tuberculosis
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Tuberculosis (TB) is an infectious disease usually caused by ''
Mycobacterium tuberculosis
Mycobacterium tuberculosis
'' (MTB)
bacteria
bacteria
. Tuberculosis generally affects the s, but it can also affect other parts of the body. Most infections show no symptoms, in which case it is known as latent tuberculosis. Around 10% of latent infections progress to active disease which, if left untreated, kill about half of those affected. Typical symptoms of active TB are chronic cough with mucus, , night sweats, and weight loss. It was historically referred to as consumption due to the weight loss associated with the disease. of other organs can cause a wide range of symptoms. Tuberculosis is spread from one person to the next through the air when people who have active TB in their lungs cough, spit, speak, or sneeze. People with Latent TB do not spread the disease. Active infection occurs more often in people with HIV/AIDS and in those who . Diagnosis of active TB is based on s, as well as microscopic examination and
culture Culture () is an umbrella term which encompasses the social behavior, institutions, and Social norm, norms found in human Society, societies, as well as the knowledge, beliefs, arts, laws, Social norm, customs, capabilities, and habits of the ...
of body fluids. Diagnosis of Latent TB relies on the (TST) or blood tests. Prevention of TB involves screening those at high risk, early detection and treatment of cases, and vaccination with the bacillus Calmette-Guérin (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 substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...
s over a long period of time.
Antibiotic resistance Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. P ...
is a growing problem with increasing rates of multiple drug-resistant tuberculosis (MDR-TB). In 2018, one quarter of the world's population was thought to have a latent infection of 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, making it the second leading cause of death from an infectious disease after
COVID-19 Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...
. 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 seven countries: India (27%), China (9%), Indonesia (8%), the Philippines (6%), Pakistan (6%), Nigeria (4%), and Bangladesh (4%). By 2021 the number of new cases each year was decreasing by around 2% 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 via the tuberculin test. Tuberculosis has been present in humans since
ancient times Ancient history is a time period from the History of writing, beginning of writing and recorded human history to as far as late antiquity. The span of recorded history is roughly 5,000 years, beginning with the Sumerian language, Sumerian c ...
.


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 medical term for a loss of appetite Appetite is the desire to eat food items, usually due to Hunger (physiology), hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced ...
, 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 cough up blood in small amounts, and in very rare cases, the infection may erode into the
pulmonary artery A pulmonary artery is an artery in the pulmonary circulation that carries deoxygenated blood from the right side of the heart to the lungs. The largest pulmonary artery is the ''main pulmonary artery'' or ''pulmonary trunk'' from the heart, and t ...
or a Rasmussen's aneurysm, 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, , meaning "water") is the fluid that flows through the lymphatic system, a system composed of lymph vessels (channels) and intervening lymph nodes whose function, like the venous system, is to return fluid from the tissues to ...
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 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 overlying the lungs and the inside of the surrounding chest walls. The inner pleura, called the visceral pleura, covers the surface of each lung and dips bet ...
(in tuberculous pleurisy), the
central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...
(in
tuberculous meningitis Tuberculous meningitis, also known as TB meningitis or tubercular meningitis, is a specific type of bacterial meningitis caused by the ''Mycobacterium tuberculosis'' infection of the meninges—the system of Mesothelium, membranes which envelop the ...
), the
lymphatic system The lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. It consists of a large network of lymphatic vessels, lymph nodes, lymphatic or lymphoid o ...
(in scrofula of the neck), the
genitourinary system The genitourinary system, or urogenital system, are the organs In biology, an organ is a collection of Tissue (biology), tissues joined in a structural unit to serve a common function. In the biological organization, hierarchy of life, an org ...
(in urogenital tuberculosis), and the
bone A bone is a rigid organ Organ may refer to: Biology * Organ (biology), a part of an organism Musical instruments * Organ (music), a family of keyboard musical instruments characterized by sustained tone ** Electronic organ, an electronic ...
s and joints (in Pott disease 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 TB currently makes up about 10% of extrapulmonary cases.


