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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

Baseline IP-10 concentrations by HIV status, Smear status, and TB culture/GeneXpert result.Box plots show medians and ranges for patients, grouped based on HIV, Smear, and culture/GeneXpert result (**p<0.01).
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pone.0129552.g001: Baseline IP-10 concentrations by HIV status, Smear status, and TB culture/GeneXpert result.Box plots show medians and ranges for patients, grouped based on HIV, Smear, and culture/GeneXpert result (**p<0.01).

Mentions: The median serum level of IP-10 at diagnosis (day 0) was elevated in culture/GeneXpert positive patients compared to culture/GeneXpert negative patients (p<0.001; Fig 1). Among patients with positive culture/GeneXpert results, IP-10 levels were significantly higher in HIV-positive than in HIV-negative patients (p<0.01). There was no association between smear positivity and IP-10 level on enrolment (p = 0.484; Fig 1).


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)

Baseline IP-10 concentrations by HIV status, Smear status, and TB culture/GeneXpert result.Box plots show medians and ranges for patients, grouped based on HIV, Smear, and culture/GeneXpert result (**p<0.01).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0129552.g001: Baseline IP-10 concentrations by HIV status, Smear status, and TB culture/GeneXpert result.Box plots show medians and ranges for patients, grouped based on HIV, Smear, and culture/GeneXpert result (**p<0.01).
Mentions: The median serum level of IP-10 at diagnosis (day 0) was elevated in culture/GeneXpert positive patients compared to culture/GeneXpert negative patients (p<0.001; Fig 1). Among patients with positive culture/GeneXpert results, IP-10 levels were significantly higher in HIV-positive than in HIV-negative patients (p<0.01). There was no association between smear positivity and IP-10 level on enrolment (p = 0.484; Fig 1).

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