Tuberculosis

Tuberculosis

Overview
Tuberculosis, MTB, or TB (short for tubercle bacillus
Bacillus (shape)
The word bacillus may be used to describe any rod-shaped bacterium, and such bacilli are found in many different taxonomic groups of bacteria. However, the name Bacillus, capitalized and italicized, refers to a specific genus of bacteria...

) is a common, and in many cases lethal, infectious disease
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...

 caused by various strains of mycobacteria
Mycobacterium
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy...

, usually Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

. Tuberculosis usually attacks the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

s but can also affect other parts of the body. It is spread through the air when people who have an active MTB infection cough, sneeze, or otherwise transmit their saliva through the air. Most infections in humans result in an asymptomatic
Asymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical...

, latent infection, and about one in ten latent infections eventually progresses to active disease, which, if left untreated, kills more than 50% of those infected.

The classic symptoms are a chronic cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...

 with blood-tinged
Hemoptysis
Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...

 sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....

, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, night sweats, and weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

 (the last giving rise to the formerly prevalent colloquial term "consumption").
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Encyclopedia
Tuberculosis, MTB, or TB (short for tubercle bacillus
Bacillus (shape)
The word bacillus may be used to describe any rod-shaped bacterium, and such bacilli are found in many different taxonomic groups of bacteria. However, the name Bacillus, capitalized and italicized, refers to a specific genus of bacteria...

) is a common, and in many cases lethal, infectious disease
Infectious disease
Infectious diseases, also known as communicable diseases, contagious diseases or transmissible diseases comprise clinically evident illness resulting from the infection, presence and growth of pathogenic biological agents in an individual host organism...

 caused by various strains of mycobacteria
Mycobacterium
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy...

, usually Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

. Tuberculosis usually attacks the lung
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

s but can also affect other parts of the body. It is spread through the air when people who have an active MTB infection cough, sneeze, or otherwise transmit their saliva through the air. Most infections in humans result in an asymptomatic
Asymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical...

, latent infection, and about one in ten latent infections eventually progresses to active disease, which, if left untreated, kills more than 50% of those infected.

The classic symptoms are a chronic cough
Cough
A cough is a sudden and often repetitively occurring reflex which helps to clear the large breathing passages from secretions, irritants, foreign particles and microbes...

 with blood-tinged
Hemoptysis
Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...

 sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....

, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, night sweats, and weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

 (the last giving rise to the formerly prevalent colloquial term "consumption"). Infection of other organs causes a wide range of symptoms. Diagnosis
Medical diagnosis
Medical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...

 relies on radiology
Tuberculosis radiology
Radiology is used in the diagnosis of tuberculosis.-Chest X-ray:A posterior-anterior chest X-ray is the standard view used; other views or CT scans may be necessary....

 (commonly chest X-ray
Chest X-ray
In medicine, a chest radiograph, commonly called a chest X-ray , is a projection radiograph of the chest used to diagnose conditions affecting the chest, its contents, and nearby structures...

s), a tuberculin skin test
Mantoux test
The Mantoux test is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test...

, blood tests, as well as microscopic examination and microbiological culture
Microbiological culture
A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture media under controlled laboratory conditions. Microbial cultures are used to determine the type of organism, its abundance in the sample being tested,...

 of bodily fluids. Treatment
Tuberculosis treatment
Tuberculosis treatment refers to the medical treatment of the infectious disease tuberculosis .The standard "short" course treatment for TB is isoniazid, rifampicin , pyrazinamide, and ethambutol for two months, then isoniazid and rifampicin alone for a further four months...

 is difficult and requires long courses of multiple antibiotics. Social contacts are also screened and treated if necessary. Antibiotic resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 is a growing problem in (extensively
Extensively drug-resistant tuberculosis
Extensively drug-resistant tuberculosis is a form of TB caused by bacteria that are resistant to the most effective anti-TB drugs. Some contend that XDR-TB strains have emerged from the mismanagement of multidrug-resistant TB and once created, can spread from one person to another...

) multi-drug-resistant tuberculosis
Multi-drug-resistant tuberculosis
Multi-drug-resistant tuberculosis is defined as TB that is resistant at least to isoniazid and rifampicin , the two most powerful first-line anti-TB drugs...

. Prevention relies on screening programs and vaccination
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...

, usually with Bacillus Calmette-Guérin
Bacillus Calmette-Guérin
Bacillus Calmette-Guérin is a vaccine against tuberculosis that is prepared from a strain of the attenuated live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans by being specially subcultured in an artificial medium for 13 years, and also prepared from...

 vaccine.

One third of the world's population
World population
The world population is the total number of living humans on the planet Earth. As of today, it is estimated to be  billion by the United States Census Bureau...

 is thought to be infected with M. tuberculosis, and new infections occur at a rate of about one per second. The proportion of people who become sick with tuberculosis each year is stable or falling worldwide but, because of population growth, the absolute number of new cases is still increasing. In 2007 there were an estimated 13.7 million chronic active cases, 9.3 million new cases, and 1.8 million deaths, mostly in developing countries. In addition, more people in the developed world
Developed country
A developed country is a country that has a high level of development according to some criteria. Which criteria, and which countries are classified as being developed, is a contentious issue...

 contract tuberculosis because their immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

s are more likely to be compromised due to higher exposure to immunosuppressive drug
Immunosuppressive drug
Immunosuppressive drugs or immunosuppressive agents are drugs that inhibit or prevent activity of the immune system. They are used in immunosuppressive therapy to:...

s, substance abuse
Substance abuse
A substance-related disorder is an umbrella term used to describe several different conditions associated with several different substances .A substance related disorder is a condition in which an individual uses or abuses a...

, or AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...

. The distribution of tuberculosis is not uniform across the globe; about 80% of the population in many Asian and African countries test positive in tuberculin tests, while only 5–10% of the U.S. population test positive.

Signs and symptoms


When tuberculosis becomes active, 75% of cases involve infection in the lungs (pulmonary TB). Symptoms include chest pain
Chest pain
Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...

, coughing up blood
Hemoptysis
Hemoptysis or haemoptysis is the expectoration of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis is the expectoration (coughing up) of blood or of blood-stained sputum from the bronchi, larynx, trachea, or lungs Hemoptysis or haemoptysis ...

, and a productive, prolonged cough for more than three weeks. Systemic symptoms include fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...

, chills
Rigor (medicine)
Rigor is a shaking occurring during a high fever. It occurs because cytokines and prostaglandins are released as part of an immune response and increase the set point for body temperature in the hypothalamus....

, night sweats, appetite loss, weight loss
Weight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...

, pallor
Pallor
Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....

, and fatigue.

In the other 25% of active cases, the infection moves from the lungs, causing other kinds of TB, collectively denoted extrapulmonary tuberculosis. This occurs more commonly in immunosuppressed persons and young children. Extrapulmonary infection sites include the pleura in tuberculous pleurisy, the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 in meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...

, the lymphatic system
Lymphatic system
The lymphoid system is the part of the immune system comprising a network of conduits called lymphatic vessels that carry a clear fluid called lymph unidirectionally toward the heart. Lymphoid tissue is found in many organs, particularly the lymph nodes, and in the lymphoid follicles associated...

 in scrofula
Scrofula
Tuberculous cervical lymphadenitis refers to a lymphadenitis of the cervical lymph nodes associated with tuberculosis. It was previously known as "scrofula".-The disease:...

 of the neck, the genitourinary system
Genitourinary system
In anatomy, the genitourinary system or urogenital system is the organ system of the reproductive organs and the urinary system. These are grouped together because of their proximity to each other, their common embryological origin and the use of common pathways, like the male urethra...

 in urogenital tuberculosis
Urogenital tuberculosis
Urogenital tuberculosis is a form of tuberculosis that affects the urogenital system.-Epidemiology:It usually strikes young adults with tuberculosis in other places of the body as well...

, and the bones and joints in Pott's disease
Pott's disease
Pott's disease is a presentation of extrapulmonary tuberculosis that affects the spine, a kind of tuberculous arthritis of the intervertebral joints...

 of the spine. When spread to the bones it is also known as "osseous tuberculosis", a form of Osteomyelitis
Osteomyelitis
Osteomyelitis simply means an infection of the bone or bone marrow...

