"Captain among these Men of Death"
(John Bunyon 1660)
White Death
White Plague
Consumption
Tuberculosis...
Where did TB come from?
Mycobacteria
are Gram-resistant (waxy cell walls), non-motile,
pleomorphic rods, related to the Actinomyces. Most Mycobacteria are found
in habitats such as water or soil. However, a few are intracellular
pathogens
of animals and humans. Mycobacterium tuberculosis, along with M.
bovis, M. africanum, and M. microti all cause the disease
known as tuberculosis (TB) and are members of the tuberculosis species complex.
Each member of the TB complex is pathogenic, but M. tuberculosis is
pathogenic for humans while M. bovis is usually pathogenic for
animals.
M. bovis was causing TB in the animal kingdom long before invading humans.
However, after the domestication of cattle between 8000-4000 BC, there is archaeological
evidence of human infection by M. bovis probably through milk consumption.
M. tuberculosis is probably a human-specialized form of M. bovis
developed among milk-drinking Indo-Europeans who then spread the disease during
their migration into western Europe and Eurasia. By 1000 BC, M. tuberculosis
and pulmonary TB had spread throughout the known world.
What are Mycobacteria?
Tuberculosis complex organisms are:
Obligate aerobes growing most successfully in tissues with a high
oxygen content, such as the lungs.
Facultative intracellular pathogens usually infecting mononuclear
phagocytes (e.g. macrophages).
Slow-growing with a generation time of 12 to 18 hours (c.f. 20-30
minutes for Escherichia coli).
Hydrophobic with a high lipid content in the cell wall. Because the
cells are hydrophobic and tend to clump together, they are impermeable to
the usual stains, e.g. Gram's stain.
Known as "acid-fast bacilli" because of their lipid-rich
cell walls, which are relatively impermeable to various basic dyes unless
the dyes are combined with phenol. Once stained, the cells resist decolorization
with acidified organic solvents and are therefore called "acid-fast".
(Other bacteria which also contain mycolic acids, such as Nocardia,
can also exhibit this feature.)
The video shows M. tuberculosis cells subjected to the Ziehl-Neelsen
acid-fast staining procedure, a commonly used diagnostic method for
Mycobacteria:
How is TB diagnosed?
Symptoms of tuberculosis include:
Fever
Night-time sweating
Loss of weight
Persistent cough
Constant tiredness
Loss of appetite
Diagnosis of tuberculosis is made by a positive tuberculin skin test, an immune
reaction to a small quantity of tuberculosis antigens. It can be confirmed by
X rays of the chest and microscopic examination of sputum. Detection of significant
numbers of acid-fast bacilli (using the Ziehl-Neelsen stain) in sputum or tissue
samples is considered a positive diagnosis, although disease may confirmed by
laboratory culture of the bacterium (difficult, dangerous and slow - takes at
least 4 weeks).
Ziehl-Neelsen acid-fast staining procedure:
Heat fix cells on glass microscope slide.
Flood the slide with carbol fuchsin stain.
Heat the slide gently until it steams (5 min).
Pour off the carbol fuchsin.
Wash slide thoroughly with water.
Decolourize with acid-alcohol (5 min).
Wash slide thoroughly with water.
Flood slide with methylene blue counterstain
for 1 min.
Wash with water.
Blot excess water and dry in hand over bunsen flame.
How does TB kill people?
Tuberculosis kills 3,000,000 people in the world every year, more than AIDS,
malaria, and other tropical disease combined. One third of the world's population
is infected with tuberculosis. Tuberculosis is the leading infectious disease
cause of death and represents more than a quarter of the world's preventable
deaths.
Transmission of TB occurs primarily by the aerosol route but can also
occur through the gastrointestinal tract. Coughing by people with active TB
produces droplet nuclei containing infectious organisms which can remain suspended
in the air for several hours. Infection occurs if inhalation of these droplets
results in the organism reaching the alveoli of the lungs. Only 10% of immunocompetent
people infected with M. tuberculosis develop active disease in their
lifetime - the other 90% do not become ill and cannot transmit the organism.
However, in some groups such as infants or the immunodeficient (e.g. those with
AIDS or malnutrition), the proportion who develop clinical TB is much higher.
In the lung, the organism is taken up by alveolar macrophages and carried
to lymph nodes, from where it may spread to multiple organs. Two to eight
weeks after infection, cell mediated immunity (CMI) and hypersensitivity (DTH)
develop leading to the characteristic reaction to the tuberculin test
and, in immunocompetent individuals, containment of infection. Inflammatory
immune responses eventually result in lung damage.
How is TB treated?
In many countries, vaccination against TB is routinely practised. The Bacillus
Calmette-Guerin (BCG) vaccine is a live, attenuated strain of Mycobacterium
bovis which was introduced in 1922. However, the true efficacy of BCG is
unknown. Early clinical trials in Europe showed up to 80% protection, but more
recent trials in India and Africa showed little value.
Mycobacteria
are Gram-resistant (waxy cell walls), non-motile,
pleomorphic rods, related to the Actinomyces. Most Mycobacteria are found
in habitats such as water or soil. However, a few are intracellular
pathogens
of animals and humans. Mycobacterium tuberculosis, along with M.
bovis, M. africanum, and M. microti all cause the disease
known as tuberculosis (TB) and are members of the tuberculosis species complex.
Each member of the TB complex is pathogenic, but M. tuberculosis is
pathogenic for humans while M. bovis is usually pathogenic for
animals.
Timebomb:
The Global Epidemic of Multi-Drug Resistant Tuberculosis