) is a common and
often deadly infectious disease
caused by mycobacteria
in humans. Tuberculosis usually attacks the
but can also affect other parts of the
body. It is spread through the air, when people who have the
disease cough, sneeze, or spit. Most infections in humans result in
, latent infection, and
about one in ten latent infections eventually progresses to active
disease, which, if left untreated, kills more than half of its
The classic symptoms are a chronic cough
, night sweats
, and weight
. Infection of other organs causes a wide range of
(commonly chest X-rays
), a tuberculin skin test
, blood tests, as well as
microscopic examination and microbiological culture
difficult and requires long courses of multiple antibiotics.
Contacts are also screened and treated if necessary. Antibiotic resistance
is a growing
problem in (extensively
. Prevention relies on screening programs and
, usually with Bacillus Calmette-Guérin
A third of the world's population has been infected with M.
. New infections occur at a rate of 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
contracting tuberculosis because their immune systems
are compromised by immunosuppressive drugs
, substance abuse
, or AIDS
. 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 US population test positive.
The current clinical classification system for tuberculosis (TB) is
based on the pathogenesis of the disease.
Classification System for TB
||No TB exposure
|No history of exposure
Negative reaction to tuberculin skin
No evidence of infection
|History of exposure
Negative reaction to tuberculin skin test
|Positive reaction to tuberculin skin test
Negative bacteriologic studies (if done)
No clinical, bacteriologic, or radiographic evidence of TB
||TB, clinically active
||M. tuberculosis cultured (if done)
Clinical, bacteriologic, or radiographic evidence of current
Not clinically active
|History of episode(s) of TB
Abnormal but stable radiographic findings
Positive reaction to the tuberculin skin test
Negative bacteriologic studies (if done)
No clinical or radiographic evidence of current disease
TB disease should be ruled in or out within 3 months
Signs and symptoms
Main symptoms of variants and stages
of tuberculosis, with many symptoms overlapping with other
variants, while others are more (but not entirely) specific for
Multiple variants may be present simultaneously.
When the disease becomes active, 75% of the cases are pulmonary
TB, that is, TB in the lungs. Symptoms
include chest pain
, coughing up blood
, and a productive, prolonged
cough for more than three weeks. Systemic symptoms include fever
, appetite loss
, and often a tendency to
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 tuberculosis pleurisy, the central nervous system
, the lymphatic system
of the neck, the genitourinary system
in urogenital tuberculosis
, and bones
and joints in Pott's disease
spine. An especially serious form is disseminated TB, more commonly
known as miliary tuberculosis
Extrapulmonary TB may co-exist with pulmonary TB as well.
The primary cause of TB, Mycobacterium tuberculosis
is a small aerobic
. High lipid
content of this pathogen accounts for many of its unique clinical
characteristics. It divides
to 20 hours, an extremely slow rate compared with other bacteria,
which usually divide in less than an hour. (For example, one of the
fastest-growing bacteria is a strain of E.
that can divide roughly every 20 minutes.) Since MTB
has a cell wall but lacks a phospholipid outer membrane
, it is classified
as a Gram-positive
bacterium. However, if a
is performed, MTB either
stains very weakly Gram-positive or does not retain dye due to the
high lipid & mycolic acid content of its cell wall. MTB can
withstand weak disinfectants
survive in a dry state
for weeks. In
nature, the bacterium can grow only within the cells of a host
organism, but M. tuberculosis
can be cultured in vitro
stains on expectorate
samples from phlegm
(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
(AFB). The most common acid-fast staining technique,
the Ziehl-Neelsen stain
AFBs a bright red that stands out clearly against a blue
background. Other ways to visualize AFBs include an auramine-rhodamine stain
The M. tuberculosis
complex includes three other
: M. bovis
, M. africanum
, and M. microti
. M. africanum
is not widespread,
but in parts of Africa it is a significant cause of tuberculosis.
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.
is mostly seen in immunodeficient people, although it
is possible that the prevalence
pathogen has been underestimated.
Other known pathogenic mycobacteria
, Mycobacterium avium
. The last two are part of the nontuberculous mycobacteria
(NTM) group. Nontuberculous mycobacteria cause neither TB nor
, but they do
pulmonary diseases resembling TB.
Persons with silicosis
greater risk for developing TB.