 (as a complication of tuberculosis). An especially serious form is disseminated TB, more commonly known as miliary tuberculosis
Miliary tuberculosis
Miliary tuberculosis is a form of tuberculosis that is characterized by a wide dissemination into the human body and by the tiny size of the lesions...

. Extrapulmonary TB may co-exist with pulmonary TB.

The radiological findings of tuberculosis
Tuberculosis radiology
Radiology is used in the diagnosis of tuberculosis.-Chest X-ray:A posterior-anterior chest X-ray is the standard view used; other views or CT scans may be necessary....

 are well described and chest x-ray plays an important role in its diagnosis.

Causes


The main cause of TB, Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

(MTB), is a small aerobic
Aerobic organism
An aerobic organism or aerobe is an organism that can survive and grow in an oxygenated environment.Faculitative anaerobes grow and survive in an oxygenated environment and so do aerotolerant anaerobes.-Glucose:...

 non-motile bacillus
Bacillus
Bacillus is a genus of Gram-positive, rod-shaped bacteria and a member of the division Firmicutes. Bacillus species can be obligate aerobes or facultative anaerobes, and test positive for the enzyme catalase. Ubiquitous in nature, Bacillus includes both free-living and pathogenic species...

. High lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

 content of this pathogen accounts for many of its unique clinical characteristics. It divides
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...

 every 16 to 20 hours, an extremely slow rate compared with other bacteria, which usually divide in less than an hour. Since MTB has a cell wall but lacks a phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...

 outer membrane
Bacterial cell structure
Bacteria, despite their simplicity, contain a well-developed cell structure which is responsible for many of their unique biological properties. Many structural features are unique to bacteria and are not found among archaea or eukaryotes...

, it is classified
Tuberculosis classification
-Tuberculosis classification system:The current clinical classification system for tuberculosis is based on the pathogenesis of the disease.Health care providers should comply with local laws and regulations requiring the reporting of TB. All persons with class 3 or class 5 TB should be reported...

 as a Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...

 bacterium. However, if a Gram stain is performed, MTB either stains very weakly Gram-positive or does not retain dye as a result of the high lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...

 and mycolic acid
Mycolic acid
Mycolic acids are long fatty acids found in the cell walls of the mycolata taxon, a group of bacteria that includes Mycobacterium tuberculosis, the causative agent of the disease tuberculosis. They form the major component of the cell wall of mycolata species...

 content of its cell wall. MTB can withstand weak disinfectants and survive in a dry state
Endospore
An endospore is a dormant, tough, and temporarily non-reproductive structure produced by certain bacteria from the Firmicute phylum. The name "endospore" is suggestive of a spore or seed-like form , but it is not a true spore . It is a stripped-down, dormant form to which the bacterium can reduce...

 for weeks. In nature, the bacterium can grow only within the cells of a host
Host (biology)
In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...

 organism, but M. tuberculosis can be cultured in vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...

.

Using histological
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...

 stains on expectorate samples from phlegm
Phlegm
Phlegm is a liquid secreted by the mucous membranes of mammalians. Its definition is limited to the mucus produced by the respiratory system, excluding that from the nasal passages, and particularly that which is expelled by coughing . Phlegm is in essence a water-based gel consisting of...

 (also called sputum), scientists can identify MTB under a regular microscope. Since MTB retains certain stains after being treated with acidic solution, it is classified as an acid-fast bacillus (AFB). The most common acid-fast staining technique, the Ziehl-Neelsen stain
Ziehl-Neelsen stain
The Ziehl–Neelsen stain, also known as the acid-fast stain, was first described by two German doctors; Franz Ziehl , a bacteriologist and Friedrich Neelsen , a pathologist. It is a special bacteriological stain used to identify acid-fast organisms, mainly Mycobacteria...

, dyes AFBs a bright red that stands out clearly against a blue background. Other ways to visualize AFBs include an auramine-rhodamine stain
Auramine-rhodamine stain
The auramine-rhodamine stain , also known as the Truant auramine-rhodamine stain, is a histological technique used to visualize acid-fast bacilli using fluorescence microscopy, notably species in the Mycobacterium genus. Acid-fast organisms display a reddish-yellow fluorescence. Although the...

 and fluorescent microscopy
Fluorescence microscope
A fluorescence microscope is an optical microscope used to study properties of organic or inorganic substances using the phenomena of fluorescence and phosphorescence instead of, or in addition to, reflection and absorption...

.

The M. tuberculosis complex includes four other TB-causing mycobacteria
Mycobacterium
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy...

: M. bovis
Mycobacterium bovis
Mycobacterium bovis is a slow-growing , aerobic bacterium and the causative agent of tuberculosis in cattle...

, M. africanum
Mycobacterium africanum
Mycobacterium africanum is a species of Mycobacterium that is most commonly found in West African countries. The symptoms of infection resemble those of M. tuberculosis.It is a member of the Mycobacterium tuberculosis complex.-Epidemiology:M...

, M. canetti
Mycobacterium canetti
Mycobacterium canettii, a novel pathogenic taxon of the Mycobacterium tuberculosis complex , was first reported in 1969 by the French microbiologist Georges Canetti from which the organism has been named. It formed smooth and shiny colonies, which is highly exceptional for the MTBC. It was...

, and M. microti
Mycobacterium microti
Mycobacterium microti*Member of the Mycobacterium tuberculosis complex *Also known as the 'Vole bacillus'*Etymology: microtus is a genus that includes the vole.-Description:Gram-positive, nonmotile and acid-fast rods....

. M. africanum
Mycobacterium africanum
Mycobacterium africanum is a species of Mycobacterium that is most commonly found in West African countries. The symptoms of infection resemble those of M. tuberculosis.It is a member of the Mycobacterium tuberculosis complex.-Epidemiology:M...

is not widespread, but in parts of Africa it is a significant cause of tuberculosis. M. bovis
Mycobacterium bovis
Mycobacterium bovis is a slow-growing , aerobic bacterium and the causative agent of tuberculosis in cattle...

was once a common cause of tuberculosis, but the introduction of pasteurized milk has largely eliminated this as a public health problem in developed countries. M. canetti is rare and seems to be limited to Africa, although a few cases have been seen in African emigrants. M. microti is mostly seen in immunodeficient people, although it is possible that the prevalence
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...

 of this pathogen has been underestimated.

Other known pathogenic mycobacteria
Mycobacterium
Mycobacterium is a genus of Actinobacteria, given its own family, the Mycobacteriaceae. The genus includes pathogens known to cause serious diseases in mammals, including tuberculosis and leprosy...

 include Mycobacterium leprae
Mycobacterium leprae
Mycobacterium leprae, also known as Hansen’s coccus spirilly, mostly found in warm tropical countries, is a bacterium that causes leprosy . It is an intracellular, pleomorphic, acid-fast bacterium. M. leprae is an aerobic bacillus surrounded by the characteristic waxy coating unique to mycobacteria...

, Mycobacterium avium
Mycobacterium avium complex
Mycobacterium avium complex is a group of genetically related bacteria belonging to the genus Mycobacterium. It includes Mycobacterium avium and Mycobacterium intracellulare....

, and M. kansasii. The latter two are part of the nontuberculous mycobacteria
Nontuberculous mycobacteria
Nontuberculous mycobacteria , also known as environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis , are mycobacteria which do not cause tuberculosis or Hansen's disease ....

 (NTM) group. Nontuberculous mycobacteria cause neither TB nor leprosy
Leprosy
Leprosy or Hansen's disease is a chronic disease caused by the bacteria Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract; skin lesions...

, but they do cause pulmonary diseases resembling TB.

Risk factors


People with silicosis
Silicosis
Silicosis, also known as Potter's rot, is a form of occupational lung disease caused by inhalation of crystalline silica dust, and is marked by inflammation and scarring in forms of nodular lesions in the upper lobes of the lungs...

 have an approximately 30-fold greater risk for developing TB. Silica particles irritate the respiratory system, causing immunogenic responses such as phagocytosis, which results in high lymphatic vessel deposits. It is probably this interference and blockage of macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

 function that increases the risk of tuberculosis. Persons with chronic renal failure and also on hemodialysis have an increased risk.
Persons with diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...

 have a risk for developing active TB that is two to four times greater than persons without diabetes mellitus, and this risk is likely to be greater in persons with insulin-dependent or poorly controlled diabetes. Other clinical conditions that have been associated with active TB include gastrectomy
Gastrectomy
A gastrectomy is a partial or full surgical removal of the stomach.-Indications:Gastrectomies are performed to treat cancer and perforations of the stomach wall....

 with attendant weight loss and malabsorption, jejunoileal bypass, renal and cardiac transplantation, carcinoma of the head or neck, and other neoplasms (e.g., lung cancer, lymphoma, and leukemia).

