Cytokine Kinetics in the First Week of Tuberculosis Therapy as a Tool to Confirm a Clinical Diagnosis and Guide Therapy

den Hertog, Alice L., Montero-Martín, María, Saunders, Rachel, Blakiston, Matthew, Menting, Sandra, Sherchand, Jeevan B., Lawson, Lovett, Oladimeji, Olanrewaju, Abdurrahman, Saddiq T., Cuevas, Luis ORCID: https://orcid.org/0000-0002-6581-0587 and Anthony, Richard M. (2015) 'Cytokine Kinetics in the First Week of Tuberculosis Therapy as a Tool to Confirm a Clinical Diagnosis and Guide Therapy'. PLoS ONE, Vol 10, Issue 6, e0129552.

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Abstract

Background

Many patients treated for tuberculosis (TB) in low and middle income countries are treated based on clinical suspicion without bacteriological confirmation. This is often due to lack of rapid simple accurate diagnostics and low healthcare provider confidence in the predictive value of current tests. We previously reported in an animal TB model that levels of host markers rapidly change in response to treatment initiation.

Methods

We assessed the potential of host biomarker kinetics of TB patients during the first two weeks of therapy to identify patients responding to treatment. Adult patients clinically diagnosed with and treated for TB, 29 in Nigeria and 24 in Nepal, were analyzed.

Results

Changes in concentrations of non-specific host biomarkers, particularly IP-10, in response to the first week of anti-TB therapy were strongly associated with bacteriological confirmation of TB. A decrease in IP-10 level of >300pg/ml between 0 and 7 days of treatment identified 75% of both smear-positive and smear-negative culture positive patients and correctly excluded TB in all nine culture negative patients.

Conclusions

Monitoring of early IP-10 responses to treatment could form the basis of a simplified assay and could help identify patients who were erroneously clinically diagnosed with TB or those infected with drug resistant strains on inappropriate treatment. We believe this approach may be particularly appropriate for difficult to diagnose patients, e.g. smear-negative HIV-positive, or those with extra-pulmonary TB, often treated without bacterial confirmation.

Item Type:	Article
Subjects:	QW Microbiology and Immunology > Immunity by Type > QW 568 Cellular immunity. Immunologic cytotoxicity. Immunocompetence. Immunologic factors (General) WA Public Health > WA 30 Socioeconomic factors in public health (General) WF Respiratory System > Tuberculosis > WF 200 Tuberculosis (General) WF Respiratory System > Tuberculosis > WF 220 Diagnosis. Prognosis WF Respiratory System > Tuberculosis > WF 310 Therapy
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.pone.0129552
Depositing User:	Lynn Roberts-Maloney
Date Deposited:	21 Oct 2015 11:25
Last Modified:	06 Feb 2018 13:10
URI:	https://archive.lstmed.ac.uk/id/eprint/5369

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