Causes


Mycobacteria

The main cause of TB is '''' (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 ...
, nonmotile
bacillus ''Bacillus'' (Latin "stick") is a genus of Gram-positive, rod-shaped bacteria, a member of the phylum ''Bacillota'', with 266 named species. The term is also used to describe bacillus (shape), the shape (rod) of other so-shaped bacteria; and the ...
. The high
lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins Vitamin A, A, Vitamin D, D, Vitamin E, E and Vitamin K, K), monoglycerides, diglycerides, phospholipids, and o ...
content of this
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a Germ ...
accounts for many of its unique clinical characteristics. 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. Mycobacteria have an outer membrane lipid bilayer. If a
Gram stain In microbiology and bacteriology, Gram stain (Gram staining or Gram's method), is a method of staining used to classify bacterial species into two large groups: gram-positive bacteria and gram-negative bacteria. The name comes from the Danish bac ...
is performed, MTB either stains very weakly "Gram-positive" or does not retain dye as a result of the high lipid and
mycolic acid Mycolic acids are long fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most natura ...
content of its cell wall. MTB can withstand weak
disinfectant A disinfectant is a chemical substance or compound used to inactivate or destroy microorganisms on inert surfaces. Disinfection does not necessarily kill all microorganisms, especially resistant endospore, bacterial spores; it is less effecti ...
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 An alcoholic beverage (also called an alcoholic drink, adult beverage, or a drink) is a drink that contains eth ...
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 ( ...
organism, but ''M. tuberculosis'' can be cultured in the laboratory. Using
histological Histology, also known as microscopic anatomy or microanatomy, is the branch of biology which studies the microscopic anatomy of biological tissue (biology), tissues. Histology is the microscopic counterpart to gross anatomy, which looks at larg ...
stains on expectorated 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 ...
(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 Ziehl–Neelsen staining is a type of acid-fast stain, first introduced by Paul Ehrlich. Ziehl–Neelsen staining is a bacteriological stain used to identify acid-fast organisms, mainly Mycobacteria. It is named for two German doctors who modif ...
and the Kinyoun stain, 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 propertie ...
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 used in the biological classification of extant taxon, living and fossil organisms as well as Virus classification#ICTV classification, viruses. In the hierarchy of biol ...
: '' 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 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 and Geopolitics, geopolitical region in East Africa.Robert Stock, ''Africa South of the Sahara, Second Edition: A Geographical Interpretation'', (The Guilford P ...
, 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, prevalence is the proportion of a particular population found to be affected by a medical condition (typically a disease or a risk factor such as smoking or seatbelt use) at a specific time. It is derived by comparing the number o ...
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 which do not cause tuberculosis or leprosy (also known as Hansen's disease). NTM do ...
" (NTM) or atypical mycobacteria. NTM cause neither TB nor
leprosy Leprosy, also known as Hansen's disease (HD), is a Chronic condition, long-term infection by the bacteria ''Mycobacterium leprae'' or ''Mycobacterium lepromatosis''. Infection can lead to damage of the Peripheral nervous system, nerves, respira ...
, 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 is a suspension (chemistry), suspension of fine solid particles or liquid Drop (liquid), droplets in air or another gas. Aerosols can be natural or Human impact on the environment, anthropogenic. Examples of natural aerosols are fog o ...
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, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host (biology), host. The Pathogen#Pathogenicity, pathogen ...
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 nonresistant 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 is, geographically, the area and regions of the continent of Africa that lies south of the Sahara. These include West Africa, East Africa, Central Africa, and Southern Africa. Geopolitically, in addition to the List of sov ...
, 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 hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones. Two main classes of corticosteroids, glucocorticoids and mineralocorticoids, are involve ...
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 fu ...
(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 infrastruct ...
. Other risk factors include:
alcoholism Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognize ...
,
diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a hyperglycemia, high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, Polydipsia, increase ...
(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 Nodule (medicine), nodular lesions in the upper lobes of the lungs. It is a type of pneumo ...
(30-fold increased risk),
tobacco smoking Tobacco smoking is the practice of burning tobacco and ingesting the resulting tobacco smoke, smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with tobacco pipes, pipes and cig ...
(2-fold increased risk),
indoor air pollution Indoor air quality (IAQ) is the air quality within and around buildings and Nonbuilding structure, structures. IAQ is known to affect the health, comfort, and well-being of building occupants. Poor indoor air quality has been linked to Sick Buil ...