Given that silicosis greatly increases the risk of tuberculosis, more research about the effect of various indoor or outdoor air pollutants on the disease would be necessary. Some possible indoor sources of silica include paint, concrete
Concrete
Concrete is a composite construction material, composed of cement and other cementitious materials such as fly ash and slag cement, aggregate , water and chemical admixtures.The word concrete comes from the Latin word...

, and Portland cement
Portland cement
Portland cement is the most common type of cement in general use around the world because it is a basic ingredient of concrete, mortar, stucco and most non-specialty grout...

. Crystalline silica is found in concrete, masonry, sandstone, rock, paint, and other abrasives. The cutting, breaking, crushing, drilling, grinding, or abrasive blasting of these materials may produce fine silica dust. It can also be in soil, mortar, plaster, and shingles.

HIV is a major risk factor for tuberculosis. The risk of developing TB is estimated to be between 20-37 times greater in people living with HIV than among those without HIV infection. TB is a leading cause of morbidity and mortality among people living with HIV. In 2009, there were 9.4 million new cases of TB, of which 1.2 (13%) million were among people living with HIV. Of the 1.7 million people who died of TB, 400,000 (24%) were living with HIV.

Low body weight is associated with risk of tuberculosis. A body mass index
Body mass index
The body mass index , or Quetelet index, is a heuristic proxy for human body fat based on an individual's weight and height. BMI does not actually measure the percentage of body fat. It was invented between 1830 and 1850 by the Belgian polymath Adolphe Quetelet during the course of developing...

 (BMI) below 18.5 increases the risk by 2 to 3 times. An increase in body weight lowers the risk. People with diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...

 are at increased risk of contracting tuberculosis, and they have a poorer response to treatment, possibly due to poorer drug absorption.

Diabetes increases the risk of TB three-fold. The correlation between diabetes mellitus and TB is concerning for public health because it shows a distinct connection between a contagious disease and a chronic disease. TB is a highly contagious air-borne bacteria. Therefore, contracting tuberculosis depends on whether or not a person comes into contact with the bacteria. Diabetics do not have an increased risk of contracting latent tuberculosis but studies have shown that people with diabetes mellitus are more likely to move from a latent form of TB to an active form of TB. This is where the public concern comes from, because when TB is active it is contagious and potentially fatal.

Other conditions that increase risk include the sharing of needles among IV drug users, recent TB infection or a history of inadequately treated TB, chest X-ray suggestive of previous TB, showing fibrotic lesions and nodules, prolonged corticosteroid
Corticosteroid
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte...

 therapy and other immunosuppressive therapy, compromised immune system (30–40% of people with AIDS worldwide also have TB), hematologic
Hematology
Hematology, also spelled haematology , is the branch of biology physiology, internal medicine, pathology, clinical laboratory work, and pediatrics that is concerned with the study of blood, the blood-forming organs, and blood diseases...

 and reticuloendothelial
Reticuloendothelial system
"Reticuloendothelial system" is an older term for the mononuclear phagocyte system. The mononuclear phagocyte system consists primarily of monocytes and macrophages. The spleen is the largest unit of the mononuclear phagocyte system. The monocyte is formed in the bone marrow and transported by the...

 diseases, such as leukemia
Leukemia
Leukemia or leukaemia is a type of cancer of the blood or bone marrow characterized by an abnormal increase of immature white blood cells called "blasts". Leukemia is a broad term covering a spectrum of diseases...

 and Hodgkin's disease
Hodgkin's lymphoma
Hodgkin's lymphoma, previously known as Hodgkin's disease, is a type of lymphoma, which is a cancer originating from white blood cells called lymphocytes...

, end-stage kidney disease, intestinal bypass, chronic malabsorption
Malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal tract.Impairment can be of single or multiple nutrients depending on the abnormality...

 syndromes, vitamin D deficiency, and low body weight.

Twin studies
Twin study
Twin studies help disentangle the relative importance of environmental and genetic influences on individual traits and behaviors. Twin research is considered a key tool in behavioral genetics and related fields...

 in the 1940s showed that susceptibility to TB was heritable. If one of a pair of twins got TB, then the other was more likely to get TB if he was identical than if he was not. These findings were more recently confirmed by a series of studies in South Africa
South Africa
The Republic of South Africa is a country in southern Africa. Located at the southern tip of Africa, it is divided into nine provinces, with of coastline on the Atlantic and Indian oceans...

. Specific gene polymorphisms in IL12B have been linked to tuberculosis susceptibility.

Some drugs, including rheumatoid arthritis
Rheumatoid arthritis
Rheumatoid arthritis is a chronic, systemic inflammatory disorder that may affect many tissues and organs, but principally attacks synovial joints. The process produces an inflammatory response of the synovium secondary to hyperplasia of synovial cells, excess synovial fluid, and the development...

 drugs that work by blocking tumor necrosis factor-alpha (an inflammation-causing cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...

), raise the risk of activating a latent infection due to the importance of this cytokine in the immune defense against TB.

Transmission


When people suffering from active pulmonary TB cough, sneeze, speak, sing, or spit, they expel infectious aerosol droplets 0.5 to 5 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 low and inhaling fewer than ten bacteria may cause an infection.

People with prolonged, frequent, or intense contact are at particularly high risk of becoming infected, with an estimated 22% infection rate. A person with active but untreated tuberculosis can infect 10–15 other people per year. Others at risk include people in areas where TB is common, people who inject illicit drugs, residents and employees of high-risk congregate settings, medically under-served and low-income populations, high-risk racial or ethnic minority populations, children exposed to adults in high-risk categories, those who are immunocompromised by conditions such as HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

/AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...

, people who take immunosuppressant drugs, and health care workers serving these high-risk clients.

Transmission can only occur from people with active—not latent—TB. The probability of transmission from one person to another depends upon the number of infectious droplets expelled by a carrier, the effectiveness of ventilation, the duration of exposure, and the virulence
Virulence
Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

 of the M. tuberculosis strain
Strain (biology)
In biology, a strain is a low-level taxonomic rank used in three related ways.-Microbiology and virology:A strain is a genetic variant or subtype of a micro-organism . For example, a "flu strain" is a certain biological form of the influenza or "flu" virus...

. The chain of transmission can be broken by isolating people with active disease and starting effective anti-tuberculous therapy. After two weeks of such treatment, people with non-resistant
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 active TB generally cease to be contagious. If someone does become infected, then it will take three to four weeks before the newly infected person can transmit the disease to others.

Pathogenesis


About 90% of those infected with Mycobacterium tuberculosis have asymptomatic
Asymptomatic
In medicine, a disease is considered asymptomatic if a patient is a carrier for a disease or infection but experiences no symptoms. A condition might be asymptomatic if it fails to show the noticeable symptoms with which it is usually associated. Asymptomatic infections are also called subclinical...

, latent TB infection (sometimes called LTBI), with only a 10% lifetime chance that a latent infection will progress to TB disease. However, if untreated, the death rate for these active TB cases is more than 50%.

TB infection begins when the mycobacteria reach the pulmonary alveoli
Pulmonary alveolus
An alveolus is an anatomical structure that has the form of a hollow cavity. Found in the lung parenchyma, the pulmonary alveoli are the dead ends of the respiratory tree, which outcrop from either alveolar sacs or alveolar ducts, which are both sites of gas exchange with the blood as well...

, where they invade and replicate within the endosomes of alveolar macrophages. The primary site of infection in the lungs is called the Ghon focus
Ghon focus
A Ghon focus is a primary lesion caused by mycobacterium bacilli developed in the lung of a previously uninfected individual. It is named for Anton Ghon , an Austrian pathologist....

, and is generally located in either the upper part of the lower lobe, or the lower part of the upper lobe
Lung
The lung is the essential respiration organ in many air-breathing animals, including most tetrapods, a few fish and a few snails. In mammals and the more complex life forms, the two lungs are located near the backbone on either side of the heart...

