Tuberculosis
Tuberculosis, also known colloquially as the "white death", or historically as consumption, is a contagious disease usually caused by Mycobacterium tuberculosis 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 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 blood-containing mucus, 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 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. A latent infection is more likely to become active in those with weakened immune systems. There are two principal tests for TB: interferon-gamma release assay of a blood sample, and the tuberculin skin test.
Prevention of TB involves screening those at high risk, early detection and treatment of cases, and vaccination with the bacillus Calmette-Guérin 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.
Tuberculosis has been present in humans since ancient times. 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 multi-drug-resistant tuberculosis. It is estimated that one quarter of the world's population, approximately 2 billion people, have latent TB. In 2024, TB is estimated to have newly infected 10.7 million people and caused 1.23 million deaths, making it the leading cause of death from an infectious disease.
History
Tuberculosis has existed since antiquity. Skeletal remains show some prehistoric humans had TB, and researchers have found tubercular decay in the spines of Egyptian mummies dating from 3000 to 2400 BC. 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 consumptions were caused by microbes which 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" 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.
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 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 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. 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.
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 bacille Calmette–Guérin. 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.
Drug resistant tuberculosis
A few years after the first antibiotic treatment for TB in 1943, some strains of the TB bacteria developed resistance to the standard drugs.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. The resurgence of tuberculosis, caused in part by drug resistance and in part by the HIV pandemic, resulted in the declaration of a global health emergency by the World Health Organization in 1993.
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 develops during TB treatment. A person with fully drug-susceptible TB may develop secondary resistance during therapy because of inadequate treatment, not taking the prescribed regimen appropriately, or using low-quality drugs.
To fully identify drug resistance and guide treatment, drug susceptibility testing 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 is resistant to the drug rifampicin. Multi-drug resistant tuberculosis is defined as resistance to the two most effective first-line TB drugs: rifampicin and isoniazid. Extensively drug-resistant tuberculosis is resistant to rifampicin, and is also resistant to at least one fluoroquinolone and to at least one other Group A drug. 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.
, 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.
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 regimens can run for up to two years, compared to the six months of first-line drug 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.
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. Extrapulmonary TB occurs when tuberculosis develops in organs other than the lungs; it may coexist with pulmonary TB.General signs and symptoms include fever, chills, night sweats, loss of appetite, weight loss, and fatigue.