Tuberculosis

in the British Museum – tubercular decay has been found in the spine. Tuberculosis (RP: , ) has existed since antiquity. Genetic studies suggest the presence of TB-like bacteria in Southern America from about AD 140. Identification Although Richard Morton established the pulmonary form associated with tubercles as a pathology in 1689, due to the variety of its symptoms, TB was not identified as a single disease until the 1820s. Benjamin Marten conjectured in 1720 that consumption was caused by microbes that were spread by people living close to each other. In 1819, René Laennec claimed that tubercles were the cause of pulmonary tuberculosis. J. L. Schönlein first published the name "tuberculosis" (German: Tuberkulose) in 1832. In 1865, Jean Antoine Villemin demonstrated that tuberculosis could be transmitted, via inoculation, from humans to animals and among animals. Villemin's findings were confirmed in 1867 and 1868 by John Burdon-Sanderson. discovered the tuberculosis bacillus. Robert Koch identified and described the bacillus causing tuberculosis, M. tuberculosis, on 24 March 1882. In 1905, he was awarded the Nobel Prize in Physiology or Medicine for this discovery. Development of treatments In Europe, rates of tuberculosis began to rise in the early 1600s to a peak level in the 1800s, when it caused nearly 25% of all deaths. In the 18th and 19th century, tuberculosis had become epidemic in Europe, showing a seasonal pattern. Tuberculosis caused widespread public concern in the 19th and early 20th centuries as the disease became common among the urban poor. In 1815, one in four deaths in England was due to "consumption". By 1918, TB still caused one in six deaths in France. Between 1838 and 1845, John Croghan, the owner of Mammoth Cave in Kentucky from 1839 onwards, brought many people with tuberculosis into the cave in the hope of curing the disease with the constant temperature and purity of the cave air; each died within a year. Hermann Brehmer opened the first TB sanatorium in 1859 in Görbersdorf (now Sokołowsko) in Silesia. After TB was determined to be contagious, in the 1880s, it was put on a notifiable-disease list in Britain. Campaigns started to stop people from spitting in public places, and the infected poor were "encouraged" to enter sanatoria that resembled prisons. The sanatoria for the middle and upper classes offered excellent care and constant medical attention. World Tuberculosis Day is marked on 24 March each year, the anniversary of Koch's original scientific announcement. When the Medical Research Council was formed in Britain in 1913, it initially focused on tuberculosis research. Albert Calmette and Camille Guérin achieved the first genuine success in immunization against tuberculosis in 1906, using attenuated bovine-strain tuberculosis. It was called bacille Calmette–Guérin (BCG). The BCG vaccine was first used on humans in 1921 in France, but achieved widespread acceptance in the US, Great Britain, and Germany only after World War II. In 1946, the development of the antibiotic streptomycin made effective treatment and cure of TB a reality. Before the introduction of this medication, the only treatment was surgical intervention, including the "pneumothorax technique", which involved collapsing an infected lung to "rest" it and to allow tuberculous lesions to heal. By the 1950s, mortality in Europe had decreased by about 90%. Improvements in sanitation, vaccination, and other public-health measures began significantly reducing rates of tuberculosis even before the arrival of streptomycin and other antibiotics, although the disease remained a significant threat. Drug-resistant tuberculosis (total cases) and incidence (annual new cases) of MDR-TB from 1990 to 2021 A few years after the first antibiotic treatment for TB in 1943, some strains of the TB bacteria developed resistance to the standard drugs (streptomycin, para-aminosalicylic acid, and isoniazid). Between 1970 and 1990, there were numerous outbreaks of drug-resistant tuberculosis involving strains resistant to two or more drugs; these strains are called multi-drug resistant TB (MDR-TB). Drug resistance to TB can come in two forms: primary and secondary. Primary drug resistance is caused by person-to-person transmission of drug-resistant TB bacteria. Secondary drug resistance (also called acquired resistance) develops during TB treatment. A person with fully drug-susceptible TB may develop secondary (acquired) resistance during therapy because of inadequate treatment, not taking the prescribed regimen appropriately (lack of compliance), or using low-quality drugs. To fully identify drug resistance and guide treatment, drug susceptibility testing (DST) determines which drugs can kill TB bacteria. WHO guidelines recommend a rapid molecular test, Xpert MTB/RIF, to diagnose TB and simultaneously detect rifampicin resistance. DST is crucial for fully identifying drug resistance and guiding treatment. Rifampicin-resistant TB (RR-TB) is resistant to the drug rifampicin. Multi-drug resistant tuberculosis (MDR-TB) is defined as resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Extensively drug-resistant tuberculosis (XDR-TB) is resistant to rifampicin (and may also be resistant to isoniazid), and is also resistant to at least one fluoroquinolone (levofloxacin or moxifloxacin) and to at least one other Group A drug (bedaquiline or linezolid). It was first observed in 2003 in Italy, but not widely reported until 2012, and has also been found in Iran, India, and South Africa. , the WHO estimates that 3.2% of new TB infections globally are RR-TB or MDR-TB; this went down from 4.0% in 2015. Treatment regimens can run for up to two years, compared to the six months of first-line drug treatment. In low-income countries, the impact of MDR-TB on the families of its victims is severe, affecting income, mental health, and social well-being. Families may become impoverished due to the financial strain of MDR-TB treatment, with studies reporting that a significant portion of household income can be spent on healthcare. == Signs and symptoms ==

