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Tuberculosis (TB) is an
infectious disease An infection is the invasion of an organism's body Tissue (biology), tissues by Pathogen, disease-causing agents, their multiplication, and the reaction of host (biology), host tissues to the infectious agents and the toxins they produce. An inf ...
usually caused by ''
Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria Pathogenic bacteria are bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They constitute a large d ...

Mycobacterium tuberculosis
'' (MTB)
bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of biological cell The cell (from Latin ''cella'', meaning "small room") is the basic structural, functional, and biological unit of all known organisms. Cells are the sm ...

bacteria
. Tuberculosis generally affects the
lung The lungs are the primary organs An organ is a group of tissues with similar functions. Plant life and animal life rely on many organs that co-exist in organ systems. A given organ's tissues can be broadly categorized as parenchyma ...

lung
s, but can also affect other parts of the body. Most infections show no symptoms, in which case it is known as
latent tuberculosis Latent tuberculosis (LTB), also called latent tuberculosis infection (LTBI) is when a person is infected with ''Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria in the family Mycobacteriaceae ...
. About 10% of latent infections progress to active disease which, if left untreated, kills about half of those affected. Typical symptoms of active TB are a chronic
cough A cough is a sudden expulsion of air through the large breathing passages that can help clear them of fluids, irritants, foreign particles and microbes A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an o ...
with
mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membrane A mucous membrane or mucosa is a biological membrane, membrane that lines various cavities in the body and covers the surface of internal organs. It consists o ...
,
fever Fever, also referred to as pyrexia, is defined as having a temperature Temperature ( ) is a physical quantity that expresses hot and cold. It is the manifestation of thermal energy Thermal radiation in visible light can be seen on th ...

fever
,
night sweats Night sweats, or also referred to as nocturnal hyperhidrosis (Hyperhidrosis - a medical term for excessive sweating + nocturnal - night) is the repeated occurrence of hyperhidrosis, excessive sweating during sleep. The person may or may not also ...
, and
weight loss Weight loss, in the context of medicine, health, or physical fitness Physical fitness is a state of health Health, according to the World Health Organization, is "a state of complete physical, Mental health, mental and social well-bein ...
. It was historically called consumption due to the weight loss.
Infection An infection is the invasion of an organism's body by , their multiplication, and the reaction of tissues to the infectious agents and the s they produce. An infectious disease, also known as a transmissible disease or communicable disease, i ...

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 A sneeze (also known as sternutation) is a semi-autonomous, convulsive A convulsion is a medical condition where body muscles Muscle is a soft tissue found in most animals. Muscle cells contain protein Proteins are large biomolecules ...
. People with Latent TB do not spread the disease. Active infection occurs more often in people with
HIV/AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection An infection is the invasion of an organism's body by , their multiplication, and the reaction of ...
and in those who
smoke Smoke is a collection of airborne and es emitted when a material undergoes or , together with the quantity of air that is or otherwise mixed into the mass. It is commonly an unwanted of fires (including s, s, s, s, and s), but may als ...

smoke
.
Diagnosis Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different academic discipline, disciplines, with variations in the use of logic, analytics, and experience, to determine "causality, cause an ...
of active TB is based on
chest X-ray A chest radiograph, called a chest X-ray (CXR), or chest film, is a Projectional radiography, projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most ...
s, as well as
microscopic The microscopic scale (from , ''mikrós'', "small" and σκοπέω, ''skopéō'' "look") is the scale of objects and events smaller than those that can easily be seen by the naked eye Naked eye, also called bare eye or unaided eye, is the pr ...

microscopic
examination and
culture Culture () is an umbrella term which encompasses the social behavior and Norm (social), norms found in human Society, societies, as well as the knowledge, beliefs, arts, laws, Social norm, customs, capabilities, and habits of the individuals i ...
of body fluids. Diagnosis of Latent TB relies on the
tuberculin skin test The Mantoux test or Mendel–Mantoux test (also known as the Mantoux screening test, tuberculin sensitivity test, Pirquet test, or PPD test for purified protein derivative) is a tool for screening for tuberculosis (TB) and for tuberculosis diag ...

tuberculin skin test
(TST) or blood tests. Prevention of TB involves screening those at high risk, early detection and treatment of cases, and
vaccination Vaccination is the administration of a vaccine to help the immune system develop protection from a disease. Vaccines contain a microorganism or virus in a weakened, live or killed state, or proteins or toxins from the organism. In stimulating ...

vaccination
with the
bacillus Calmette-Guérin Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against tuberculosis (TB). It is partly named after its inventors Albert Calmette and Camille Guérin. In countries where TB or leprosy is common, one dose is recommended in h ...
(BCG) vaccine. Those at high risk include household, workplace, and social contacts of people with active TB. Treatment requires the use of multiple
antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organism () is any organic, life, living system t ...
s over a long period of time.
Antibiotic resistance Antimicrobial resistance (AMR or AR) occurs when microbe A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is some ...

