Mycobacterium tuberculosis and Mycobacterium leprae

13,010 views 67 slides Apr 29, 2016
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About This Presentation

Mycobacterium leprae (uncommon)
Mycobacterium avium-intracellulaire Complex (MAC) or (M. avium)
Mycobacterium leprae


Slide Content

TB has been known
as Pthisis, King’s
Evil, Pott’s
disease,
consumption, and
the White Plague.
Egyptian mummies
from 3500 BCE
have the presence
of Mycobacterium
tuberculosis

Started in Europe
in 1600’s
Reigned for around
200 years
Named for the loss
of skin color of
those infected

Infected the New
World before the
Europeans
10% deaths in the 19
t h

century were due to
TB
Isolated the infected
in sanitariums, which
served as waiting
rooms for death

Mycobacterium tuberculosis
Mycobacterium
tuberculosis is the
etiologic agent of
tuberculosis  in
humans.
Humans are the only
reservoir for the
bacterium.
Humans can also be
infected by the
consumption of
unpasteurized milk.
This route of
transmission can lead
to the development of
extrapulmonary TB,

Cell Morphology
Weakly gram-positive,
strongly acid-fast, aerobic
bacilli (rod).
The rods are 2-4
micrometers in length and
0.2-0.5 um in width.
Lipid-rich cell wall,
making the organism
resistant to disinfectants,
detergents, common
antimicrobial drugs and
traditional stains.
Capable of intracellular
growth in inactivated
alveolar macrophages.
Disease primarily from
host response to infection.
Arranged in colonies

SEM of M. tuberculosis
M. Tuberculosis
(stained in purple)

Humans are the only reservoir
Inhalation of droplet nuclei containing
M.tuberculosis
Replication in lungs
(granuloma formation)
Lymphohematogenous spread:
dissemination throughout body inside
macrophages
Cell-mediate immune response leads to
granuloma formation:
Latent infection
Reactivation

Granuloma formation:
activated lymphocytes,
macrophages, Langhans
giant cells, fibroblasts and
capillaries
Caseous necrosis:  leads
to liquefaction of necrotic
tissue leads to cavitations
in lungs
MTB in granuloma  latent
for years and then if
immunity wanes the AFB
can reactivate

The photomicrograph shows a caseous granulomatous lesion in a lymph
node and the causative agents are not decernible in the H&E stained
section. The inserted image(right hand corner) shows the section
following a Ziehl-Neelsen acid-fast special stain viewed under an oil
objective. The pink rod microbes,the causative agents engulfed in the
giant cells, are Mycobacteria tuberculosis.”
LYMPH NODE LUNGS TISSUE

M. Tuberculosis in sputum
(stained in red)
M. tuberculosis:
- Acid Fast Bacilli (AFB)
- Risk group 3 bacterium
- Humans are the only reservoir
Pathogenesis:
- Inhalation of infectious droplet nuclei
- unrestricted replication  spreads throughout body
- Cell-mediated immune response
- Granuloma formation  latent infection
- Reactivation if immunity wanes
Public Health Risk
- Pulmonary TB highest risk for spread
- HIV link
- MDR: multi-drug resistant strains

TB infection is detected by the administration of a tuberculin skin
test on the arm. A single needle is used to put some testing
material, called tuberculin, under the skin. In two or three days, a
nurse or a doctor will check to see if there is a reaction to the
test. The test is "positive" if a bump about the size of a pencil
eraser or bigger appears on the arm. This bump means a person
probably has TB infection. A chest X-ray is done to see if
someone with a positive skin tests (TB infection) also has TB
disease.
People who are infected with TB do not feel sick, do not have
any symptoms and have a normal chest X-ray cannot spread TB.
However, they may develop TB disease at some time in the
future. People with TB infection but are not yet sick can take
medicine so that they will never develop TB disease.

M. Tuberculosis in sputum
(stained in red)

Extra-pulmonary TB: Symptoms depend on location of infection
General symptoms: fatigue, fever, loss of appetite, weight loss.
TB of lymph nodes: swelling of lymph nodes
TB meningitis: neurological symptoms including headache
Spinal TB: Mobility impairments, pain

•Mycobacterium tuberculosis is the
bacterial specie that causes most cases
of tuberculosis.
•Like all bacteria, Mycobacterium
tuberculosis is an extremely small
organism, having a rod-like body that is
only a few microns (1/10,000 of an inch)
in length.
•In many individuals, the body mounts
an immune response to this infection that
is successful in either clearing out the
bacteria or walling them off so they exist
in a dormant state.
•the invading organisms proceed to
destroy tissue and create lesions
(tubercles) in the lungs.

