Tuberculosis

Tuberculosis (TB), also known colloquially as the

"white death", or historically as consumption,[7] is a Tuberculosis
contagious disease usually caused by Mycobacterium Other Phthisis, phthisis pulmonalis,
tuberculosis (MTB) bacteria.[1] Tuberculosis generally names consumption, great white plague
affects the lungs, but it can also affect other parts of the
body.[1] Most infections show no symptoms, in which
case it is known as latent tuberculosis.[1] Around 10%
of latent infections progress to active disease that, if
left untreated, kill about half of those affected.[1]
Typical symptoms of active TB are chronic cough with
blood-containing mucus, fever, night sweats, and
weight loss.[1] Infection of other organs can cause a
wide range of symptoms.[8]

Tuberculosis is spread from one person to the next Chest X-ray of a person with advanced
through the air when people who have active TB in tuberculosis: Infection in both lungs is marked
their lungs cough, spit, speak, or sneeze.[1][9] People by white arrow-heads, and the formation of a
with latent TB do not spread the disease.[1] Active cavity is marked by black arrows.
infection occurs more often in people with HIV/AIDS Specialty Infectious disease, pulmonology
and in those who smoke.[1] Diagnosis of active TB is Symptoms Chronic cough, fever, cough with
based on chest X-rays, as well as microscopic bloody mucus, weight loss[1]
examination and culture of bodily fluids.[10] Diagnosis
Causes Mycobacterium tuberculosis[1]
of latent TB relies on the tuberculin skin test (TST) or
blood tests.[10] Risk factors Smoking, HIV/AIDS[1]
Diagnostic CXR, culture, tuberculin skin
Prevention of TB involves screening those at high risk, method test, QuantiFERON[1]
early detection and treatment of cases, and vaccination
Differential Pneumonia, histoplasmosis,
with the bacillus Calmette-Guérin (BCG)
[3][4][5]
diagnosis sarcoidosis,
vaccine. Those at high risk include household, coccidioidomycosis[2]
workplace, and social contacts of people with active
Prevention Screening those at high risk,
TB.[4] Treatment requires the use of multiple
treatment of those infected,
antibiotics over a long period of time.[1] Antibiotic
vaccination with bacillus
resistance is a growing problem, with increasing rates
Calmette-Guérin (BCG)[3][4][5]
of multiple drug-resistant tuberculosis (MDR-TB).[1]
Treatment Antibiotics[1]
In 2018, one quarter of the world's population was Frequency 25% of people (latent TB)[6] 10.6
thought to have a latent infection of TB.[6] New million (active TB)[1]
infections occur in about 1% of the population each
Deaths 1.3 million (2022)[6]
year.[11] In 2022, an estimated 10.6 million people
developed active TB, resulting in 1.3 million deaths,
making it the second leading cause of death from an infectious disease after COVID-19.[1] As of 2018,
most TB cases occurred in the WHO 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%).[12] By
2021, the number of new cases each year was decreasing by around 2% annually.[1] 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.[13] Tuberculosis has been present in humans since ancient times.[14]

History
Tuberculosis has existed since antiquity.[14] The
oldest unambiguously detected M. tuberculosis gives
evidence of the disease in the remains of bison in
0:00
Wyoming dated to around 17,000 years ago.[15]
However, whether tuberculosis originated in bovines,
then transferred to humans, or whether both bovine Video summary (script)
and human tuberculosis diverged from a common
ancestor, remains unclear.[16] A comparison of the
genes of M. tuberculosis complex (MTBC) in humans to MTBC
in animals suggests humans did not acquire MTBC from animals
during animal domestication, as researchers previously believed.
Both strains of the tuberculosis bacteria share a common ancestor,
which could have infected humans even before the Neolithic
Revolution.[17] Skeletal remains show some prehistoric humans
(4000 BC) had TB, and researchers have found tubercular decay in
the spines of Egyptian mummies dating from 3000 to 2400 BC.[18]
An Egyptian mummy in the British
Genetic studies suggest the presence of TB in the Americas from
Museum – tubercular decay has
about AD 100.[19] been found in the spine.

