avoid destruction by the host's immune system. macrophages and dendritic cells in the granulomas are unable to present antigen to lymphocytes; thus the immune response is suppressed. bacteria inside the granuloma can become dormant, resulting in latent infection. another feature of the granulomas is the development of abnormal cell death (necrosis) in the center of tubercles. to the naked eye, this has the texture of soft, white cheese and is termed caseous necrosis. if tb bacteria gain entry to the blood stream from an area of damaged tissue, they can spread throughout the body and set up many foci of infection, all appearing as tiny, white tubercles in the tissues. this severe form of tb disease, most common in young children and those with hiv, is called miliary tuberculosis. people with this disseminated tb have a high fatality rate even with treatment (about 30%). in many people, the infection waxes and wanes. tissue destruction and necrosis are often balanced by healing and fibrosis. affected tissue is replaced by scarring and cavities filled with caseous necrotic material. during active disease, some of these cavities are joined to the air passages (bronchi) and this material can be coughed up. it contains living bacteria and thus can spread the infection. treatment with appropriate antibiotics kills bacteria and allows healing to take place. upon cure, affected areas are eventually replaced by scar tissue. diagnosis main article: tuberculosis diagnosis m. tuberculosis (stained red) in sputum active tuberculosis diagnosing active tuberculosis based only on signs and symptoms is difficult, as is diagnosing the disease in those who have a weakened immune system. a diagnosis of tb should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. a chest x-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation. interferon-γ release assays (igra) and tuberculin skin tests are of little use in most of the developing world. igra have similar limitations in those with hiv. a definitive diagnosis of tb is made by identifying m. tuberculosis in a clinical sample (e.g., sputum, pus, or a tissue biopsy). however, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture. thus, treatment is often begun before cultures are confirmed. nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of tb. blood tests to detect antibodies are not specific or sensitive, so they are not recommended. latent tuberculosis main article: latent tuberculosis mantoux tuberculin skin test the mantoux tuberculin skin test is often used to screen people at high risk for tb. those who have been previously immunized with the bacille calmette-guerin vaccine may have a false-positive test result. the test may be falsely negative in those with sarcoidosis, hodgkin's lymphoma, malnutrition, and most notably, active tuberculosis. interferon gamma release assays, on a blood sample, are recommended in those who are positive to the mantoux test. these are not affected by immunization or most environmental mycobacteria, so they generate fewer false-positive results. however, they are affected by m. szulgai, m. marinum, and m. kansasii. igras may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone. the us preventive services task force (uspstf) has recommended screening people who are at high risk for latent tuberculosis with either tuberculin skin tests or interferon-gamma release assays. while some have recommend testing health care workers, evidence of benefit for this is poor as of 2019. the centers for disease control and prevention (cdc) stopped recommending yearly testing of health care workers without known exposure in 2019. prevention tuberculosis public health campaign in ireland, c. 1905 tuberculosis prevention and control efforts rely primarily on the vaccination of infants and the detection and appropriate treatment of active cases. the world health organization (who) has achieved some success with improved treatment regimens, and a small decrease in case numbers. some countries have legislation to involuntarily detain or examine those suspected to have tuberculosis, or involuntarily treat them if infected. vaccines main articles: tuberculosis vaccines and bcg vaccine the only available vaccine as of 2021 is bacillus calmette-guérin (bcg). in children it decreases the risk of getting the infection by 20% and the risk of infection turning into active disease by nearly 60%. it is the most widely used vaccine worldwide, with more than 90% of all children being vaccinated. the immunity it induces decreases after about ten years. as tuberculosis is uncommon in most of canada, western europe, and the united states, bcg is administered to only those people at high risk. part of the reasoning against the use of the vaccine is that it makes the tuberculin skin test falsely positive, reducing the test's usefulness as a screening tool. several vaccines are being developed. intradermal mva85a vaccine in addition to bcg injection is not effective in preventing tuberculosis. public health public health campaigns which have focused on overcrowding, public spitting and regular sanitation (including hand washing) during the 1800s helped to either interrupt or slow spread which when combined with contact tracing, isolation and treatment helped to dramatically curb the transmission of both tuberculosis and other airborne diseases which led to the elimination of tuberculosis as a major public health issue in most developed economies. other risk factors which worsened tb spread such as malnutrition were also ameliorated, but since the emergence of hiv a new population of immunocompromised individuals was available for tb to infect. the world health organization (who) declared tb a "global health emergency" in 1993, and in 2006, the stop tb partnership developed a global plan to stop tuberculosis that aimed to save 14 million lives between its launch and 2015. a number of targets they set were not achieved by 2015, mostly due to the increase in hiv-associated tuberculosis and the emergence of multiple drug-resistant tuberculosis. a tuberculosis classification system developed by the american thoracic society is used primarily in public health programs. in 2015, it launched the end tb strategy to reduce deaths by 95% and incidence by 90% before 2035. the goal of tuberculosis elimination is hampered by the lack of rapid testing, of short and effective treatment courses, and of completely effective vaccines. the benefits and risks of giving anti-tubercular