Baseline characteristics of population under study.

<p>Characteristics of 275 subjects with the number of positive responders for each category are presented in the table. Percentages are indicated in parentheses. The statistical variance between groups was calculated using Chi squared test and p value. P < 0.05 was considered statistically significant. Statistical analysis was done using MedCalc statistical software (version 10.1.2.0).</p><p>Df, Degrees of freedom.</p><p>Baseline characteristics of population under study.</p

Mean BMI, Leptin, QFT and TST values in different categories.

<p>Bar graphs represent the mean values in different study groups. Graphs were plotted using GraphPad Prism (version 5.03). Error bars represent mean ± standard deviation. BMI- Body mass index, TST-Tuberculin Skin Test, Cut-off point is atleast 10 mm, QFT- QuantiFERON-TB Gold, Cut-off is atleast 0.35 IU/μl, Leptin values are indicated as absorbance at 450 nm. Leptin levels were evaluated in serum SPIbio Human EIA kit.</p

Representative 1-DE gel images of identified proteins in different categories.

<p>Boxes indicate the differentially expressed protein bands in different study groups. Gel imaging and analysis was done using Image Lab software (version 4.0, BioRad). The protein bands in the test groups were compared against healthy control group.</p

Expression of proteins by densitometric analysis.

<p>Pie charts represent the intensities of protein bands assessed by densitometric analysis in different study groups. Gel analysis was done using Image Lab software (BioRad) (Version 4.0)</p

Protein functions in tuberculosis and malnutrition.

<p>Table enlists the roles of the three identified proteins in malnutrition and tuberculosis reported in various studies.</p><p>Protein functions in tuberculosis and malnutrition.</p

Hematological parameters of the population under study.

<p>Hematological parameters of 275 subjects from Melghat are listed in the table. Complete blood count was done in the Pathology department, CIIMS, Nagpur using commercial kits. The normal detection ranges of each parameter are indicated in the brackets. P < 0.05 was considered statistically significant. Values are reported as Mean ± SD. Statistical analysis was done using GraphPad Prism (version 5.03). Statistical variance between groups was calculated using mean values through ANOVA test with Tukey post test.</p><p>* Statistically significant when the significance level is set as P < 0.05 based on the Tukey correction</p><p>Hematological parameters of the population under study.</p

Evaluation of TB biomarkers in original and follow-up samples of the population under study.

<p>Chart shows a comparison between the levels of TB biomarkers (30 kDa antigen, ADA; Adenosine deaminase, Mycobacterial Dormancy Regulon Protein Rv2623, Multiplex antigens; Ag85B; <i>M</i>.<i>tb</i> Ag85B secretory protein, Hsp-16; 16 kDa heat-shock protein, 45kDa antigen, GroES; <i>M</i>.<i>tb</i> 10kDa chaperonin, ESAT-6; 6 kDa early secretory antigenic target and CFP-10; 10 kDa culture filtrate protein, QFT; QunatiFERON-TB Gold test and TST; Tuberculin Skin Test) in original and follow-up cases of Melghat categorized into three groups; Latent to Active TB group (n = 1), Latent to Latent TB Group (n = 5) and Active to Active TB group (n = 3).</p

Study participation diagram.

<p>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)</p

Mechanisms involved in the acute phase protein response in malnutrition and TB.

<p>Malnutrition and the anorectic effects of pro-inflammatory cytokines in the brain result in a negatively changed hepatic synthesis. In diseased condition, the pro-inflammatory cytokines TNF-α, IL-1 and IL-6 play a key role in the hepatic APR. They activate hepatocytic receptors, and synthesis of varying APPs starts. During latent form of infection, release of IL-10 by the Kupffer cells results in suppression of the local IL-6 production by gene suppression pathways coactivated on receptor binding. This results in rapid hepatic removal of circulating cytokines followed by down-regulation of hepatocytic APR.</p

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

<div><p>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 <i>Mycobacterium tuberculosis</i> (<i>M</i>.<i>tb</i>) 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.</p></div