, 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 (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 but experiences no Signs and symptoms, symptoms. Whenever a medical condition fails to show noticeable symptoms after a diagnosis it migh ...
, 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 of alveolar
macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system The immune system is a network of biological pro ...
. 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. A cell that performs phagocytosis i ...
. 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 In chemistry, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of ...
and acid to kill the bacterium. However, ''M. tuberculosis'' has a thick, waxy
mycolic acid Mycolic acids are long fatty acid In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated and unsaturated compounds#Organic chemistry, saturated or unsaturated. Most natura ...
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. 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 The heart is a muscular organ Organ may refer to: Biology * Organ (biology), a part of an organism Musical instruments * Organ (music), a family of keyboard musical instruments characterized by sustained tone ** Electronic organ, an el ...
,
skeletal muscle Skeletal muscles (commonly referred to as muscles) are Organ (biology), organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other ...
s,
pancreas The pancreas is an Organ (anatomy), organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdominal cavity, abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine ...
, or
thyroid The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans it is in the neck and consists of two connected lobe (anatomy), lobes. The lower two thirds of the lobes are connected by a thin band of Connective tissue, tissue cal ...
. Tuberculosis is classified as one of the
granuloma A granuloma is an aggregation of macrophages that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Such substances include infectious o ...
tous inflammatory diseases.
Macrophage Macrophages (abbreviated as MPhi, φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ...
s,
epithelioid cell According to a common point of view epithelioid cells (also called epithelioid histiocytes) are derivatives of activated macrophages resembling Epithelium, epithelial cells. Structure and function Structurally, epithelioid cells (when examined ...
s,
T lymphocytes A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell rec ...
, B lymphocytes, and
fibroblast A fibroblast is a type of cell (biology), biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework (Stroma (tissue), stroma) for animal Tissue (biology), tissues, and plays a critical role in wound ...
s aggregate to form granulomas, with
lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of gnathostomata, most vertebrates. Lymphocytes include natural killer cells (which function in cell-mediated immunity, cell-mediated, cytotoxicity, cytotoxic innate imm ...
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 cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds ...
s 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 Necrosis () is a form of cell injury which results in the premature death of Cell (biology), cells in living Tissue (biology), tissue by Autolysis (biology), autolysis. Necrosis is caused by factors external to the cell or tissue, such as infec ...
) in the center of
tubercles In anatomy, a tubercle (literally 'small tuber', Latin for 'lump') is any round Nodule (medicine), nodule, small wikt:eminence, eminence, or warty outgrowth found on external or internal Organ (anatomy), organs of a plant or an animal. In plant ...
. To the naked eye, this has the texture of soft, white cheese and is termed
caseous necrosis Caseous necrosis or caseous degeneration () is a unique form of cell death in which the tissue maintains a cheese-like appearance.Robbins and Cotran: Pathologic Basis of Disease, 8th Ed. 2010. Pg. 16 It is also a distinctive form of coagulative nec ...
. 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 Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue Connective tissue is one of the four primary types of animal tissue (biology), tissue, along with epithelial tissue, muscle tissue, and nerv ...
. 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 A bronchus is a passage or airway in the lower respiratory tract that conducts Atmosphere of Earth, air into the lungs. The first or primary bronchi pronounced (BRAN-KAI) to branch from the trachea at the Carina of trachea, carina are the right ma ...
) 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 substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...
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 and multiple
sputum culture A sputum culture is a Experiment, test to detect and identify bacteria or Fungus, fungi that infect the lungs or Bronchus, breathing passages. Sputum is a thick fluid produced in the lungs and in the adjacent airways. Normally, fresh morning sam ...
s for
acid-fast bacilli Acid-fastness is a physical property of certain bacterial and Eukaryote, eukaryotic cell (biology), cells, as well as some Sub-cellular, sub-cellular structures, specifically their resistance to decolorization by acids during laboratory staining p ...
are typically part of the initial evaluation. Interferon-γ release assays (IGRA) and tuberculin skin tests are of little use in most of the developing world. 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
biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiology, interventional cardiologist. The process involves extraction of sampling (medicine), sample Cell (biology), cells or Biologica ...
). 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 specific or sensitive, so they are not recommended.