. Simon foci
Simon focus
A Simon focus is a tuberculosis nodule that can form in the apex of the lung when a primary TB infection elsewhere in the body spreads to the lung apex via the bloodstream. Simon focus nodules are often calcified....

 may also be present. Bacteria are picked up by dendritic cell
Dendritic cell
Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...

s, which do not allow replication, although these cells can transport the bacilli to local (mediastinal) lymph node
Lymph node
A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

s. Further spread is through the bloodstream to other tissues and organs where secondary TB lesions can develop in other parts of the lung (particularly the apex of the upper lobes), peripheral lymph nodes, kidneys, brain, and bone. All parts of the body can be affected by the disease, though it rarely affects the heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...

, skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...

s, pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...

 and thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...

.

Tuberculosis is classified as one of the granuloma
Granuloma
Granuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...

tous inflammatory conditions. Macrophage
Macrophage
Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

s, T lymphocytes
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

, B lymphocytes
B cell
B cells are lymphocytes that play a large role in the humoral immune response . The principal functions of B cells are to make antibodies against antigens, perform the role of antigen-presenting cells and eventually develop into memory B cells after activation by antigen interaction...

, and fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...

s are among the cells that aggregate to form granuloma
Granuloma
Granuloma is a medical term for a tiny collection of immune cells known as macrophages. Granulomas form when the immune system attempts to wall off substances that it perceives as foreign but is unable to eliminate. Such substances include infectious organisms such as bacteria and fungi as well as...

s, with lymphocytes surrounding the infected macrophages. The granuloma prevents dissemination of the mycobacteria and provides a local environment for interaction of cells of the immune system. Bacteria inside the granuloma can become dormant, resulting in a latent infection. Another feature of the granulomas of human tuberculosis is the development of abnormal cell death (necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

) in the center of tubercles. To the naked eye this has the texture of soft white cheese and is termed caseous necrosis
Necrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...

.

If TB bacteria gain entry to the bloodstream from an area of damaged tissue they spread through the body and set up many foci of infection, all appearing as tiny white tubercles in the tissues. This severe form of TB disease is most common in infants and the elderly and is called miliary tuberculosis
Miliary tuberculosis
Miliary tuberculosis is a form of tuberculosis that is characterized by a wide dissemination into the human body and by the tiny size of the lesions...

. People with this disseminated TB have a fatality rate near 100% if untreated. However, if treated early, the fatality rate is reduced to about 10%.

In many people the infection waxes and wanes. Tissue destruction and necrosis are balanced by healing and fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...

. Affected tissue is replaced by scarring and cavities filled with cheese-like white 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 can therefore spread the infection. Treatment with appropriate antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...

s kills bacteria and allows healing to take place. Upon cure, affected areas are eventually replaced by scar tissue.

If untreated, infection with Mycobacterium tuberculosis can cause lobar pneumonia
Lobar pneumonia
Lobar pneumonia is a form of pneumonia that affects a large and continuous area of the lobe of a lung.It is one of the two anatomic classifications of pneumonia .- Symptoms :...

.

Diagnosis


Tuberculosis is diagnosed definitively by identifying the causative organism (Mycobacterium tuberculosis
Mycobacterium tuberculosis
Mycobacterium tuberculosis is a pathogenic bacterial species in the genus Mycobacterium and the causative agent of most cases of tuberculosis . First discovered in 1882 by Robert Koch, M...

) in a clinical sample (for example, sputum
Sputum
Sputum is mucus that is coughed up from the lower airways. It is usually used for microbiological investigations of respiratory infections....

 or pus
Pus
Pus is a viscous exudate, typically whitish-yellow, yellow, or yellow-brown, formed at the site of inflammatory during infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collection of pus within or beneath the epidermis is known as a pustule or...

). When this is not possible, a probable—although sometimes inconclusive—diagnosis may be made using imaging (X-rays or scans), a tuberculin skin test (Mantoux test)
Mantoux test
The Mantoux test is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test...

, or a, Interferon Gamma Release Assay (IGRA).

The main problem with tuberculosis diagnosis is the difficulty in culturing this slow-growing organism in the laboratory (it may take 4 to 12 weeks for blood or sputum culture). A complete medical evaluation for TB must include a medical history, a physical examination, a chest X-ray
Tuberculosis radiology
Radiology is used in the diagnosis of tuberculosis.-Chest X-ray:A posterior-anterior chest X-ray is the standard view used; other views or CT scans may be necessary....

, microbiological smears, and cultures. It may also include a tuberculin skin test
Mantoux test
The Mantoux test is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test...

, a serological
Serology
Serology is the scientific study of blood serum and other bodily fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum...

 test. The interpretation of the tuberculin skin test depends upon the person's risk factors for infection and progression to TB disease, such as exposure to other cases of TB or immunosuppression.

Currently, latent infection is diagnosed in a non-immunized person by a tuberculin skin test, which yields a delayed hypersensitivity type response to an extract
Mantoux test
The Mantoux test is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test...

 made from M. tuberculosis. Those immunized for TB or with past-cleared infection will respond with delayed hypersensitivity parallel to those currently in a state of infection, so the test must be used with caution, particularly with regard to persons from countries where TB immunization is common. Tuberculin tests have the disadvantage of producing false negatives, especially when the person is co-morbid with sarcoidosis
Sarcoidosis
Sarcoidosis , also called sarcoid, Besnier-Boeck disease or Besnier-Boeck-Schaumann disease, is a disease in which abnormal collections of chronic inflammatory cells form as nodules in multiple organs. The cause of sarcoidosis is unknown...

, Hodgkins lymphoma, malnutrition, or most notably active tuberculosis disease. The newer interferon release assays (IGRAs) such as T-SPOT.TB
T-SPOT.TB
T-SPOT.TB is a type of ELISPOT assay used for tuberculosis diagnosis. It is available in most European countries, the United States as well as various other territories. It was developed by researchers at the University of Oxford in England. It counts the number of effector T cells, white blood...

 and QuantiFERON
QuantiFERON
QuantiFERON, also known as QFT, is the registered trademark of the test for tuberculosis infection or latent tuberculosis. QFT is an interferon-γ release assay used in tuberculosis diagnosis.- QuantiFERON-TB :...

-TB Gold In Tube overcome many of these problems. IGRAs are in vitro blood tests that are more specific than the skin test. IGRAs detect the release of interferon gamma in response to mycobacterial proteins such as ESAT-6
ESAT-6
ESAT-6, the 6 kDa early secretory antigenic target of Mycobacterium tuberculosis, is a secretory protein and potent T cell antigen. It is used in tuberculosis diagnosis by the whole blood interferon γ test QuantiFERON-TB Gold, in conjunction with CFP-10 and TB7.7.ESAT-6 has been shown to directly...

. These are not affected by immunization or environmental mycobacteria, so generate fewer false positive results. There is also evidence that IGRAs are more sensitive than the skin test.

New TB tests have been developed that are fast and accurate. These include polymerase chain reaction
Polymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....

 assays for the detection of bacterial DNA. One such molecular diagnostics test gives results in 100 minutes and is currently being offered to 116 low- and middle-income countries at a discount with support from WHO and the Bill and Melinda Gates foundation.

Another such test, which was approved by the FDA in 1996, is the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe). This test yields results in 2.5 to 3.5 hours, and it is highly sensitive and specific when used to test smears positive for acid-fast bacilli (AFB).

Screening


Mantoux tuberculin skin tests
Mantoux test
The Mantoux test is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test...

 are often used for routine screening of high risk individuals.

Prevention



TB prevention and control takes two parallel approaches. In the first, people with TB and their contacts are identified and then treated. Identification of infections often involves testing high-risk groups for TB. In the second approach, children are vaccinated
Vaccination
Vaccination is the administration of antigenic material to stimulate the immune system of an individual to develop adaptive immunity to a disease. Vaccines can prevent or ameliorate the effects of infection by many pathogens...

 to protect them from TB. No vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

 is available that provides reliable protection for adults. However, in tropical areas where the levels of other species of mycobacteria are high, exposure to nontuberculous mycobacteria
Nontuberculous mycobacteria
Nontuberculous mycobacteria , also known as environmental mycobacteria, atypical mycobacteria and mycobacteria other than tuberculosis , are mycobacteria which do not cause tuberculosis or Hansen's disease ....

 gives some protection against TB.

