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

den Hertog AL, Montero-Martín M, Saunders RL, Blakiston M, Menting S, Sherchand JB, Lawson L, Oladimeji O, Abdurrahman ST, Cuevas LE, Anthony RM - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Royal Tropical Institute (KIT), KIT Biomedical Research, Amsterdam, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus

Serum MCP-1 levels of TB patients at day 0 and day 7 of therapy.See legend Fig 2 for details on the panels and labels. There are no significant differences between day 0 and day 7 for either culture/GeneXpert positive patients or culture/GeneXpert negative patients.
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pone.0129552.g007: Serum MCP-1 levels of TB patients at day 0 and day 7 of therapy.See legend Fig 2 for details on the panels and labels. There are no significant differences between day 0 and day 7 for either culture/GeneXpert positive patients or culture/GeneXpert negative patients.

Mentions: No changes in MCP-1 concentrations could be consistently correlated to culture/GeneXpert result (p>0.05; Fig 7, S7 Fig), nor to appropriate treatment (AUC of ROC curve day0-day7: 0.67 [95% CI 0.47 to 0.87], p>0.05, Panel F in S2 Fig).


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

den Hertog AL, Montero-Martín M, Saunders RL, Blakiston M, Menting S, Sherchand JB, Lawson L, Oladimeji O, Abdurrahman ST, Cuevas LE, Anthony RM - PLoS ONE (2015)

Serum MCP-1 levels of TB patients at day 0 and day 7 of therapy.See legend Fig 2 for details on the panels and labels. There are no significant differences between day 0 and day 7 for either culture/GeneXpert positive patients or culture/GeneXpert negative patients.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482639&req=5

pone.0129552.g007: Serum MCP-1 levels of TB patients at day 0 and day 7 of therapy.See legend Fig 2 for details on the panels and labels. There are no significant differences between day 0 and day 7 for either culture/GeneXpert positive patients or culture/GeneXpert negative patients.
Mentions: No changes in MCP-1 concentrations could be consistently correlated to culture/GeneXpert result (p>0.05; Fig 7, S7 Fig), nor to appropriate treatment (AUC of ROC curve day0-day7: 0.67 [95% CI 0.47 to 0.87], p>0.05, Panel F in S2 Fig).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Royal Tropical Institute (KIT), KIT Biomedical Research, Amsterdam, The Netherlands.

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.

No MeSH data available.


Related in: MedlinePlus