Stellenbosch University

Max-planck-gesellschaft Zur F&#xf6;rderung Der Wissenschaften E. V.

University of Cape Town

Seattle Children's Hospital

United Kingdom Research and Innovation

Gerhard Walzl

Novel Njweipi Chegou

Stefan H E Kaufmann

Daniel Edward Zak

Ethan Greene Thompson

Thomas Jens Scriba

Sara Suliman

Regan Shane Solomons

Masilo Charles Manyelo

Paulin Essone Ndong

Jayne Suzanne Sutherland

Ruschca Jacobs

Adane Mihret

Methods, devices, kits and computer-implemented methods for diagnosing (and optionally treating) tuberculous meningitis (TBM) are provided. In one embodiment, the method comprises testing a cerebrospinal fluid (CSF) sample from a subject suspected of having TBM for the presence of MPO and at least two other biomarkers, at least one of the other biomarkers being selected from the group consisting of IFN-γ, sICAM-1, VEGF-A and CXCL8. For example, the method can comprise testing the sample for MPO, IFN-γ and VEGF-A or for MPO, IFN-γ, sICAM-1 and CXCL8. In another embodiment, the method comprises testing a blood sample from a subject suspected of having TBM for the presence of at least one biomarker selected from the group consisting of adipsin (complement factor D), Ab42 and IL-10, and at least two other biomarkers. In one example, the method comprises testing the sample for the presence of adipsin (complement factor D), Ab42 and EL-10.

Biomarkers for diagnosing tuberculous meningitis

The invention provides a gene signature for use in determining a likelihood of a latent tuberculosis (TB) infection in a subject transitioning to active TB disease. The gene signature comprises at least SEPT4 and BLK, and optionally also GAS6 and/or CD1C. Expression levels of these genes are detected in a sample from the subject, and the ratios of expression of at least two of the above genes are calculated (e.g. SEPT4:BLK, SEPT4:CD1C, GAS6:BLK and/or GAS6:CD1C). A score is assigned to each ratio, the score being indicative of the likelihood of the latent TB infection transitioning into active TB disease, based on the ratio for the respective gene pair. The subject can be identified as having a latent TB infection that is likely to transition into active TB disease or that is not likely to transition into active TB disease based on the score or on the average of the scores.

Method for predicting progression to active tuberculosis disease

A method of diagnosing tuberculosis (TB) disease and distinguishing between active TB and latent TB infection in a subject is described herein. A sample from the subject is stimulated with at least one() infection phase-dependent antigen selected from Rv0081, Rv2032, Rv1737c, Rv2389c, Rv0867c, TB18.2, Rv2099c, Rv1733c,PPD, PHA and ESAT-6/CFP-10 and the presence of at least one host marker in the sample is detected, the host marker being selected from EGF, TGF-&#x3b1;, TNF-&#x3b1;, VEGF, RANTES, IL-12(p40), IL-12(p70), IL-10, IP-10, IFN-&#x3b1;2, fractalkine, IFN-&#x3b3;, IL-13, IL-1Ra, IL-3, IL-4, IL-5, MIP-1&#x3b1;, ENA-78, BCA-1, TARC, X6-Ckine, eotaxin, eotaxin-2, SCF, APOA-1, APOE, HPALBN, HCF, Serum amyloid protein A (SAA), C-reactive protein (CRP), serum amyloid protein P (SAP), TIMP-1, MIP-1&#x3b2;, IL-6, GM-CSF, IL-1&#x3b1;, MMP-9, MMP-2, MCP-1, TRAIL, IL-15, IL-17F, IL-22, TNF-&#x3b2;, MCP-2 and MCP-4. Additional host markers may also be detected in an unstimulated sample from the subject.

Method for diagnosing tuberculosis disease by detecting induced markers after stimulation of T-cells with antigens

Growing community of inventors

Cape Town, South Africa

Gerhard Walzl