Antibiotic resistance
is a growing problem with increasing rates of multiple drug-resistant tuberculosis (MDR-TB). As of 2018, one quarter of the world's population was thought to have latent infection with TB. New infections occur in about 1% of the population each year. In 2020, an estimated 10 million people developed active TB, resulting in 1.5 million deaths and making it the second leading cause of death from an infectious disease after
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease A contagious disease is a disease A disease is a particular abnormal condition that negatively affects the structure A structure is an arrangement and organization o ...

COVID-19
. As of 2018, most TB cases occurred in the regions of South-East Asia (44%), Africa (24%) and the Western Pacific (18%), with more than 50% of cases being diagnosed in eight countries: India (27%), China (9%), Indonesia (8%), the Philippines (6%), Pakistan (6%), Nigeria (4%) and Bangladesh (4%). The number of new cases each year is decreasing by around 2 percent annually. About 80% of people in many Asian and African countries test positive while 5–10% of people in the United States population test positive by the tuberculin test. Tuberculosis has been present in humans since
ancient times Ancient history is the aggregate of past eventsWordNet Search – 3.0
"History"
from t ...

ancient times
.


Signs and symptoms

Tuberculosis may infect any part of the body, but most commonly occurs in the lungs (known as pulmonary tuberculosis). Extrapulmonary TB occurs when tuberculosis develops outside of the lungs, although extrapulmonary TB may coexist with pulmonary TB. General signs and symptoms include fever,
chills Chills is a feeling of coldness occurring during a high fever, but sometimes is also a common symptom which occurs alone in specific people. It occurs during fever due to the release of cytokines and prostaglandins as part of the Inflammation, ...
, night sweats,
loss of appetite Anorexia is a decreased appetite Appetite is the desire to eat food Food is any substance consumed to provide nutritional support for an organism In biology, an organism (from Ancient Greek, Greek: ὀργανισμός, ''organis ...
, weight loss, and
fatigue Fatigue describes a state of tiredness that does not resolve with rest or sleep. In general usage, fatigue is synonymous with extreme tiredness or exhaustion that normally follows prolonged physical or mental activity. When it does not resolve ...
. Significant
nail clubbing Nail clubbing, also known as digital clubbing or clubbing, is a deformity of the finger or toe Nail (anatomy), nails associated with a number of diseases, mostly of the heart disease, heart and lung disease, lungs.Freedberg, et al. (2003). ''Fitz ...
may also occur.


Pulmonary

If a tuberculosis infection does become active, it most commonly involves the lungs (in about 90% of cases). Symptoms may include
chest pain Chest pain is pain or discomfort in the chest, typically the front of the chest. It may be described as sharp, dull, pressure, heaviness or squeezing. Associated symptoms may include pain in the shoulder, arm, upper abdomen, or jaw, along with na ...
and a prolonged cough producing sputum. About 25% of people may not have any symptoms (i.e. they remain asymptomatic). Occasionally, people may in small amounts, and in very rare cases, the infection may erode into the
pulmonary artery A pulmonary artery is an artery An artery (plural arteries) () is a blood vessel that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry oxygenated blood; the two exceptions are t ...

pulmonary artery
or a
Rasmussen's aneurysmRasmussen's aneurysm is a pulmonary artery A pulmonary artery is an artery An artery (plural arteries) () is a blood vessel that takes blood away from the heart to one or more parts of the body (tissues, lungs, brain etc.). Most arteries carry ...
, resulting in massive bleeding. Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs. The upper lung lobes are more frequently affected by tuberculosis than the lower ones. The reason for this difference is not clear. It may be due to either better air flow, or poor
lymph Lymph (from Latin, ''lympha'' meaning "water") is the fluid that flows through the lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the circulatory system and the immune system. It is ...
drainage within the upper lungs.


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 Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that a ...
and young children. In those with HIV, this occurs in more than 50% of cases. Notable extrapulmonary infection sites include the
pleura The pulmonary pleurae (''sing.'' pleura) are the two opposing layers of serous membrane In anatomy Anatomy (Greek ''anatomē'', 'dissection') is the branch of biology concerned with the study of the structure of organism In biology ...
(in tuberculous pleurisy), the
central nervous system The central nervous system (CNS) is the part of the nervous system In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecu ...

central nervous system
(in
tuberculous meningitis Tuberculous meningitis, also known as TB meningitis or tubercular meningitis, is a specific type of bacterial meningitis Meningitis is an Acute (medical), acute inflammation of the protective membranes covering the brain and spinal cord, known c ...
), the
lymphatic system The lymphatic system, or lymphoid system, is an in vertebrates that is part of the and the . It is made up of a large network of lymph, s, lymph nodes, lymphatic or lymphoid organs, and lymphoid tissues. The vessels carry a clear fluid called ...

lymphatic system
(in scrofula of the neck), the
genitourinary system The genitourinary system, or urogenital system, are the organs of the reproductive system and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathwa ...
(in urogenital tuberculosis), and the
bone A bone is a rigid tissue Tissue may refer to: Biology * Tissue (biology), an ensemble of similar cells that together carry out a specific function * ''Triphosa haesitata'', a species of geometer moth found in North America * ''Triphosa dubit ...

bone
s and joints (in
Pott disease Pott disease is tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but can also affect other parts of the body. Most infection ...
of the spine), among others. A potentially more serious, widespread form of TB is called "disseminated tuberculosis", it is also known as
miliary tuberculosis Miliary tuberculosis is a form of tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but can also affect other parts of the body. ...
. Miliary TB currently makes up about 10% of extrapulmonary cases.


