Evaluation and screening of vaccines against tuberculosis depends on development of proper cost effective disease models along with identification of different immune markers that can be used as surrogate endpoints of protection in preclinical and clinical studies. The objective of the present study was therefore evaluation of subcutaneous model of M.tuberculosis infection along with investigation of different immune biomarkers of tuberculosis infection in BALB/c mice. Groups of mice were infected subcutaneously with two different doses : high (2x10(6) CFU) and low doses (2x10(2) CFU) of M.tuberculosis and immune markers including humoral and cellular markers were evaluated 30 days post M.tuberculosis infections. Based on results, we found that high dose of subcutaneous infection produced chronic disease with significant (p<0.001) production of immune markers of infection like IFNgamma, heat shock antigens (65, 71) and antibody titres against panel of M.tuberculosis antigens (ESAT-6, CFP-10, Ag85B, 45kDa, GroES, Hsp-16) all of which correlated with high bacterial burden in lungs and spleen. To conclude high dose of subcutaneous infection produces chronic TB infection in mice and can be used as convenient alternative to aerosol models in resource limited settings. Moreover assessment of immune markers namely mycobacterial antigens and antibodies can provide us valuable insights on modulation of immune response post infection. However further investigations along with optimization of study protocols are needed to justify the outcome of present study and establish such markers as surrogate endpoints of vaccine protection in preclinical and clinical studies in future.
Animals ; Antibodies ; Biomarkers* ; Chronic Disease ; Hot Temperature ; Lung ; Mass Screening ; Mice* ; Shock ; Spleen ; Tuberculosis* ; Vaccines

Introduction: Correlation of Pirani score and foot bimalleolar (FBM) angle has been used in few studies but correlation of FBM angle with ultrasonography has never been evaluated so they are being correlated in assessing the severity of clubfoot in neonates treated by Ponseti method. Material and Methods: Thirty-two feet with congenital talipes equinovarus (CTEV) deformity in neonates were prospectively treated by the Ponseti method. FBM angle and ultrasound parameters were measured three times i.e. at the time of initial presentation, at four weeks of treatment and at completion of treatment. The feet were divided according to the Pirani score in groups: one (0-2.0), two (2.5-4) and three (4.5-6). Correlation between FBM angle and ultrasound parameters were evaluated using Pearson correlation/regression. Results: Correlation between FBM angle and ultrasound parameters were statistically significant (p-value < 0.05). Conclusion: Ultrasound has the potential to accurately depict the pathoanatomy in clubfoot. FBM angle and ultrasound are objective methods to assess the severity of clubfoot. FBM angle and ultrasonography correlated in severity of deformity and correction achieved along the course of treatment.