Diagnostic Potential of Novel Salivary Host Biomarkers as Candidates for the Immunological Diagnosis of Tuberculosis Disease and Monitoring of Tuberculosis Treatment Response.

BACKGROUND
There is an urgent need for new tools for the early diagnosis of TB disease and monitoring response to treatment, particularly in resource-limited settings. We investigated the usefulness of the host marker detected in saliva as biomarker candidates for immunological diagnosis of TB disease and monitoring treatment response.


METHOD
We prospectively collected saliva samples from 51 individuals who presented with signs and symptoms suggestive of TB disease in a health center in Cape Town, South Africa, prior to the establishment of a clinical diagnosis. Patients were then classified as having tuberculosis or other respiratory diseases (ORD), using a combination of clinical findings, radiological and laboratory. We evaluate the concentration of the marker 69 in the home side a saliva sample using a multiplex cytokine platform, and assess the diagnostic potential of these markers by the receiver operator characteristic (ROC) curve analysis, and general discriminant analysis.


RESULTS
Of the 51 study participants, 18 (35.4%) were diagnosed with TB disease and 12 (23.5%) were HIV-infected. Only two of the 69 markers were evaluated hosts (IL-16 and IL-23) were diagnosed with TB disease individually with an area under the ROC curve ≥0.70.

A biosignature five markers consisting of IL-1β, IL-23, ECM-1, HCC1 and fibrinogen diagnosed TB disease with a sensitivity of 88.9% (95% CI, 76.7 to 99.9%) and specificity of 89.7 % (95% CI, 60.4 to 96.6%) after a leave-one-out cross validation, regardless of their HIV infection status. biosignatures eight markers performed with a sensitivity of 100% (95% CI, 83.2 to 100%) and a specificity of 95% (95% CI, 68.1 to 99.9%) in the absence of HIV infection. In addition, the concentration of 11 markers change during the treatment, suggesting that they may be useful in monitoring response to treatment of TB.


CONCLUSION
We have identified a new saliva biosignatures that may be useful in the diagnosis of TB disease and monitoring response to treatment of TB. Our findings require further validation in larger studies before it could be considered biosignatures for point-of-care screening test development.

 Diagnostic Potential of Novel Salivary Host Biomarkers as Candidates for the Immunological Diagnosis of Tuberculosis Disease and Monitoring of Tuberculosis Treatment Response.
Diagnostic Potential of Novel Salivary Host Biomarkers as Candidates for the Immunological Diagnosis of Tuberculosis Disease and Monitoring of Tuberculosis Treatment Response.

Learning from epidemiological studies, clinical and immunology in Mycobacterium africanum to improve the current understanding of host-pathogen interactions, and for the development and evaluation of diagnostic, host-directed therapies, and vaccines for tuberculosis.

Mycobacterium africanum comprises two phylogenetic lineages in the Mycobacterium tuberculosis complex (MTBC). M. africanum first described and isolated in 1968 from Senegal sputum of patients with pulmonary tuberculosis (TB) and has been identified increasingly as an important cause of human tuberculosis, particularly prevalent in West Africa.

M. africanum limited geographical distribution, in contrast with comprehensive global distribution of other species of MTBC, requires an explanation. The available data suggest that M. africanum may also have important differences in transmission, pathogenesis and host-pathogen interactions, which may affect the evaluation of new TB intervention tools (diagnostics and vaccines) -they are being used and those under development.

p38

MBS8533658-01mLAF405S 0.1mL(AF405S)
EUR 565

p38

MBS8533658-01mLAF610 0.1mL(AF610)
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p38

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P38 mAb

MBS435304-005mL 0.05mL
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P38 mAb

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P38 mAb

MBS435304-5x01mL 5x0.1mL
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p38 MAPK

E8ET1702-65 100ul
EUR 275
Description: Available in various conjugation types.