The World Health Organization
World Health Organization
The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

 (WHO) declared TB a global health emergency in 1993, and the Stop TB Partnership developed a Global Plan to Stop Tuberculosis
Global Plan to Stop Tuberculosis
The promotes , which calls for a total of $56 billion between 2006 and 2015 to treat 50 million tuberculosis patients and save 14 million lives during that period. Full funding of the Plan will help achieve the Millennium Development Goal to have "halted by 2015 and begun to reverse the incidence...

 that aims to save 14 million lives between 2006 and 2015. Since humans are the only host of Mycobacterium tuberculosis, eradication would be possible. This goal would be helped greatly by an effective vaccine.

Vaccines


Many countries use the Bacillus Calmette-Guérin
Bacillus Calmette-Guérin
Bacillus Calmette-Guérin is a vaccine against tuberculosis that is prepared from a strain of the attenuated live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans by being specially subcultured in an artificial medium for 13 years, and also prepared from...

 (BCG) vaccine as part of their TB control programmes, especially for infants. The BCG vaccine is one of the most widely used of all current vaccines, reaching >80% of neonates and infants in countries with a national vaccination schedule. In the US, where TB is uncommon, BCG is not widely administered. BCG was the first vaccine for TB. From 1905, Albert Calmette
Albert Calmette
Léon Charles Albert Calmette ForMemRS was a French physician, bacteriologist and immunologist, and an important officer of the Pasteur Institute. He discovered the Bacillus Calmette-Guérin, an attenuated form of Mycobacterium used in the BCG vaccine against tuberculosis...

 and Camille Guérin
Camille Guérin
Jean-Marie Camille Guérin was a French veterinarian, bacteriologist and immunologist who, together with Albert Calmette, developed the Bacillus Calmette-Guérin , a vaccine for immunization against tuberculosis....

 worked at the Institut Pasteur de Lille
Institut Pasteur de Lille
The Institut Pasteur de Lille is a research centre, membre of the Pasteur Institute network.It includes 14 research units, 1150 employees including 626 researchers located in Lille . 300 employees located outside the Pasteur site come in addition...

 and the Pasteur Institute
Pasteur Institute
The Pasteur Institute is a French non-profit private foundation dedicated to the study of biology, micro-organisms, diseases, and vaccines. It is named after Louis Pasteur, who made some of the greatest breakthroughs in modern medicine at the time, including pasteurization and vaccines for anthrax...

 in France developing BCG, administering the first human trials in 1921. However, deaths due to flawed manufacturing processes created public resistance to BCG, delaying mass vaccinations until after World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...

. The protective efficacy of BCG for preventing serious forms of TB (e.g. meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...

) in children is greater than 80%. Its protective efficacy for preventing pulmonary TB in adolescents and adults varies by country (as low as 0% in South India); in the United Kingdom, its effectiveness exceeds 75%.

In South Africa, the country with the highest prevalence of TB, BCG is given to all children under age three. However, BCG is less effective in areas where mycobacteria are less prevalent
Prevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...

; therefore BCG is not given to the entire population in such countries. In the USA, for example, BCG vaccine is not recommended except for people who meet specific criteria:
  • Infants or children with negative skin test results who are continually exposed to untreated or ineffectively treated people or will be continually exposed to multi-drug-resistant tuberculosis
    Multi-drug-resistant tuberculosis
    Multi-drug-resistant tuberculosis is defined as TB that is resistant at least to isoniazid and rifampicin , the two most powerful first-line anti-TB drugs...

     (MDR-TB).
  • Healthcare workers considered on an individual basis in settings in which a high percentage of MDR-TB has been found, transmission of MDR-TB is likely, and TB control precautions have been implemented and were not successful.


BCG provides some protection against severe forms of pediatric TB, but has been shown to be unreliable against adult pulmonary TB, which accounts for most of the disease burden worldwide. Currently, there are more cases of TB on the planet than at any other time in history and most agree there is an urgent need for a newer, more effective vaccine that would prevent all forms of TB—including drug resistant strains—in all age groups and among people with HIV.

Several new vaccines to prevent TB infection are being developed, among others by Aeras and TBVI
TBVI
TuBerculosis Vaccine Initiative is a European-based foundation that facilitates the development of new tuberculosis vaccines. The goal is to protect future generations against tuberculosis....

. The first recombinant
Genetic recombination
Genetic recombination is a process by which a molecule of nucleic acid is broken and then joined to a different one. Recombination can occur between similar molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-homologous end joining. Recombination is a common method...

 tuberculosis vaccine
Vaccine
A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe or its toxins...

, Mtb72F, entered clinical trial
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

s in the United States in 2004, sponsored by the National Institute of Allergy and Infectious Diseases
National Institute of Allergy and Infectious Diseases
The National Institute of Allergy and Infectious Diseases is one of the 27 institutes and centers that make up the National Institutes of Health , an agency of the United States Department of Health and Human Services...

 (NIAID). A 2005 study showed that a DNA TB vaccine given with conventional chemotherapy
Chemotherapy
Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

 can accelerate the disappearance of bacteria as well as protect against re-infection in mice; it may take four to five years to be available in humans. Another TB vaccine, MVA85A
MVA85A
MVA85A is a new-generation vaccine against tuberculosis developed by researchers at Oxford University. This vaccine produces higher levels of long-lasting cellular immunity when used together with the old TB vaccine called BCG. Phase I clinical trials have been completed and phase II clinical...

, is currently in phase II trials
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

 in South Africa, and is based on a genetically modified vaccinia
Vaccinia
Vaccinia virus is a large, complex, enveloped virus belonging to the poxvirus family. It has a linear, double-stranded DNA genome approximately 190 kbp in length, and which encodes for approximately 250 genes. The dimensions of the virion are roughly 360 × 270 × 250 nm, with a mass of...

 virus. Many other strategies are also being used to develop novel vaccines, including both subunit vaccines (fusion molecules composed of two recombinant
Genetic recombination
Genetic recombination is a process by which a molecule of nucleic acid is broken and then joined to a different one. Recombination can occur between similar molecules of DNA, as in homologous recombination, or dissimilar molecules, as in non-homologous end joining. Recombination is a common method...

 proteins delivered in an adjuvant
Immunologic adjuvant
In immunology, an adjuvant is an agent that may stimulate the immune system and increase the response to a vaccine, without having any specific antigenic effect in itself. The word “adjuvant” comes from the Latin word adiuvare, meaning to help or aid...

) such as Hybrid-1, HyVac4, or M72, and recombinant adenoviruses such as Ad35. Some of these vaccines can be effectively administered without needles, making them preferable for areas where HIV is common. All of these vaccines have been successfully tested in humans and are now in extended testing in TB-endemic regions. To encourage further discovery, researchers and policymakers are promoting new economic models of vaccine development including prizes, tax incentives, and advance market commitments
Advance market commitments
An advance market commitment is a binding contract, typically offered by a government or other financial entity, used to guarantee a viable market if a vaccine or other medicine is successfully developed. As a result of such a commitment, the market for vaccines or drugs for neglected diseases...

.

An experimental vaccine, with positive results in mouse models, may be effective in not only preventing infection, but also in eradicating the infection once established. A tuberculosis vaccine aimed at sterile Mtb eradication should be able to target latent Mtb as well as Mtb that causes early-stage tuberculosis.
The vaccine is a combination of antigens Ag85B and ESAT-6
ESAT-6
ESAT-6, the 6 kDa early secretory antigenic target of Mycobacterium tuberculosis, is a secretory protein and potent T cell antigen. It is used in tuberculosis diagnosis by the whole blood interferon γ test QuantiFERON-TB Gold, in conjunction with CFP-10 and TB7.7.ESAT-6 has been shown to directly...

 as well as the protein Rv2660c. Ag85B and ESAT-6 together form the vaccine Hybrid-1, while Rv2660c is a protein that is expressed even in late-stage infections, when protein transcription
Transcription (genetics)
Transcription is the process of creating a complementary RNA copy of a sequence of DNA. Both RNA and DNA are nucleic acids, which use base pairs of nucleotides as a complementary language that can be converted back and forth from DNA to RNA by the action of the correct enzymes...

 is generally reduced. The novel combination of Ag85B, ESAT-6, and Rv2660c allows for both short- and long-term protection as a result of the continued expression of target proteins. The new vaccine, currently referred to as H56, works by promoting a polyfunctional CD4+ T cell response
T cell
T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

 against tuberculosis protein components. Phase I clinical trials
Clinical trial
Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

 are scheduled to begin in Cape Town
Cape Town
Cape Town is the second-most populous city in South Africa, and the provincial capital and primate city of the Western Cape. As the seat of the National Parliament, it is also the legislative capital of the country. It forms part of the City of Cape Town metropolitan municipality...