Causes


Mycobacteria

The main cause of TB is ''
Mycobacterium tuberculosis ''Mycobacterium tuberculosis'' (M. tb) is a species of pathogenic bacteria Pathogenic bacteria are bacteria Bacteria (; common noun bacteria, singular bacterium) are a type of Cell (biology), biological cell. They constitute a large d ...

Mycobacterium tuberculosis
'' (MTB), a small,
aerobic Aerobic means "requiring Earth's atmosphere, air," in which "air" usually means oxygen. Aerobic may also refer to * Aerobic exercise, prolonged exercise of moderate intensity * Aerobics, a form of aerobic exercise * Cellular respiration#Aerobic r ...
, nonmotile
bacillus ''Bacillus'' (Latin "stick") is a genus Genus (plural genera) is a taxonomic rank Taxonomy (general) is the practice and science of classification of things or concepts, including the principles that underlie such classification. The term ma ...

bacillus
. The high
lipid In biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Molecular biology, molecular interactions, Physiology, physiological mechanis ...
content of this
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ theory ...
accounts for many of its unique clinical characteristics. It
divides In mathematics Mathematics (from Ancient Greek, Greek: ) includes the study of such topics as quantity (number theory), mathematical structure, structure (algebra), space (geometry), and calculus, change (mathematical analysis, analysis). ...

divides
every 16 to 20 hours, which is an extremely slow rate compared with other bacteria, which usually divide in less than an hour. Mycobacteria have an lipid bilayer. If a
Gram stain Gram stain or Gram staining, also called Gram's method, is a method of staining specimen, sandwiched between a glass microscope slide. Staining is a technique used to enhance contrast in samples, generally at the Microscope, microscopic leve ...

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 acidMycolic acids are long fatty acid fatty acids have perfectly straight chain structure. Unsaturated ones are typically bent, unless they have a trans configuration. In chemistry Chemistry is the scientific discipline involved with Chemical ...
content of its cell wall. MTB can withstand weak
disinfectant A disinfectant is a chemical A chemical substance is a form of matter In classical physics and general chemistry, matter is any substance that has mass and takes up space by having volume. All everyday objects that can be touched are ...
s and survive in a
dry state A dry state was a state in the United States in which the manufacture, distribution, importation, and sale of alcoholic beverages was Alcohol prohibition in the United States, prohibited or tightly restricted. Some states, such as North Dakota, ente ...
for weeks. In nature, the bacterium can grow only within the cells of a
host A host is a person responsible for guests at an event or for providing hospitality during it. Host may also refer to: Places *Host, Pennsylvania, a village in Berks County People *Jim Host (born 1937), American businessman *Michel Host (19 ...
organism, but ''M. tuberculosis'' can be cultured . Using
histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology Biology is the natural science that studies life and living organisms, including their anatomy, physical structure, Biochemistry, chemical processes, Mol ...

histological
stains on
expectorate Spitting is the act of forcibly ejecting saliva Saliva (commonly referred to as spit) is an extracellular fluid Extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy a ...
d samples from
phlegm Phlegm (; , ''phlégma'', "inflammation", "humour Humour (English in the Commonwealth of Nations, Commonwealth English) or humor (American English) is the tendency of experiences to provoke laughter and provide amusement. The term derives fro ...
(also called sputum), scientists can identify MTB under a microscope. Since MTB retains certain stains even after being treated with acidic solution, it is classified as an acid-fast bacillus. The most common acid-fast staining techniques are the
Ziehl–Neelsen stain Image:Mycobacterium tuberculosis Ziehl-Neelsen stain 02.jpg, ''Mycobacterium tuberculosis'' visualization using the Ziehl–Neelsen stain Ziehl-Neelsen staining is a type of acid-fast stain, first introduced by Paul Ehrlich. Ziehl–Neelsen staini ...
and the
Kinyoun stainThe Kinyoun method or Kinyoun stain (cold method), developed by Joseph J. Kinyoun, is a procedure used to staining (biology), stain acid-fast species of the bacterial genera ''Mycobacterium'' and ''Nocardia'' and the apicomplexan genus ''Cryptosporid ...
, which dye acid-fast bacilli a bright red that stands out against a blue background. Auramine-rhodamine staining and
fluorescence microscopy A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection (physics), reflection, and attenuation or absorption (electromagnetic radiation), absorption, to study the properties ...