drugs in those exposed to mdr-tb is unclear. making haart therapy available to hiv-positive individuals significantly reduces the risk of progression to an active tb infection by up to 90% and can mitigate the spread through this population. treatment main article: tuberculosis management tuberculosis phototherapy treatment on 3 march 1934, in kuopio, finland treatment of tb uses antibiotics to kill the bacteria. effective tb treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which hinders the entry of drugs and makes many antibiotics ineffective. active tb is best treated with combinations of several antibiotics to reduce the risk of the bacteria developing antibiotic resistance. the routine use of rifabutin instead of rifampicin in hiv-positive people with tuberculosis is of unclear benefit as of 2007. latent tb latent tb is treated with either isoniazid or rifampin alone, or a combination of isoniazid with either rifampicin or rifapentine. the treatment takes three to nine months depending on the medications used. people with latent infections are treated to prevent them from progressing to active tb disease later in life. education or counselling may improve the latent tuberculosis treatment completion rates. new onset the recommended treatment of new-onset pulmonary tuberculosis, as of 2010, is six months of a combination of antibiotics containing rifampicin, isoniazid, pyrazinamide, and ethambutol for the first two months, and only rifampicin and isoniazid for the last four months. where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative. treatment with anti-tb drugs for at least 6 months results in higher success rates when compared with treatment less than 6 months, even though the difference is small. shorter treatment regimen may be recommended for those with compliance issues. there is also no evidence to support shorter anti-tuberculosis treatment regimens when compared to a 6-month treatment regimen. however recently, results from an international, randomized, controlled clinical trial indicate that a four-month daily treatment regimen containing high-dose, or "optimized", rifapentine with moxifloxacin (2phzm/2phm) is as safe and effective as the existing standard six-month daily regimen at curing drug-susceptible tuberculosis (tb) disease. recurrent disease if tuberculosis recurs, testing to determine which antibiotics it is sensitive to is important before determining treatment. if multiple drug-resistant tb (mdr-tb) is detected, treatment with at least four effective antibiotics for 18 to 24 months is recommended. medication administration directly observed therapy, i.e., having a health care provider watch the person take their medications, is recommended by the world health organization (who) in an effort to reduce the number of people not appropriately taking antibiotics. the evidence to support this practice over people simply taking their medications independently is of poor quality. there is no strong evidence indicating that directly observed therapy improves the number of people who were cured or the number of people who complete their medicine. moderate quality evidence suggests that there is also no difference if people are observed at home versus at a clinic, or by a family member versus a health care worker. methods to remind people of the importance of treatment and appointments may result in a small but important improvement. there is also not enough evidence to support intermittent rifampicin-containing therapy given two to three times a week has equal effectiveness as daily dose regimen on improving cure rates and reducing relapsing rates. there is also not enough evidence on effectiveness of giving intermittent twice or thrice weekly short course regimen compared to daily dosing regimen in treating children with tuberculosis. medication resistance primary resistance occurs when a person becomes infected with a resistant strain of tb. a person with fully susceptible mtb may develop secondary (acquired) resistance during therapy because of inadequate treatment, not taking the prescribed regimen appropriately (lack of compliance), or using low-quality medication. drug-resistant tb is a serious public health issue in many developing countries, as its treatment is longer and requires more expensive drugs. mdr-tb is defined as resistance to the two most effective first-line tb drugs: rifampicin and isoniazid. extensively drug-resistant tb is also resistant to three or more of the six classes of second-line drugs. totally drug-resistant tb is resistant to all currently used drugs. it was first observed in 2003 in italy, but not widely reported until 2012, and has also been found in iran and india. there is some efficacy for linezolid to treat those with xdr-tb but side effects and discontinuation of medications were common. bedaquiline is tentatively supported for use in multiple drug-resistant tb. xdr-tb is a term sometimes used to define extensively resistant tb, and constitutes one in ten cases of mdr-tb. cases of xdr tb have been identified in more than 90% of countries. for those with known rifampicin or mdr-tb, molecular tests such as the genotype mtbdrsl assay (performed on culture isolates or smear positive specimens) may be useful to detect second-line anti-tubercular drug resistance. prognosis age-standardized disability-adjusted life years caused by tuberculosis per 100,000 inhabitants in 2004. no data ≤10 10–25 25–50 50–75 75–100 100–250 250–500 500–750 750–1000 1000–2000 2000–3000 ≥ 3000 progression from tb infection to overt tb disease occurs when the bacilli overcome the immune system defenses and begin to multiply. in primary tb disease (some 1–5% of cases), this occurs soon after the initial infection. however, in the majority of cases, a latent infection occurs with no obvious symptoms. these dormant bacilli produce active tuberculosis in 5–10% of these latent cases, often many years after infection. the risk of reactivation increases with immunosuppression, such as that caused by infection with hiv. in people coinfected with m. tuberculosis and hiv, the risk of reactivation increases to 10% per year. studies using dna fingerprinting of m. tuberculosis strains have shown reinfection contributes more substantially to recurrent tb than previously thought, with estimates that it might account for more than 50% of reactivated cases in areas where tb is common. the chance of death from a case of tuberculosis is about 4% as of 2008, down from 8%