Gene Expression Analysis for Bacterial Meningitis Detection

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Solution Overview

Problem

Current methods for diagnosing bacterial meningitis are invasive, costly, and often delayed, leading to increased mortality and antibiotic resistance due to the need for lumbar punctures and the challenges of slow-growing bacteria, which can result in unnecessary antibiotic treatment.

Innovation Solution

A method involving the analysis of blood samples for specific gene expression ratios, such as ELANE and IFI44L, to detect bacterial infections in the bloodstream or central nervous system, allowing for prompt antibiotic initiation without the need for invasive procedures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If lumbar puncture is performed to obtain cerebrospinal fluid for diagnosis, then diagnostic accuracy is improved, but patient discomfort and procedural risk increase

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidpatient discomfort and procedural risk
Core Design Contradiction:
Measurement precisionVSObject-affected harmful factors

Solution Approach 1:

The invention extracts the diagnostic function from the invasive lumbar puncture procedure by identifying and measuring specific gene expression markers (ELANE and IFI44L) in easily obtainable blood samples. This extraction allows the diagnostic capability to be separated from the harmful invasive procedure, achieving accurate diagnosis without lumbar puncture in many cases

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces gene expression markers as intermediary substances that mediate between the blood sample and the diagnostic conclusion. These markers serve as proxies that indirectly indicate bacterial meningitis presence, allowing diagnosis without direct examination of cerebrospinal fluid through invasive procedures

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If blood culture is used to detect bacterial meningitis, then diagnostic specificity is improved, but diagnosis time is delayed due to slow bacterial growth

Engineering Contradiction:
Improvediagnostic specificityVSAvoiddiagnosis time
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The invention performs preliminary detection of bacterial infection through gene expression analysis in blood samples before the slow-growing bacteria would be detectable by culture methods. By measuring host gene responses (ELANE and IFI44L) that change rapidly upon bacterial infection, the diagnosis is accelerated while maintaining specificity

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent replaces the mechanical/biological process of bacterial culture (which requires days for slow-growing bacteria) with a molecular biology-based gene expression measurement system. This substitution uses PCR or similar techniques to amplify and detect gene markers, providing rapid results without waiting for bacterial colonies to form

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

3Loss of time

If empirical antibiotic treatment is initiated without confirmation, then treatment time is reduced, but unnecessary antibiotic use increases leading to resistance

Engineering Contradiction:
Improvetreatment timeVSAvoidantibiotic resistance
Core Design Contradiction:
Loss of timeVSObject-generated harmful factors

Solution Approach 1:

The invention implements a feedback mechanism where the gene expression test results directly inform the treatment decision. The ELANE/IFI44L ratio provides feedback that confirms or rules out bacterial meningitis, allowing clinicians to initiate antibiotics only when the feedback indicates bacterial infection is present, thereby avoiding unnecessary antibiotic use

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The rapid gene expression test performs a preliminary assessment of bacterial infection presence before antibiotic initiation. This preliminary action provides sufficient information to make treatment decisions without waiting for slow-growing bacterial cultures, enabling timely and appropriate antibiotic prescription

Inventive Principle:
Principle #10Preliminary action

Data Source

PatentEP3365462B1Detection of bacterial infection
Publication Date: 2021.09.29 UNIV OF LIVERPOOL
  • EP3365462B1 patent drawingFigure 1
  • EP3365462B1 patent drawingFigure 2
  • EP3365462B1 patent drawingFigure 3

AI summary

The present invention relates to methods of detecting and treating a bacterial infection, such as bacterial meningitis, and addresses the problem of misdiagnosis of bacterial infections. The medical use of antibacterial agents in the treatment of a bacterial infection in a subject identified by the methods of the invention is also described. The methods of the invention comprise assaying a sample from the subject to obtain data of the relative abundance of target molecules indicative of the expression of at least one gene pair, determining the presence or absence of a bacterial infection in the subject in dependence on the data, and optionally treating the subject with an antibacterial agent if required.