tuberculosis tuberculosis tuberculosis (tb) is an infectious disease usually caused by mycobacterium tuberculosis (mtb) bacteria. tuberculosis generally affects the lungs, but it can also affect other parts of the body. most infections show no symptoms, in which case it is known as latent tuberculosis. around 10% of latent infections progress to active disease which, if left untreated, kill about half of those affected. typical symptoms of active tb are chronic cough with blood-containing mucus, fever, night sweats, and weight loss. it was historically referred to as consumption due to the weight loss associated with the disease. infection of other organs can cause a wide range of symptoms. tuberculosisother namesphthisis, phthisis pulmonalis, consumption, great white plaguechest x-ray of a person with advanced tuberculosis: infection in both lungs is marked by white arrow-heads, and the formation of a cavity is marked by black arrows.specialtyinfectious disease, pulmonologysymptomschronic cough, fever, cough with bloody mucus, weight losscausesmycobacterium tuberculosisrisk factorssmoking, hiv/aidsdiagnostic methodcxr, culture, tuberculin skin test, quantiferondifferential diagnosispneumonia, histoplasmosis, sarcoidosis, coccidioidomycosispreventionscreening those at high risk, treatment of those infected, vaccination with bacillus calmette-guérin (bcg)treatmentantibioticsfrequency25% of people (latent tb)deaths1.5 million (2020) depiction of a man with tuberculosis tuberculosis is spread from one person to the next through the air when people who have active tb in their lungs cough, spit, speak, or sneeze. people with latent tb do not spread the disease. active infection occurs more often in people with hiv/aids and in those who smoke. diagnosis of active tb is based on chest x-rays, as well as microscopic examination and culture of body fluids. diagnosis of latent tb relies on the tuberculin skin test (tst) or blood tests. prevention of tb involves screening those at high risk, early detection and treatment of cases, and vaccination with the bacillus calmette-guérin (bcg) vaccine. those at high risk include household, workplace, and social contacts of people with active tb. treatment requires the use of multiple antibiotics over a long period of time. antibiotic resistance is a growing problem, with increasing rates of multiple drug-resistant tuberculosis (mdr-tb). in 2018, one quarter of the world's population was thought to have a latent infection of tb. new infections occur in about 1% of the population each year. in 2020, an estimated 10 million people developed active tb, resulting in 1.5 million deaths, making it the second leading cause of death from an infectious disease after covid-19. as of 2018, most tb cases occurred in the regions of south-east asia (44%), africa (24%), and the western pacific (18%), with more than 50% of cases being diagnosed in seven countries: india (27%), china (9%), indonesia (8%), the philippines (6%), pakistan (6%), nigeria (4%), and bangladesh (4%). by 2021, the number of new cases each year was decreasing by around 2% annually. about 80% of people in many asian and african countries test positive, while 5–10% of people in the united states test positive via the tuberculin test. tuberculosis has been present in humans since ancient times. signs and symptoms the main symptoms of variants and stages of tuberculosis are given, with many symptoms overlapping with other variants, while others are more (but not entirely) specific for certain variants. multiple variants may be present simultaneously. tuberculosis may infect any part of the body, but most commonly occurs in the lungs (known as pulmonary tuberculosis). extrapulmonary tb occurs when tuberculosis develops outside of the lungs, although extrapulmonary tb may coexist with pulmonary tb. general signs and symptoms include fever, chills, night sweats, loss of appetite, weight loss, and fatigue. significant nail clubbing may also occur. pulmonary if a tuberculosis infection does become active, it most commonly involves the lungs (in about 90% of cases). symptoms may include chest pain and a prolonged cough producing sputum. about 25% of people may not have any symptoms (i.e., they remain asymptomatic). occasionally, people may cough up blood in small amounts, and in very rare cases, the infection may erode into the pulmonary artery or a rasmussen's aneurysm, resulting in massive bleeding. tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs. the upper lung lobes are more frequently affected by tuberculosis than the lower ones. the reason for this difference is not clear. it may be due to either better air flow, or poor lymph drainage within the upper lungs. extrapulmonary main article: extrapulmonary tuberculosis in 15–20% of active cases, the infection spreads outside the lungs, causing other kinds of tb. these are collectively denoted as extrapulmonary tuberculosis. extrapulmonary tb occurs more commonly in people with a weakened immune system and young children. in those with hiv, this occurs in more than 50% of cases. notable extrapulmonary infection sites include the pleura (in tuberculous pleurisy), the central nervous system (in tuberculous meningitis), the lymphatic system (in scrofula of the neck), the genitourinary system (in urogenital tuberculosis), and the bones and joints (in pott disease of the spine), among others. a potentially more serious, widespread form of tb is called "disseminated tuberculosis", it is also known as miliary tuberculosis. miliary tb currently makes up about 10% of extrapulmonary cases. causes mycobacteria main article: mycobacterium tuberculosis scanning electron micrograph of m. tuberculosis the main cause of tb is mycobacterium tuberculosis (mtb), a small, aerobic, nonmotile bacillus. the high lipid content of this pathogen accounts for many of its unique clinical characteristics. it divides every 16 to 20 hours, which is an extremely slow rate compared with other bacteria, which usually divide in less than an hour. mycobacteria have an outer membrane lipid bilayer. if a gram stain is performed, mtb either stains very weakly "gram-positive" or does not retain dye as a result of the high lipid and mycolic acid content of its cell wall. mtb can withstand weak disinfectants and survive in a dry state for weeks. in nature, the bacterium can grow only within the cells of a host organism, but m. tuberculosis can be cultured in the laboratory. using histological stains on expectorated samples from phlegm (also called sputum), scientists can identify mtb under a microscope. since mtb retains