Persons with chronic renal failure who are on hemodialysis also
have an increased risk: 10—25 times greater than the general
population. Persons with diabetes
have a risk for developing active TB that is two to
four times greater than persons without diabetes mellitus, and this
risk is likely greater in persons with insulin-dependent or poorly
controlled diabetes. Other clinical conditions that have been
associated with active TB include gastrectomy
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) air pollutants
on the disease would be necessary. Some possible indoor source of
silica includes paint
Low body weight is associated with risk of tuberculosis as well. A
body mass index
(BMI) below 18.5
increases the risk by 2—3 times. On the other hand, an increase in
body weight lowers the risk 
. Patients with diabetes mellitus
are at increased risk of
contracting tuberculosis, and they have a poorer response to
treatment, possibly due to poorer drug absorption
Other conditions that increase risk include IV drug abuse
; recent TB infection or a
history of inadequately treated TB; chest X-ray suggestive of
previous TB, showing fibrotic lesions and nodules; prolonged
therapy and other
immunosuppressive therapy;Immunocompromised patients (30-40% of
AIDS patients in the world also have TB) hematologic
such as leukemia
and Hodgkin's disease; end-stage kidney disease
intestinal bypass; chronic malabsorption
syndromes; vitamin D deficiency;
and low body weight.
in the 1940s showed that
susceptibility to TB was heritable. If one of a pair of twins got
TB, then and the other was more likely to get TB if he was
identical than if he was not. Since then, specific gene
polymorphisms in IL12B
linked to tuberculosis susceptibility.
Some drugs, including rheumatoid
drugs that work by blocking tumor necrosis factor-alpha
), raise the
risk of activating a latent infection due to the importance of this
cytokine in the immune defense against TB.
When people suffering from active pulmonary TB cough, sneeze,
speak, 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
the inhalation of just a single bacterium can cause a new
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 drugs using
unsanitary needles, 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, patients immunocompromised
by conditions such as
, people who take
immunosuppressant drugs, and health care workers serving these
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
of the M.
. The chain
of transmission can, therefore, be broken by isolating patients
with active disease and starting effective anti-tuberculous
therapy. After two weeks of such treatment, people with non-resistant
active TB generally
cease to be contagious. If someone does become infected, then it
will take at least 21 days, or three to four weeks, before the
newly infected person can transmit the disease to others.TB can
also be transmitted by eating meat infected with TB.
causes TB in cattle. (See details
About 90% of those infected with Mycobacterium
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
, where they invade and
replicate within the endosomes
. The primary site of
infection in the lungs is called the Ghon
, and is generally located in either the upper part of the
lower lobe, or the lower part of the upper
. Bacteria are picked up by dendritic cells
, which do not allow
replication, although these cells can transport the bacilli to
) lymph nodes
. 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
, skeletal muscles
Tuberculosis is classified as one of the granulomatous
inflammatory conditions. Macrophages
, T lymphocytes
are among the cells that aggregate to
form a granuloma
, with lymphocytes
surrounding the infected
macrophages. The granuloma functions not only to prevent
dissemination of the mycobacteria, but also provides a local
environment for communication of cells of the immune system. Within
the granuloma, T lymphocytes secrete cytokines
such as interferon gamma
, which activates
macrophages to destroy the bacteria with which they are infected.
Cytotoxic T cells
can also directly
kill infected cells, by secreting perforin
Importantly, bacteria are not always eliminated within the
granuloma, but can become dormant, resulting in a latent infection.
Another feature of the granulomas of human tuberculosis is the
development of cell death, also called necrosis
, in the center of tubercles
. To the naked eye this has the
texture of soft white cheese and was termed caseous necrosis
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
. Patients with this disseminated TB have a
fatality rate of approximately 20%, even with intensive
In many patients the infection waxes and wanes. Tissue destruction
and necrosis are balanced by healing and fibrosis
. 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
and this material can be
coughed up. It contains living bacteria and can therefore pass on
infection. Treatment with appropriate antibiotics
kills bacteria and allows healing to
take place. Upon cure, affected areas are eventually replaced by
If untreated, infection with Mycobacterium tuberculosis
can become lobar pneumonia
Tuberculosis is diagnosed definitively by identifying the causative
) in a clinical sample (for example, sputum
). When this is not
possible, a probable diagnosis may be made using imaging (X-rays or
scans) and/or a tuberculin skin test
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
microbiological smears, and cultures. It may also include a
tuberculin skin test,
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
. 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 in that they may produce false negatives,
especially when the patient is co-morbid
, Hodgkins lymphoma,
malnutrition, or most notably active tuberculosis disease. New TB
tests are being developed that offer the hope of cheap, fast and
more accurate TB testing. These include polymerase chain reaction
detection of bacterial DNA, and assays to detect the release of
in response to
mycobacterial proteins such as ESAT-6
are not affected by immunization or environmental mycobacteria
generate fewer false positive
results. The development of a rapid and inexpensive diagnostic test
would be particularly valuable in the developing world.