Before the Industrial Revolution, folklore often associated

tuberculosis 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.[20]

Identification
Although Richard Morton established the pulmonary form associated with tubercles as a pathology in
1689,[21][22] 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.[23] In 1819, René Laennec claimed that tubercles were the cause of
pulmonary tuberculosis.[24] J. L. Schönlein first published the name "tuberculosis" (German:
Tuberkulose) in 1832.[25][26]

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.[27] Hermann Brehmer opened the
first TB sanatorium in 1859 in Görbersdorf (now Sokołowsko) in Silesia.[28] In 1865, Jean Antoine
Villemin demonstrated that tuberculosis could be transmitted, via inoculation, from humans to animals
and among animals.[29] (Villemin's findings were confirmed in 1867 and 1868 by John Burdon-
Sanderson.[30])

Robert Koch identified and described the bacillus causing tuberculosis, M.

tuberculosis, on 24 March 1882.[31][32] In 1905, he was awarded the
Nobel Prize in Physiology or Medicine for this discovery.[33]

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.[34] In the 18th
and 19th century, tuberculosis had become epidemic in Europe, showing a
seasonal pattern.[35][36] 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. Robert Koch discovered the
tuberculosis bacillus.
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.[28] What later became known as the Alexandra Hospital for Children with Hip Disease
(tuberculous arthritis) was opened in London in 1867.[37] 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 (c.
1916).[28]

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.[38] 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.[39]

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,[40] but achieved widespread
acceptance in the US, Great Britain, and Germany only after World War II.[41]

By the 1950s mortality in Europe had decreased about 90%.[42] 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.[42] 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.[43]

Current reemergence
Because of the emergence of multidrug-resistant tuberculosis (MDR-TB), surgery has been re-introduced
for certain cases of TB infections. It involves the removal of infected chest cavities ("bullae") in the lungs
to reduce the number of bacteria and to increase exposure of the remaining bacteria to antibiotics in the
bloodstream.[44] Hopes of eliminating TB ended with the rise of drug-resistant strains in the 1980s. The
subsequent resurgence of tuberculosis resulted in the declaration of a global health emergency by the
World Health Organization (WHO) in 1993.[45]

Signs and symptoms

There is a popular misconception that
tuberculosis is purely a disease of the lungs that
manifests as coughing.[47] Tuberculosis may
infect many organs, even though it most
commonly occurs in the lungs (known as
pulmonary tuberculosis).[8] Extrapulmonary TB
occurs when tuberculosis develops outside of the
lungs, although extrapulmonary TB may coexist
with pulmonary TB.[8]

General signs and symptoms include fever, chills,

night sweats, loss of appetite, weight loss, and
fatigue.[8] Significant nail clubbing may also
occur.[48]

The main symptoms of variants and stages of

Pulmonary tuberculosis are given,[46] with many symptoms
overlapping with other variants, while others are more,
If a tuberculosis infection does become active, it but not entirely, specific for certain variants. Multiple
most commonly involves the lungs (in about variants may be present simultaneously.
90% of cases).[14][49] 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).[14]
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 aneurysm, resulting in massive bleeding.[8][50]
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.[8] The reason for
this difference is not clear.[13] It may be due to either better air flow,[13] or poor lymph drainage within
the upper lungs.[8]

Extrapulmonary
In 15–20% of active cases, the infection spreads outside the lungs,
causing other kinds of TB.[51] These are collectively denoted as
extrapulmonary tuberculosis.[52] 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.[52] 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 Tuberculosis of the lip, secondary to
the bones and joints (in Pott disease of the spine), among others. A open pulmonary TB
potentially more serious, widespread form of TB is called
"disseminated tuberculosis"; it is also known as miliary
tuberculosis.[8] Miliary TB currently makes up about 10% of extrapulmonary cases.[53]

Causes

Mycobacteria
The main cause of TB is Mycobacterium tuberculosis (MTB), a
small, aerobic, nonmotile bacillus.[8] The high lipid content of this
pathogen accounts for many of its unique clinical
characteristics.[54] 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.[55] Mycobacteria have an outer
membrane lipid bilayer.[56] 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.[57] MTB can withstand weak disinfectants and survive in a
dry state for weeks. In nature, the bacterium can grow only within Scanning electron micrograph of M.
the cells of a host organism, but M. tuberculosis can be cultured in tuberculosis
the laboratory.[58]

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.[13][57] The most common acid-fast staining techniques are
the Ziehl–Neelsen stain[59] and the Kinyoun stain, which dye acid-fast bacilli a bright red that stands out
against a blue background.[60] Auramine-rhodamine staining[61] and fluorescence microscopy[62] are also
used.