, South Africa, in March 2011.

Treatment



Treatment for 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 makes many antibiotics ineffective and hinders the entry of drugs. The two antibiotics most commonly used are isoniazid
Isoniazid
Isoniazid , also known as isonicotinylhydrazine , is an organic compound that is the first-line antituberculosis medication in prevention and treatment. It was first discovered in 1912, and later in 1951 it was found to be effective against tuberculosis by inhibiting its mycolic acid...

 and rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...

. However, instead of the short course of antibiotics typically used to cure other bacterial infections, TB requires much longer periods of treatment (around 6 to 24 months) to entirely eliminate mycobacteria from the body. Latent TB treatment usually uses a single antibiotic, while active TB disease is best treated with combinations of several antibiotics, to reduce the risk of the bacteria developing antibiotic resistance
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

. People with latent infections are treated to prevent them from progressing to active TB disease later in life.

Drug-resistant tuberculosis is transmitted in the same way as regular TB. Primary resistance occurs in persons infected with a resistant strain of TB. A person with fully susceptible TB develops secondary resistance (acquired resistance) during TB therapy because of inadequate treatment, not taking the prescribed regimen appropriately, or using low-quality medication. Drug-resistant TB is a public health issue in many developing countries, as treatment is longer and requires more expensive drugs. Multi-drug-resistant tuberculosis
Multi-drug-resistant tuberculosis
Multi-drug-resistant tuberculosis is defined as TB that is resistant at least to isoniazid and rifampicin , the two most powerful first-line anti-TB drugs...

 (MDR-TB) is defined as resistance to the two most effective first-line TB drugs: rifampicin
Rifampicin
Rifampicin or rifampin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica ...

 and isoniazid
Isoniazid
Isoniazid , also known as isonicotinylhydrazine , is an organic compound that is the first-line antituberculosis medication in prevention and treatment. It was first discovered in 1912, and later in 1951 it was found to be effective against tuberculosis by inhibiting its mycolic acid...

. Extensively drug-resistant TB
Extensively drug-resistant tuberculosis
Extensively drug-resistant tuberculosis is a form of TB caused by bacteria that are resistant to the most effective anti-TB drugs. Some contend that XDR-TB strains have emerged from the mismanagement of multidrug-resistant TB and once created, can spread from one person to another...

 (XDR-TB) is also resistant to three or more of the six classes of second-line drugs.

The DOTS
Dots
Dots is the plural of dot.Dots may also refer to:*Dots , produced by Tootsie Roll Industries*Dots and Boxes, a pencil and paper game for two or more players*Dots - another pencil and paper game...

 (Directly Observed Treatment Short-course) strategy of tuberculosis treatment recommended by WHO was based on clinical trials done in the 1970s by the Tuberculosis Research Centre in Chennai, India. The country in which a person with TB lives can determine what treatment they receive. This is because multi-drug-resistant tuberculosis is resistant to most first-line medications, so the use of second-line antituberculosis medications is necessary to cure the person. However, the price of these medications is high; thus, poor people in the developing world have no or limited access to these treatments.

In the early 1900s to 1950s doctors would try to collapse the infected lung by breaking several ribs or inflating that half of the chest with air.

Prognosis


Progression from TB infection to TB disease occurs when the TB bacilli overcome the immune system defenses and begin to multiply. In primary TB disease—1–5% of cases—this occurs soon after infection. However, in the majority of cases, a latent infection
Latent tuberculosis
Also called latent tuberculosis infection, latent TB or LTBI.Latent tuberculosis is where a patient is infected with Mycobacterium tuberculosis, but does not have active tuberculosis disease. Patients with latent tuberculosis are not infectious, and it is not possible to get TB from someone with...

 occurs that has no obvious symptoms. These dormant bacilli can produce tuberculosis in 2–23% of these latent cases, often many years after infection.

The risk of reactivation increases with immunosuppression, such as that caused by infection with HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

. In people co-infected with M. tuberculosis and HIV, the risk of reactivation increases to 10% per year. Studies utilizing DNA fingerprinting of M. tuberculosis strains have shown that reinfection contributes more substantially to recurrent TB than previously thought, with between 12% and 77% of cases attributable to reinfection (instead of reactivation).

Epidemiology


Roughly a third of the world's population has been infected with M. tuberculosis, and new infections occur at a rate of one per second. However, not all infections with M. tuberculosis cause TB disease and many infections are asymptomatic. In 2007, an estimated 13.7 million people had active TB disease, with 9.3 million new cases and 1.8 million deaths; the annual incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...

 rate varied from 363 per 100,000 in Africa to 32 per 100,000 in the Americas
Americas
The Americas, or America , are lands in the Western hemisphere, also known as the New World. In English, the plural form the Americas is often used to refer to the landmasses of North America and South America with their associated islands and regions, while the singular form America is primarily...

. Tuberculosis is the world's greatest infectious killer of women of reproductive age and the leading cause of death among people with HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

/AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...

.

The rise in HIV infections and the neglect of TB control programs have enabled a resurgence of tuberculosis. The emergence of drug-resistant
Antibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

 strains has also contributed to this new epidemic with, from 2000 to 2004, 20% of TB cases being resistant to standard treatments and 2% resistant to second-line drugs. The rate at which new TB cases occur varies widely, even in neighbouring countries, apparently because of differences in health care systems.

In 2007, the country with the highest estimated incidence rate
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...

 of TB was Swaziland
Swaziland
Swaziland, officially the Kingdom of Swaziland , and sometimes called Ngwane or Swatini, is a landlocked country in Southern Africa, bordered to the north, south and west by South Africa, and to the east by Mozambique...

, with 1200 cases per 100,000 people. India had the largest total incidence, with an estimated 2.0 million new cases. In developed countries, tuberculosis is less common and is mainly an urban disease. In the United Kingdom, the national average was 15 per 100,000 in 2007, and the highest incidence rates in Western Europe
Western Europe
Western Europe is a loose term for the collection of countries in the western most region of the European continents, though this definition is context-dependent and carries cultural and political connotations. One definition describes Western Europe as a geographic entity—the region lying in the...

 were 30 per 100,000 in Portugal and Spain. These rates compared with 98 per 100,000 in China
Tuberculosis in China
Tuberculosis is a major public health problem in China. China has the world's second largest tuberculosis epidemic , but progress in tuberculosis control was slow during the 1990s. Detection of tuberculosis had stagnated at around 30% of the estimated total of new cases, and multidrug-resistant...

 and 48 per 100,000 in Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...

. In the United States, the overall tuberculosis case rate was 4 per 100,000 persons in 2007. In Canada, tuberculosis is still endemic in some rural areas.

The incidence of TB varies with age. In Africa, TB primarily affects adolescents and young adults. However, in countries where TB has gone from high to low incidence, such as the United States, TB is mainly a disease of older people, or of the immunocompromised.

There are a number of known factors that make people more susceptible to TB infection; worldwide the most important of these is HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...

. Co-infection with HIV is a particular problem in Sub-Saharan Africa
Sub-Saharan Africa
Sub-Saharan Africa as a geographical term refers to the area of the African continent which lies south of the Sahara. A political definition of Sub-Saharan Africa, instead, covers all African countries which are fully or partially located south of the Sahara...

, due to the high incidence of HIV in these countries. Smoking more than 20 cigarette
Cigarette
A cigarette is a small roll of finely cut tobacco leaves wrapped in a cylinder of thin paper for smoking. The cigarette is ignited at one end and allowed to smoulder; its smoke is inhaled from the other end, which is held in or to the mouth and in some cases a cigarette holder may be used as well...

s a day increases the risk of TB by two to four times. Diabetes mellitus is also an important risk factor that is growing in importance in developing countries. Other disease states that increase the risk of developing tuberculosis are Hodgkin lymphoma, end-stage renal disease, chronic lung disease, malnutrition
Malnutrition
Malnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....

