Tuberculosis Tuberculosis is an infection with the bacterium Mycobacterium tuberculosis, which most commonly affects the lungs (pulmonary TB) but can also affect the central nervous system (meningitis), lymphatic system, circulatory system (miliary TB), bones and joints. Tuberculosis is the most common major infectious disease today, infecting two billion people or one-third of the world's population, with nine million new cases of active disease annually, resulting in two million deaths, mostly in developing countries. Most of those infected (90 percent) have asymptomatic latent TB infection (LTBI). While only 10 percent of TB infection progresses to TB disease, if untreated the death rate is 50 percent. TB is the second largest killing disease in the world. The neglect of TB control programs and immigration has caused a resurgence of tuberculosis. Multiple drug resistant strains of TB are also increasing. The World Health Organization declared TB a global health emergency in 1993. The bacterium The cause of tuberculosis, Mycobacterium tuberculosis (MTB), is a slow-growing Gram-positive aerobic bacterium that divides every 16 to 20 hours. This is extremely slow compared to other bacteria. It is a small rod-like bacillus that can withstand weak disinfectants and can survive in a dry state for weeks but can only grow within a host organism. MTB is identified microscopically by its staining characteristics: it retains certain stains after being treated with acidic solution. In the most common staining technique, MTB are stained bright red, which stands out clearly against a blue background. It can also be visualized by fluorescent microscopy. The disease Transmission TB is spread through water droplets that are expelled when persons with infectious TB disease cough, sneeze or speak. People who live close to patients affected with active TB are at high risk. The probability of transmission depends upon: infectiousness of the person with TB, environment of exposure, duration of exposure, and virulence of the organism. The chain of transmission can be stopped by isolating patients with active disease and starting effective anti-tuberculous therapy. Infection TB infection begins when TB bacilli reach the pulmonary alveoli, from which they may spread to local lymph nodes, and then through the bloodstream to the more distant tissues and organs where TB disease is likely to develop: lungs, lymph nodes, kidneys, brain, and bone. Usually the immune system is able to halt the multiplication of TB bacilli, preventing further spread in about 90 percent of cases. However if a person has a weak immune system or is poorly nourished, bacteria are not eliminated and proliferate. The tubercles enlarge and there is local tissue destruction. Another feature of tuberculosis is the development of cell death, necrosis, in the center of tubercles. This has the texture of soft white cheese and was termed caseous necrosis. If TB bacteria gain entry to the blood stream from an area of tissue damage, they spread through the body and infect the tissues, appearing as tiny white tubercles. This is called miliary tuberculosis and has a high case fatality. In many patients the infection waxes and wanes. Healing and fibrosis balance tissue destruction and necrosis. Affected tissue is replaced by scarring and cavities filled with cheese-like white necrotic material. In the lung some of these cavities are in continuity with the air passages bronchi. This material may therefore be coughed up. It contains living bacteria and can pass on infection. Treatment with appropriate antibiotics kills bacteria and allows healing to take place. Affected areas are eventually replaced by scar tissue. Disease In those people in whom TB bacilli overcome the immune system defenses and begin to multiply, there is progression from TB infection to TB disease. This may occur soon after infection (primary TB disease - 1 to 5 percent) or many years after infection (post primary TB, secondary TB, reactivation TB disease of dormant bacilli - 5 to 9 percent). About five percent of infected persons will develop TB disease in the first two years, and another five percent will develop disease later in life. In all, about 10 percent of infected persons with normal immune systems will develop TB disease in their lifetime. A complete medical evaluation for TB includes a medical history, a physical examination, a tuberculin skin test, a chest X-ray, and microbiologic smears and cultures. TB disease most commonly affects the lungs (75 percent or more), where it is called pulmonary TB. Symptoms include a productive, prolonged cough of more than three weeks duration, chest pain, and hemoptysis. Systemic symptoms include fever, chills, night sweats, appetite loss, weight loss, and easy fatigability. Treatment Persons with TB infection (class 2 or class 4 TB), but who do not have TB disease (class 3 or class 5 TB), cannot spread the infection to other people. TB infection in a person who does not have TB disease is not considered a case of TB and is often referred to as latent TB infection (LTBI). This distinction is important because treatment options will be different for a person who has LTBI instead of active TB disease. Prevention Prevention and control efforts include three priority strategies: · Identifying and treating all persons who have TB disease · Finding and evaluating persons who have been in contact with TB patients to determine whether they have TB infection or disease, and treating them appropriately, and · Testing high-risk groups for TB infection In tropical areas where the incidence of atypical mycobacteria is high, exposure to nontuberculous mycobacteria gives some protection against TB. Drug-resistant TB is transmitted in the same way as drug-susceptible TB. Primary resistance develops in persons initially infected with resistant organisms. Secondary resistance (acquired resistance) develops during TB therapy due to inadequate treatment regimen, not taking the prescribed regimen appropriately or using low quality medication. BCG vaccine Many countries use BCG vaccine as part of their TB control programs, especially for infants. The protective efficacy of BCG for preventing serious forms of TB (e.g. meningitis) in children is high (greater than 80 percent). However, the protective efficacy for preventing pulmonary TB in adolescents and adults is variable, from 0 to 80 percent. The effectiveness of BCG is much lower than in areas where mycobacteria are much less prevalent. The first recombinant tuberculosis vaccine entered clinical trials in the United States in 2004 sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). A 2005 study showed that a DNA TB vaccine given with conventional chemotherapy could accelerate the disappearance of bacteria as well as protecting against re-infection in mice; it may take four to five years to be available in humans.