There is a popular misconception that tuberculosis is purely a disease of the lungs that manifests as coughing. Tuberculosis may infect many organs, even though it most commonly occurs in the lungs (known as pulmonary tuberculosis). Without treatment, an estimated 5% to 15% of cases will progress into active TB during the person's lifetime. Symptoms may include chest pain, a prolonged cough producing sputum which may be bloody, tiredness, temperature, loss of appetite, wasting and general malaise. In very rare cases, the infection may erode into the pulmonary artery or a Rasmussen aneurysm, resulting in massive bleeding. Tuberculosis may cause extensive scarring of the lungs, which persists after successful disease treatment. Survivors continue to experience chronic respiratory symptoms such as cough, sputum production, and shortness of breath. Pyopneumothorax is a rare and serious complication of pulmonary tuberculosis, with a high rate of morbidity and mortality. It is caused by both air and pus accumulating in the pleural space, simultaneously causing a pneumothorax and empyema, usually as the result of a rupture of a subpleural caseous necrosis (a collection of dead cells enclosed within a granuloma). Initial symptoms include abrupt onset chest pain, high fever with chills, severe dyspnea, and less commonly pain & numbness in the extremities. In rare cases, a pyopneumothorax can cause peripheral blood clots resulting in an infarction, gangrene and tissue necrosis of one or more limbs, requiring amputation unless caught early; death can result if the gangrenous limb isn't amputated in time. Extrapulmonary 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. Urogenital tuberculosis, however, typically presents differently, as this manifestation most commonly appears decades after the resolution of pulmonary symptoms. Most patients with chronic urogenital TB do not have pulmonary symptoms at the time of diagnosis. Urogenital tuberculosis most commonly presents with urinary 'storage symptoms' such as increased frequency and/or urgency of urination, flank pain, hematuria, and nonspecific symptoms such as fever and malaise. == Causes ==