Latent tuberculosis

The 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 Sarcoidosis (also known as ''Besnier-Boeck-Schaumann disease'') is a disease involving abnormal collections of inflammatory cells that form lumps known as granulomata. The disease usually begins in the lungs, skin, or lymph nodes. Less commonly af ...
,
Hodgkin's lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition wa ...
,
malnutrition Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a Deficiency (medicine), deficiency, excess, or imbalance of energy, protein and Vitamin deficiency, other nutrients" wh ...
, and most notably, active tuberculosis.
Interferon gamma release assay Interferon-γ release assays (IGRA) are medical tests used in the diagnosis of some infectious diseases, especially tuberculosis. Interferon-γ (IFN-γ) release assays rely on the fact that T-lymphocytes will release IFN-γ when exposed to specific ...
s, 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 The Centers for Disease Control and Prevention (CDC) is the National public health institutes, national public health agency of the United States. It is a Federal agencies of the United States, United States federal agency, under the United S ...
(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 The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainme ...
(WHO) has achieved some success with improved treatment regimens, and a small decrease in case numbers. Some countries have legislation to involuntarily detain or examine those suspected to have tuberculosis, or involuntarily treat them if infected.


Vaccines

The only available
vaccine A vaccine is a biological Dosage form, preparation that provides active acquired immunity to a particular infectious disease, infectious or cancer, malignant disease. The safety and effectiveness of vaccines has been widely studied and verifie ...
is bacillus Calmette-Guérin (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 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 The American Thoracic Society (ATS) is a nonprofit organization focused on improving care for pulmonary diseases, critical illnesses and sleep-related breathing disorders. It was established in 1905 as the American Sanatorium Association, and ch ...
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 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 A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biolog ...
, 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 Antimicrobial resistance (AMR) occurs when microbes evolve mechanisms that protect them from the effects of antimicrobials. All classes of microbes can evolve resistance. Fungi evolve antifungal resistance. Viruses evolve antiviral resistance. P ...
. The routine use of
rifabutin Rifabutin (Rfb) is an antibiotic used to treat tuberculosis and prevent and treat Mycobacterium avium complex, ''Mycobacterium avium'' complex. It is typically only used in those who cannot tolerate rifampin such as people with HIV/AIDS on antiret ...
instead of
rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), mycobacterium avium complex, ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. ...
in HIV-positive people with tuberculosis is of unclear benefit .