fluorescence microscopy
are also used. The ''M. tuberculosis'' complex (MTBC) includes four other TB-causing
mycobacteria ''Mycobacterium'' is a genus Genus (plural genera) is a taxonomic rank Taxonomy (general) is the practice and science of classification of things or concepts, including the principles that underlie such classification. The term may also refer ...
: '' M. bovis'', '' M. africanum'', '' M. canetti'', and '' M. microti''. ''M. africanum'' is not widespread, but it is a significant cause of tuberculosis in parts of Africa. ''M. bovis'' was once a common cause of tuberculosis, but the introduction of
pasteurized milk Pasteurization or pasteurisation is a process in which packaged and non-packaged foods (such as milk Milk is a nutrient-rich liquid food produced by the mammary gland A mammary gland is an exocrine gland in humans and other mammal ...
has almost eliminated this as a public health problem in developed countries. ''M. canetti'' is rare and seems to be limited to the
Horn of Africa The Horn of Africa (HoA), also known as the Somali Peninsula, is a large peninsula of East Africa.Robert Stock, ''Africa South of the Sahara, Second Edition: A Geographical Interpretation'', (The Guilford Press; 2004), p. 26 Located on the ea ...

Horn of Africa
, although a few cases have been seen in African emigrants. ''M. microti'' is also rare and is seen almost only in immunodeficient people, although its
prevalence In epidemiology Epidemiology is the study and analysis of the distribution (who, when, and where), patterns and determinants In mathematics, the determinant is a Scalar (mathematics), scalar value that is a function (mathematics), function of ...

prevalence
may be significantly underestimated. Other known pathogenic mycobacteria include '' M. leprae'', '' M. avium'', and '' M. kansasii''. The latter two species are classified as "
nontuberculous mycobacteria Nontuberculous mycobacteria (NTM), also known as environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis (MOTT), are mycobacteria ''Mycobacterium'' is a genus Genus (plural genera) is a taxonomic rank Taxono ...
" (NTM) or atypical mycobacteria. NTM cause neither TB nor
leprosy Leprosy, also known as Hansen's disease (HD), is a long-term Long-Term Capital Management L.P. (LTCM) was a hedge fund''A financial History of the United States Volume II: 1970–2001'', Jerry W. Markham, Chapter 5: "Bank Consolidation", M. E. ...

leprosy
, but they do cause lung diseases that resemble TB.


Transmission

When people with active pulmonary TB cough, sneeze, speak, sing, or spit, they expel infectious
aerosol An aerosol (abbreviation of "aero-solution") is a suspension Suspension or suspended may refer to: Science and engineering * Suspension (topology), in mathematics * Suspension (dynamical systems), in mathematics * Suspension of a ring, in math ...

aerosol
droplets 0.5 to 5.0 µm in diameter. A single sneeze can release up to 40,000 droplets. Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is very small (the inhalation of fewer than 10 bacteria may cause an infection).


Risk of transmission

People with prolonged, frequent, or close contact with people with TB are at particularly high risk of becoming infected, with an estimated 22% infection rate. A person with active but untreated tuberculosis may infect 10–15 (or more) other people per year. Transmission should occur from only people with active TB – those with latent infection are not thought to be contagious. The probability of transmission from one person to another depends upon several factors, including the number of infectious droplets expelled by the carrier, the effectiveness of ventilation, the duration of exposure, the
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most contexts, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host (biology), host. The Pathogen#Pathogenicity, ...
of the ''M. tuberculosis'' strain, the level of immunity in the uninfected person, and others. The cascade of person-to-person spread can be circumvented by segregating those with active ("overt") TB and putting them on anti-TB drug regimens. After about two weeks of effective treatment, subjects with active infections generally do not remain contagious to others. If someone does become infected, it typically takes three to four weeks before the newly infected person becomes infectious enough to transmit the disease to others.


Risk factors

A number of factors make individuals more susceptible to TB infection and/or disease.


Active disease risk

The most important risk factor globally for developing active TB is concurrent HIV infection; 13% of those with TB are also infected with HIV. This is a particular problem in
sub-Saharan Africa Sub-Saharan Africa (commonly called Black Africa) is, geographically, the area of the continent of Africa that lies south of the Sahara. According to the United Nations, it consists of all list of sovereign states and dependent territories i ...