Mxi2, p38

MBS603655-01mg 0.1mg
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Mxi2, p38

MBS603655-5x01mg 5x0.1mg
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p38 MAPK

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p38 MAPK

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p38 MAPK

MBS8534372-01mLAF610 0.1mL(AF610)
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p38 MAPK

MBS8534372-01mLAF635 0.1mL(AF635)
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p38 protein

E20-80078 20ug
EUR 275
Description: N/A

p38 protein

E20-80079 20ug
EUR 275
Description: N/A

p38 protein

MBS8526800-002mg 0.02mg
EUR 345

p38 protein

MBS8526800-5x002mg 5x0.02mg
EUR 1410

p38 protein

MBS8526801-002mg 0.02mg
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p38 Antibody

20-abx141038
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p38 Antibody

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p38 Antibody

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p38 Antibody

48644 100ul
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p38 Antibody

48644-100ul 100ul
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p38 Antibody

48644-50ul 50ul
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p38 Antibody

35478 100ul
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35478-100ul 100ul
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abx236076-100ug 100 ug
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p38 Antibody

E38PA4721 100ul
EUR 225
Description: Available in various conjugation types.

p38 Antibody

E38PA5060 100ul
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Description: Available in various conjugation types.

p38 Antibody

E38PA5094 100ul
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Description: Available in various conjugation types.

p38 Antibody

E38PA7126 100ul
EUR 225
Description: Available in various conjugation types.

p38 Antibody

E38PA3186 100ul
EUR 225
Description: Available in various conjugation types.

p38 antibody

70R-51505 100 ul
EUR 242
Description: Purified Polyclonal p38 antibody

p38 antibody

70R-51506 100 ul
EUR 286
Description: Purified Polyclonal p38 antibody

p38 Antibody

abx236076-100g 100 µg
EUR 350

p38 Antibody

MBS9409774-01mL 0.1mL
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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

MBS8584173-01mLAF610 0.1mL(AF610)
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p38 Antibody

MBS8584173-01mLAF635 0.1mL(AF635)
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p38 Antibody

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p38 Antibody

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p38 Antibody

MBS8582665-01mLAF405S 0.1mL(AF405S)
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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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EUR 465

p38 Antibody

MBS8582905-01mLAF405S 0.1mL(AF405S)
EUR 465

p38 Antibody

MBS8582905-01mLAF610 0.1mL(AF610)
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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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p38 Antibody

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B0798-100ul 100μl
EUR 217
Description: p38 Rabbit Polyclonal Antibody

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B0798-50ul 50μl
EUR 143.5
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p38 Antibody

B0799-100ul 100μl
EUR 217
Description: p38 Rabbit Polyclonal Antibody

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EUR 143.5
Description: p38 Rabbit Polyclonal Antibody

p38 Antibody

B7178-100ul 100μl
EUR 217
Description: p38 Rabbit Polyclonal Antibody

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B7178-50ul 50μl
EUR 143.5
Description: p38 Rabbit Polyclonal Antibody

p38 Substrate

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MAP Kinase p38, Control Cell Extracts (Mitogen Activated Protein Kinase p38, MAPK p38)

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MAP Kinase p38, phosphorylated (Thr180, Tyr182) (Mitogen Activated Protein Kinase p38, MAPK p38)

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MAP Kinase p38, phosphorylated (Thr180, Tyr182) (Mitogen Activated Protein Kinase p38, MAPK p38)

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MAP Kinase p38, phosphorylated (Thr180, Ty182) (Mitogen Activated Protein Kinase p38, MAPK p38)

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MAP Kinase p38, phosphorylated (Thr180, Ty182) (Mitogen Activated Protein Kinase p38, MAPK p38)

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MAP Kinase p38, phosphorylated (Thr180, Ty182) (Mitogen Activated Protein Kinase p38, MAPK p38)

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MAP Kinase p38, phosphorylated (Thr180, Ty182) (Mitogen Activated Protein Kinase p38, MAPK p38)

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MAP Kinase p38, phosphorylated (Thr180, Tyr182) (Mitogen Activated Protein Kinase p38, MAPK p38)

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MAP Kinase p38, phosphorylated (Thr180, Tyr182) (Mitogen Activated Protein Kinase p38, MAPK p38)