The M. tuberculosis complex (MTBC) includes four other TB-causing mycobacteria: M. bovis, M.
africanum, M. canettii, and M. microti.[63] M. africanum is not widespread, but it is a significant cause of
tuberculosis in parts of Africa.[64][65] 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.[13][66] M. canettii is rare and seems to be limited to the Horn of Africa, although a few cases
have been seen in African emigrants.[67][68] M. microti is also rare and is seen almost only in
immunodeficient people, although its prevalence may be significantly underestimated.[69]

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.[70]

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.[71]
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).[72]

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.[73] A person with active but
untreated tuberculosis may infect 10–15 (or more) other people
per year.[74] Transmission should occur from only people with
active TB – those with latent infection are not thought to be
Public health campaigns in the
contagious.[13] The probability of transmission from one person to
1920s tried to halt the spread of TB.
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.[75]

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.[73] 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.[76]

Risk factors
A number of factors make individuals more susceptible to TB infection or disease.[77]

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.[78] This is a particular problem in sub-Saharan Africa, where
HIV infection rates are high.[79][80] Of those without HIV infection who are infected with tuberculosis,
about 5–10% develop active disease during their lifetimes;[48] in contrast, 30% of those co-infected with
HIV develop the active disease.[48]
Use of certain medications, such as corticosteroids and infliximab (an anti-αTNF monoclonal antibody),
is another important risk factor, especially in the developed world.[14]

Other risk factors include: alcoholism,[14] diabetes mellitus (3-fold increased risk),[81] silicosis (30-fold
increased risk),[82] tobacco smoking (2-fold increased risk),[83] indoor air pollution, malnutrition, young
age,[77] recently acquired TB infection, recreational drug use, severe kidney disease, low body weight,
organ transplant, head and neck cancer,[84] and genetic susceptibility[85] (the overall importance of
genetic risk factors remains undefined[14]).

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.[77]

Pathogenesis
About 90% of those infected with M. tuberculosis have asymptomatic,
latent TB infections (sometimes called LTBI),[87] with only a 10% lifetime
chance that the latent infection will progress to overt, active tuberculous
disease.[88] In those with HIV, the risk of developing active TB increases
to nearly 10% a year.[88] If effective treatment is not given, the death rate
for active TB cases is up to 66%.[74]

TB infection begins when the mycobacteria reach the alveolar air sacs of
the lungs, where they invade and replicate within endosomes of alveolar
macrophages.[13][89][90] 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
Robert Carswell's
membrane-bound vesicle called a phagosome. The phagosome then
illustration of tubercle[86]
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.[13] Tuberculosis of the
lungs may also occur via infection from the blood stream. This is Microscopy of tuberculous
known as a Simon focus and is typically found in the top of the epididymitis. H&E stain
lung. [91] This hematogenous transmission can also spread
infection to more distant sites, such as peripheral lymph nodes, the
kidneys, the brain, and the bones.[13][92] 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.[93]
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.[94]

However, more recent evidence suggests that the bacteria use the granulomas to 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.[95] 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.[94]

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.[96] This
severe form of TB disease, most common in young children and those with HIV, is called miliary
tuberculosis.[97] People with this disseminated TB have a high fatality rate even with treatment (about
30%).[53][98]

In many people, the infection waxes and wanes. Tissue destruction and necrosis are often balanced by
healing and fibrosis.[94] 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.[94]

Diagnosis

Active tuberculosis
Diagnosing active tuberculosis based only on signs and symptoms
is difficult,[99] as is diagnosing the disease in those who have a
weakened immune system.[100] A diagnosis of TB should,
however, be considered in those with signs of lung disease or
constitutional symptoms lasting longer than two weeks.[100] A
chest X-ray and multiple sputum cultures for acid-fast bacilli are
typically part of the initial evaluation.[100] Interferon-γ release
assays (IGRA) and tuberculin skin tests are of little use in most of
the developing world.[101][102] IGRA have similar limitations in M. tuberculosis (stained red) in
those with HIV.[102][103] sputum

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.[104] Thus,
treatment is often begun before cultures are confirmed.[105]
Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of TB.[99]
Blood tests to detect antibodies are not specific or sensitive, so they are not recommended.[106]

Latent tuberculosis
The Mantoux tuberculin skin test is often used to screen people at
high risk for TB.[100] Those who have been previously immunized
with the Bacille Calmette-Guerin vaccine may have a false-
positive test result.[107] The test may be falsely negative in those
with sarcoidosis, Hodgkin's lymphoma, malnutrition, and most
notably, active tuberculosis.[13] Interferon gamma release assays,
on a blood sample, are recommended in those who are positive to
the Mantoux test.[105] These are not affected by immunization or A Mantoux tuberculin skin test
most environmental mycobacteria, so they generate fewer false-
positive results.[108] However, they are affected by M. szulgai, M.
marinum, and M. kansasii.[109] IGRAs may increase sensitivity when used in addition to the skin test, but
may be less sensitive than the skin test when used alone.[110]