sub-Saharan Africa
, where HIV infection rates are high. Of those without HIV infection who are infected with tuberculosis, about 5–10% develop active disease during their lifetimes; in contrast, 30% of those co-infected with HIV develop the active disease. Use of certain medications, such as
corticosteroids Corticosteroids are a class of steroid hormone A steroid hormone is a steroid , hypothetical a steroid with 32 carbon atoms. Its core ring system (ABCD), composed of 17 carbon atoms, is shown with IUPAC The International Union of Pure a ...
and
infliximab Infliximab, a chimeric monoclonal antibody, sold under the brand name Remicade among others, is a medication used to treat a number of autoimmune diseases An autoimmune disease is a condition arising from an abnormal immune response to a func ...
(an anti-αTNF monoclonal antibody), is another important risk factor, especially in the
developed world A developed country (or industrialized country, high-income country, more economically developed country (MEDC), advanced country) is a sovereign state that has a high quality of life, developed economy and advanced technological infrastructu ...
. Other risk factors include:
alcoholism Alcoholism is, broadly, any drinking of alcohol In , alcohol is an that carries at least one (−OH) bound to a atom. The term alcohol originally referred to the primary alcohol (ethyl alcohol), which is and is the main alcoho ...
,
diabetes mellitus Diabetes mellitus, commonly known as just diabetes, is a group of metabolic disorders characterized by a hyperglycemia, high blood sugar level over a prolonged period of time. Symptoms often include frequent urination, Polydipsia, increased th ...
(3-fold increased risk),
silicosis Silicosis is a form of occupational lung disease caused by inhalation of crystalline silica dust. It is marked by inflammation and scarring in the form of nodular lesions in the upper lobes of the lungs. It is a type of pneumoconiosis. Silico ...

silicosis
(30-fold increased risk),
tobacco smoking Tobacco smoking is the practice of burning tobacco Tobacco is the common name of several plants in the ' of the , and the general term for any product prepared from the of these plants. of tobacco are known, but the chief commerci ...

tobacco smoking
(2-fold increased risk),
indoor air pollution Indoor air quality (IAQ) is the air quality Air pollution is the presence of substances in the atmosphere An atmosphere (from the greek words ἀτμός ''(atmos)'', meaning 'vapour', and σφαῖρα ''(sphaira)'', meaning 'ball' or ...
, malnutrition, young age, recently acquired TB infection, recreational drug use, severe kidney disease, low body weight, organ transplant, head and neck cancer, and
genetic susceptibility Public health genomics is the use of genomics information to benefit public health. This is visualized as more effective preventive care and disease treatments with better Specificity (statistics), specificity, tailored to the genetic makeup of eac ...
(the overall importance of genetic risk factors remains undefined).


Infection susceptibility

Tobacco smoking increases the risk of infections (in addition to increasing the risk of active disease and death). Additional factors increasing infection susceptibility include young age.


Pathogenesis

About 90% of those infected with ''M. tuberculosis'' have
asymptomatic In medicine, any disease is classified asymptomatic if a patient tests as carrier for a disease or infection An infection is the invasion of an organism's body Tissue (biology), tissues by Pathogen, disease-causing agents, their multiplicatio ...
, latent TB infections (sometimes called LTBI), with only a 10% lifetime chance that the latent infection will progress to overt, active tuberculous disease. In those with HIV, the risk of developing active TB increases to nearly 10% a year. If effective treatment is not given, the death rate for active TB cases is up to 66%. TB infection begins when the mycobacteria reach the alveolar air sacs of the lungs, where they invade and replicate within
endosomes Endosomes are a collection of intracellular sorting organelles In cell biology Cell biology (also cellular biology or cytology) is a branch of biology Biology is the natural science that studies life and living organisms, including th ...
of alveolar
macrophages Macrophages (abbreviated as Mφ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell White blood cells (WBCs), also called leukocytes or leucocytes, are the ...
. Macrophages identify the bacterium as foreign and attempt to eliminate it by
phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis Endocytosis is a cellular process i ...

phagocytosis
. During this process, the bacterium is enveloped by the macrophage and stored temporarily in a membrane-bound vesicle called a phagosome. The phagosome then combines with a lysosome to create a phagolysosome. In the phagolysosome, the cell attempts to use
reactive oxygen species Reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from O2. Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen (O2) produce ...
and acid to kill the bacterium. However, ''M. tuberculosis'' has a thick, waxy
mycolic acidMycolic acids are long fatty acid fatty acids have perfectly straight chain structure. Unsaturated ones are typically bent, unless they have a trans configuration. In chemistry Chemistry is the scientific discipline involved with Chemical ...
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 lung, upper lobe. Tuberculosis of the lungs may also occur via infection from the blood stream. This is known as a Simon focus and is typically found in the top of the lung. This hematogenous transmission can also spread infection to more distant sites, such as peripheral lymph nodes, the kidneys, the brain, and the bones. All parts of the body can be affected by the disease, though for unknown reasons it rarely affects the heart, skeletal muscles, pancreas, or thyroid. Tuberculosis is classified as one of the granulomatous inflammatory diseases. Macrophages, epithelioid cells, T cell, T lymphocytes, B cell, B lymphocytes, and fibroblasts aggregate to form granulomas, with lymphocytes surrounding the infected macrophages. When other macrophages attack the infected macrophage, they fuse together to form a giant multinucleated cell in the alveolar lumen. The granuloma may prevent dissemination of the mycobacteria and provide a local environment for interaction of cells of the immune system. However, more recent evidence suggests that the bacteria use the granulomas to 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. 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 Tubercle (anatomy), tubercles. To the naked eye, this has the texture of soft, white cheese and is termed caseous necrosis. 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
antibiotic An antibiotic is a type of antimicrobial An antimicrobial is an agent that kills microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism In biology, an organism () is any organic, life, living system t ...
s kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.


