This double blinded, randomized, placebo controlled trial on the clinical efficacy and antimicrobial mechanisms of quadrate therapy(Chicoric Acid, 13-Cis Retinoic Acid(Aerosolized), Minocycline and Vitamin D) as a Potent Quadrate Therapy Against Tuberculosis. 200 men and women will be enrolled , who are age 18 to 65 years inclusive, have at least two positive sputum smears for tuberculosis (TB), and have given informed consent to participate in the study. All of the enrollees will have active TB . The effect of the quadrate therapy status will be examined in the context of a randomized trial conducted in Egyptian or Saudi Arabian Subjects will be randomized to receive either the quadrate therapy or placebo from the start of their TB therapy, through the 1 months of anti-TB therapy, and until the last recruited patient reaches 6 months of follow up. Thus, the first subject is likely to be followed for 12 months, assuming the duration of recruitment is 12 months. The endpoints of interest include bacteriologic cure, immune response parameters, and clinical outcomes. The researchers will also examine the utility of these immune response parameters as surrogate markers for treatment efficacy in TB, irrespective of the quadrate therapy and other risk factors. The study will be carried out as a collaborative effort between. Kafr elshiekh university ,Faculty of Medicine, Egypt and First health cluster ,Ministry of health ,Saudia Arabia. Subjects will be randomly assigned to receive A) Minocycline i.v. 4,5 mg/kg gradual in 2 divided doses increases from 4,5 mg/kg from the first week to 7.5 and 10 mg/kg to the last week. In addition to Aerosolized 13 cis retinoic acid or All trans retinoic acid or 9 cis retinoic acid gradual in 2 divided doses increases from 0.2 mg/kg/day to 4 mg/kg/day as inhaled retinoic acid therapy for 30 days. Moreover, the patients will receive Echinacea Purpurea Extract Capsules Polyphenols Chicoric Acid .Chicoric acid (also known as cichoric acid and dicaffeoyltar- taric acid) is the main phenolic compound found in Echinacea purpurea. Echinacea phytochemical profile Each tablet is comprised of the equivalent of 1275 mg of echinacea root, as follows: A) Echinacea purpurea - 675 mg root yields 112.5 mg dried extract, standardized to contain 2.1mg alkamides. Each batch of tablets Caffeic acid derivative levels are typically as follows: caftaric acid = 0.5 to 2.0 mg/tablet; cichoric acid = 3.4 to 8.5 mg/tablet; chlorogenic acid = \< 0.5 mg/tablet; dicaffeoyl quinic acids (including cynarin) = 0.7 to 2.0 mg/tablet; echinacoside = 1.0 to 1.7 mg/tablet. Furthermore, the patients will receive Cholecalciferol(Vitamin D) Intramuscular injection of 600,000 units of Cholecalciferol for 2 doses given at week 0 and week 4 (b) placebo. The primary objectives are to: (1) determine the efficacy of the quadrate therapy on sputum and culture negativity at one month and two months; (2) determine the efficacy of micronutrient supplements on survival between two arms at 8 and 24 months; and (3) determine the efficacy of micronutrient supplements on TB relapse and reinfection. Secondary study objectives are to: (1) compare the treatment arms with respect to absolute change in CD4 counts from 0 to 1, 6, 12 months; (2) compare the treatment arms with respect to weight change from baseline and1 months, 6 months, and 12 months; (3) compare the treatment arms with respect to immunological parameters, namely ex vivo lymphocyte proliferation; and cytokine production, namely IL-2, IL-6, INF-g INF-Alpha, IL-12, and TNF-a, and Interferon alpha at 1, 6, 12 months; and (4) correlate the above mentioned immunological markers with smear conversion rates at 1 month, 2 months, cure, relapse, and death. Finally, we suggest that this combination therapy will effectively inhibit tuberculosis infection and achieve treatment with significant effect against (TB)