Mycobacteria of M. tuberculosis The principal microbial cause of TB is Mycobacterium tuberculosis (MTB), a small, aerobic, non-motile and rod-shaped bacillus. Mycobacteria have a complex, lipid-rich cell envelope, with the high lipid content of the outer membrane acting as a robust barrier contributing to their drug resistance. 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. The term M. tuberculosis complex describes a genetically related group of Mycobacterium species that can cause tuberculosis in humans or other animals. Among its members are four other TB-causing mycobacteria: M. bovis, M. africanum, M. canettii, and M. microti. M. bovis causes bovine TB and was once a common cause of human TB, but the introduction of pasteurized milk has almost eliminated this as a public health problem in developed countries. M. africanum is not widespread, but it is a significant cause of human TB in parts of Africa. M. canettii is rare and seems to be limited to the Horn of Africa, although a few cases have been seen in African emigrants. M. microti appears to have a natural reservoir in small rodents such as mice and voles, but can infect larger mammals. It is rare in humans and is seen almost only in immunodeficient people, although its prevalence may be significantly underestimated. There are other known mycobacteria which cause lung disease resembling TB. M. avium complex is an environmental microorganism found in soil and water sources worldwide, which tends to present as an opportunistic infection in immunocompromised people. The natural reservoir of M. kansasii is unknown, but it has been found in tap water; it is most likely to infect humans with lung disease or who smoke. These two species are classified as "nontuberculous mycobacteria". Transmission Tuberculosis spreads through the air when people with active pulmonary TB cough, sneeze, speak, or sing, releasing tiny airborne droplets containing the bacteria. Anyone nearby can breathe in these droplets and become infected. The droplets can remain airborne and infective for several hours, and are more likely to persist in poorly ventilated areas. TB is not spread by shaking hands, sharing food, drinks, or utensils, touching bed linens and toilet seats, sharing toothbrushes, or kissing. Transmission is most likely to occur from only people with active TB – those with latent infection are not thought to be contagious. Environmental factors Environmental factors which weaken the body's protective mechanisms and may put a person at additional risk of contracting TB include air pollution, exposure to smoke (including tobacco smoke), and exposure (often occupational) to dust or particulates. Sub-Saharan Africa has a particularly high burden of HIV-associated TB. People living with HIV are estimated 16 times more likely to fall ill with TB than people without HIV; TB is the leading cause of death among people with HIV. Other risk factors include: heavy alcohol use, diabetes mellitus, silicosis, tobacco smoking, recreational drug use, severe kidney disease, head and neck cancer, and low body weight. Children, especially those under age five, have undeveloped immune systems and are at higher risk. == Pathogenesis ==

TB infection begins when a M. tuberculosis bacterium, inhaled from the air, penetrates the lungs and reaches the alveoli. Here it encounters an alveolar macrophage, a cell of the body's immune system, which attempts to destroy it. However, M. tuberculosis can neutralise and colonise the macrophage, leading to persistent infection. Once inside this macrophage, the bacterium is trapped in a compartment called a phagosome; the phagosome subsequently merges with a lysosome to form a phagolysosome. The lysosome is an organelle which contains digestive enzymes; these are released into the phagolysosome and kill the invader. The M. tuberculosis bacterium can subvert the normal process by inhibiting phagosome development and preventing fusion with the lysosome. In tuberculosis, the granuloma contains necrotic tissue at its centre, and appears as a small white nodule, also known as a tubercle, from which the disease derives its name. Granulomas are most common in the lung, but they can appear anywhere in the body. As long as the infection is contained within granulomas, there are no outward symptoms and the infection is latent. 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 connect 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 ==

) in sputumDiagnosis of tuberculosis is often difficult. Symptoms manifest slowly and are generally non-specific, e.g., cough, fatigue, fever, which have many possible causes. The conclusive test for pulmonary TB is a bacterial culture taken from a sample of sputum, but this is slow to give a result, and does not detect latent TB. Extra-pulmonary TB infection can affect the kidneys, spine, brain, lymph nodes, or bones - a sample cannot easily be obtained for culture. Tests based on the immune response are sensitive but are likely to give false negatives in those with weak immune systems such as very young patients and those coinfected with HIV. Another issue affecting diagnosis in many parts of the world is that TB infection is most common in resource-poor settings where sophisticated laboratories are rarely available. A diagnosis of TB should be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. Diagnosis of TB, whether latent or active, starts with medical history and physical examination. Subsequently several tests can be performed to refine the diagnosis: A chest X-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation. The result of the test is read after 48 to 72 hours. A person who has been exposed to the bacteria would be expected to mount an immune response; the reaction is read by measuring the diameter of the raised area. Vaccination with Bacille Calmette-Guerin (BCG) may result in a false-positive result. Several factors may lead to false negatives; these include HIV infection, some viral illnesses, and overwhelming TB disease. Interferon-Gamma Release Assay The Interferon Gamma Release Assay (IGRA) is recommended for those who are positive to the Mantoux test. This test mixes a blood sample with antigenic material derived from the TB bacterium. If the patient has developed an immune response to a TB infection, white blood cells in the sample will release interferon-gamma (IFN-γ), which can be measured. This test is more reliable than the Mantoux test, and does not give a false positive after BCG vaccination; Chest radiograph In active pulmonary TB, infiltrates (opaque areas) or scarring are visible in the lungs on a chest X-ray. Infiltrates are suggestive but not necessarily diagnostic of TB. Other lung diseases can mimic the appearance of TB, and this test will not detect extrapulmonary infection or a recent infection. Microbiological studies '' in a culture medium A definitive diagnosis of tuberculosis can be made by detecting Mycobacterium tuberculosis organisms in a specimen taken from the patient (most often sputum, but may also be pus, cerebrospinal fluid, biopsied tissue, etc.). The bacterium is slow growing, so a cell culture may take several weeks to yield a result. Other tests Nucleic acid amplification tests (NAAT) 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. Polymerase chain reaction testing of urine for Mycobacterium tuberculosis is often required for the diagnosis of urogenital tuberculosis and may also be used to diagnose tuberculosis in biopsy samples from tissues. It is highly sensitive and specific, with good turnaround time. == Prevention ==

