving and nonsurviving mice, and passive transfer of anti-Asp f3 antibodies did not protect immunosuppressed recipients from aspergillosis. We experimentally confirmed Asp f3's predicted peroxisomal localization in A. fumigatus hyphae. We found that fungal Asp f3 is inaccessible to antibodies, unless both cell walls and membranes have been permeabilized. Antibodyinduced depletion of CD4 ؉ T cells reduced the survival of recombinant Asp f3 (rAsp f3)-vaccinated mice to nonimmune levels, and transplantation of purified CD4 ؉ T cells from rAsp f3-vaccinated mice into nonimmunized recipients transferred antifungal protection. In addition, residues 60 to 79 and 75 to 94 of Asp f3 contain epitopes that induce proliferation of T cells from vaccinated survivors. Vaccine-primed CD4 ؉ T cells are not expected to clear the fungal pathogen directly; however, they may locally activate immunosuppressed phagocytes that elicit the antifungal effect.

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The mechanism for low yield of blood culture in invasive aspergillosis; the clinical importance of antigen detection tests revisited

Abstract: The mechanism for low yield of blood culture in invasive aspergillosis; the clinical importance of antigen detection tests revisited Bone Marrow Transplantation (2005) 36, 85-86.

Cited by 12 publications

References 6 publications

Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens

Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens

Identification of the most common pathogenic bacteria in patients with suspected sepsis by multiplex PCR

CD4⁺T Cells Mediate the Protective Effect of the Recombinant Asp f3-Based Anti-Aspergillosis Vaccine

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The mechanism for low yield of blood culture in invasive aspergillosis; the clinical importance of antigen detection tests revisited

Abstract: The mechanism for low yield of blood culture in invasive aspergillosis; the clinical importance of antigen detection tests revisited Bone Marrow Transplantation (2005) 36, 85-86.

Cited by 12 publications

References 6 publications

Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens

Improved Detection of Invasive Pulmonary Aspergillosis Arising during Leukemia Treatment Using a Panel of Host Response Proteins and Fungal Antigens

Identification of the most common pathogenic bacteria in patients with suspected sepsis by multiplex PCR

CD4+T Cells Mediate the Protective Effect of the Recombinant Asp f3-Based Anti-Aspergillosis Vaccine

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Product

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CD4⁺T Cells Mediate the Protective Effect of the Recombinant Asp f3-Based Anti-Aspergillosis Vaccine