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.[111] While
some have recommend testing health care workers, evidence of benefit for this is poor as of 2019.[112]
The Centers for Disease Control and Prevention (CDC) stopped recommending yearly testing of health
care workers without known exposure in 2019.[113]

Prevention
Tuberculosis prevention and control efforts rely primarily on the
vaccination of infants and the detection and appropriate treatment
of active cases.[14] The World Health Organization (WHO) has
achieved some success with improved treatment regimens, and a
small decrease in case numbers.[14] Some countries have
legislation to involuntarily detain or examine those suspected to
have tuberculosis, or involuntarily treat them if infected.[114]

Vaccines
The only available vaccine as of 2021 is bacillus Calmette-Guérin
(BCG).[115][116] In children it decreases the risk of getting the
infection by 20% and the risk of infection turning into active
disease by nearly 60%.[117][118]
A tuberculosis public health
It is the most widely used vaccine worldwide, with more than 90% campaign in Ireland, 1905
of all children being vaccinated.[14] The immunity it induces
decreases after about ten years.[14] As tuberculosis is uncommon
in most of Canada, Western Europe, and the United States, BCG is administered to only those people at
high risk.[119][120][121] 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.[121] Several vaccines are being
developed.[14]

Intradermal MVA85A vaccine in addition to BCG injection is not effective in preventing

tuberculosis.[122]

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.[123][124] 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.

Source control in the US

During the HIV/AIDS epidemic in the US, up to 35% of those
affected by TB were also infected by HIV.[125] Handling of TB-
infected patients in US hospitals was known to create airborne TB
that could infect others, especially in unventilated spaces.[126]

Multiple US agencies rolled out new public health rules as a result

of the TB spread: the CDC brought in new guidelines mandating
HEPA filters and HEPA respirators,[127] NIOSH pushed through
new 42 CFR 84 respirator regulations in 1995 (like the N95),[128] NIOSH video on tuberculosis
and OSHA created a proposed rule for TB in 1997, a result of respiratory protection, 2002
pressure from groups like the Labor Coalition to Fight TB in the
Workplace.[129][130]

However, in 2003, OSHA dropped their proposed TB rules, citing a decline of TB in the US, and public
disapproval.[131]

Worldwide campaigns
The World Health Organization (WHO) declared TB a "global health emergency" in 1993,[14] 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.[132] 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.[14] A tuberculosis classification system developed by the American Thoracic Society is used
primarily in public health programs.[133] 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 being hampered by the
lack of rapid testing, short and effective treatment courses, and completely effective vaccines.[134]
The benefits and risks of giving anti-tubercular drugs to those exposed to MDR-TB is unclear.[135]
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.[136]

Management
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.[137]

Active TB is best treated with combinations of several antibiotics

to reduce the risk of the bacteria developing antibiotic
resistance.[14] The routine use of rifabutin instead of rifampicin in
HIV-positive people with tuberculosis is of unclear benefit as of Tuberculosis phototherapy
2007.[138] treatment in Kuopio, Finland, 1934

Acetylsalicylic acid (aspirin) at a dose of 100 mg per day has been

shown to improve clinical signs and symptoms, reduce cavitary lesions, lower inflammatory markers, and
increase the rate of sputum-negative conversion in patients with pulmonary tuberculosis.[139]

Latent TB
Latent TB is treated with either isoniazid or rifampin alone, or a combination of isoniazid with either
rifampicin or rifapentine.[140][141][142]

The treatment takes three to nine months depending on the medications used.[75][140][143][142] People with
latent infections are treated to prevent them from progressing to active TB disease later in life.[144]

Education or counselling may improve the latent tuberculosis treatment completion rates.[145]

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.[14] Where resistance to isoniazid
is high, ethambutol may be added for the last four months as an alternative.[14] 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.[146] There is also no evidence to support shorter anti-tuberculosis treatment
regimens when compared to a 6-month treatment regimen.[147] However, results presented in 2020 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.[148]

Recurrent disease
If tuberculosis recurs, testing to determine which antibiotics it is sensitive to is important before
determining treatment.[14] If multiple drug-resistant TB (MDR-TB) is detected, treatment with at least
four effective antibiotics for 18 to 24 months is recommended.[14]

