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Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India.

Bapat PR, Satav AR, Husain AA, Shekhawat SD, Kawle AP, Chu JJ, Purohit HJ, Daginawala HF, Taori GM, Kashyap RS - PLoS ONE (2015)

Bottom Line: Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB).This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts.Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.

ABSTRACT
Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

No MeSH data available.


Related in: MedlinePlus

Study participation diagram.The figure represents the inclusion/exclusion criteria adopted for recruitment of the study population. The population was categorized into four groups namely: Malnourished group with Active TB (n = 32), Malnourished group with Latent TB (n = 90), Malnourished group (n = 130) and Healthy control group (n = 23) (Grey boxes indicate the groups included in the final analysis). TB-Tuberculosis, TST-Tuberculin Skin Test, Cut-off point is atleast 10 mm, QFT- QuantiFERON-TB Gold, Cut-off is atleast 0.35 IU/μl. TLC-Total leukocyte count, Hb-Hemoglobin count (g/ml)
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pone.0133928.g002: Study participation diagram.The figure represents the inclusion/exclusion criteria adopted for recruitment of the study population. The population was categorized into four groups namely: Malnourished group with Active TB (n = 32), Malnourished group with Latent TB (n = 90), Malnourished group (n = 130) and Healthy control group (n = 23) (Grey boxes indicate the groups included in the final analysis). TB-Tuberculosis, TST-Tuberculin Skin Test, Cut-off point is atleast 10 mm, QFT- QuantiFERON-TB Gold, Cut-off is atleast 0.35 IU/μl. TLC-Total leukocyte count, Hb-Hemoglobin count (g/ml)

Mentions: A total of 419 participants were enrolled for the study. Of these individuals, a total of 63 participants refused to give blood and were excluded from the study. Pregnant women (n = 12) and children below the age of 10 years (n = 9) were also excluded to avoid the impact of BCG reactivity on TST. 14 participants with invalid TST or QuantiFERON-TB Gold test (QFT) results and 29 participants who had other bacterial/fungal or viral infections were also excluded. The remaining 292 participants were recruited for further analysis. A minimum sample size of 267 participants was calculated. Fig 2 represents the inclusion/exclusion criteria adopted for recruitment of the study population.


Differential Levels of Alpha-2-Macroglobulin, Haptoglobin and Sero-Transferrin as Adjunct Markers for TB Diagnosis and Disease Progression in the Malnourished Tribal Population of Melghat, India.

Bapat PR, Satav AR, Husain AA, Shekhawat SD, Kawle AP, Chu JJ, Purohit HJ, Daginawala HF, Taori GM, Kashyap RS - PLoS ONE (2015)

Study participation diagram.The figure represents the inclusion/exclusion criteria adopted for recruitment of the study population. The population was categorized into four groups namely: Malnourished group with Active TB (n = 32), Malnourished group with Latent TB (n = 90), Malnourished group (n = 130) and Healthy control group (n = 23) (Grey boxes indicate the groups included in the final analysis). TB-Tuberculosis, TST-Tuberculin Skin Test, Cut-off point is atleast 10 mm, QFT- QuantiFERON-TB Gold, Cut-off is atleast 0.35 IU/μl. TLC-Total leukocyte count, Hb-Hemoglobin count (g/ml)
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4524608&req=5

pone.0133928.g002: Study participation diagram.The figure represents the inclusion/exclusion criteria adopted for recruitment of the study population. The population was categorized into four groups namely: Malnourished group with Active TB (n = 32), Malnourished group with Latent TB (n = 90), Malnourished group (n = 130) and Healthy control group (n = 23) (Grey boxes indicate the groups included in the final analysis). TB-Tuberculosis, TST-Tuberculin Skin Test, Cut-off point is atleast 10 mm, QFT- QuantiFERON-TB Gold, Cut-off is atleast 0.35 IU/μl. TLC-Total leukocyte count, Hb-Hemoglobin count (g/ml)
Mentions: A total of 419 participants were enrolled for the study. Of these individuals, a total of 63 participants refused to give blood and were excluded from the study. Pregnant women (n = 12) and children below the age of 10 years (n = 9) were also excluded to avoid the impact of BCG reactivity on TST. 14 participants with invalid TST or QuantiFERON-TB Gold test (QFT) results and 29 participants who had other bacterial/fungal or viral infections were also excluded. The remaining 292 participants were recruited for further analysis. A minimum sample size of 267 participants was calculated. Fig 2 represents the inclusion/exclusion criteria adopted for recruitment of the study population.

Bottom Line: Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB).This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts.Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

View Article: PubMed Central - PubMed

Affiliation: Biochemistry Research Centre, Central India Institute of Medical Sciences, Nagpur, Maharashtra, India.

ABSTRACT
Lack of diagnostic capacity has been a crucial barrier preventing an effective response to the challenges of malnutrition and tuberculosis (TB). Point-of-care diagnostic tests for TB in immuno-incompetent, malnourished population are thus needed to ensure rapid and accurate detection. The aim of the study was to identify potential biomarkers specific for TB infection and progression to overt disease in the malnourished population of Melghat. A prospective cohort study was conducted in the year 2009 through 2011 in six villages of the Melghat region. 275 participants consisting of malnourished cases with a) active TB (n = 32), b) latent TB infection (n = 90), c) with no clinical or bacteriological signs of active or latent TB (n = 130) and healthy control subjects (n = 23) were recruited for the study. The proteome changes of the host serum in response to Mycobacterium tuberculosis (M.tb) infection were investigated using one dimensional electrophoresis in combination with matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three most differentially expressed proteins; alpha-2-macroglobulin (A-2-M), sero-transferrin and haptoglobin were identified by MALDI-TOF MS analysis, which were up-regulated in the malnourished patients with active TB and down-regulated in the malnourished patients compared with the healthy controls. Additionally, follow-up studies indicated that the expression of these proteins increased to nearly two folds in patients who developed active disease from latent state. Our preliminary results suggest that A-2-M, sero-transferrin and haptoglobin may be clinically relevant host biomarkers for TB diagnosis and disease progression in the malnourished population. This study provides preliminary framework for an in-depth analysis of the biomarkers in larger well-characterized cohorts. Evaluation of these biomarkers in follow-up cases may further aid in improving TB diagnosis.

No MeSH data available.


Related in: MedlinePlus