The main strategies to prevent infection with TB are treatment of both active and latent TB, as well as vaccination of children who are at risk. 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; however, it is important to complete the full course of treatment, which is usually six months. In areas where tuberculosis is not common, only children at high risk are typically immunized, while suspected cases of tuberculosis are individually tested for and treated. In countries where tuberculosis is common, one dose is recommended in healthy babies as soon after birth as possible. It is not effective if administered to adults. Airborne infection control Airborne infection control (AIC) for tuberculosis is a set of administrative, environmental, and personal protective actions taken to reduce the spread of TB through infectious airborne respiratory particles. AIC is critical in prevention and treatment strategies for the disease globally. Hierarchy of controls The WHO outlines a three‑level hierarchy of TB infection prevention and control measures: Infrastructure scale‑up has included the establishment of over 6,400 molecular diagnostic laboratories and 81 culture and drug susceptibility testing centres, alongside infection control interventions in hospitals and medical colleges. The initiative advocates for airborne IPC as a global priority, supports research and evidence dissemination, and promotes capacity building to prevent transmission in health care, community, and congregate settings. In the United States, concern about the spread of tuberculosis played a role in the movement to prohibit public spitting except into spittoons. Worldwide campaigns sailors being screened for tuberculosis (1940) The World Health Organization (WHO) declared TB a "global health emergency" in 1993, Several targets they set were not achieved by 2015, mostly due to the increase in HIV-associated tuberculosis and the emergence of multi-drug resistant tuberculosis. However, by 2020 only a 9% reduction in incidence per population was achieved globally, with the European region achieving 19% and the African region achieving 16% reductions. == Treatment ==

in Kuopio, Finland, 1934 The antibiotic drugs used for treating TB are generally classified as either first-line or second-line. Treatment with a combination of first-line drugs (Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol) is preferred; they are more effective, and have fewer side effects. Second-line drugs are used if a person's TB infection either develops resistance to one or more first-line drugs, or if the infection comprises a drug-resistant strain. The second-line drugs are generally less effective, have more severe side effects, and must be taken over a longer period of time. The 6 month regime, known by the acronym HRZE, comprises all four first-line drugs (Isoniazid (H), Rifapentine (R), Pyrazinamide (Z), and Ethambutol (E)) taken daily for two months, followed by just the H and R drugs for the remaining four months. Evidence indicates that it is highly effective if followed through properly. The four-month regime, known by the acronym HMPZ, has moderate evidence of effectiveness and several contra-indications. For the first 2 months, four drugs are taken (Isoniazid (H), Rifapentine (P), Moxifloxacin (M), and Pyrazinamide (Z)); followed by two more months with the H, P, and M components. , WHO recommends two shorter 6-month regimens and two 9-month regimens for DR-TB and MDR-TB using a combination of second-line drugs taken orally; all have good evidence of effectiveness. The 6-month regimens are known by the acronyms BPaLM and BDLLfx: • BPaLM (bedaquiline, pretomanid, linezolid, moxifloxacin). • BDLLfxC (bedaquiline, delamanid , and linezolid in combination with either levofloxacin (Lfx) or clofazimine (C)) In areas without public health systems, prolonged treatment is expensive. Failure to complete a course of treatment can result in the emergence of drug-resistant tuberculosis. One form of support is directly observed therapy - a healthcare worker watches the TB patient swallow the drugs, either in person or online. Other forms of support include having an assigned case manager, digital monitoring, health education, counseling, and community support. == Prognosis ==