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.[149] The evidence to support this practice over people simply taking their
medications independently is of poor quality.[150] 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.[150] 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.[150]

Methods to remind people of the importance of treatment and appointments may result in a small but
important improvement.[151] 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.[152] 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.[153]

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.[154] 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.[155] Totally drug-resistant TB is resistant to all
currently used drugs.[156] It was first observed in 2003 in Italy,[157] but not widely reported until
2012,[156][158] and has also been found in Iran and India.[159] There is some efficacy for linezolid to treat
those with XDR-TB but side effects and discontinuation of medications were common.[160][161]
Bedaquiline is tentatively supported for use in multiple drug-resistant TB.[162]

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.[159]
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.[163][164]

Prognosis
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.[13] However, in the
majority of cases, a latent infection occurs with no
obvious symptoms.[13] These dormant bacilli
produce active tuberculosis in 5–10% of these latent Age-standardized disability-adjusted life years
cases, often many years after infection.[48] caused by tuberculosis per 100,000 inhabitants,
2004:[165]
The risk of reactivation increases with no data
immunosuppression, such as that caused by ≤10
infection with HIV. In people coinfected with M. 10–25
25–50
tuberculosis and HIV, the risk of reactivation
50–75
increases to 10% per year.[13] Studies using DNA 75–100
fingerprinting of M. tuberculosis strains have shown 100–250
reinfection contributes more substantially to 250–500
recurrent TB than previously thought,[166] with 500–750
estimates that it might account for more than 50% of 750–1000
reactivated cases in areas where TB is 1000–2000
2000–3000
common.[167] The chance of death from a case of
≥ 3000
tuberculosis is about 4% as of 2008, down from 8%
in 1995.[14]

In people with smear-positive pulmonary TB (without HIV co-infection), after 5 years without treatment,
50–60% die while 20–25% achieve spontaneous resolution (cure). TB is almost always fatal in those with
untreated HIV co-infection and death rates are increased even with antiretroviral treatment of HIV.[168]

Epidemiology
Roughly one-quarter of the world's population has been infected with M. tuberculosis,[6] with new
infections occurring in about 1% of the population each year.[11] However, most infections with M.
tuberculosis do not cause disease,[169] and 90–95% of infections remain asymptomatic.[87] In 2012, an
estimated 8.6 million chronic cases were active.[170] In 2010, 8.8 million new cases of tuberculosis were
diagnosed, and 1.20–1.45 million deaths occurred (most of these occurring in developing
countries).[78][171] Of these, about 0.35 million occur in those also infected with HIV.[172] In 2018,
tuberculosis was the leading cause of death worldwide from a single infectious agent.[1] The total number
of tuberculosis cases has been decreasing since 2005, while new cases have decreased since 2002.[78]
Tuberculosis incidence is seasonal, with peaks occurring every spring and summer.[173][174][175][176] The
reasons for this are unclear, but may be related to vitamin D deficiency during the winter.[176][177] There
are also studies linking tuberculosis to different weather conditions like low temperature, low humidity
and low rainfall. It has been suggested that tuberculosis incidence rates may be connected to climate
change.[178]

At-risk groups
Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal
diseases of poverty.[14] Those at high risk thus include: people who inject illicit drugs, inhabitants and
employees of locales where vulnerable people gather (e.g., prisons and homeless shelters), medically
underprivileged and resource-poor communities, high-risk ethnic minorities, children in close contact
with high-risk category patients, and health-care providers serving these patients.[179]

The rate of tuberculosis varies with age. In Africa, it primarily affects adolescents and young adults.[180]
However, in countries where incidence rates have declined dramatically (such as the United States),
tuberculosis is mainly a disease of the elderly and immunocompromised (risk factors are listed
above).[13][181] Worldwide, 22 "high-burden" states or countries together experience 80% of cases as well
as 83% of deaths.[159]

In Canada and Australia, tuberculosis is many times more common among the Indigenous peoples,
especially in remote areas.[182][183] Factors contributing to this include higher prevalence of predisposing
health conditions and behaviours, and overcrowding and poverty. In some Canadian Indigenous groups,
genetic susceptibility may play a role.[77]

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.[77]

Geographical epidemiology
The distribution of tuberculosis is not uniform across the globe; about 80% of the population in many
African, Caribbean, South Asian, and eastern European countries test positive in tuberculin tests, while
only 5–10% of the U.S. population test positive.[13] 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.[14]

