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Inflammatory Markers and Incident TB: An International Case-control Study

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Joined 2014-05-06

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In this lecture Dr. Amita Gupta presents data from a study nested within a larger clinical trial to evaluate inflammatory markers and the risk of incident TB. She concludes with potential ways forward, including the possibility of developing a risk score for use in larger studies.
Speaker: Dr. Amita Gupta

     
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Joined 2014-05-04

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Very nice presentation by Dr Amita. Some comments -
1. Serial testing of CRP and biomarkers would be more helpful rather than one point.
2. In the study sites intercurrent infections could be responsible for the CRP positivity rather than TB alone.
3. HIV itself could have high CRP and may take longer time to return to normal after initiation of ART and differ from patient to patient.
4. Baseline CD4 if low in HIV patients - more prone for opportunistic infections hence CRP may remain high and there might be reactivation of previous TB as ART is started ( IRIS). As discussed need to see if the TB was reactivation or new infection. Same is true with low BMI - more prone for infections- high CRP.
5. Doing CRP and albumin assays on patients being treated with ART is possible and can be looked at in a prospective study in children if possible.

More work for NIKHIL - statistics!!

     
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inflammatory markers like Myeloperoxidase , hCrp and Nitric oxide assay can be useful ?

     
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Indeed a very good study, very well analyzed and an excellent presentation too. A few comments:

Plasma levels of various cytokines may give information on the presence, or even predictive value of inflammatory processes involved in various diseases including HIV/TB as well as immune-modulatory effects of foods or drugs.

Study by McDermid etal: “Host iron redistribution as a risk factor for incident tuberculosis in HIV infection: an 11-year retrospective cohort study.” BMC Infectious Diseases201313:48. Suggest host iron redistribution as a risk factor for incident tuberculosis in HIV infection. Plasma transferrin(IRR=0.53,0.33-0.84)and ferritin(IRR=1.26,1.05-1.51) were significantly associated with TB after adjusting for TB susceptibility factors Participants that subsequently developed TB had lower Tf and iron, and higher ferritin concentrations than participants who did not develop TB.
Study by Ying Zheng etal (Nov 2013) suggest that possible abnormalities in ghrelin and leptin regulation (high levels of leptin and low levels of ghrelin) may be associated with low BMI and may account for the poor nutrition associated with TB and TB+T2DM

The best part of the study was ROC analysis, this was interesting; otherwise we routinely do a ROC analysis in evaluating a new diagnostic test. Besides ROC, I also felt that you could have also looked at various correlations between the risk factors and some of pertinent cytokines levels.

In this study combining various risk factors and cytokines and looking at the AUC values as you rightly said can come across a hypothesis generation and probably you could come out with a sort of algorithm to detect patients who are potential high risk individuals to develop TB. This needs to be further studied in a prospective study. I was also wondering if we can also see the cytokines levels and its relation to TB mortality and probably some intervention to reduce some of these risk factors.

     
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a very good study.Can most of them be IRIS?.In our setting when we start ART in patients with low CD4 count we are looking out for IRIS.especially in first 6-12 weeks.as your patients had incident TB at 96 weeks do you suggest any treatment or monitoring guidelines specially in those regions where many of biomarker investigations are not available?It is known that low BMI,Albumin and HB are a risk factors but most of all our patients have these features.can we also include some other clinical biomarkers like skin fold thickness to monitor?
                    Dr Anita Basavaraj