Latent TB

Latent TB is treated with either
isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the Tuberculosis management, treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomyci ...
or
rifampin Rifampicin, also known as rifampin, is an ansamycin Ansamycins is a family of bacterial secondary metabolites that show antimicrobial activity against many Gram-positive and some Gram-negative bacteria, and includes various compounds, includi ...
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 Pyrazinamide is a medication used to treat tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect o ...
, and
ethambutol Ethambutol (EMB, E) is a medication primarily used to treat tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it ca ...
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 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 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. There is some efficacy for
linezolid Linezolid is an antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications ...
to treat those with XDR-TB but side effects and discontinuation of medications were common. 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. 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 infection An infection is the invasion of tissue (biology), tissues by pathogens, their multiplication, and the reaction of host (biology), host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmiss ...
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 Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reacti ...
, 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 DNA profiling (also called DNA fingerprinting) is the process of determining an individual's DNA characteristics. DNA analysis intended to identify a species, rather than an individual, is called DNA barcoding. DNA profiling is a Forensic DNA ...
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 countries A developing country is a sovereign state with a lesser developed Industrial sector, industrial base and a lower Human Development Index (HDI) relative to other countries. However, this definition is not universally agreed upon. There is al ...
). 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 Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a Deficiency (medicine), deficiency, excess, or imbalance of energy, protein and Vitamin deficiency, other nutrients" wh ...
, making it one of the principal
diseases of poverty Diseases of poverty (also known as poverty-related diseases) are diseases that are more prevalent in low-income populations. They include infectious diseases, as well as diseases related to malnutrition and poor health behaviour. Poverty is one o ...
. 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 Indigenous peoples are culturally distinct ethnic groups whose members are directly descended from the earliest known inhabitants of a particular geographic region and, to some extent, maintain the language and culture of those original people ...
, 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 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 Eswatini ( ; ss, eSwatini ), officially the Kingdom of Eswatini and formerly named Swaziland ( ; officially renamed in 2018), is a landlocked country in Southern Africa. It is bordered by Mozambique to its northeast and South Africa to its no ...
, 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 Lesotho ( ), officially the Kingdom of Lesotho, is a country landlocked country, landlocked as an Enclave and exclave, enclave in South Africa. It is situated in the Maloti Mountains and contains the Thabana Ntlenyana, highest mountains in Sou ...
, 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 The World Health Organization (WHO) is a list of specialized agencies of the United Nations, specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainme ...
(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 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 Western Europe is the western region of Europe. The region's countries and territories vary depending on context. The concept of "the West" appeared in Europe in juxtaposition to "the East" and originally applied to the ancient Mediterranean ...
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
antiquity Antiquity or Antiquities may refer to: Historical objects or periods Artifacts *Antiquities Antiquities are objects from Ancient history, antiquity, especially the civilizations of the Mediterranean: the Classical antiquity of Greece and Ro ...
. 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
gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian inheritance#History, Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanin ...
s 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 The Neolithic Revolution, or the (First) Agricultural Revolution, was the wide-scale transition of many human cultures during the Neolithic period from a lifestyle of hunter-gatherer, hunting and gathering to one of agriculture and sedentism, ...
. Skeletal remains show some prehistoric humans (4000 BC) had TB, and researchers have found tubercular decay in the spines of
Egypt Egypt ( ar, مصر , ), officially the Arab Republic of Egypt, is a List of transcontinental countries, transcontinental country spanning the North Africa, northeast corner of Africa and Western Asia, southwest corner of Asia via a land bridg ...
ian
mummies A mummy is a dead human or an animal whose soft tissues and Organ (anatomy), organs have been preserved by either intentional or accidental exposure to Chemical substance, chemicals, extreme cold, very low humidity, or lack of air, so that th ...
dating from 3000 to 2400 BC. Genetic studies suggest the presence of TB in
the Americas The Americas, which are sometimes collectively called America, are a landmass comprising the totality of North America, North and South America. The Americas make up most of the land in Earth's Western Hemisphere and comprise the New World. ...
from about AD 100. Before the
Industrial Revolution The Industrial Revolution was the transition to new manufacturing processes in Great Britain, continental Europe, and the United States, that occurred during the period from around 1760 to about 1820–1840. This transition included going fr ...
, folklore often associated tuberculosis with
vampire A vampire is a mythical creature that subsists by feeding on the Vitalism, vital essence (generally in the form of blood) of the living. In European folklore, vampires are undead, undead creatures that often visited loved ones and caused mi ...
s. 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 Richard Morton established the pulmonary form associated with
tubercles In anatomy, a tubercle (literally 'small tuber', Latin for 'lump') is any round Nodule (medicine), nodule, small wikt:eminence, eminence, or warty outgrowth found on external or internal Organ (anatomy), organs of a plant or an animal. In plant ...
as a pathology in 1689, due to the variety of its symptoms, TB was not identified as a single disease until the 1820s. Benjamin Marten conjectured in 1720 that consumptions were caused by microbes which were spread by people living close to each other. In 1819, René Laennec claimed that tubercles were the cause of pulmonary tuberculosis. J. L. Schönlein first published the name "tuberculosis" (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 A sanatorium (from Latin ''wikt:sanare, sānāre'' 'to heal, make healthy'), also sanitarium or sanitorium, are antiquated names for Hospital#Specialized, specialised hospitals, for the treatment of specific diseases, related ailments and conv ...
in 1859 in Görbersdorf (now Sokołowsko) in
Silesia Silesia (, also , ) is a historical region of Central Europe that lies mostly within Poland, with small parts in the Czech Silesia, Czech Republic and Germany. Its area is approximately , and the population is estimated at around 8,000,000. S ...
. 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 Heinrich Hermann Robert Koch ( , ; 11 December 1843 – 27 May 1910) was a German physician and microbiologist. As the discoverer of the specific causative agents of deadly infectious diseases including tuberculosis, cholera (though the Vibrio ...
identified and described the bacillus causing tuberculosis, ''M. tuberculosis'', on 24 March 1882. In 1905, he was awarded the
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute, Nobel Assembly at the Karolinska Institutet, Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Pr ...
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 Pasteurization American and British English spelling differences#-ise, -ize (-isation, -ization), or pasteurisation is a process of food preservation in which packaged and non-packaged foods (such as milk and fruit juices) are treated with mi ...
process. Koch announced a
glycerine Glycerol (), also called glycerine in British English and glycerin in American English, is a simple triol compound. It is a colorless, odorless, viscous liquid that is sweet-tasting and non-toxic. The glycerol backbone is found in lipids known ...
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 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 notifiable-disease list in Britain; campaigns started to stop people from spitting in public places, and the infected poor were "encouraged" to enter
sanatoria A sanatorium (from Latin Latin (, or , ) is a classical language belonging to the Italic languages, Italic branch of the Indo-European languages. Latin was originally a dialect spoken in the lower Tiber area (then known as Latium) aroun ...
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 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, 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 Streptomycin is an antibiotic medication used to treat a number of bacterial infections, including tuberculosis, Mycobacterium avium complex, ''Mycobacterium avium'' complex, endocarditis, brucellosis, Burkholderia infection, ''Burkholderia'' i ...
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 A pneumothorax is an abnormal collection of air in the pleural space between the lung and the chest wall. Symptoms typically include sudden onset of sharp, one-sided chest pain and dyspnea, shortness of breath. In a minority of cases, a one-way ...
technique", which involved collapsing an infected lung to "rest" it and to allow tuberculous lesions to heal. In India, tuberculosis prevalence was first investigated by Dr. Arthur Colborne Lankester, an English medical missionary and physician. He was selected by the government to undertake the study for one year and collaborate with all the provincial governments of India to expand the reach of the research. He eventually published a book titled ''Tuberculosis in India.'' ' 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. 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.


