Tuberculosis ( TB), also known colloquially as the " white death", or historically as consumption, is a contagious disease usually caused by Mycobacterium tuberculosis (MTB) bacteria. Tuberculosis generally affects the , but it can also affect other parts of the body. Most infections show no symptoms, in which case it is known as inactive or latent tuberculosis. A small proportion of latent infections progress to active disease that, if left untreated, can be fatal. Typical symptoms of active TB are chronic cough with hemoptysis sputum, fever, night sweats, and weight loss. Infection of other organs can cause a wide range of symptoms.
Tuberculosis is spread from one person to the next Airborne disease when people who have active TB in their lungs cough, spit, speak, or sneeze. People with latent TB do not spread the disease. A latent infection is more likely to become active in those with weakened Immunodeficiency. There are two principal tests for TB: interferon-gamma release assay (IGRA) of a blood sample, and the Mantoux test.
Prevention of TB involves screening those at high risk, early detection and treatment of cases, and vaccination with the bacillus Calmette-Guérin (BCG) vaccine.
Tuberculosis has been present in humans since Ancient history. In the 1800s, when it was known as consumption, it was responsible for an estimated quarter of all deaths in Europe. The incidence of TB decreased during the 20th century with improvement in sanitation and efficient vaccination campaigns. However, since the 1980s, antibiotic resistance has become a growing problem, with increasing rates of drug-resistant tuberculosis. It is estimated that one quarter of the world's population have latent TB. In 2023, TB is estimated to have newly infected 10.8 million people and caused 1.25 million deaths, making it the leading cause of death from an infectious disease.
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.Burdon-Sanderson, John Scott. (1870) "Introductory Report on the Intimate Pathology of Contagion." Appendix to: Twelfth Report to the Lords of Her Majesty's Most Honourable Privy Council of the Medical Officer of the Privy Council for, Parliamentary Papers (1870), vol. 38, 229–256.
Robert Koch identified and described the bacillus causing tuberculosis, M. tuberculosis, on 24 March 1882.
Between 1838 and 1845, John Croghan, the owner of Mammoth Cave in Kentucky from 1839 onwards, brought a number of 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 sanatorium that resembled prisons. The sanatoria for the middle and upper classes offered excellent care and constant medical attention. Whatever the benefits of the "fresh air" and labor in the sanatoria, even under the best conditions, 50% of those who entered died within five years ( 1916).
Robert Koch did not believe the cattle and human tuberculosis diseases were similar, which delayed the recognition of infected milk as a source of infection. During the first half of the 1900s, the risk of transmission from this source was dramatically reduced after the application of the pasteurization process. Koch announced a glycerine extract of the tubercle bacilli as a "remedy" for tuberculosis in 1890, calling it "tuberculin". Although it was not effective, it was later successfully adapted as a screening test for the presence of pre-symptomatic tuberculosis. World Tuberculosis Day is marked on 24 March each year, the anniversary of Koch's original scientific announcement. When the Medical Research Council 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 BCG vaccine (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. Prior to 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 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.
Treatment of MDR-TB requires treatment with second-line drugs, which in general are less effective, more toxic and more expensive than first-line drugs. Treatment regimes can run for two years, compared to the six months of first-line drug treatment.Kaplan, Jeffrey. 2017. "Tuberculosis" American University. Lecture.
General signs and symptoms include fever, chills, night sweats, loss of appetite, weight loss, and fatigue.
Tuberculosis may cause extensive scarring of the lungs, which persists after successful treatment of the disease. Survivors continue to experience chronic respiratory symptoms such as cough, sputum production, and shortness of breath.
Symptoms of extrapulmonary TB usually include the general signs and symptoms as above, with additional symptoms related to the part of the body which is affected. 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.
The term M. tuberculosis complex describes a genetically related group of Mycobacterium species that can cause tuberculosis in humans or other animals. It includes four other TB-causing mycobacterium: 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 pasteurisation has almost eliminated this as a public health problem in developed countries.
There are other known Mycobacterium 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".
Another important risk factor is use of medications which suppress the immune system. These include (but are not limited to), chemotherapy; medication after an organ transplant; and medication for lupus or rheumatoid arthritis. Other risk factors include: alcoholism, diabetes mellitus, silicosis, cigarette, 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.
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.