In developed countries, tuberculosis is less common and is found mainly in urban areas. In Europe,
deaths from TB fell from 500 out of 100,000 in 1850 to 50 out of 100,000 by 1950. Improvements in
public health were reducing tuberculosis even before the arrival of antibiotics, although the disease
remained a significant threat to public health, such that when the Medical Research Council was formed
in Britain in 1913 its initial focus was tuberculosis research.[184]
In 2010, rates per 100,000 people in different areas of the world were: globally 178, Africa 332, the
Americas 36, Eastern Mediterranean 173, Europe 63, Southeast Asia 278, and Western Pacific 139.[172]

In 2023, tuberculosis overtook COVID-19 as the leading cause of infectious disease-related deaths
globally, according to a World Health Organization.[185] Around 8.2 million people were newly diagnosed
with TB last year, allowing them access to treatment—a record high since WHO’s tracking began in 1995
and an increase from 7.5 million cases in 2022.[186] The report highlights ongoing obstacles in combating
TB, including severe funding shortages that hinder efforts toward eradication. Although TB-related
deaths decreased slightly to 1.25 million in 2023 from 1.32 million in 2022, the overall number of new
cases rose marginally to an estimated 10.8 million.

Russia
Russia has achieved particularly dramatic progress with a decline in its TB mortality rate—from 61.9 per
100,000 in 1965 to 2.7 per 100,000 in 1993;[187][188] however, mortality rate increased to 24 per 100,000
in 2005 and then recoiled to 11 per 100,000 by 2015.[189]

China
China has achieved particularly dramatic progress, with about an 80% reduction in its TB mortality rate
between 1990 and 2010.[172] The number of new cases has declined by 17% between 2004 and 2014.[159]

Africa
In 2007, the country with the highest estimated incidence rate of TB was Eswatini, with 1,200 cases per
100,000 people. In 2017, the country with the highest estimated incidence rate as a % of the population
was Lesotho, with 665 cases per 100,000 people.[190]

In South Africa, 54,200 people died in 2022 from TB. The incidence rate was 468 per 100,000 people; in
2015, this was 988 per 100,000. The total incidence was 280,000 in 2022; in 2015, this was 552,000.[191]

India
As of 2017, India had the largest total incidence, with an estimated 2,740,000 cases.[190] According to the
World Health Organization (WHO), in 2000–2015, India's estimated mortality rate dropped from 55 to 36
per 100,000 population per year with estimated 480 thousand people died of TB in 2015.[192][193] In India
a major proportion of tuberculosis patients are being treated by private partners and private hospitals.
Evidence indicates that the tuberculosis national survey does not represent the number of cases that are
diagnosed and recorded by private clinics and hospitals in India.[194]

North America
In Canada, tuberculosis was endemic in some rural areas as of 1998.[195] The tuberculosis case rate in
Canada in 2021 was 4.8 per 100,000 persons. The rates were highest among Inuit (135.1 per 100,000),
First Nations (16.1 per 100,000) and people born outside of Canada (12.3 per 100,000).[196]

In the United States, Native Americans have a fivefold greater mortality from TB,[197] and racial and
ethnic minorities accounted for 88% of all reported TB cases.[198] The overall tuberculosis case rate in the
United States was 2.9 per 100,000 persons in 2023, representing a 16% increase in cases compared to
2022.[198]

In 2024, Long Beach, California authorized a public health emergency in response to a local outbreak of
TB.[199]

Western Europe
In 2017, in the United Kingdom, the national average was 9 per 100,000 and the highest incidence rates
in Western Europe were 20 per 100,000 in Portugal.

Number of new cases of tuberculosis per

100,000 people, 2016[200]

Tuberculosis deaths per million persons, 2012

 Tuberculosis deaths by region, 1990 to 2017[201]

Society and culture

Names
Tuberculosis has been known by many names from the technical to the familiar.[202] Phthisis (φθίσις) is
the Greek word for consumption, an old term for pulmonary tuberculosis;[7] around 460 BCE,
Hippocrates described phthisis as a disease of dry seasons.[203] The abbreviation TB is short for tubercle
bacillus. Consumption was the most common nineteenth century English word for the disease, and was
also in use well into the twentieth century. The Latin root con meaning 'completely' is linked to sumere
meaning 'to take up from under'.[204] In The Life and Death of Mr Badman by John Bunyan, the author
calls consumption "the captain of all these men of death."[205] "Great white plague" has also been
used.[202]