Society and culture


Names

Tuberculosis has been known by many names from the technical to the familiar. () is a Greek word for consumption, an old term for pulmonary tuberculosis; around 460 BCE,
Hippocrates Hippocrates of Kos (; grc-gre, Ἱπποκράτης ὁ Κῷος, Hippokrátēs ho Kôios; ), also known as Hippocrates II, was a Greek physician of the Classical Greece, classical period who is considered one of the most outstanding figures ...
described phthisis as a disease of dry seasons. The abbreviation ''TB'' is short for ''tubercle
bacillus ''Bacillus'' (Latin "stick") is a genus of Gram-positive, rod-shaped bacteria, a member of the phylum ''Bacillota'', with 266 named species. The term is also used to describe bacillus (shape), the shape (rod) of other so-shaped bacteria; and the ...
''. ''Consumption'' was the most common nineteenth century English word for the disease. The Latin root meaning 'completely' is linked to meaning 'to take up from under'. In '' The Life and Death of Mr Badman'' by
John Bunyan John Bunyan (; baptised 30 November 162831 August 1688) was an English people, English writer and Puritan preacher best remembered as the author of the Christian allegory ''The Pilgrim's Progress,'' which also became an influential literary mod ...
, 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
poet A poet is a person who studies and creates poetry. Poets may describe themselves as such or be described as such by others. A poet may simply be the creator (thought, thinker, songwriter, writer, or author) who creates (composes) poems (oral t ...
ic and
art Art is a diverse range of human activity, and resulting product, that involves creative or imaginative talent expressive of technical proficiency, beauty, emotional power, or conceptual ideas. There is no generally agreed definition of wha ...
istic qualities among those infected, and was also known as "the romantic disease". Major artistic figures such as the poets
John Keats John Keats (31 October 1795 – 23 February 1821) was an English poet of the second generation of Romanticism, Romantic poets, with Lord Byron and Percy Bysshe Shelley. His poems had been in publication for less than four years when he died o ...
,
Percy Bysshe Shelley Percy Bysshe Shelley ( ; 4 August 17928 July 1822) was one of the major Romantic literature in English, English Romantic poetry, Romantic poets. A radical in his poetry as well as in his political and social views, Shelley did not achieve fame ...
, and
Edgar Allan Poe Edgar Allan Poe (; Edgar Poe; January 19, 1809 – October 7, 1849) was an American writer, poet, editor, and literary criticism, literary critic. Poe is best known for his poetry and short stories, particularly his tales of mystery and the ...
, the composer Frédéric Chopin, the playwright
Anton Chekhov Anton Pavlovich Chekhov (; 29 January 1860 Old Style date 17 January. – 15 July 1904 Old Style date 2 July.) was a Russian playwright and short-story writer who is considered to be one of the greatest writers of all time. His career ...
, the novelists
Franz Kafka Franz Kafka (3 July 1883 – 3 June 1924) was a German-speaking Bohemian novelist and short-story writer, widely regarded as one of the major figures of 20th century in literature, 20th-century literature. His work fuses elements of Litera ...
,
Katherine Mansfield Kathleen Mansfield Murry (née Beauchamp; 14 October 1888 – 9 January 1923) was a New Zealand New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island ( ...
, Charlotte Brontë,
Fyodor Dostoevsky Fyodor Mikhailovich Dostoevsky (, ; rus, Фёдор Михайлович Достоевский, Fyódor Mikháylovich Dostoyévskiy, p=ˈfʲɵdər mʲɪˈxajləvʲɪdʑ dəstɐˈjefskʲɪj, a=ru-Dostoevsky.ogg, links=yes; 11 November 18219 ...
,
Thomas Mann Paul Thomas Mann ( , ; ; 6 June 1875 – 12 August 1955) was a German novelist, short story writer, social critic, philanthropist, essayist, and the 1929 Nobel Prize in Literature laureate. His highly symbolic and ironic epic novels and novella ...
, W. Somerset Maugham,
George Orwell Eric Arthur Blair (25 June 1903 – 21 January 1950), better known by his pen name George Orwell, was an English novelist, essayist, journalist, and critic. His work is characterised by lucid prose, social criticism, opposition to totalit ...
, and
Robert Louis Stevenson Robert Louis Stevenson (born Robert Lewis Balfour Stevenson; 13 November 1850 – 3 December 1894) was a Scottish novelist, essayist, poet and travel writer. He is best known for works such as ''Treasure Island'', ''Strange Case of Dr Jekyll a ...
, and the artists Alice Neel,
Jean-Antoine Watteau Jean-Antoine Watteau (, , ; baptised October 10, 1684died July 18, 1721) Alsavailablevia Oxford Art Online (subscription needed). was a French Painting, painter and Drawing, draughtsman whose brief career spurred the revival of interest in colou ...
, Elizabeth Siddal,
Marie Bashkirtseff Marie Bashkirtseff (born Mariya Konstantinovna Bashkirtseva, russian: Мария Константиновна Башки́рцева; 1858–1884) was a Ukrainian artist from the Russian Empire who worked in Paris, France. She died aged 25. Li ...