The defence mechanism of the macrophage begins when a foreign body, such as a bacterial cell, binds to Immune receptor on the surface of the macrophage. The macrophage then stretches itself around the bacterium and engulfs it. 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 is able to subvert the normal process by inhibiting the development of the phagosome and preventing it from fusing with the lysosome. The bacterium is able to survive and replicate within the phagosome; it will eventually destroy its host macrophage, releasing progeny bacteria which spread the infection.
In the next stage of infection, , , T cell and aggregate to form a granuloma, which surrounds and isolates the infected macrophages. This does not destroy the tuberculosis bacilli, but contains them, preventing spread of the infection to other parts of the body. They are nevertheless able to survive within the granuloma. In tuberculosis, the granuloma contains Necrosis 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. However, if the immune system is unable to control the infection, the disease can progress to active TB, which can cause significant damage to the lungs and other organs.
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 kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.
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 a number of tests can be performed to refine the diagnosis: A chest X-ray and multiple for acid-fast bacilli are typically part of the initial evaluation.
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.
Although latent TB is not infective, it should be treated in order to prevent its development into active pulmonary TB, which is infective. 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.
TB was made a notifiable disease in Britain; there were campaigns to stop spitting in public places, and the infected poor were pressured to enter sanatoria that resembled prisons.McCarthy 2001:413-7 In the United States, concern about the spread of tuberculosis played a role in the movement to prohibit public spitting except into .
In 2014, the WHO adopted the "End TB" strategy which aims to reduce TB incidence by 80% and TB deaths by 90% by 2030. The strategy contains a milestone to reduce TB incidence by 20% and TB deaths by 35% by 2020. 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. Similarly, the number of deaths only fell by 14%, missing the 2020 milestone of a 35% reduction, with some regions making better progress (31% reduction in Europe and 19% in Africa). Correspondingly, also treatment, prevention and funding milestones were missed in 2020, for example only 6.3 million people were started on TB prevention short of the target of 30 million.
The goal of tuberculosis elimination is being hampered by the lack of rapid testing, short and effective treatment courses, and completely effective vaccines.
Public health bodies recommend that patients be given support during the period of treatment. 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.
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.
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). A further categorization, totally drug resistant tuberculosis, has been used to describe strains with even greater drug resistance. , it has no accepted definition, but it is most commonly described as 'resistance to all first- and second-line drugs used to treat TB'. 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.
Treatment for both MDR-TB and XDR-TB involves combinations of several drugs, typically including second-line anti-TB medications like bedaquiline, linezolid, and fluoroquinolones. Treatment regimens are individualized based on drug susceptibility testing and patient-specific factors, and may extend for up to 20 months.
, the WHO estimates that 3.2% of new TB infections globally are RR-TB or MDR-TB; this is a decrease from 4.0% in 2015. Among those who have been previously treated for TB, the proportion of people with RR-TB or MDR-TB has also decreased from 25% in 2015 to an estimated 16% in 2023.
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. Antibiotic sensitivity testing is crucial for fully identifying drug resistance and guiding treatment.
Treatment of MDR-TB is significantly more costly than treating regular TB. As an example, in the UK in 2013 the cost of standard TB treatment was estimated at £5,000 while the cost of treating MDR-TB was estimated to be more than 10 times greater, ranging from £50,000 to £70,000 per case.
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.
]]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 3 years of diagnosis.
Progression from TB infection to overt TB disease occurs when the bacilli overcome the immune system defenses and begin to multiply. In 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. Over an individual's lifetime these dormant bacilli produce active tuberculosis in 5–10% of these latent cases, often many years after infection.
The risk of reactivation increases in those whose Immunodeficiency, such as may be caused by certain drug treatments, or by infection with HIV. In people Coinfection with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year.
Tuberculosis (TB) prognosis is significantly worsened by HIV co-infection, leading to higher mortality rates and poorer treatment outcomes. People with HIV are much more susceptible to developing active TB, and even with treatment, they face increased risks of unsuccessful treatment and death compared to those without HIV.
Phylogenetics analysis of DNA lineages indicate that the ancestors of the tuberculosis bacterium adapted to human hosts in Africa around 70,000 years ago, and spread across the globe with migrating humans.
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). Most infections with M. tuberculosis do not cause disease, and 90–95% of infections remain asymptomatic.
TB infection disproportionally affects low-income populations and countries. Factors like poverty, inadequate living conditions, and Malnutrition contribute to higher TB prevalence and incidence in these settings. Globally, the highest burden of TB is concentrated in low-income countries.