Art and literature

Tuberculosis was for centuries associated with poetic and artistic qualities among those infected, and was
also known as "the romantic disease".[202][206] Major artistic figures such as the poets John Keats, Percy
Bysshe Shelley, and Edgar Allan Poe, the composer Frédéric Chopin,[207] the playwright Anton Chekhov,
the novelists Franz Kafka, Katherine Mansfield,[208] Charlotte Brontë, Fyodor Dostoevsky, Thomas
Mann, W. Somerset Maugham,[209] George Orwell,[210] and Robert Louis Stevenson, and the artists Alice
Neel,[211] 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 that it caused, allegedly helping them to see life more clearly and to act
decisively.[212][213][214]
Tuberculosis formed an often-reused theme in literature, as in
Thomas Mann's The Magic Mountain, set in a sanatorium;[215] in
music, as in Van Morrison's song "T.B. Sheets";[216] in opera, as in
Puccini's La bohème and Verdi's La Traviata;[214] in art, as in
Munch's painting of his ill sister;[217] and in film, such as the 1945
The Bells of St. Mary's starring Ingrid Bergman as a nun with
tuberculosis.[218]

Public health efforts

In 2014, the WHO adopted the "End TB" strategy which aims to
reduce TB incidence by 80% and TB deaths by 90% by 2030.[219] Painting The Sick Child by Edvard
The strategy contains a milestone to reduce TB incidence by 20% Munch, 1885–1886, depicts the
and TB deaths by 35% by 2020. [220] However, by 2020 only a 9% illness of his sister Sophie, who died
of tuberculosis when Edvard was
reduction in incidence per population was achieved globally, with
14; his mother also died of the
the European region achieving 19% and the African region disease.
achieving 16% reductions.[220] 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).[220]
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.[220]

The World Health Organization (WHO), the Bill and Melinda Gates Foundation, and the U.S.
government are subsidizing a fast-acting diagnostic tuberculosis test for use in low- and middle-income
countries as of 2012.[221][222][223] In addition to being fast-acting, the test can determine if there is
resistance to the antibiotic rifampicin which may indicate multi-drug resistant tuberculosis and is accurate
in those who are also infected with HIV.[221][224] Many resource-poor places as of 2011 have access to
only sputum microscopy.[225]

India had the highest total number of TB cases worldwide in 2010, in part due to poor disease
management within the private and public health care sector.[226] Programs such as the Revised National
Tuberculosis Control Program are working to reduce TB levels among people receiving public health
care.[227][228]

A 2014 EIU-healthcare report finds there is a need to address apathy and urges for increased funding. The
report cites among others Lucica Ditui "[TB] is like an orphan. It has been neglected even in countries
with a high burden and often forgotten by donors and those investing in health interventions."[159]

Slow progress has led to frustration, expressed by the executive director of the Global Fund to Fight
AIDS, Tuberculosis and Malaria – Mark Dybul: "we have the tools to end TB as a pandemic and public
health threat on the planet, but we are not doing it."[159] Several international organizations are pushing
for more transparency in treatment, and more countries are implementing mandatory reporting of cases to
the government as of 2014, although adherence is often variable. Commercial treatment providers may at
times overprescribe second-line drugs as well as supplementary treatment, promoting demands for further
regulations.[159]
The government of Brazil provides universal TB care, which reduces this problem.[159] Conversely,
falling rates of TB infection may not relate to the number of programs directed at reducing infection rates
but may be tied to an increased level of education, income, and health of the population.[159] Costs of the
disease, as calculated by the World Bank in 2009 may exceed US$150 billion per year in "high burden"
countries.[159] Lack of progress eradicating the disease may also be due to lack of patient follow-up – as
among the 250 million rural migrants in China.[159]

There is insufficient data to show that active contact tracing helps to improve case detection rates for
tuberculosis.[229] Interventions such as house-to-house visits, educational leaflets, mass media strategies,
educational sessions may increase tuberculosis detection rates in short-term.[230] There is no study that
compares new methods of contact tracing such as social network analysis with existing contact tracing
methods.[231]

Stigma
Slow progress in preventing the disease may in part be due to stigma associated with TB.[159] Stigma may
be due to the fear of transmission from affected individuals. This stigma may additionally arise due to
links between TB and poverty, and in Africa, AIDS.[159] Such stigmatization may be both real and
perceived; for example, in Ghana, individuals with TB are banned from attending public gatherings.[232]