•Due to the notable slow growth rate of this
bacteria, death for the victim can take many
months or even years.
•Within the lungs, Mycobacterium
tuberculosis cells are ingested by specialized
cells of the body's immune system known as
macrophages.
• Due to their unique waxy surface coating, the
bacteria are not destroyed by this action as other
invaders would be, but instead begin to replicate
themselves within the macrophages.
•Other immune cells then swarm to the site of
infection to keep it from spreading further,
resulting in the formation of a dense spherical
mass termed a granuloma.
•n others, the bacteria persist and remain viable,
albeit in a dormant walled-off nodule. While the
latter outcome does lead to an asymptomatic
latent infection, this is nevertheless fully capable
of causing tuberculosis later in life if the body's
immune system becomes weakened or
compromised.

Proteins that are actively secreted during culture on synthetic
media represent a particular group of great current interest.
At least eight proteins secreted by Mycobacterium tuberculosis
have been isolated and characterized to various extents.
All of them contain typical signal sequences.
The proteins of the antigen 85 complex, which form the main
subject of this review, are often the most common proteins in
M. tuberculosis culture fluid.
The constituents denoted 85A, 85B, and 85C are encoded by
three genes located at different sites in the mycobacterial
genome and show extensive cross-reactivity as well as
homology at amino acid and gene levels.
Secreted mycobacterial antigens are expected to be of
particular significance in induction of various immune responses
that are responsible for development of protective immunity in
some individuals and for clinical symptoms and complications
of the ensuing disease in others.

M. tuberculosis requires oxygen to grow. It does not
retain any bacteriological stain due to high lipid
content in its wall, and thus is neither Gram-positive
nor Gram-negative; hence Ziehl-Neelsen staining, or
acid-fast staining, is used. While mycobacteria do not
seem to fit the Gram-positive category from an
empirical standpoint (i.e., they do not retain the
crystal violet stain), they are classified as acid-fast
Gram-positive bacteria due to their lack of an outer
cell membrane.
[1]

M. tuberculosis divides every 15–20 hours,
which is extremely slow compared to other
bacteria, which tend to have division times
measured in minutes (Escherichia coli can
divide roughly 20 minutes).
M. tuberculosis is characterized by
caseating granulomas containing
Langhans giant cells, which have a
"horseshoe" pattern of nuclei.
Organisms are identified by their red
color on acid-fast staining.

The use of blood agar media for the recovery of M. tuberculosis was
reported early in the last century but has been removed from
contemporary microbiology manuals (4, 6). However, there have
been more recent reports, including one from 1998 in which Arvand
et al. isolated M. tuberculosis from a lymph node when investigating a
diagnosis of cat scratch disease (1). Even earlier, a comparative study
of different media conducted in 1977 suggested that penicillin blood
agar would be at least as good as, if not better than, Löwenstein-
Jensen medium for recovering M. tuberculosis (3).
The study of Drancourt et al. with clinical samples is very useful in once
again highlighting the ability of these media to grow M. tuberculosis,
in particular when this is not the organism being sought. Moreover, we
agree with Drancourt et al. in highlighting the importance of handling
in a secure manner culture media which are not specific for
mycobacteria but require prolonged incubation, as we have already
stated in our paper. Sealing the agar plates with adhesive tape
(Micropore surgical tape; 3M, St. Paul, Minn.) is a simple way to avoid
risks.

Tuberculosis (TB) is the most common major infectious disease today. It is
estimated that two billion people--or one-third of the world's population--are
chronically infected without active symptoms. Nine million new cases of
active disease are diagnosed annually, resulting in two million deaths. TB is
predominantly a lung disease. It is caused by a microbe called
Mycobacterium tuberculosis which infects lung cells, but it is still not clear how
exactly this happens. Ludovic Tailleux, Olivier Neyrolles, and colleagues (from
the Pasteur Institute, in collaboration with the Necker and Saint-Louis Hospitals,
in Paris) have found that a molecule called DC-SIGN plays a crucial part.

