Methods of diagnosing and treating active tuberculosis in an individual
Inventors
Russell, Roslin • Stegle, Oliver • Shah, Mahesh
Assignees
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Publication Number
US-10191052-B2
Publication Date
2019-01-29
Expiration Date
Abstract
The invention relates to biomarkers for diagnosing, monitoring and/or treating tuberculosis in both immunocompetent and immunocompromised individuals with or without co-infection with HIV, monitoring the responses of individuals to anti-mycobacterial chemotherapy, monitoring the progression of latent tuberculosis to active tuberculosis, differentiating active tuberculosis from latent tuberculosis, and from other clinical conditions that mimic tuberculosis (TB). The invention also relates to methods for diagnosing, monitoring and/or treating tuberculosis using said biomarkers. The above pertain in all aspects both to pulmonary and extrapulmonary Mycobacterium tuberculosis infections, with Mycobacterium tuberculosis being the causative organism in tuberculosis. The invention therefore finds great utility in assisting with future drug discovery efforts for tuberculosis and also provides proxy clinical end points as well as being an effective predictor of a response to treatment.
Core Innovation
The invention relates to TB biomarker panel(s) for differentiating active (smear positive) tuberculosis from latent tuberculosis in an individual. A test biological sample is obtained and biomarker amounts are quantified, where three or more biomarkers are selected to include IFN gamma and IL-10.
The quantified biomarker amounts in the test biological sample are compared with amounts present in one or more control samples. The difference in the biomarker levels is indicative of a differential diagnosis of active (smear positive) tuberculosis over latent tuberculosis.
The invention further links the differential diagnosis to treatment by administering an anti-tuberculosis medicament to the individual if there is a positive diagnosis for active (smear positive) tuberculosis. The described biomarker panel includes, in particular, a 15-marker panel and subsets, with performance support using ROC/AUC-based cross-validation analyses.
Claims Coverage
The provided material contains one independent claim (clm-00001), covering a differential diagnosis of active (smear positive) tuberculosis versus latent tuberculosis using quantified biomarker levels compared to control samples, followed by administering an anti-tuberculosis medicament when active TB is diagnosed. The claim uses at least three biomarkers selected from specified markers, requiring IFN gamma and IL-10 among them, with a comparison against one or more control samples to generate a differential diagnosis.
Differential diagnosis from biomarker quantification versus controls
Quantifying the amount of three or more biomarkers selected from CD14, CD22, CD25, CD64, IL-10, CXCL10, and IFN gamma in a test biological sample, wherein at least one biomarker is IFN gamma and at least one biomarker is IL-10; comparing biomarker amounts in the test biological sample with amounts present in one or more control samples, such that a difference in biomarker levels is indicative of a differential diagnosis of active (smear positive) tuberculosis over latent tuberculosis.
Treatment based on positive active TB diagnosis
Administering an anti-tuberculosis medicament to the individual if there is a positive diagnosis for active (smear positive) tuberculosis.
In claim coverage, differential diagnosis is driven by quantifying a minimum set of specified biomarkers (including IFN gamma and IL-10) in a test sample and comparing the results to control samples to indicate active (smear positive) TB over latent TB; treatment is then initiated by administering an anti-tuberculosis medicament only when active TB is positively diagnosed.
Stated Advantages
Rapid serological diagnosis.
Improved performance in HIV/immunocompromised patients.
Biomarker-based proxy endpoints for therapy response.
Documented Applications
Diagnosis and treatment linkage for active (smear positive) tuberculosis versus latent tuberculosis, including use in immunocompromised individuals with and without HIV co-infection, across pulmonary and extrapulmonary TB.
Using TB biomarker panels to distinguish TB from symptomatic non-TB conditions.
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