Stigma towards TB may result in delays in seeking treatment,[159] lower treatment compliance, and
family members keeping cause of death secret[232] – allowing the disease to spread further.[159] In
contrast, in Russia stigma was associated with increased treatment compliance.[232] TB stigma also
affects socially marginalized individuals to a greater degree and varies between regions.[232]

One way to decrease stigma may be through the promotion of "TB clubs", where those infected may
share experiences and offer support, or through counseling.[232] Some studies have shown TB education
programs to be effective in decreasing stigma, and may thus be effective in increasing treatment
adherence.[232] Despite this, studies on the relationship between reduced stigma and mortality are lacking
as of 2010, and similar efforts to decrease stigma surrounding AIDS have been minimally effective.[232]
Some have claimed the stigma to be worse than the disease, and healthcare providers may unintentionally
reinforce stigma, as those with TB are often perceived as difficult or otherwise undesirable.[159] A greater
understanding of the social and cultural dimensions of tuberculosis may also help with stigma
reduction.[233]

Research
The BCG vaccine has limitations and research to develop new TB vaccines is ongoing.[234] A number of
potential candidates are currently in phase I and II clinical trials.[234][235] Two main approaches are used
to attempt to improve the efficacy of available vaccines. One approach involves adding a subunit vaccine
to BCG, while the other strategy is attempting to create new and better live vaccines.[234] MVA85A, an
example of a subunit vaccine, is in trials in South Africa as of 2006, is based on a genetically modified
vaccinia virus.[236] Vaccines are hoped to play a significant role in treatment of both latent and active
disease.[237]
To encourage further discovery, researchers and policymakers are promoting new economic models of
vaccine development as of 2006, including prizes, tax incentives, and advance market
commitments.[238][239] A number of groups, including the Stop TB Partnership,[240] the South African
Tuberculosis Vaccine Initiative, and the Aeras Global TB Vaccine Foundation, are involved with
research.[241] Among these, the Aeras Global TB Vaccine Foundation received a gift of more than
$280 million (US) from the Bill and Melinda Gates Foundation to develop and license an improved
vaccine against tuberculosis for use in high burden countries.[242][243]

In 2012 a new medication regimen was approved in the US for multidrug-resistant tuberculosis, using
bedaquiline as well as existing drugs. There were initial concerns about the safety of this
drug,[244][245][246][247][248] but later research on larger groups found that this regimen improved health
outcomes.[249] By 2017 the drug was used in at least 89 countries.[250] Another new drug is delamanid,
which was first approved by the European Medicines Agency in 2013 to be used in multidrug-resistant
tuberculosis patients,[251] and by 2017 was used in at least 54 countries.[250]

Steroids add-on therapy has not shown any benefits for active pulmonary tuberculosis infection.[252]

Other animals
Mycobacteria infect many different animals, including birds,[253] fish, rodents,[254] and reptiles.[255] The
subspecies Mycobacterium tuberculosis, though, is rarely present in wild animals.[256] An effort to
eradicate bovine tuberculosis caused by Mycobacterium bovis from the cattle and deer herds of New
Zealand has been relatively successful.[257] Efforts in Great Britain have been less successful.[258][259]

As of 2015, 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.[260][261]

See also

Medicine portal

Post-tuberculosis lung disease

List of deaths due to tuberculosis
Bibliography of tuberculosis

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External links
"Tuberculosis (TB)" (https://www.cdc.gov/tb/default.ht Wikipedia's health care articles can
m). Centers for Disease Control and Prevention be viewed offline with the Medical
(CDC). 24 October 2018. Wikipedia app.

"Tuberculosis (TB)" (https://web.archive.org/web/2007

0705100742/http://www.hpa.org.uk/infections/topics_az/tb/menu.htm). London: Health
Protection Agency. Archived from the original (http://www.hpa.org.uk/infections/topics_az/tb/
menu.htm) on 5 July 2007.
WHO global 2016 TB report (infographic) (https://www.who.int/tb/global-tb-report-infographi
c.pdf?ua=1)
WHO tuberculosis country profiles (https://www.who.int/tb/country/data/profiles/en/)
"Tuberculosis Among African Americans" (https://americanarchive.org/catalog/cpb-aacip_52
9-1c1td9p67s), 1990-11-01, In Black America; KUT Radio, American Archive of Public
Broadcasting (WGBH and the Library of Congress)
Working Group on New TB drugs (https://www.newtbdrugs.org/), tracking clinical trials and
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