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SB-203580 p38 MAPK(p38 MAP kinase) Inhibitor

E1B1863 1mg
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SB-203580 p38 MAPK (p38 MAP kinase) Inhibitor

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p38 (411-425) M.leprae

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MAP Kinase p38, phosphorylated (Thr180, Ty182) (Mitogen Activated Protein Kinase p38, MAPK p38) (Agarose)

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Anti - p38-a

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Anti - p38-a

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Anti - p38-a

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Anti - p38-b

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Anti - p38-b

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Anti - p38-b

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Anti - p38-g

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Anti - p38-d

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Anti - p38-d

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Anti - p38-d

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EUR 2925

p38 Mouse mAb

E2220879 100ul
EUR 225
Description: Available in various conjugation types.

p38 Mouse mAb

E2222580 100ul
EUR 255
Description: Biotin-Conjugated, FITC-Conjugated , AF350 Conjugated , AF405M-Conjugated ,AF488-Conjugated, AF514-Conjugated ,AF532-Conjugated, AF555-Conjugated ,AF568-Conjugated , HRP-Conjugated, AF405S-Conjugated, AF405L-Conjugated , AF546-Conjugated, AF594-Conjugated , AF610-Conjugated, AF635-Conjugated , AF647-Conjugated , AF680-Conjugated , AF700-Conjugated , AF750-Conjugated , AF790-Conjugated , APC-Conjugated , PE-Conjugated , Cy3-Conjugated , Cy5-Conjugated , Cy5.5-Conjugated , Cy7-Conjugated Antibody

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p38 Mouse mAb

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p38 Mouse mAb

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EUR 565

p38 Mouse mAb

MBS8539086-01mLAF635 0.1mL(AF635)
EUR 565

p38 Rabbit pAb

E2340697 100ul
EUR 225
Description: Available in various conjugation types.

p38 Rabbit pAb

E2380881 100ul
EUR 225
Description: Available in various conjugation types.

p38 Rabbit pAb

E2381051 100ul
EUR 225
Description: Available in various conjugation types.

p38 Rabbit mAb

E2R25239 100μl
EUR 225
Description: Available in various conjugation types.

p38 Rabbit mAb

E2R27123 100μl
EUR 225
Description: Available in various conjugation types.

p38 Rabbit pAb

E2251338 100ul
EUR 225
Description: Available in various conjugation types.

p38 Rabbit pAb

E2251719 100ul
EUR 225
Description: Available in various conjugation types.

anti-Crk p38

YF-PA11088 50 ul
EUR 435.6
Description: Mouse polyclonal to Crk p38

anti-Crk p38

YF-PA11089 50 ug
EUR 435.6
Description: Mouse polyclonal to Crk p38

anti-Crk p38

YF-PA11090 100 ug
EUR 483.6
Description: Rabbit polyclonal to Crk p38

anti-Crk p38

YF-PA23509 50 ul
EUR 400.8
Description: Mouse polyclonal to Crk p38

p38 Rabbit pAb

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EUR 305

p38 Rabbit pAb

MBS8539985-01mLAF405L 0.1mL(AF405L)
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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 Rabbit pAb

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p38 HOG Kinase

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p38 HOG Kinase

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EUR 1760

p38 Rabbit mAb

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p38 Rabbit mAb

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p38 Rabbit mAb

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p38 Rabbit mAb

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p38 beta, Active

7763-100 each
EUR 5214

p38 beta, Active

7763-5 each
EUR 444

p38 beta protein

30R-2875 5 ug
EUR 425
Description: Purified recombinant Human p38 beta protein

Crk p38 Antibody

AF6323 200ul
EUR 420

Uneven geographical distribution and dissemination of MTBC species means that the research findings of individuals from one country or region can not be generalized across the continent. Thus, the generalization of data from previous research studies and ongoing in the MTBC may be inaccurate and inappropriate. A major rethink is needed about the design and structure of future clinical trials of new interventions. West, Central, East and Southern Africa EDCTP Networks of Excellence provides an opportunity to take forward this pan-African studies.