Diagnosis


Active tuberculosis

Diagnosing active tuberculosis based only on signs and symptoms is difficult, as is diagnosing the disease in those who have a weakened immune system. A diagnosis of TB should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. A
chest X-ray A chest radiograph, called a chest X-ray (CXR), or chest film, is a Projectional radiography, projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures. Chest radiographs are the most ...
and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation. Interferon-γ release assays and tuberculin skin tests are of little use in most of the developing world. Interferon gamma release assays (IGRA) have similar limitations in those with HIV. A definitive diagnosis of TB is made by identifying ''M. tuberculosis'' in a clinical sample (e.g., sputum, pus, or a Tissue (biology), tissue biopsy). However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture. Thus, treatment is often begun before cultures are confirmed. Nucleic acid amplification tests and adenosine deaminase testing may allow rapid diagnosis of TB. Blood tests to detect antibodies are not sensitivity and specificity, specific or sensitive, so they are not recommended.


Latent tuberculosis

The Mantoux test, Mantoux tuberculin skin test is often used to screen people at high risk for TB. Those who have been previously immunized with the Bacille Calmette-Guerin vaccine may have a false-positive test result. The test may be falsely negative in those with sarcoidosis, Hodgkin's lymphoma, malnutrition, and most notably, active tuberculosis. Interferon gamma release assays, on a blood sample, are recommended in those who are positive to the Mantoux test. These are not affected by immunization or most environmental mycobacteria, so they generate fewer false-positive results. However, they are affected by ''M. szulgai'', ''M. marinum'', and ''M. kansasii''. IGRAs may increase sensitivity when used in addition to the skin test, but may be less sensitive than the skin test when used alone. 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. While some have recommend testing health care workers, evidence of benefit for this is poor . The Centers for Disease Control and Prevention (CDC) stopped recommending yearly testing of health care workers without known exposure in 2019.


Prevention

Tuberculosis prevention and control efforts rely primarily on the vaccination of infants and the detection and appropriate treatment of active cases. The World Health Organization (WHO) has achieved some success with improved treatment regimens, and a small decrease in case numbers.


Vaccines

The only available vaccine is
bacillus Calmette-Guérin Bacillus Calmette–Guérin (BCG) vaccine is a vaccine primarily used against tuberculosis (TB). It is partly named after its inventors Albert Calmette and Camille Guérin. In countries where TB or leprosy is common, one dose is recommended in h ...
(BCG). In children it decreases the risk of getting the infection by 20% and the risk of infection turning into active disease by nearly 60%. It is the most widely used vaccine worldwide, with more than 90% of all children being vaccinated. The immunity it induces decreases after about ten years. As tuberculosis is uncommon in most of Canada, Western Europe, and the United States, BCG is administered to only those people at high risk. 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. Several vaccines are being developed. Intradermal MVA85A vaccine in addition to BCG injection is not effective in preventing tuberculosis.


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 Tuberculosis elimination, elimination of tuberculosis as a major public health issue in most developed economies. 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. The World Health Organization (WHO) declared TB a "global health emergency" in 1993, 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. 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. A tuberculosis classification system developed by the American Thoracic Society is used primarily in public health programs. 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 hampered by the lack of rapid testing, of short and effective treatment courses, and of tuberculosis vaccine, completely effective vaccines. The benefits and risks of giving anti-tubercular drugs in those exposed to MDR-TB is unclear. 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.


Treatment

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. Active TB is best treated with combinations of several antibiotics to reduce the risk of the bacteria developing antibiotic resistance. The routine use of rifabutin instead of rifampicin in HIV-positive people with tuberculosis is of unclear benefit .


Latent TB

Latent TB is treated with either isoniazid or rifampin alone, or a combination of isoniazid with either rifampicin or rifapentine. The treatment takes three to nine months depending on the medications used. People with latent infections are treated to prevent them from progressing to active TB disease later in life. Education or counselling may improve the latent tuberculosis treatment completion rates.


New onset

The recommended treatment of new-onset pulmonary tuberculosis, , 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. Where resistance to isoniazid is high, ethambutol may be added for the last four months as an alternative. 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. There is also no evidence to support shorter anti-tuberculosis treatment regimens when compared to a 6-month treatment regimen. However recently, results 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.


Recurrent disease

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


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. The evidence to support this practice over people simply taking their medications independently is of poor quality. 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. 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. Methods to remind people of the importance of treatment and appointments may result in a small but important improvement. 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. 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.