disability-adjusted life years caused by tuberculosis per 100,000 inhabitants, 2004: Tuberculosis (TB) is generally curable with prompt and appropriate treatment, but can be fatal if left untreated. The prognosis depends on factors like disease stage, drug resistance, and a person's overall health. While treatment is effective, delays or inadequate treatment can lead to severe illness and death. Without treatment, about two-thirds of people with TB will die of the disease, on average, within three years of diagnosis. In people coinfected with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year. == Epidemiology ==

Reports of tuberculosis can be found throughout recorded history. In Europe, Hippocrates, writing around 400 BCE describes phthisis; in India, the Vedas (composed 1500–1200 BCE) refer to yaksma; both of these are generally equated with tuberculosis. Earlier evidence of tuberculosis has been found in prehistoric human remains in Europe, Africa, Asia, and the Americas, with the earliest dating to the early Neolithic era (approximately 10,000-11,000 years ago). The World Health Organization estimates that roughly one-quarter of the world's population carry infection with M. tuberculosis (prevalence), with new infections occurring in about 11 million people each year (incidence). and 90–95% of infections remain asymptomatic. TB infection disproportionally affects low-income populations and countries. Factors like poverty, inadequate living conditions, and poor nutrition contribute to higher TB prevalence and incidence in these settings. People living with HIV have a significantly higher risk of developing tuberculosis (TB) compared to those without HIV. HIV weakens the immune system, making individuals more susceptible to TB infection and increasing the likelihood of progression from latent to active TB. TB is also a leading cause of death among people with HIV. File:Tuberculosis incidence (per 100,000 people), OWID.svg|alt=Number of new cases of tuberculosis per 100,000 people in 2022.|Number of new cases of tuberculosis per 100,000 people, 2022 File:TB mortality rates in HIV-negative people 2023.webp|Map showing the rate of TB deaths worldwide in HIV-negative people, by country, 2023. File:Tuberculosis-deaths-by-age.svg|Deaths from tuberculosis, by age, World, 1990 to 2019 At-risk groups People deemed to be at higher risk for exposure to or infection from M. tuberculosis include those who frequently travel to or live in countries where TB disease is common; residents and employees of densely-occupied settings such as homeless shelters, detention and correctional facilities, and nursing homes; health care workers; populations defined locally as having an increased incidence of TB disease; those who are malnourished; and residents of resource-poor communities. There is a strong correlation between the risk for TB and socioeconomic status (SES). Specifically, people of low SES are more likely to contract TB. They also have more risk factors for TB disease, including malnutrition, HIV co-infection, more exposure to crowded and poorly ventilated spaces, and limited access to healthcare. Moreover, inadequate healthcare translates to those living with TB disease not being diagnosed and treated promptly, resulting in continued spread of the disease to others. Globally, Indigenous peoples are disproportionately impacted by TB. Australian Indigenous populations face disproportionately higher TB rates, more than four times those of non-Indigenous Australian-born. In 2023, the rate of TB disease among First Nations in Canada was over 3 times that of the overall Canadian population. Contributing factors are the result of ongoing inequities stemming from historical and ongoing impacts of colonization including isolation from health services, food insecurity, higher prevalence of health conditions such as diabetes, overcrowding, and poverty. However progress stalled and even reversed in some regions after the 1990s due to factors like drug resistance and the HIV/AIDS pandemic. Global monitoring of TB incidence is primarily done through annual reports by the World Health Organization (WHO), which has been collecting data and publishing comprehensive reports on the disease since 1997. Geographical epidemiology The distribution of tuberculosis is not uniform across the globe; it is concentrated in low- and middle-income countries, with high-burden regions including the WHO South-East Asia, African, and Western Pacific regions. Hopes of totally controlling the disease have been dramatically dampened because of many factors, including the difficulty of developing an effective vaccine, the expensive and time-consuming diagnostic process, the necessity of many months of treatment, the increase in HIV-associated tuberculosis, and the emergence of drug-resistant cases in the 1980s. This is attributed to widespread poverty, malnutrition, overcrowding, and poor hygiene, which facilitate transmission and disease development. Factors like stigma, lack of awareness, delayed diagnosis, and the high financial burden of treatment hinder progress. The emergence of multi-drug resistant TB, together with weak healthcare infrastructure contribute to the persistence of the disease, despite national control programs. Overall, the rate of TB incidence (the annual total of new infections) in India has decreased from nearly 300 per 100,000 population in 2010 to 200 in 2023. Factors contributing to this include a family history of TB, malnutrition, inappropriate ventilation, diabetes mellitus, smoking behavior, and low income level. Incidence of TB infection increased in 2020 and subsequent years; this has been attributed to strain on health systems caused by the COVID-19 pandemic. China The incidence of TB in China has decreased over time, from 67 new cases per 100,000 of population in 2010 to 40 in 2023. Quality of care is inconsistent, despite efforts by the Chinese Center for Disease Control and Prevention to improve diagnosis, referral and treatment nationwide. Philippines As of 2023, the Philippines accounts for 6.8% of global TB cases, the 4th worldwide. Lesotho Lesotho has an estimated 664 new infections per 100,000 population in 2023. This compares favourably with the figure of 1,184 in 2010. It is still one of the highest TB incidence rates globally. Other factors include lack of funding, mountainous territory making access to care difficult, and poor adherence to therapy regimens. == Society and culture ==