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
to protect them from TB. No
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
gives some protection against TB.
The World Health
(W.H.O.) declared TB a global health emergency in
1993, and the Stop TB Partnership developed a Global Plan to Stop
that aims to save 14 million lives between 2006
and 2015. Since humans are the only host of Mycobacterium
, eradication would be possible: a goal that would
be helped greatly by an effective vaccine.
Many countries use Bacillus Calmette-Guérin
vaccine as part of their TB control programs, especially for
infants. According to the W.H.O., this is the most often used
vaccine worldwide, with 85% of infants in 172 countries immunized
in 1993. This was the first vaccine for TB and
developed at the Pasteur Institute in France between 1905 and 1921.
mass vaccination with BCG did not start until after World War II
. The protective efficacy of BCG
for preventing serious forms of TB (e.g. meningitis
) in children is greater than 80%; its
protective efficacy for preventing pulmonary TB in adolescents and
adults is variable, ranging from 0 to 80%.
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
; therefore BCG is not given to the
entire population in these countries. In the USA, for example, BCG
vaccine is not recommended except for people who meet specific
- Infants or children with negative skin test results who are
continually exposed to untreated or ineffectively treated patients
or will be continually exposed to multidrug-resistant TB.
- Healthcare workers considered on an individual basis in
settings in which a high percentage of MDR-TB patients 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
Several new vaccines to prevent TB infection are being developed.
The first recombinant
in the United States
in 2004, sponsored by the National
Institute of Allergy and Infectious Diseases
(NIAID). A 2005
study showed that a DNA TB vaccine
with conventional chemotherapy
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. A very promising TB vaccine, MVA85A, is currently in phase II trials in South Africa by a group
led by Oxford
University, and is
based on a genetically modified vaccinia
Many other strategies are also being used to develop
novel vaccines, including both subunit vaccines
molecules composed of two recombinant
proteins delivered in an
) 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 very common. All of these
vaccines have been successfully tested in humans and are now in
extended testing in TB-endemic regions. In order to encourage
further discovery, researchers and policymakers are promoting new
economic models of vaccine development including prizes, tax
incentives and advance market
The Bill and Melinda
has been a strong supporter of new TB vaccine
development. Most recently, it announced a $200 million grant to
the Aeras Global TB
for clinical trials on up to six different
TB vaccine candidates currently in the pipeline.
Mantoux tuberculin skin test
used for routine screening of high risk individuals.
are blood tests used in the diagnosis of some infectious
diseases. There are currently two interferon-γ release assays
available for the diagnosis of tuberculosis:
been used in the past for mass screening for tuberculosis.
Treatment for TB uses antibiotics
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 rifampicin
. 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
. 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 who are infected
with a resistant strain of TB. A patient 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
(MDR-TB) is defined as resistance to the two most
effective first-line TB drugs: rifampicin
(XDR-TB) is also resistant to three or more
of the six classes of second-line drugs. The DOTS
(Directly Observed Treatment Short-course)
strategy of tuberculosis treatment recommended by WHO was based on
clinical trials done in the 1970s by Tuberculosis Research Centre,
Chennai, India. The country in which a person with TB lives can
determine what treatment they receive. This is because
multidrug-resistant tuberculosis is resistant to most first-line
medications, the use of alternative treatments, often referred as
"second-line" antituberculosis medications, is necessary to cure
the patient. However, the price of these medications is exorbitant,
and thus poor people in the developing world have no or limited
access to these treatments.
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
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
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
. In patients
co-infected with M. tuberculosis
and HIV, the risk of
reactivation increases to 10% per year.
[[Image:Tuberculosis world map - DALY - WHO2002.svg|thumb|Disability-adjusted life year
for tuberculosis per 100,000 inhabitants.
