Evidence map›Paper›PMID 27333027›Full record

ArticleEBioMedicine2016

A Broad-Spectrum Infection Diagnostic that Detects Pathogen-Associated Molecular Patterns (PAMPs) in Whole Blood.

Mark Cartwright, Martin Rottman, Nathan I Shapiro, Benjamin Seiler, Patrick Lombardo, Nazita Gamini, Julie Tomolonis, Alexander L Watters, Anna Waterhouse, Dan Leslie and 8 more

Open access · goldAbstract read
In one paragraph

Article in EBioMedicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 46 citations in OpenAlex.

  1. Trial
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  7. A Simple and Rapid Methicillin-ResistantJournal of microbiology and biotechnology · 2023
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  10. Materials-based vaccines for infectious diseases.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2022
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 3 institutions in 2 countries.

Mark CartwrightWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Martin RottmanWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States; Hôpitaux Universitaires Paris Ile de France Ouest (AP-HP), UMR INSERM U1173-UFR SSSV Université de Versailles St Quentin en Yvelines, Montigny, France.
Nathan I ShapiroDepartment of Emergency Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, United States.
Benjamin SeilerWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Patrick LombardoWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Nazita GaminiWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Julie TomolonisWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Alexander L WattersWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Anna WaterhouseWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Dan LeslieWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Dana BolgenWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Amanda GravelineWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Joo H KangWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Tohid DidarWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Nikolaos DimitrakakisWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
David CartwrightWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Michael SuperWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States.
Donald E IngberWyss Institute for Biologically Inspired Engineering at Harvard University, Boston, MA, United States; Vascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, MA, United States; Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, United States. Electronic address: don.ingber@wyss.harvard.edu.
Harvard University · USBeth Israel Deaconess Medical Center · USBoston Children's Hospital · US

Funding

Harvard Clinical and Translational Science CenterUL1TR001102 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$106.2M
NCATS NIH HHS UL1 TR001102
6 · The paper itself

Abstract

backgroundBlood cultures, and molecular diagnostic tests that directly detect pathogen DNA in blood, fail to detect bloodstream infections in most infected patients. Thus, there is a need for a rapid test that can diagnose the presence of infection to triage patients, guide therapy, and decrease the incidence of sepsis.

methodsAn Enzyme-Linked Lectin-Sorbent Assay (ELLecSA) that uses magnetic microbeads coated with an engineered version of the human opsonin, Mannose Binding Lectin, containing the Fc immunoglobulin domain linked to its carbohydrate recognition domain (FcMBL) was developed to quantify pathogen-associated molecular patterns (PAMPs) in whole blood. This assay was tested in rats and pigs to explore whether it can detect infections and monitor disease progression, and in prospectively enrolled, emergency room patients with suspected sepsis. These results were also compared with data obtained from non-infected patients with or without traumatic injuries.

resultsThe FcMBL ELLecSA was able to detect PAMPS present on, or released by, 85% of clinical isolates representing 47 of 55 different pathogen species, including the most common causes of sepsis. The PAMP assay rapidly (<1h) detected the presence of active infection in animals, even when blood cultures were negative and bacteriocidal antibiotics were administered. In patients with suspected sepsis, the FcMBL ELLecSA detected infection in 55 of 67 patients with high sensitivity (>81%), specificity (>89%), and diagnostic accuracy of 0·87. It also distinguished infection from trauma-related inflammation in the same patient cohorts with a higher specificity than the clinical sepsis biomarker, C-reactive Protein.

conclusionThe FcMBL ELLecSA-based PAMP assay offers a rapid, simple, sensitive and specific method for diagnosing infections, even when blood cultures are negative and antibiotic therapy has been initiated. It may help to triage patients with suspected systemic infections, and serve as a companion diagnostic to guide administration of emerging dialysis-like sepsis therapies.

Indexed as

ImmunoassayAgedAnimalsAnti-Bacterial AgentsArea Under CurveBacteriaC-Reactive ProteinDisease Models, AnimalEnzyme-Linked Immunosorbent AssayEscherichia coliFemaleHumansLectinsLipopolysaccharidesMaleMaltose-Binding ProteinsAnti-Bacterial AgentsC-Reactive ProteinLectinsLipopolysaccharidesMaltose-Binding ProteinsPathogen-Associated Molecular Pattern MoleculesBiomarkerBlood cultureC-reactive proteinInfection diagnosticMannose binding lectinSepsis

Identifiers

PMID27333027
PMCPMC4972566
OpenAlexW2416084911

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.