Names In different ages and cultures, tuberculosis went by many names. () in ancient Greek translates to decay or wasting disease, presumed to refer to pulmonary tuberculosis; around 460 BCE, Hippocrates described phthisis as a disease of dry seasons. Tabes in ancient Latin has a similar meaning. In The Life and Death of Mr Badman by John Bunyan, the author calls consumption "the captain of all these men of death." "Great white plague" has also been used. Major artistic figures such as the poets John Keats, Percy Bysshe Shelley, and Edgar Allan Poe, the composer Frédéric Chopin, the playwright Anton Chekhov, the novelists Franz Kafka, Katherine Mansfield, Charlotte Brontë, Fyodor Dostoevsky, Thomas Mann, W. Somerset Maugham, George Orwell, and Robert Louis Stevenson, and the artists Alice Neel, Jean-Antoine Watteau, Elizabeth Siddal, Marie Bashkirtseff, Edvard Munch, Aubrey Beardsley and Amedeo Modigliani either had the disease or were surrounded by people who did. A widespread belief was that tuberculosis assisted artistic talent. Physical mechanisms proposed for this effect included the slight fever and toxaemia it caused, allegedly helping them to see life more clearly and to act decisively. Tuberculosis formed an often-reused theme in literature, as in Thomas Mann's The Magic Mountain, set in a sanatorium; in music, as in Van Morrison's song "T.B. Sheets"; in opera, as in Puccini's La bohème and Verdi's La Traviata; and in film, such as the 1945 ''The Bells of St. Mary's'' starring Ingrid Bergman as a nun with tuberculosis. Folklore In 19th-century New England, tuberculosis deaths were associated with vampires. When one member of a family died from the disease, the other infected members would lose their health slowly. People believed this was caused by the original person with TB draining the life from the other family members. Law Historically, some countries, including Czech Republic, England, Estonia, Germany, Israel, Norway, Russia and Switzerland had legislation to involuntarily detain or examine those suspected to have tuberculosis, or involuntarily treat them if infected. As of 2025, many countries require TB cases to be notified to a national surveillance organisation (UK, US, European Union.). Many countries make either short term or long term entry visas for potential migrants conditional on a negative TB test. Stigma Tuberculosis stigma is discrimination experienced by many people with TB, which acts as a major barrier to health-seeking, treatment adherence, and overall disease control. Depending on the setting, between 42% and 82% of people with TB report experience of stigma. Slow progress in preventing the disease may in part be due to stigma associated with TB. Stigma may result in delays in seeking treatment, – allowing the disease to spread further. and may be assigned junior staff in health facilities. In India, people with TB may lose their job or be unable to marry. == Global programs ==