, and alcoholism
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...

.

Diet may also modulate risk. For example, among immigrants in London from the Indian subcontinent, vegetarian Hindu
Hindu
Hindu refers to an identity associated with the philosophical, religious and cultural systems that are indigenous to the Indian subcontinent. As used in the Constitution of India, the word "Hindu" is also attributed to all persons professing any Indian religion...

 Asians
Asian people
Asian people or Asiatic people is a term with multiple meanings that refers to people who descend from a portion of Asia's population.- Central Asia :...

 were found to have an 8.5 fold increased risk of tuberculosis, compared to Muslim
Muslim
A Muslim, also spelled Moslem, is an adherent of Islam, a monotheistic, Abrahamic religion based on the Quran, which Muslims consider the verbatim word of God as revealed to prophet Muhammad. "Muslim" is the Arabic term for "submitter" .Muslims believe that God is one and incomparable...

s who ate meat and fish daily. Although a causal link is not proved by this data, this increased risk could be caused by micronutrient
Micronutrient
Micronutrients are nutrients required by humans and other living things throughout life in small quantities to orchestrate a whole range of physiological functions, but which the organism itself cannot produce. For people, they include dietary trace minerals in amounts generally less than 100...

 deficiencies: possibly iron, vitamin B12 or vitamin D. Further studies have provided more evidence of a link between vitamin D deficiency and an increased risk of contracting tuberculosis. Globally, the severe malnutrition
Malnutrition
Malnutrition is the condition that results from taking an unbalanced diet in which certain nutrients are lacking, in excess , or in the wrong proportions....

 common in parts of the developing world causes a large increase in the risk of developing active tuberculosis, due to its damaging effects on the immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

. Along with overcrowding, poor nutrition may contribute to the strong link observed between tuberculosis and poverty
Poverty
Poverty is the lack of a certain amount of material possessions or money. Absolute poverty or destitution is inability to afford basic human needs, which commonly includes clean and fresh water, nutrition, health care, education, clothing and shelter. About 1.7 billion people are estimated to live...

.

Prisoners are particularly vulnerable to infectious diseases such as HIV/AIDS and TB. Imprisonment facilities provide conditions that allow TB to spread rapidly due to overcrowding, poor nutrition, and a lack of health services. TB outbreaks have been reported in prisons and jails throughout the world, and is particularly concerning in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, which incarcerates a larger proportion of its population than any other nation. The prevalence of TB in prisons is much higher than among the general population—in some countries as much as 40 times higher.

A new rapid test to identify tuberculosis, combined with aggressive treatment strategies in developing world countries, has resulted in a recent drop in the number of TB cases and deaths. As of 2010, the number of global cases had dropped to 8.8 million, after peaking at 9 million in 2005. The number of deaths had also fallen to 1.4 million in 2010, down from a peak of 1.8 million in 2003.

A 2011 World Health Organisation report showed that if trends continue, all regions except Africa are on track to achieve a 50 percent decline in TB mortality by 2015. African mortality also declined, but at a slower rate due to the complicating factor of widespread HIV. China has achieved particularly dramatic progress, with an 80 percent decline in its TB mortality rate.

History




Tuberculosis has been present in humans since antiquity
Ancient history
Ancient history is the study of the written past from the beginning of recorded human history to the Early Middle Ages. The span of recorded history is roughly 5,000 years, with Cuneiform script, the oldest discovered form of coherent writing, from the protoliterate period around the 30th century BC...

. The earliest unambiguous detection of Mycobacterium tuberculosis is in the remains of bison dated 17,000 years before the present. However, whether tuberculosis originated in cattle and then transferred to humans, or diverged from a common ancestor, is currently unclear. Skeletal remains show prehistoric humans (4000 BCE
Common Era
Common Era ,abbreviated as CE, is an alternative designation for the calendar era originally introduced by Dionysius Exiguus in the 6th century, traditionally identified with Anno Domini .Dates before the year 1 CE are indicated by the usage of BCE, short for Before the Common Era Common Era...

) had TB, and tubercular decay has been found in the spines of Egypt
Egypt
Egypt , officially the Arab Republic of Egypt, Arabic: , is a country mainly in North Africa, with the Sinai Peninsula forming a land bridge in Southwest Asia. Egypt is thus a transcontinental country, and a major power in Africa, the Mediterranean Basin, the Middle East and the Muslim world...

ian mummies
Mummy
A mummy is a body, human or animal, whose skin and organs have been preserved by either intentional or incidental exposure to chemicals, extreme coldness , very low humidity, or lack of air when bodies are submerged in bogs, so that the recovered body will not decay further if kept in cool and dry...

 from 3000-2400 BCE. Phthisis is a Greek term for consumption; around 460 BCE, Hippocrates
Hippocrates
Hippocrates of Cos or Hippokrates of Kos was an ancient Greek physician of the Age of Pericles , and is considered one of the most outstanding figures in the history of medicine...

 identified phthisis as the most widespread disease of the times involving coughing up blood and fever, which was almost always fatal. Genetic studies suggest that TB was present in The Americas from about the year 100 CE.

Before the Industrial Revolution
Industrial Revolution
The Industrial Revolution was a period from the 18th to the 19th century where major changes in agriculture, manufacturing, mining, transportation, and technology had a profound effect on the social, economic and cultural conditions of the times...

, tuberculosis may sometimes have been regarded as vampirism. When one member of a family died from it, the other members that were infected would lose their health slowly. People believed that this was caused by the original victim draining the life from the other family members. Furthermore, people who had TB exhibited symptoms similar to what people considered to be vampire traits. People with TB often have symptoms such as red, swollen eyes (which also creates a sensitivity to bright light), pale skin and coughing blood, suggesting the idea that the only way for the afflicted to replenish this loss of blood was by sucking blood.

Although it was established that the pulmonary form was associated with 'tubercles' by Dr Richard Morton in 1689, due to the variety of its symptoms, TB was not identified as a single disease until the 1820s and was not named 'tuberculosis' until 1839 by J. L. Schönlein
Johann Lukas Schönlein
Johann Lukas Schönlein was a German naturalist, and professor of medicine, born in Bamberg. He studied medicine at Landshut, Jena, Göttingen, and Würzburg...

. During the years 1838–1845, Dr. John Croghan, the owner of Mammoth Cave, brought a number of tuberculosis sufferers into the cave in the hope of curing the disease with the constant temperature and purity of the cave air: they died within a year. The first TB sanatorium
Sanatorium
A sanatorium is a medical facility for long-term illness, most typically associated with treatment of tuberculosis before antibiotics...

 opened in 1859 in Sokołowsko, Poland by Hermann Brehmer.

The bacillus causing tuberculosis, Mycobacterium tuberculosis, was identified and described on March 24, 1882 by Robert Koch
Robert Koch
Heinrich Hermann Robert Koch was a German physician. He became famous for isolating Bacillus anthracis , the Tuberculosis bacillus and the Vibrio cholerae and for his development of Koch's postulates....

. He received the Nobel Prize in physiology or medicine
Nobel Prize in Physiology or Medicine
The Nobel Prize in Physiology or Medicine administered by the Nobel Foundation, is awarded once a year for outstanding discoveries in the field of life science and medicine. It is one of five Nobel Prizes established in 1895 by Swedish chemist Alfred Nobel, the inventor of dynamite, in his will...

 in 1905 for this discovery. Koch did not believe that bovine (cattle) and human tuberculosis were similar, which delayed the recognition of infected milk as a source of infection. Later, this source was eliminated by the pasteurization
Pasteurization
Pasteurization is a process of heating a food, usually liquid, to a specific temperature for a definite length of time, and then cooling it immediately. This process slows microbial growth in food...

 process. Koch announced a glycerine extract of the tubercle bacilli as a "remedy" for tuberculosis in 1890, calling it 'tuberculin'. It was not effective, but was later adapted as a test for pre-symptomatic tuberculosis.