Medication resistance

Primary resistance occurs when a person becomes infected with a resistant strain of TB. A person with fully susceptible Mycobacterium tuberculosis, 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. 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. Totally drug-resistant TB is resistant to all currently used drugs. It was first observed in 2003 in Italy, but not widely reported until 2012, and has also been found in Iran and India. Bedaquiline is tentatively supported for use in multiple drug-resistant TB. 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. There is some efficacy for linezolid to treat those with XDR-TB but side effects and discontinuation of medications were common. 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.


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. However, in the majority of cases, a Latent tuberculosis, latent infection occurs with no obvious symptoms. These dormant bacilli produce active tuberculosis in 5–10% of these latent cases, often many years after infection. The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV. In people coinfected with ''M. tuberculosis'' and HIV, the risk of reactivation increases to 10% per year. Studies using DNA fingerprinting of ''M. tuberculosis'' strains have shown reinfection contributes more substantially to recurrent TB than previously thought, with estimates that it might account for more than 50% of reactivated cases in areas where TB is common. The chance of death from a case of tuberculosis is about 4% , down from 8% in 1995. 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.


Epidemiology

Roughly one-quarter of the world's population has been infected with ''M. tuberculosis'', with new infections occurring in about 1% of the population each year. However, most infections with ''M. tuberculosis'' do not cause disease, and 90–95% of infections remain asymptomatic. In 2012, an estimated 8.6 million chronic cases were active. 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 nation, developing countries). Of these, about 0.35 million occur in those also infected with HIV. In 2018, tuberculosis was the leading cause of death worldwide from a single infectious agent. The total number of tuberculosis cases has been decreasing since 2005, while new cases have decreased since 2002. Tuberculosis incidence is seasonal, with peaks occurring every spring and summer. The reasons for this are unclear, but may be related to vitamin D deficiency during the winter. 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.


At-risk groups

Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty. 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. The rate of tuberculosis varies with age. In Africa, it primarily affects adolescents and young adults. 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). Worldwide, 22 "high-burden" states or countries together experience 80% of cases as well as 83% of deaths. In Canada and Australia, tuberculosis is many times more common among the aboriginal peoples, especially in remote areas. Factors contributing to this include higher prevalence of predisposing health conditions and behaviours, and overcrowding and poverty. In some Canadian aboriginal groups, genetic susceptibility may play a role. 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.


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. 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. 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 (UK), Medical Research Council was formed in Britain in 1913 its initial focus was tuberculosis research. 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.


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;Global Tuberculosis Control
, World Health Organization, 2011.
however, mortality rate increased to 24 per 100,000 in 2005 and then recoiled to 11 per 100,000 by 2015.


China

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


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 (epidemiology), incidence rate as a % of the population was Lesotho, with 665 cases per 100,000 people.


India

As of 2017, India had the largest total incidence, with an estimated 2,740,000 cases. 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. 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.


North America

In the United States Native Americans in the United States, Native Americans have a fivefold greater mortality from TB, and racial and ethnic minorities accounted for 84% of all reported TB cases. In the United States, the overall tuberculosis case rate was 3 per 100,000 persons in 2017. In Canada, tuberculosis is still endemic in some rural areas.


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. File:Tuberculosis incidence (per 100,000 people), OWID.svg, Number of new cases of tuberculosis per 100,000 people in 2016. File:Tuberculosis world map-Deaths per million persons-WHO2012.svg, Tuberculosis deaths per million persons in 2012 File:Tuberculosis deaths by region, OWID.svg, Tuberculosis deaths by region, 1990 to 2017.


History

Tuberculosis has existed since Ancient history, antiquity. The oldest unambiguously detected ''M. tuberculosis'' gives evidence of the disease in the remains of bison in Wyoming dated to around 17,000 years ago. However, whether tuberculosis originated in bovines, then transferred to humans, or whether both bovine and human tuberculosis diverged from a common ancestor, remains unclear. 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. Skeletal remains show some prehistoric humans (4000 Common Era, BC) had TB, and researchers have found tubercular decay in the spines of Egyptian mummy, mummies dating from 3000 to 2400 BC. Genetic studies suggest the presence of TB in the Americas from about 100 AD. 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. Although Dr Richard Morton, Richard Morton established the pulmonary form associated with tubercle (anatomy), 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 in close proximity to each other. In 1819 René Laennec claimed that tubercles were the cause of pulmonary tuberculosis. Johann Lukas Schönlein, J. L. Schönlein first published the name "tuberculosis" (German: ''Tuberkulose'') in 1832. 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. 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. He received the Nobel Prize in Physiology or Medicine in 1905 for this discovery. 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. 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, 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. 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. After TB was determined to be contagious, in the 1880s, it was put on a List of notifiable diseases, notifiable-disease list in Britain; campaigns started to stop people from spitting in public places, and the infected poor were "encouraged" to enter sanatorium, 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 ( 1916). When the Medical Research Council (UK), Medical Research Council formed in Britain in 1913, it initially focused on tuberculosis research. 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, History of tuberculosis#Epidemic tuberculosis, tuberculosis had become epidemic in Europe, showing a seasonal pattern. 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. 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. Because of the emergence of Multidrug-resistant tuberculosis, 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. Hopes of eliminating TB ended with the rise of Antibiotic resistant, 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.