The World Health Organization has formulated and promoted several strategies to combat TB globally. The first of these, launched in 1995, was DOTS (Directly Observed Treatment, Short-course), which promoted a standard course of treatment together with the appropriate resources and state support. In 2006, WHO adopted the Stop TB Strategy which implemented millennium development goal 6c (by 2015, to halt and reverse the incidence major diseases). This included and continued the DOTS program, with additional emphasis on sustainable financing, improved technology, and improved emphasis on drug resistance and HIV co-infection. to 2014, when TB incidence was estimated at 9.6 million new cases. The Stop TB Strategy was followed in 2014 by the End TB Strategy. This sets targets of a 90% reduction in TB deaths and 80% reduction in TB incidence by 2030, followed by reductions of 95% and 90%, respectively, by 2035. A third target is that no TB-affected households experience catastrophic costs due to the disease by 2020. This incorporated the principles of the previous strategies, while introducing objectives for prevention based on the identification and treatment of individuals with latent TB infection. This is a rapid molecular test used to diagnose TB and simultaneously detect rifampicin resistance. It provides results in about 2 hours, which is much faster than traditional TB culture methods. The test is designed for use with the GeneXpert System. == Research directions ==

As part of the End TB strategy, the WHO has identified four areas where research-based innovations are needed. These are 1) diagnostics, 2) treatment of active TB, 3) treatment of latent TB, and 4) vaccines. Diagnostics Diagnosis of TB infection is difficult, slow, and expensive. This is particularly true of latent TB infection, or infection outside the lungs. Diagnostics can be improved by developing faster, more sensitive tests, preferably based on molecular testing of a blood sample rather than traditional cultivation of a sputum smear; as well as creating ultra-portable diagnostic devices for point-of-care use. Treatment Treatment for TB generally involves taking a cocktail of (sometimes expensive) drugs daily over a period of months. It is not surprising that people forget to take their medication or drop out entirely before completing a course of treatment. Shorter and simpler treatment regimens, as well as the introduction of new drugs, have the potential to improve adherence and thus improve outcomes. Vaccines Although it was originally developed over a century ago, , BCG remains the only vaccine that is licensed for use; this is despite it having highly variable effectiveness. A promising vaccine candidate, MVA85A, failed in 2019 to demonstrate effectiveness in clinical trials. There is an urgent need for improved vaccines, which could be effective both before exposure to TB and also post exposure. details of the chain of steps which culminate in TB transmission, and the social and political obstacles to effective implementation of the elimination strategy. == Other animals ==

Members of the genus Mycobacterium infect many different animals, including birds, fish, rodents, and reptiles. The species Mycobacterium tuberculosis, though, is rarely present in wild animals. An effort to eradicate bovine tuberculosis caused by Mycobacterium bovis from the cattle and deer herds of New Zealand has been relatively successful. Efforts in Great Britain have been less successful. , tuberculosis appears to be widespread among captive elephants in the US. It is believed that the animals originally acquired the disease from humans, a process called reverse zoonosis. Because the disease can spread through the air to infect both humans and other animals, it is a public health concern affecting circuses and zoos. Transmission of both Mycobacterium bovis and Mycobacterium tuberculosis between humans and cattle has been documented, underscoring the importance of zooanthroponosis (human‑to‑animal transmission) and zoonotic tuberculosis (animal‑to‑human transmission). This highlights the need for a One Health approach that targets all four recognized reservoirs of tuberculosis—active TB disease and latent TB infection in humans, and active TB disease and latent TB infection in animals—if elimination is to be achieved. Diagnostic challenges further complicate control efforts, as commonly used nucleic acid amplification tests cannot reliably distinguish between members of the M. tuberculosis complex, and infections with M. bovis are naturally resistant to the first‑line drug pyrazinamide, making species‑specific diagnostic tools essential for effective treatment and surveillance. == See also ==