The first genuine success in immunizing against tuberculosis was developed from attenuated bovine-strain tuberculosis by Albert Calmette
Albert Calmette
Léon Charles Albert Calmette ForMemRS was a French physician, bacteriologist and immunologist, and an important officer of the Pasteur Institute. He discovered the Bacillus Calmette-Guérin, an attenuated form of Mycobacterium used in the BCG vaccine against tuberculosis...

 and Camille Guerin
Camille Guérin
Jean-Marie Camille Guérin was a French veterinarian, bacteriologist and immunologist who, together with Albert Calmette, developed the Bacillus Calmette-Guérin , a vaccine for immunization against tuberculosis....

 in 1906. It was called 'BCG' (Bacillus of Calmette and Guerin
Bacillus Calmette-Guérin
Bacillus Calmette-Guérin is a vaccine against tuberculosis that is prepared from a strain of the attenuated live bovine tuberculosis bacillus, Mycobacterium bovis, that has lost its virulence in humans by being specially subcultured in an artificial medium for 13 years, and also prepared from...

). The BCG vaccine was first used on humans in 1921 in France
France
The French Republic , The French Republic , The French Republic , (commonly known as France , is a unitary semi-presidential republic in Western Europe with several overseas territories and islands located on other continents and in the Indian, Pacific, and Atlantic oceans. Metropolitan France...

, but it wasn't until after World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...

 that BCG received widespread acceptance in the USA
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...

, Great Britain
Great Britain
Great Britain or Britain is an island situated to the northwest of Continental Europe. It is the ninth largest island in the world, and the largest European island, as well as the largest of the British Isles...

, and Germany
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...

.

Tuberculosis caused the most widespread public concern in the 19th and early 20th centuries as an endemic
Endemic (epidemiology)
In epidemiology, an infection is said to be endemic in a population when that infection is maintained in the population without the need for external inputs. For example, chickenpox is endemic in the UK, but malaria is not...

 disease of the urban poor. In 1815, one in four deaths in England was of consumption; by 1918 one in six deaths in France were still caused by TB. After the establishment in the 1880s that the disease was contagious, TB was made a notifiable disease in Britain; there were campaigns to stop spitting in public places, and the infected poor were "encouraged" to enter sanatoria
Sanatorium
A sanatorium is a medical facility for long-term illness, most typically associated with treatment of tuberculosis before antibiotics...

 that resembled prisons; the sanatoria for the middle and upper classes offered excellent care and constant medical attention. Whatever the purported benefits of the fresh air and labor in the sanatoria, even under the best conditions, 50% of those who entered were dead within five years (1916).

The promotion of Christmas Seals began in Denmark during 1904 as a way to raise money for tuberculosis programs. It expanded to the United States and Canada in 1907–08 to help the National Tuberculosis Association (later called the American Lung Association
American Lung Association
The American Lung Association is a voluntary health organization whose mission is to save lives by improving lung health and preventing lung disease.-History:...

).

In the United States, concern about the spread of tuberculosis played a role in the movement to prohibit public spitting except into spittoon
Spittoon
A spittoon is a receptacle made for spitting into, especially by users of chewing and dipping tobacco. It is also known as a cuspidor , although that term is also used for a type of spitting sink used in dentistry."Spittoon" can also be slang American English...

s.

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
Medical Research Council
Medical Research Council may refer to:* Medical Research Council , a UK organisation* National Health and Medical Research Council, Australia's peak funding body for medical research...

 was formed in Britain in 1913 its initial focus was tuberculosis research.

It was not until 1946 with the development of the antibiotic streptomycin
Streptomycin
Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium Streptomyces griseus. Streptomycin is a bactericidal antibiotic. Streptomycin cannot be given...

 that effective treatment and cure became possible. Prior to the introduction of this drug, the only treatment besides sanatoria were surgical interventions, including the pneumothorax
Pneumothorax
Pneumothorax is a collection of air or gas in the pleural cavity of the chest between the lung and the chest wall. It may occur spontaneously in people without chronic lung conditions as well as in those with lung disease , and many pneumothoraces occur after physical trauma to the chest, blast...

 technique—collapsing an infected lung to "rest" it and allow lesions to heal—a technique that was of little benefit and was largely discontinued by the 1950s. The emergence of multidrug-resistant TB has again introduced surgery as part of the treatment for these infections. Here, surgical removal of chest cavities will reduce the number of bacteria in the lungs, as well as increasing the exposure of the remaining bacteria to drugs in the bloodstream, and is therefore thought increase the effectiveness of the chemotherapy.

Hope that the disease could be completely eliminated have been dashed since the rise of drug-resistant strains in the 1980s. For example, tuberculosis cases in Britain, numbering around 50,000 in 1955, had fallen to around 5,500 in 1987, but in 2000 there were over 7,000 confirmed cases. Due to the elimination of public health facilities in New York and the emergence of HIV, there was a resurgence in the late 1980s. The number of those failing to complete their course of drugs is high. NY had to cope with more than 20,000 "unnecessary" TB-patients with multidrug-resistant strains (resistant to, at least, both Rifampin and Isoniazid). The resurgence of tuberculosis resulted in the declaration of a global health emergency by the World Health Organization in 1993.

Animal infection


Tuberculosis can be carried by mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...

s; domesticated species, such as cats and dogs, are generally free of tuberculosis, but wild animals may be carriers. In some places, regulations aiming to prevent the spread of TB restrict the ownership of novelty pets; for example, the U.S. state of California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...

 forbids the ownership of pet gerbil
Gerbil
A gerbil is a small mammal of the order Rodentia. Once known simply as "desert rats", the gerbil subfamily includes about 110 species of African, Indian, and Asian rodents, including sand rats and jirds, all of which are adapted to arid habitats...

s.

Mycobacterium bovis
Mycobacterium bovis
Mycobacterium bovis is a slow-growing , aerobic bacterium and the causative agent of tuberculosis in cattle...

 causes TB in cattle. An effort to eradicate bovine tuberculosis from the cattle and deer herds of New Zealand
New Zealand
New Zealand is an island country in the south-western Pacific Ocean comprising two main landmasses and numerous smaller islands. The country is situated some east of Australia across the Tasman Sea, and roughly south of the Pacific island nations of New Caledonia, Fiji, and Tonga...

 is under way. It has been found that herd infection is more likely in areas where infected vector species such as Australian brush-tailed possums come into contact with domestic livestock
Livestock
Livestock refers to one or more domesticated animals raised in an agricultural setting to produce commodities such as food, fiber and labor. The term "livestock" as used in this article does not include poultry or farmed fish; however the inclusion of these, especially poultry, within the meaning...

 at farm/bush borders. Controlling the vectors through possum eradication and monitoring the level of disease in livestock herds through regular surveillance are seen as a "two-pronged" approach to ridding New Zealand of the disease.

In both the Republic of Ireland
Republic of Ireland
Ireland , described as the Republic of Ireland , is a sovereign state in Europe occupying approximately five-sixths of the island of the same name. Its capital is Dublin. Ireland, which had a population of 4.58 million in 2011, is a constitutional republic governed as a parliamentary democracy,...

 and Northern Ireland
Northern Ireland
Northern Ireland is one of the four countries of the United Kingdom. Situated in the north-east of the island of Ireland, it shares a border with the Republic of Ireland to the south and west...

, badger
Eurasian Badger
The European Badger is a species of badger of the genus Meles, native to almost all of Europe. It is classed as Least Concern for extinction by the IUCN, due to its wide distribution and large population....

s have been identified as a vector species for the transmission of bovine tuberculosis. As a result, the government in both regions has mounted an active campaign of eradication of the species in an effort to reduce the incidence of the disease. Badgers have been culled primarily by snaring and gassing. It remains a contentious issue, with proponents and opponents of the scheme citing their own studies to support their position.

See also

  • Mycobacterium Tuberculosis Structural Genomics Consortium
    Mycobacterium Tuberculosis Structural Genomics Consortium
    The TB Structural Genomics Consortium is a worldwide consortium of scientists developing a foundation for tuberculosis diagnosis and treatment by determining the 3-dimensional structures of proteins from M. Tuberculosis. The consortium seeks to solve structures of proteins that are of great...

  • TBVI
    TBVI
    TuBerculosis Vaccine Initiative is a European-based foundation that facilitates the development of new tuberculosis vaccines. The goal is to protect future generations against tuberculosis....

    The Tuberculosis Vaccine Initiative

External links