Tuberculosis infection can develop in different courses due to difference in the ability of immune system to fight against it and age of infected person. When TB occurs in a person who is not infected before, his/her infection is known as Primary TB. They have not developed any antibody or immunity against it. First, aerosolized respiratory droplets containing tubercle bacillus produced from person with TB in lungs are inhaled by the surrounding people and settle on the alveoli through bronchus and bronchial tree. Since M. tuberculosis is neither gram negative nor positive, they actually do not have exotoxins or endotoxins which can induce inflammatory response in humans. The bacilli are then engulfed by macrophages through phagocytosis, but are not easily killed off because of their waxy complex cell wall. As M. tuberculosis are slow-growing bacteria and even inhibit formation of phagolysosome, they divide everyday (every 25-32 hours) in the macrophage in alveoli, which is long enough for the macrophage to lyse some of them and expose antigen to the receptor of T-cells. After few weeks, more and more bacteria are proliferated in macrophages until it induces an anti-mycobacterial T-cell-mediated immune response. Activated T-cells called T-helper 1 now turn to activate the macrophages which start destroying many ingested mycobacterium. Besides, granulomas are formed from the aggregates of epithelioid cells (differentiated macrophages), sensitized T-cells and bacilli. It is also called Ghon`s focus, a giant white cells with soft, caseous necrotic tissue in the centre surrounded by a rim of fibrous tissues. The tuberculin test may give positive result as the evidence for primary infection. The granuloma then grow into Ghon`s complex due to invasion of the tubercle bacilli into the lymph nodes of the lungs via lymph channels and this forms another caseous granuloma in lymph nodes, together with the primary lung lesion. Primary TB may resolve or progress as there are still tubercle bacilli not being killed in the healed granuloma, resulting in reactivation of TB and spread to other area.????????Reactivation of tuberculosis in previously infected and sensitized person is known as secondary tuberculosis. It usually occurs after some times the primary TB get treated. This is because the body defense system (cell-mediated immunity) gets weakened or not all the tubercle bacilli in the granuloma being destroyed in the primary TB. As a result, a large number of bacteria are found until the immune system is unable to afford protection against them. When the granulomatous inflammatory response spreads to bronchi, cavitation then occur and is surrounded by caseous granuloma with tubercle bacilli inside. The cavities coalesce and expand into the airway, leading to the sputum containing large number of bacilli when the person coughs. Reactivation differs from reinfection because latent infection is often reactivated in areas with low incidence compared to reinfection which occur in areas where TB is quite common. M. tuberculosis is facultative intracellular microorganism and not easy to be destroyed, so multiple antibiotic drugs have to be taken for long time by the infected person. Gradually, the bacteria develop resistance to two or more drugs, for sure including at least Isoniazid and Rifampin drugs, known as Multidrug-resistant TB. Besides, HIV infected person is more vulnerable to get co-infection with TB as their immune system is ‘turned off’ by the obstinate virus. It is the main culprit of death in many cases of TB infection. The common diagnostic tools for pulmonary TB are the tuberculin skin tests and chest X-ray. Tuberculin skin test can detect the hypersensitivity reactions like allergies produced by cell-mediated immunity to the protein of tubercle bacilli. This is done by subcutaneous injection of TB antigen. Positive results – appearance of red swelling on the injected area only indicate that the person has been exposed to TB and sensitized, and not necessarily current infection. Chest X-ray has limitation as it can only detect the sufficiently large granuloma in lungs which is not common in early discovery of TB. Acid-fast stain of sputum or respiratory droplets is useful as well. STRATEGIES FOR MANAGEMENT OF TUBERCULOSISTill today, the deaths that tuberculosis brought to humans in 1993 and 2008 still lurked in our minds as the mortality rate of TB peaked with almost 2 million deaths. It spreads through the air only, but deadly enough to bring your last breath of air. There has been growing concerns from nationwide and worldwide health organizations on this issue to scheme strategies for TB control and put into practice: i. Directly Observed Treatment Shortcourse (DOTS) in 1995 – WHOii. Revised National Tuberculosis Control Programme (RNTCP) in 1997 – Indiaiii. Clinical Diagnosis and Management of Tuberculosis in 2006 – NICEiv. Three I`s for TB/HIV in 2008 – WHO & Stop TB Partnership ???? All these strategies for antituberculosis treatment were implemented with the objective of wiping out the seeds of tubercle bacillus. Infection control can reduce the morbidity rate of active and latent TB to a minimum level by preventing the spreading of TB as most of the cases are attributed to inhaling the mycobacterium-containing droplet nuclei. Other strategies to control multidrug-resistant TB and reinfection have been figured out by designing a treatment regimen consisting of multiple drugs (4-5 groups) and eliminating any inactive bacteria. The reasons why many different strategies arise are poor access or adherence to treatment and improper treatment regimens, so resulting in failure or ineffectiveness of treatment. (i) DOTS StrategyIn 1995 – the peak of death rate from TB, World Health Organization (WHO) introduced one internationally agreed TB control strategy, namely Directly Observed Treatment with short-course chemotherapy (DOTS). Principles of DOTS strategy include1. Continuous equal commitment by national government with sufficient funding2. Case finding through good quality sputum-smear microscopy3. Standardized and supervised treatment – direct observed treatment (DOT) with short-course chemotherapy4. Sufficient supply of quality-assured first line anti-TB drugs5. Regular monitoring, evaluating and reporting the therapeutic performances.