certain stains even after being treated with acidic solution, it is classified as an acid-fast bacillus. the most common acid-fast staining techniques are the ziehl–neelsen stain and the kinyoun stain, which dye acid-fast bacilli a bright red that stands out against a blue background. auramine-rhodamine staining and fluorescence microscopy are also used. the m. tuberculosis complex (mtbc) includes four other tb-causing mycobacteria: m. bovis, m. africanum, m. canetti, and m. microti. m. africanum is not widespread, but it is a significant cause of tuberculosis in parts of africa. m. bovis was once a common cause of tuberculosis, but the introduction of pasteurized milk has almost eliminated this as a public health problem in developed countries. m. canetti is rare and seems to be limited to the horn of africa, although a few cases have been seen in african emigrants. m. microti is also rare and is seen almost only in immunodeficient people, although its prevalence may be significantly underestimated. other known pathogenic mycobacteria include m. leprae, m. avium, and m. kansasii. the latter two species are classified as "nontuberculous mycobacteria" (ntm) or atypical mycobacteria. ntm cause neither tb nor leprosy, but they do cause lung diseases that resemble tb.public health campaigns in the 1920s tried to halt the spread of tb. transmission when people with active pulmonary tb cough, sneeze, speak, sing, or spit, they expel infectious aerosol droplets 0.5 to 5.0 µm in diameter. a single sneeze can release up to 40,000 droplets. each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very small (the inhalation of fewer than 10 bacteria may cause an infection). risk of transmission people with prolonged, frequent, or close contact with people with tb are at particularly high risk of becoming infected, with an estimated 22% infection rate. a person with active but untreated tuberculosis may infect 10–15 (or more) other people per year. transmission should occur from only people with active tb – those with latent infection are not thought to be contagious. the probability of transmission from one person to another depends upon several factors, including the number of infectious droplets expelled by the carrier, the effectiveness of ventilation, the duration of exposure, the virulence of the m. tuberculosis strain, the level of immunity in the uninfected person, and others. the cascade of person-to-person spread can be circumvented by segregating those with active ("overt") tb and putting them on anti-tb drug regimens. after about two weeks of effective treatment, subjects with nonresistant active infections generally do not remain contagious to others. if someone does become infected, it typically takes three to four weeks before the newly infected person becomes infectious enough to transmit the disease to others. risk factors main article: risk factors for tuberculosis a number of factors make individuals more susceptible to tb infection and/or disease. active disease risk the most important risk factor globally for developing active tb is concurrent hiv infection; 13% of those with tb are also infected with hiv. this is a particular problem in sub-saharan africa, where hiv infection rates are high. of those without hiv infection who are infected with tuberculosis, about 5–10% develop active disease during their lifetimes; in contrast, 30% of those co-infected with hiv develop the active disease. use of certain medications, such as corticosteroids and infliximab (an anti-αtnf monoclonal antibody), is another important risk factor, especially in the developed world. other risk factors include: alcoholism, diabetes mellitus (3-fold increased risk), silicosis (30-fold increased risk), tobacco smoking (2-fold increased risk), indoor air pollution, malnutrition, young age, recently acquired tb infection, recreational drug use, severe kidney disease, low body weight, organ transplant, head and neck cancer, and genetic susceptibility (the overall importance of genetic risk factors remains undefined). infection susceptibility tobacco smoking increases the risk of infections (in addition to increasing the risk of active disease and death). additional factors increasing infection susceptibility include young age. pathogenesis robert carswell's illustration of tubercle about 90% of those infected with m. tuberculosis have asymptomatic, latent tb infections (sometimes called ltbi), with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease. in those with hiv, the risk of developing active tb increases to nearly 10% a year. if effective treatment is not given, the death rate for active tb cases is up to 66%. microscopy of tuberculous epididymitis. h&e stain tb infection begins when the mycobacteria reach the alveolar air sacs of the lungs, where they invade and replicate within endosomes of alveolar macrophages. macrophages identify the bacterium as foreign and attempt to eliminate it by phagocytosis. during this process, the bacterium is enveloped by the macrophage and stored temporarily in a membrane-bound vesicle called a phagosome. the phagosome then combines with a lysosome to create a phagolysosome. in the phagolysosome, the cell attempts to use reactive oxygen species and acid to kill the bacterium. however, m. tuberculosis has a thick, waxy mycolic acid capsule that protects it from these toxic substances. m. tuberculosis is able to reproduce inside the macrophage and will eventually kill the immune cell. the primary site of infection in the lungs, known as the ghon focus, is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe. tuberculosis of the lungs may also occur via infection from the blood stream. this is known as a simon focus and is typically found in the top of the lung. this hematogenous transmission can also spread infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones. all parts of the body can be affected by the disease, though for unknown reasons it rarely affects the heart, skeletal muscles, pancreas, or thyroid. tuberculosis is classified as one of the granulomatous inflammatory diseases. macrophages, epithelioid cells, t lymphocytes, b lymphocytes, and fibroblasts aggregate to form granulomas, with lymphocytes surrounding the infected macrophages. when other macrophages attack the infected macrophage, they fuse together to form a giant multinucleated cell in the alveolar lumen. the granuloma may prevent dissemination of the mycobacteria and provide a local environment for interaction of cells of the immune system. however, more recent evidence suggests that the bacteria use the granulomas to