Annual number of new reported TB
Roughly a third of the world's population has been infected with
, and new infections occur at a rate of one
per second. Fact sheet No
104. 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
rate varied from 363 per
100,000 in Africa to 32 per 100,000 in the Americas
. Tuberculosis is the world's greatest
infectious killer of women of reproductive age and the leading
cause of death among people with HIV
The rise in HIV infections and the neglect of TB control programs
have enabled a resurgence of tuberculosis. The emergence of
also contributed to this new epidemic with, from 2000 to 2004, 20%
of TB cases being resistant to standard treatments and 2% resistant
. The rate at which new TB cases occur varies widely, even
in neighboring countries, apparently because of differences in
health care systems.
the country with the highest estimated incidence rate of TB was Swaziland, with 1200 cases per 100,000 people.
had the largest total incidence, with an estimated 2.0 million new
cases. The Philippines ranks fourth in the world for the number of
cases of tuberculosis and has the highest number of cases per head
in Southeast Asia. Almost two thirds of Filipinos have
tuberculosis, and up to an additional five million people are
infected yearly . 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
were 30 per 100,000 in Portugal and Spain. These rates compared
with 98 per 100,000 in China
and 48 per 100,000 in Brazil.
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
. Co-infection with HIV is a particular
problem in Sub-Saharan Africa
due to the high incidence of HIV in these countries. Smoking more
than 20 cigarettes
a day also 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
, end-stage renal
, chronic lung disease, malnutrition
, and alcoholism
Diet may also modulate risk. For example, among immigrants in
London from the Indian subcontinent, vegetarian Hindu Asian
were found to have an 8.5 fold increased
risk of tuberculosis, compared to Muslims
ate meat and fish daily. Although a causal link is not proved by
this data, this increased risk could be caused by micronutrient
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
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
. Along with overcrowding, poor
nutrition may contribute to the strong link observed between
tuberculosis and poverty
Tuberculosis has been present in humans since antiquity
. The earliest unambiguous
detection of Mycobacterium tuberculosis
is in the remains
of bison dated 18,000 years before the present. Whether
tuberculosis originated in cattle and then transferred to humans,
or diverged from a common ancestor infecting a different species,
is currently unclear. However, it is clear that M.
is not directly descended from M. bovis
which seems to have evolved relatively recently.
Skeletal remains from a Neolithic Settlement in the Eastern
Mediterranean show prehistoric humans (7000 BC
) had TB, and tubercular decay has been
found in the spines of mummies
BC. Phthisis is a Greek term for tuberculosis; around 460 BC,
identified phthisis as the
most widespread disease of the times involving coughing up blood
and fever, which was almost always fatal. In South America, the
earliest evidence of tuberculosis is associated with the Paracas
-Caverna culture (circa 750 BC to
circa 100 AD).
In the past, tuberculosis has been called consumption, because it
seemed to consume people from within, with a bloody cough
, fever, pallor
, and long relentless wasting. Other names
(Greek for consumption) and phthisis
affecting the lymphatic system and resulting in swollen neck
glands; tabes mesenterica
, TB of the abdomen and
, TB of the
skin; wasting disease; white plague, because sufferers appear
markedly pale; king's evil, because it was believed that a king's
touch would heal scrofula; and Pott's
, or gibbus of the spine and joints.
Dr. Robert Koch discovered the
—now commonly known as disseminated TB—occurs
when the infection invades the circulatory system, resulting in
lesions which have the appearance of millet
seeds on X-ray. TB is also called Koch's disease, after the
scientist Robert Koch
Before the Industrial
, tuberculosis may sometimes have been regarded as
. 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, extremely low body heat, a
weak heart and coughing blood, suggesting the idea that the only
way for the afflicted to replenish this loss of blood was by
sucking blood. Another folk belief told that the affected
individual was being forced, nightly, to attend fairy
revels, so that the victim wasted away owing to
lack of rest; this belief was most common when a strong connection
was seen between the fairies and the dead. Similarly, but less
commonly, it was attributed to the victims being "hagridden"—being
transformed into horses by witches (hags) to travel to their
nightly meetings, again resulting in a lack of rest.
TB was romanticized in the nineteenth century. Many people believed
TB produced feelings of euphoria referred to as Spes
("hope of the consumptive"). It was believed that TB
sufferers who were artists had bursts of creativity as the disease
progressed. It was also believed that TB sufferers acquired a final
burst of energy just before they died which made women more
beautiful and men more creative. In the early 20th century, some
believed TB to be caused by masturbation
Study and treatment
The study of tuberculosis, sometimes known as phthisiatry
, dates back to The Canon of Medicine
(Avicenna) in the 1020s. He was
the first physician to identify pulmonary tuberculosis as a
, the first to
recognise the association with diabetes, and the first to suggest
that it could spread through contact with soil
, Introduction to the History of Science
Dr. A. Zahoor and Dr. Z. Haq (1997).