The researchers wanted to examine whether lung cells from patients with TB
were different from those of healthy people or those with different lung diseases,
and what that tells us about the way the infection spreads in the lung. In
particular, they looked at the surface of the lung cells, because this is the part
directly involved in the first contact with the Mycobacterium. As they report
now in the international open-access medical journal PLoS Medicine, they
studied 74 individuals, 40 of whom had TB, 25 had other inflammatory lung
diseases, and 9 had neither active TB nor lung inflammation and served as
healthy "controls." The patients underwent a procedure called broncho-
alveolar lavage that washes out some of the secretions and cells from the lower
respiratory tract. The researchers then analyzed the cells in different ways. They
concentrated on a type of cell called a macrophage (the natural target of
Mycobacterium) and found that macrophages from patients with TB had much
more the DC-SIGN protein on their surface than macrophages from patients
with other diseases or from the control individuals.
They then took macrophages from a control individual (which had very low
levels of DC-SIGN) and infected them with Mycobaterium under laboratory
conditions. They found that shortly after infection not only the infected cells but
also some of their neighbours started to display DC-SIGN on their surface. They
also found that having DC-SIGN on the surface made uninfected cells much
more susceptible to infection.

highly fatal form if not adequately treated. In
fact, once the bacilli enter the bloodstream,
they can travel to almost any organ of the
body, including the lymph nodes, bones...
When still active, pulmonary tuberculosis is a
constant threat to the patient, because
blood-borne spread may occur at any time.
Diffuse spread of tuberculosis in the lung
(known as miliary tuberculosis)

An Infection Of The Meninges That
Cover The Brain Causes Tuberculous
Meningitis; Before The Advent Of
Specific Drugs, This Disease Was
Always Fatal, Though Most Affected
People Now Recover.
In Many Developing Countries,
Tuberculous Meningitis Is Common.

The global tuberculosis epidemic
An estimated 14 million people worldwide are infected with active
tuberculosis (TB), which is a disease of poverty affecting mainly young
adults in their most productive years. In 2009 there were 9.4 million
new cases of TB and 1.7 million deaths, including 380,000 deaths from
TB among people with HIV. The vast majority of deaths from TB are
in the developing world.
The latest data released by the World Health Organization (WHO) in
November 2010 show that the number of new cases continues to fall
globally and in five of the six WHO regions. The exception is
Southeast Asia, where incidence remains stable. In many countries TB
prevalence is declining. Worldwide, deaths from TB fell by 35 percent
between 1990 and 2009.
If current trends continue the world can meet the Millennium
Development Goal target for incidence – that new cases should be
falling by 2015 – and the Stop TB Partnership target to halve TB
mortality by 2015 in comparison with 1990.

Progress in tackling the global TB burden is associated with DOTS, the basic
package that underpins the Stop TB Strategy, which was adopted by the WHO
in 1993. The expansion of DOTS across the world since the mid-1990s is
tracked through the proportion of estimated new TB cases that are detected –
or “notified” – and successfully treated under DOTS.
In 2009 5.8 million cases of all kinds of TB were notified globally, equivalent
to a 63 percent case detection rate compared with 61 percent in 2008.*
Treatment success rates continue to be measured in terms of smear-positive
pulmonary TB only. Of the 2.6 million cases notified in 2008, 86 per cent were
successfully treated against the new 90 percent target included in the 2011-
2015 update of the Global Plan to Stop TB.
A total of 41 million TB patients were successfully treated in DOTS programs
between 1995 and 2009.
The Global Fund has helped to accelerate case detection and successful
treatment in recent years, with 1.7 million additional cases of TB detected and
treated by Global Fund-supported programs in 2010, compared with 1.4
million in 2009 and 1.3 million in 2008. Since the Global Fund’s inception in
2002, programs it has financed had supported DOTS for a total of 7.7 million
people by December 2010.

A child receiving a tuberculosis vaccine at school in Bulacan province,
Philippines, c. 1952.

The micro bacterial leprae
generation time is 12 to14
days!
 it is an Acid Fast Bacteria i.e
the decolorizer used in its
gram staining is a very strong
acid and they are very
resistant to even acid!
It presence is indicated by
the appearance of red color
in slide
Optimum temperature
required for max growth is 30
degree.
It shows preference of
growth in outer cooler
places.
 leprosy have never been
grown in artificial media!