,
Edvard Munch Edvard Munch ( , ; 12 December 1863 – 23 January 1944) was a Norwegian painter. His best known work, ''The Scream'' (1893), has become one of Western art's most iconic images. His childhood was overshadowed by illness, bereavement and the dr ...
,
Aubrey Beardsley Aubrey Vincent Beardsley (21 August 187216 March 1898) was an English illustrator An illustrator is an artist who specializes in enhancing writing or elucidating concepts by providing a visual representation that corresponds to the content ...
and
Amedeo Modigliani Amedeo Clemente Modigliani (, ; 12 July 1884 – 24 January 1920) was an Italians, Italian Painting, painter and Sculpture, sculptor who worked mainly in France. He is known for portraits and nudes in a modern art, modern style characterized by ...
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 Literature is any collection of Writing, written work, but it is also used more narrowly for writings specifically considered to be an art form, especially prose fiction, drama, and poetry. In recent centuries, the definition has expanded to ...
, as in
Thomas Mann Paul Thomas Mann ( , ; ; 6 June 1875 – 12 August 1955) was a German novelist, short story writer, social critic, philanthropist, essayist, and the 1929 Nobel Prize in Literature laureate. His highly symbolic and ironic epic novels and novella ...
's '' The Magic Mountain'', set in a
sanatorium A sanatorium (from Latin ''wikt:sanare, sānāre'' 'to heal, make healthy'), also sanitarium or sanitorium, are antiquated names for Hospital#Specialized, specialised hospitals, for the treatment of specific diseases, related ailments and conv ...
; in
music Music is generally defined as the The arts, art of arranging sound to create some combination of Musical form, form, harmony, melody, rhythm or otherwise Musical expression, expressive content. Exact definition of music, definitions of mu ...
, as in
Van Morrison Sir George Ivan Morrison (born 31 August 1945), known professionally as Van Morrison, is a Northern Irish singer-songwriter and multi-instrumentalist whose recording career spans seven decades. He has won two Grammy Awards. As a teenager in t ...
's song " T.B. Sheets"; in
opera Opera is a form of theatre Theatre or theater is a collaborative form of performing art that uses live performers, usually actor, actors or actresses, to present the experience of a real or imagined event before a live audience in a ...
, as in Puccini's ''
La bohème ''La bohème'' (; ) is an opera in four acts,Puccini called the divisions '' quadri'', '' tableaux'' or "images", rather than ''atti'' (acts). composed by Giacomo Puccini Giacomo Puccini (Lucca, 22 December 1858Brussels, Bruxelles, 29 Nov ...
'' and
Verdi Giuseppe Fortunino Francesco Verdi (; 9 or 10 October 1813 – 27 January 1901) was an Italian composer best known for his operas. He was born near Busseto to a provincial family of moderate means, receiving a musical education with the h ...
's ''
La Traviata ''La traviata'' (; ''The Fallen Woman'') is an opera Opera is a form of theatre Theatre or theater is a collaborative form of performing art that uses live performers, usually actor, actors or actresses, to present the experience ...
''; in
art Art is a diverse range of human activity, and resulting product, that involves creative or imaginative talent expressive of technical proficiency, beauty, emotional power, or conceptual ideas. There is no generally agreed definition of wha ...
, as in
Monet Oscar-Claude Monet (, , ; 14 November 1840 – 5 December 1926) was a French painter and founder of Impressionism, impressionist painting who is seen as a key precursor to modernism, especially in his attempts to paint nature as he percei ...
's painting of his first wife Camille on her deathbed; and in
film A film also called a movie, motion picture, moving picture, picture, photoplay or (slang) flick is a work of visual art that simulates experiences and otherwise communicates ideas, stories, perceptions, feelings, beauty, or atmosphere ...
, such as the 1945 '' The Bells of St. Mary's'' starring
Ingrid Bergman Ingrid Bergman (29 August 191529 August 1982) was a Swedish actress who starred in a variety of European and American films, television movies, and plays.Obituary ''Variety Obituaries, Variety'', 1 September 1982. With a career spanning five d ...
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% by 2030. The strategy contains a milestone to reduce TB incidence by 20% and TB deaths by 35% by 2020. However, by 2020 only a 9% reduction in incidence per population was achieved globally, with the European region achieving 19% and the African region achieving 16% reductions. Similarly, the number of deaths only fell by 14%, missing the 2020 milestone of a 35% reduction, with some regions making better progress (31% reduction in Europe and 19% in Africa). Correspondingly, also treatment, prevention and funding milestones were missed in 2020, for example only 6.3 million people were started on TB prevention short of the target of 30 million. The World Health Organization (WHO), the