Quotations From Famous Historians of Science
Cyberistan.) He developed the method of quarantine
in order to limit the spread of
tuberculosis. In ancient times, treatments focused on sufferers'
diets. Pliny the Elder
several methods in his Natural History
: "wolf's liver
taken in thin wine, the lard of a sow that has been fed upon grass,
or the flesh of a she-ass taken in broth".
Although it was established that the pulmonary form was associated
with "tubercles" by Dr Richard
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
. 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 opened in 1854 in Görbersdorf,
Germany (today Sokołowsko, Poland) by Hermann Brehmer.
The bacillus causing tuberculosis, Mycobacterium
, was identified and described on 24 March 1882 by
. He received the Nobel Prize in physiology
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
process. Koch announced a
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
The first genuine success in immunizing against tuberculosis was
developed from attenuated bovine-strain tuberculosis by Albert Calmette
and Camille Guérin
in 1906. It was called
"BCG" (Bacillus of
Calmette and Guérin
). The BCG vaccine was first used on humans
in 1921 in France, but it was not until after World War II
that BCG received widespread
acceptance in the USA, Great Britain, and Germany.
Tuberculosis, or "consumption" as it was commonly known, caused the
most widespread public concern in the 19th and early 20th centuries
as an endemic
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. In the 20th century, tuberculosis killed an estimated 100
million people. 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 pressured to enter sanatoria
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).
Public health campaigns tried to halt
the spread of TB
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 – 1908 to help the National Tuberculosis Association
(later called the American
In the United States, concern about the spread of tuberculosis
played a role in the movement to prohibit public spitting except
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. The
disease remained such a significant threat to public health, that
when the Medical Research
was formed in Britain in 1913, its initial focus was
It was not until 1946 with the development of the antibiotic
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
technique — collapsing an infected
lung to "rest" it and allow lesions to heal — a technique that
was of little benefit and was mostly 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. It is therefore thought to increase the
effectiveness of the chemotherapy.
Hopes 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
117,000 in 1913, had fallen to around 5,000 in 1987, but cases rose
again, reaching 6,300 in 2000 and 7,600 cases in 2005. Due to the
elimination of public health facilities in New York and the
emergence of HIV, there was a resurgence of TB in the late 1980s.
The number of patients failing to complete their course of drugs is
high. New York had to cope with more than 20,000 TB patients with
(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 (WHO) in
1993. Every year, nearly half a million new cases of
multidrug-resistant tuberculosis (MDR-TB) are estimated to occur
Tuberculosis has co-evolved
for many thousands of years, and perhaps for several million years.
The oldest known human remains showing signs of tuberculosis
infection are 9,000 years old. During this evolution
, M. tuberculosis
numerous coding and non-coding regions in its genome
, losses that can be used to distinguish
between strains of the bacteria. The implication is that M.
strains differ geographically, so their genetic
differences can be used to track the origins and movement of each
Society and culture
Through its affecting important historical figures, tuberculosis
has influenced particularly European history, and become a theme in
art – mostly literature, music, and film.
Tuberculosis is one of the three primary diseases of poverty
along with AIDS
Global Fund to Fight AIDS, Tuberculosis and Malaria
in 2002 to raise finances to address these infectious diseases.
has lead to
increased opportunities for disease spread. In 2007, a tuberculosis scare
when Andrew Speaker flew on a transatlantic flight infected with
The National Center
for HIV, STD, and TB Prevention
as part of the Center for Disease
Control and Prevention
(CDC) is responsible for public health
surveillance and prevention research in the United States.
Tuberculosis Structural Genomics Consortium
is a global
consortium of scientists conducting research regarding the
diagnosis and treatment of tuberculosis. They are attempting to
determine the 3-dimensional structures of proteins from M.
Infection of other animals
Tuberculosis can be carried by mammals
domesticated species, such as cats and dogs, are generally free of
tuberculosis, but wild animals may be carriers.
causes TB in cattle. An effort to eradicate bovine tuberculosis
from the cattle and deer herds of New Zealand is underway. It has
been found that herd infection is more likely in areas where
infected natural reservoir
Australian brush-tailed possums
contact with domestic livestock
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.
Ireland and the United Kingdom, badger have been identified as one vector
species for the transmission of bovine tuberculosis.
result, governments have come under pressure from some quarters,
primarily dairy farmers, to mount an active campaign of eradication
of badgers in certain areas with the purpose of reducing the
incidence of bovine TB. The effectiveness of culling on the
incidence of TB in cattle is a contentious issue, with proponents
and opponents citing their own studies to support their position.
