Limits...
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 IP-10 concentrations at day 0 and 7 of therapy.Each set of 2 connected points represent data from a single patient from Nigeria (blue) or Nepal (red). Panel A: IP-10 concentrations of HIV-positive, Smear (Sm) positive, and culture/Xpert (Cult) positive patients. The MDR-TB patient is shown with a dashed line. One smear-positive patient had missing culture (Open symbols). Panel B-D: IP-10 concentrations of HIV- Sm+ (B), HIV+ Sm- (C), and HIV- Sm- (D) culture/GeneXpert positive patients. E: Concentrations from Sm-Cult- patients, of which 4 had missing HIV result (open square symbols) and all others were HIV- (round symbols). IP-10 levels in culture/GeneXpert positives were significantly different between day 0 and day 7 (p<0.0001). For culture/GeneXpert negatives p>0.05 between day 0 and day 7.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4482639&req=5

pone.0129552.g002: Serum IP-10 concentrations at day 0 and 7 of therapy.Each set of 2 connected points represent data from a single patient from Nigeria (blue) or Nepal (red). Panel A: IP-10 concentrations of HIV-positive, Smear (Sm) positive, and culture/Xpert (Cult) positive patients. The MDR-TB patient is shown with a dashed line. One smear-positive patient had missing culture (Open symbols). Panel B-D: IP-10 concentrations of HIV- Sm+ (B), HIV+ Sm- (C), and HIV- Sm- (D) culture/GeneXpert positive patients. E: Concentrations from Sm-Cult- patients, of which 4 had missing HIV result (open square symbols) and all others were HIV- (round symbols). IP-10 levels in culture/GeneXpert positives were significantly different between day 0 and day 7 (p<0.0001). For culture/GeneXpert negatives p>0.05 between day 0 and day 7.

Mentions: The median IP-10 concentration of culture positive patients decreased during the course of therapy regardless of smear microscopy and HIV status (p<0.0001 overall, p<0.01 for each subgroup at day 7), as shown in Fig 2. For all culture positive sub-groups (HIV+/-, Smear +/-) IP-10 concentrations were significantly lower at days 5, 7, and 14 than on enrolment (Fig 2, S1 Fig). In contrast, culture-negative patients had similar IP-10 concentrations at the time of enrolment and at day 7 (p = 0.086; Fig 2). Although numbers of patients in each group are small, IP-10 responses of patients on established or simultaneously initiated ART had similar patterns and changes were likely related to anti-TB therapy not ART.


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 IP-10 concentrations at day 0 and 7 of therapy.Each set of 2 connected points represent data from a single patient from Nigeria (blue) or Nepal (red). Panel A: IP-10 concentrations of HIV-positive, Smear (Sm) positive, and culture/Xpert (Cult) positive patients. The MDR-TB patient is shown with a dashed line. One smear-positive patient had missing culture (Open symbols). Panel B-D: IP-10 concentrations of HIV- Sm+ (B), HIV+ Sm- (C), and HIV- Sm- (D) culture/GeneXpert positive patients. E: Concentrations from Sm-Cult- patients, of which 4 had missing HIV result (open square symbols) and all others were HIV- (round symbols). IP-10 levels in culture/GeneXpert positives were significantly different between day 0 and day 7 (p<0.0001). For culture/GeneXpert negatives p>0.05 between day 0 and day 7.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0129552.g002: Serum IP-10 concentrations at day 0 and 7 of therapy.Each set of 2 connected points represent data from a single patient from Nigeria (blue) or Nepal (red). Panel A: IP-10 concentrations of HIV-positive, Smear (Sm) positive, and culture/Xpert (Cult) positive patients. The MDR-TB patient is shown with a dashed line. One smear-positive patient had missing culture (Open symbols). Panel B-D: IP-10 concentrations of HIV- Sm+ (B), HIV+ Sm- (C), and HIV- Sm- (D) culture/GeneXpert positive patients. E: Concentrations from Sm-Cult- patients, of which 4 had missing HIV result (open square symbols) and all others were HIV- (round symbols). IP-10 levels in culture/GeneXpert positives were significantly different between day 0 and day 7 (p<0.0001). For culture/GeneXpert negatives p>0.05 between day 0 and day 7.
Mentions: The median IP-10 concentration of culture positive patients decreased during the course of therapy regardless of smear microscopy and HIV status (p<0.0001 overall, p<0.01 for each subgroup at day 7), as shown in Fig 2. For all culture positive sub-groups (HIV+/-, Smear +/-) IP-10 concentrations were significantly lower at days 5, 7, and 14 than on enrolment (Fig 2, S1 Fig). In contrast, culture-negative patients had similar IP-10 concentrations at the time of enrolment and at day 7 (p = 0.086; Fig 2). Although numbers of patients in each group are small, IP-10 responses of patients on established or simultaneously initiated ART had similar patterns and changes were likely related to anti-TB therapy not ART.

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