Latent TB Detection via Mtb Extraction from Hematopoietic Stem Cells
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Solution Overview
Problem
Current diagnostic methods for latent tuberculosis infection, such as the tuberculin skin test and interferon-gamma release assays, are unreliable, leading to unnecessary treatments and false positives/negatives, especially in individuals with compromised immune systems or those vaccinated with BCG, and fail to predict progression to active disease accurately.
Innovation Solution
A method involving the direct detection of Mycobacterium tuberculosis nucleotide sequences and polypeptides in enriched blood cell populations, particularly hematopoietic stem cells, using fluorescence-activated cell sorting, to reliably identify latent tuberculosis infection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current diagnostic methods (TST or IGRA) are used to detect latent tuberculosis infection, then the detection can be performed indirectly through immune response measurement, but the reliability is poor leading to false positives and false negatives
Solution Approach 1:
The patent extracts and detects Mtb bacteria directly from blood cell populations, particularly from intracellular compartments, rather than relying on indirect immune response measurements. This extraction of the actual pathogen from the complex immune response system eliminates cross-reactivity issues and provides direct evidence of infection.
Solution Approach 2:
The patent uses specific antibodies and detection reagents as intermediaries to identify Mtb within blood cells. These intermediaries specifically bind to Mtb components, enabling reliable detection without the cross-reactivity problems that plague TST and IGRA methods.
2Ease of operation
If TST or IGRA methods are used, then the testing process is simple and indirect, but the sensitivity is reduced to 70-90% for active TB infection
Solution Approach 1:
The patent replaces the mechanical/immunological system of TST and IGRA with a molecular detection system using specific antibodies and nucleic acid amplification. This substitution enables direct visualization and identification of Mtb at the molecular level, dramatically improving sensitivity while maintaining operational feasibility.
3Ease of operation
If TST is used for detection, then the test can be performed directly on skin, but false positive results occur due to cross-reactivity with BCG vaccination or environmental bacteria
Solution Approach 1:
The patent applies local quality by using highly specific antibodies and detection reagents that target unique Mtb components not found in BCG or environmental mycobacteria. This localized specificity at the molecular level eliminates cross-reactivity while maintaining the accessibility of blood sampling.
4Adaptability or versatility
If TST or IGRA are used in subjects with compromised immune systems, then the testing can be performed, but false negative results occur due to reduced immune system ability to react
Solution Approach 1:
The patent extracts and detects Mtb directly from blood cell populations, bypassing the need for a functional immune response. This approach works equally well in immunocompromised subjects because it detects the actual bacteria rather than relying on the immune system's ability to react to them.
5Productivity
If current methods are used to identify latent tuberculosis, then treatment decisions can be made, but unnecessary treatment occurs due to unreliable results
Solution Approach 1:
The patent provides direct feedback about the actual presence of Mtb through specific molecular detection, eliminating the ambiguous feedback from indirect immune response measurements. This accurate feedback enables reliable treatment decisions, treating only those who truly have latent tuberculosis infection.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach provides a fast and reliable detection of latent tuberculosis, overcoming the limitations of existing tests by directly identifying M. tuberculosis in blood cells, reducing false positives/negatives, and allowing for targeted treatment, including consideration of antimicrobial resistances.
Implementation Method 1
using fluorescence-activated cell sorting
Data Source
AI summary
The present invention relates to a method for the in vitro detection of a latent tuberculosis infection (LTBI) in a subject, wherein said method comprises determining at least one nucleotide sequence and/or at least one polypeptide of Mycobacterium tuberculosis (Mtb) in a blood cell population of said subject, and wherein the presence of said at least one nucleotide sequence and/or said at least one polypeptide is indicative for said latent tuberculosis infection. In particular, the blood cell population is enriched for hematopoietic stem cells. The invention also relates to a pharmaceutical composition for use in the treatment of the LTBI in the subject, wherein it is determined if the nucleotide sequence and/or the polypeptide of Mtb is/are present in the blood cell population. Further, the invention relates to kits for carrying out the methods of the invention. The invention also relates to the use of the kits.