Society and culture


Names

Tuberculosis has been known by many names from the technical to the familiar. ''Phthisis'' (Φθισις) is a Greek word for consumption, an old term for pulmonary tuberculosis; around 460 BCE, Hippocrates described phthisis as a disease of dry seasons. The abbreviation "TB" is short for ''tubercle Bacillus (shape), bacillus''. "Consumption" was the most common nineteenth century English word for the disease. The Latin root "con" meaning "completely" is linked to "sumere" meaning "to take up from under." 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.


Art and literature

Tuberculosis was for centuries associated with poetic and artistic qualities among those infected, and was also known as "the romantic disease". 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 that 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 Giacomo Puccini, Puccini's ''La bohème'' and Giuseppe Verdi, Verdi's ''La Traviata''; in art, as in Claude Monet, Monet's painting of his first wife Camille on her deathbed; and in film, such as the 1945 ''The Bells of St. Mary's'' starring Ingrid Bergman as a nun with tuberculosis.


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% until 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 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. 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. Many resource-poor places have access to only sputum microscopy. 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. Programs such as the Revised National Tuberculosis Control Program are working to reduce TB levels among people receiving public health care. A 2014 Economist Intelligence Unit, 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." 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." 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. The government of Brazil provides universal TB care, which reduces this problem. 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. Costs of the disease, as calculated by the World Bank in 2009 may exceed US$150 billion per year in "high burden" countries. Lack of progress eradicating the disease may also be due to lack of patient follow-up – as among the 250M migration in China, rural migrants in China. There is insufficient data to show that active contact tracing helps to improve case detection rates for tuberculosis. Interventions such as house-to-house visits, educational leaflets, mass media strategies, educational sessions may increase tuberculosis detection rates in short-term. There is no study that compares new methods of contact tracing such as social network analysis with existing contact tracing methods.


Stigma

Slow progress in preventing the disease may in part be due to social stigma, stigma associated with TB. 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 AIDS in Africa, Africa, AIDS. Such stigmatization may be both real and perceived; for example, in Ghana, individuals with TB are banned from attending public gatherings. Stigma towards TB may result in delays in seeking treatment, lower treatment compliance, and family members keeping cause of death secret – allowing the disease to spread further. In contrast, in Russia stigma was associated with increased treatment compliance. TB stigma also affects socially marginalized individuals to a greater degree and varies between regions. 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. Some studies have shown TB education programs to be effective in decreasing stigma, and may thus be effective in increasing treatment adherence. Despite this, studies on the relationship between reduced stigma and mortality are lacking , and similar efforts to decrease stigma surrounding AIDS have been minimally effective. 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. A greater understanding of the social and cultural dimensions of tuberculosis may also help with stigma reduction.


Research

The BCG vaccine has limitations, and research to develop new TB vaccines is ongoing. A number of potential candidates are currently in clinical trial, phase I and II clinical trials. 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. MVA85A, an example of a subunit vaccine, is in trials in South Africa as of 2006, is based on a genetically modified vaccinia virus. Vaccines are hoped to play a significant role in treatment of both latent and active disease. 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. A number of groups, including the Stop TB Partnership, the South African Tuberculosis Vaccine Initiative, and the Aeras Global TB Vaccine Foundation, are involved with research. 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. A number of medications are being studied as of 2012 for multidrug-resistant tuberculosis, including bedaquiline and delamanid. Bedaquiline received U.S. Food and Drug Administration (FDA) approval in late 2012. The safety and effectiveness of these new agents are uncertain as of 2012, because they are based on the results of relatively small studies. However, existing data suggest that patients taking bedaquiline in addition to standard TB therapy are five times more likely to die than those without the new drug, which has resulted in medical journal articles raising health policy questions about why the FDA approved the drug and whether financial ties to the company making bedaquiline influenced physicians' support for its use. Steroids add-on therapy has not shown any benefits for people with active pulmonary tuberculosis infection.


Other animals

Mycobacteria infect many different animals, including birds, fish, rodents, and reptiles. The subspecies ''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.


References


External links

* * *
WHO global 2016 TB report (infographic)

WHO tuberculosis country profilesTuberculosis Among African Americans
1990-11-01, In Black America; KUT, KUT Radio, American Archive of Public Broadcasting (WGBH Educational Foundation, WGBH and the Library of Congress)
Working Group on New TB drugs
tracking clinical trials and drug candidates {{Authority control Tuberculosis, Airborne diseases Articles containing video clips Health in Africa Healthcare-associated infections Infectious causes of cancer Mycobacterium-related cutaneous conditions Wikipedia medicine articles ready to translate (full) Wikipedia infectious disease articles ready to translate Vaccine-preventable diseases