Bill and Melinda Gates Foundation The Bill & Melinda Gates Foundation (BMGF), a merging of the William H. Gates Foundation and the Gates Learning Foundation, is an American private foundation A private foundation is a tax-exempt organization not relying on broad public suppo ...
, 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 EIU-healthcare report finds there is a need to address apathy and urges for increased funding. The report cites among others Lucica Ditui " Bis 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 The World Bank is an international financial institution that provides loans and Grant (money), grants to the governments of Least developed countries, low- and Developing country, middle-income countries for the purpose of pursuing capital pro ...
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 250 million 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 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 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 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 ''Vaccinia virus'' (VACV or VV) is a large, complex, Viral envelope, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 base pair, kbp in length, which encodes approximately 250 genes ...
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 The Bill & Melinda Gates Foundation (BMGF), a merging of the William H. Gates Foundation and the Gates Learning Foundation, is an American private foundation A private foundation is a tax-exempt organization not relying on broad public suppo ...
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 The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(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 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 ''Mycobacterium bovis'' is a slow-growing (16- to 20-hour generation time) aerobic Aerobic means "requiring Earth's atmosphere, air," in which "air" usually means oxygen. Aerobic may also refer to * Aerobic exercise, prolonged exercise of mo ...
'' from the cattle and deer herds of
New Zealand New Zealand ( mi, Aotearoa ) is an island country in the southwestern Pacific Ocean. It consists of two main landmasses—the North Island () and the South Island ()—and over 700 List of islands of New Zealand, smaller islands. It is the ...
has been relatively successful. Efforts in Great Britain have been less successful. , tuberculosis appears to be widespread among captive
elephant Elephants are the Largest and heaviest animals, largest existing land animals. Three living species are currently recognised: the African bush elephant, the African forest elephant, and the Asian elephant. They are the only surviving members ...
s in the US. It is believed that the animals originally acquired the disease from humans, a process called
reverse zoonosis A reverse zoonosis, also known as a zooanthroponosis (Greek "animal", "man", ''"''disease") or anthroponosis, is a pathogen reservoired in humans that is capable of being transmitted to non-human animals. Terminology Anthroponosis refers to p ...
. Because the disease can spread through the air to infect both humans and other animals, it is a public health concern affecting
circus A circus is a company of performers who put on diverse entertainment shows that may include clowns, acrobats, trained animals, trapeze acts, musicians, dancers, hoopers, tightrope walkers, jugglers, magicians, ventriloquists, and unicy ...
es and
zoo A zoo (short for zoological garden; also called an animal park or menagerie) is a facility in which animals are kept within enclosures for public exhibition and often bred for Conservation biology, conservation purposes. The term ''zoological g ...
s.


References


External links

* * *
WHO global 2016 TB report (infographic)

WHO tuberculosis country profiles

"Tuberculosis Among African Americans"
1990-11-01, ''
In Black America Produced at KUT, ''In Black America'' is a long-running, nationally syndicated program dedicated to all facets of the African American experience. John L Hanson Jr. profiles a diverse selection of current and historically significant figures whos ...
''; KUT Radio,
American Archive of Public Broadcasting The American Archive of Public Broadcasting (AAPB) is a collaboration between the Library of Congress The Library of Congress (LOC) is the research library A library is a collection of materials, books or media that are accessible for ...
( WGBH and the Library of Congress)
Working Group on New TB drugs
tracking clinical trials and drug candidates {{Authority control Airborne diseases Articles containing video clips Health in Africa Healthcare-associated infections Infectious causes of cancer Mycobacterium-related cutaneous conditions Vaccine-preventable diseases Wikipedia infectious disease articles ready to translate Wikipedia medicine articles ready to translate (full)