For instance, a study by an Independent Study Group on badger
culling reported on 18 June 2007 that it was unlikely to be
effective and would only make a “modest difference” to the spread
of TB and that "badger culling cannot meaningfully contribute to
the future control of cattle TB"; in contrast, another report
concluded that this policy would have a significant impact. On 4
July 2008, the UK government decided against a proposed random
- Tuberculosis Symptoms From eMedicine. Author: George
Schiffman, MD, FCCP. Last Editorial Review: 1/15/2009
- Additional symptoms for primary/early pulmonary infection:
wrongdiagnosis.com --> Diseases » Tuberculosis »
Symptoms Retrieved on 1 June 2009
- Extrapulmonary Tuberculosis: An Overview MARJORIE P.
GOLDEN, M.D., Yale University School of Medicine and Hospital of
Saint Raphael, New Haven, Connecticut. HOLENARASIPUR R. VIKRAM,
M.D., Mayo Clinic, Scottsdale, Arizona.
- Centers for Disease
Control and Prevention (CDC), Division of Tuberculosis
Elimination. Core Curriculum on Tuberculosis: What the Clinician Should
Know. 4th edition (2000). Updated August 2003.
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prevention of tuberculosis. Geneva: World Health Organization;
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1980–2005: South Africa (PDF). World Health Organization
(August 2006). Retrieved on 8 June 2007.
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Nature Reviews Microbiology. Vol. 4. June 2006.
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Diseases: Economic Perspectives (PDF). Bulletin of the
World Health Organization 79(8), 2001, pp. 693–801.
- Barder, Owen; Kremer, Michael; Williams, Heidi. "Advance
Market Commitments: A Policy to Stimulate Investment in Vaccines
for Neglected Diseases," The Economists' Voice, Vol. 3
(2006) Issue 3.
- Aeras Receives New Grant from the Gates
- See also: * * * * *
- World Health Organization (WHO)
WHO report 2008: Global tuberculosis control
Retrieved on 13 April 2009.
- Centers for Disease Control.
Fact Sheet: Tuberculosis in the United States.
17 March 2005, Retrieved on 6 October 2006.
- Stop TB Partnership. London tuberculosis rates now at Third World
proportions. PR Newswire Europe Ltd. 4 December 2002.
Retrieved on 3 October 2006.
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- World Health Organization (WHO).
Global Tuberculosis Control Report, 2006 -
Annex 1 Profiles of high-burden countries. (PDF) Retrieved on 13
- Centers for Disease
Control and Prevention (CDC). 2005 Surveillance Slide Set. (12 September
2006) Retrieved on 13 October 2006.
- World Health Organization (WHO).
Global tuberculosis control - surveillance,
planning, financing WHO Report 2006. Retrieved on 13 October
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- "South America: Prehistoric Findings".
Memorias do Instituto Oswaldo Cruz, Vol. 98 (Suppl.I)
January 2003. Retrieved on 8 February 2007.
- Tuberculosis Encyclopedia Britannica, 11th
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English Glossary of Archaic Medical Terms, Diseases and Causes
of Death, Accessed 9 October 2006
- Disseminated tuberculosis NIH Medical
Encyclopedia. Accessed 9 October 2006
- Katharine Briggs, "Consumption"
,An Encyclopedia of Fairies, Pantheon Books, 1976, p. 80. ISBN
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Literary Nationalism in the Davidson Sisters, Southey, and Poe",
Studies in the Literary Imagination, Fall 2003. Available
at findarticles.com. Retrieved on 8 June
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Practices in the United States, University of Chicago
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Education and its Relationship with the European Tradition",
Prospects 33 (4), Springer.
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Mitteilung an den Herausgeber. [Müller’s] Archiv für Anatomie,
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CNN. 27 February 2004.
Accessed 8 October 2006.
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MRC's contribution to Tuberculosis research.
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Frequently asked questions about TB and HIV. Retrieved
6 October 2006.
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drug-resistant TB. World Health Organization.
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and Brucellosis. Retrieved on 8 May 2006.
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Retrieved on 8 May 2006.
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Retrieved on 8 May 2006.
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The Greatest Story Never Told.
- General information, public health websites and epidemiology
- Patient information on tuberculosis
- Professional information and scientific research
- Sir John Crofton - Daily Telegraph