LEPROSY

Leprosy is a chronic infectious
disease caused by
mycobacterium leprae, an acid-
fast, rod-shaped bacillus.
The disease mainly affects the
skin, the peripheral nerves,
mucosa of the upper respiratory
tract and also the eyes, apart
from some other structures.
 Leprosy has afflicted humanity
since time immemorial. It once
affected every continent and it
has left behind a terrifying image
in history and human memory -
of mutilation, rejection and
exclusion from society

The bacterium that causes Leprosy is rod-
shaped and called Mycobacterium leprae.
When Mycobacterium leprae enters the
body, one of these things can happen:
1)Tuberculoid leprosy (TT) :
The body's immune cells attempt to seal off
the infection from the rest of the body by
surrounding the offending pathogen.
2)Lepromatous leprosy (LL) :
•This is the more dangerous type, in which
the body's immune system is unable to
mount a strong response to the invading
organism. Hence, the organism multiplies
freely in the skin. This type of leprosy is also
called the multibacillary (MB) leprosy,
because of the presence of large numbers
of bacteria. Occasionally, the mucous
membranes of the eyes, nose, and throat
may be involved.

Leprosy has struck fear into human beings for thousands of years, and
was well recognized in the oldest civilizations of China, Egypt and
India.
Since ancient times, leprosy has been regarded by the community as
a contagious, mutilating and incurable disease.
There are many countries in Asia, Africa and Latin America with a
significant number of leprosy cases. It is estimated that there are
between one and two million people visibly and irreversibly disabled
due to past and present leprosy who require to be cared for by the
community in which they live.
When M.leprae was discovered by G.A. Hansen in 1873, it was the
first bacterium to be identified as causing disease in man. However,
treatment for leprosy only appeared in the late 1940s with the
introduction of dapsone, and its derivatives.

The most widely held belief
was that the disease was
transmitted by contact
between cases of leprosy
and healthy persons.
More recently the
possibility of transmission
by the respiratory route is
gaining ground.
There are also other
possibilities such as
transmission through
insects which cannot be
completely ruled out
TRANSMISSION BY CONTACT:
The term 'contact' in leprosy is generally not
clearly defined. All that we know at present is that
individuals who are in close association or
proximity with leprosy patients have a greater
chance of acquiring the disease.
In general, closeness of contact is related to the
dose of infection which in turn is related to the
occurrence of disease. Of the various situations that
promote close contact, contact within the
household is the only one that is easily identified.
TRANSMISSION THROUGH INSECTS:
With the available evidence on intracutaneous
inoculation as a successful method of transmission
of M.leprae in the mouse footpad model and a
similar situation possibly existing in human beings,

"scaly skin."
 
Kingdom: Bacteria
Phylum: Actinobacteria
Order: Actinomycetales
Suborder: Corynebacterineae
Family: Mycobacteriaceae
Genus: Mycobacterium
Species: M. leprae
 
It's easy to look at a listing of the scientific classification, but why does it 
belong to each of those groups? Here is a brief explanation...

Kingdom: Bacteria
This organism belong to the kingdom bacteria because it fits the typical 
characteristics of prokaryotic bacteria,

Signs and Symptoms of Leprosy
Signs and symptoms of leprosy usually appear
three to five years after becoming infected with
Mycobacterium leprae -- the bacteria responsible
for the disease. Leprosy usually affects the skin
and peripheral nerves. However, once signs and
symptoms of leprosy begin, there can be a wide
variety of symptoms and severity. The type of
leprosy a person has is also a factor.

It is important to note that not all people with leprosy 
lose their fingers and toes. With early diagnosis and 
leprosy treatment, many of these signs and symptoms 
of leprosy can be prevented. Many patients with 
tuberculoid disease can even self-heal without benefit 
of treatment. In order to prevent problems with 
fingers or toes, people should avoid injury and 
infections to these areas and take their medicines as 
prescribed.

Mycobacterium Avium Complex (MAC) is not spread through 
person-to-person contact. This The most common TB Cousin, 
MAC, presents itself like many other illnesses. Avoiding contact 
with some source of MAC is virtually impossible. Animal, water, 
air, food, soil, tobacco products are all suspected vectors for the 
mycobacterium avium complex. MAC may be misdiagnosed as 
just another pulmonary exacerbation, or the flu. Common 
symptoms of infection include: 
Fever 
Chills 
Swollen Glans
Nigh sweats 
Fatigue

Leprosy occurs in armadillos as well 
-Men are twice as likely to catch leprosy than women 
-In some folklore, they believe if you catch leprosy 
then your limbs will fall off

Mycobacterium leprae Mycobacterium leprae

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