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.
To a certain extent, newly diagnosed TB infections tend to Seasonality; this is attributed in part to lower levels of vitamin D and indoor crowding during the colder seasons, combined with a lag between infection and diagnosis. The strength of seasonality varies with latitude, with stronger patterns observed in regions farther from the equator.
Socioeconomic status (SES) strongly affects TB risk. People of low SES are both more likely to contract TB and to be more severely affected by the disease. Those with low SES are more likely to be affected by risk factors for developing TB (e.g., malnutrition, indoor air pollution, HIV co-infection, etc.), and are additionally more likely to be exposed to crowded and poorly ventilated spaces. Inadequate healthcare also means that people with active disease who facilitate spread are not diagnosed and treated promptly; sick people thus remain in the infectious state and (continue to) spread the infection.
People with HIV are at significantly higher risk of developing tuberculosis (TB) than those without HIV; they are estimated to be 16 times more likely to fall ill. TB is a leading cause of death among people with HIV. HIV weakens the immune system, making individuals more susceptible to TB infection and progression from latent to active TB.
Globally, TB occurs mainly in adults 15 years and older; men are more likely to be infected than women. There is some evidence that, in countries with a low burden of TB such as Britain, Canada and the US, incidence rates among those 65 and older are consistently higher than in other age groups. A large portion of active TB cases in this age group are thought to be due to the reactivation of previously dormant TB infections.
In Canada and Australia, tuberculosis is many times more common among the Indigenous peoples. Factors contributing to this include smoking, Food security, higher prevalence of health conditions such as diabetes, overcrowding and poverty.
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.
Attempts to control TB were disrupted in 2020-2023 by the COVID-19 pandemic, which disrupted TB diagnosis and treatment. Subsequently new diagnosis of TB cases trended upwards in 2021 to 2023.
, eight countries accounted for more than two thirds of global TB cases: India (26%), Indonesia (10%), China (6.8%), the Philippines (6.8%), Pakistan (6.3%), Nigeria (4.6%), Bangladesh (3.5%) and the Democratic Republic of the Congo (3.1%)
, eight countries accounted for more than two thirds of global TB cases: India (26%), Indonesia (10%), China (6.8%), the Philippines (6.8%), Pakistan (6.3%), Nigeria (4.6%), Bangladesh (3.5%) and the Democratic Republic of the Congo (3.1%).
Countries with the highest incidence rates for TB are Marshall Islands (692 cases per 100,000 population), Lesotho (664), Philippines (643), Myanmar(558), and Central African Republic (540).
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 Giacomo Puccini's La bohème and Giuseppe Verdi's La Traviata; in art, as in Edvard Munch's painting of his ill sister; and in film, such as the 1945 The Bells of St. Mary's starring Ingrid Bergman as a nun with tuberculosis.
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. This program ran from 2006 (when TB incidence was estimated at 8.8 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.
In 2012, The World Health Organization (WHO), the Bill and Melinda Gates Foundation, and the U.S. government subsided a fast-acting diagnostic tuberculosis test, Xpert MTB/RIF, for use in low- and middle-income countries. This is a rapid molecular test used to diagnose TB and simultaneously detect rifampicin resistance. It provides results in about two hours, which is much faster than traditional TB culture methods. The test is designed for use with the GeneXpert System.
Slow progress in preventing the disease may in part be due to Social stigma associated with TB. Stigma may result in delays in seeking treatment, lower treatment compliance, and family members keeping diagnosis and cause of death secret – allowing the disease to spread further. Stigma may be due to misconceptions about the disease's transmissibility, cultural myths, association with poverty or (in Africa) HIV/AIDS. Studies in Ghana have found that individuals with TB may be banned from attending public gatherings, and may be assigned junior staff in health facilities. In India, people with TB may lose their job or be unable to marry.
There are two specific areas where research can lead to improvements in treatment. The first is treatment of active tuberculosis, both drug susceptible and drug resistant strains. The introduction of safer, easier, and shorter treatment regimes would improve availability and adherence, giving better outcomes. The second area is the treatment and elimination of latent TB infection in order to prevent it developing into the active form; again, improved treatment regimes would lead to better outcomes.
However there is limited evidence that improved treatment regimes would improve outcomes. It will also be necessary to improve health literacy and support structures for persons with TB.
, tuberculosis appears to be widespread among captive 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 and .
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Lesotho
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