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Mycobacterium dan

Sy. Miftahul El J.T
Droplet dispersal following a violent sneeze. Most of the 20 000 particles
seen are coming from the mouth.
(Reprinted with permission from FR Moulton (ed.), Aerobiology, 1942.
American Association for the Advancement of Science.)
Mikroorganisme Penyebab ISPA
Corynebacteriun diphteriae
Streptococcus pneumoniae
Mycobacterium tuberculosis
Candida albicans - Histoplasma capsulatum
Aspergillus niger - Cryptococcus neoformans
Rhizopus sp
Famili Orthomyxoviridae
Flu [H dan N]
Differential Diagnosa
Gram-resistant (waxy cell walls),
non-motile, pleomorphic rods, related to the Actinomyces.
found most often in dry and oily locales. The rods are 2-4
micrometers in length and 0.2-0.5 um in width.
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
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.
Slow-growing with a generation time of 12 to
18 hours (c.f. 20-30 minutes for Escherichia
coli), a physiological characteristic that may
contribute to its virulence.
Two media are used to grow MTB
Middlebrook's medium and Lowenstein
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.

Figure 29-1 Mycobacterial cell wall structure. The components include the (A) plasma membrane,
(B) peptidoglycans, (C) arabinogalactan, (D) mannose-capped lipoarabinomannan, (E) plasma-
associated and cell wall-associated proteins, (F) mycolic acids, and (G) glycolipid surface
molecules associated with the mycolic acids. (Redrawn from Karakousis et al: Cell Microbiol
6:105-116, 2004.)
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Known as "acid-fast bacilli" because of their lipid-
rich cell walls, Over 60% of the mycobacterial cell
wall is lipid. 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".
The lipid fraction of MTB's cell wall consists of three
major components: mycolic acids, cord factor, and

The high concentration of lipids in the cell wall of
Mycobacterium tuberculosis :
Impermeability to stains and dyes
Resistance to many antibiotics
Resistance to killing by acidic and alkaline compounds
Resistance to osmotic lysis via complement deposition
Resistance to lethal oxidations and survival inside of

all cause the disease known as tuberculosis
(TB) and are members of the tuberculosis
species complex. Each member of the TB
complex is pathogenic:
M. tuberculosis is pathogenic for humans
M. bovis is usually pathogenic for animals M.
bovis was causing TB in the animal kingdom long
before invading humans.
Night-time sweating
Loss of weight
Persistent cough
Constant tiredness
Loss of appetite
Symptoms of tuberculosis include
Tuberculosis: Infection vs Disease
TB Infection

TB disease in lungs

MTB present MTB present

Tuberculin skin test positive

Tuberculin skin test positive

Chest X-ray normal

Chest X-ray usually reveals lesion

Sputum smears and cultures negative

Sputum smears and cultures positive

No symptoms

Symptoms such as cough, fever,
weight loss

Not infectious Often infectious before treatment

Not defined as a case of TB

Defined as a case of TB

Tuberculin skin test, an immune reaction to a
small quantity of tuberculosis antigens.
X rays of the chest
Microscopic examination of sputum, may
confirmed by laboratory culture of the
bacterium (difficult, dangerous and slow -
takes at least 4 weeks).
PPD (purified protein derivative) is employed as the test antigen in the Mantoux test.
5 TU (tuberculin units), which equals 0.000lmg of PPD, in a 0.1 ml volume is
intracutaneously injected in the forearm. The test is read within 48-72 hours.
Positive if the diameter of the resulting lesion is 10 mm or greater. The lesion is
characterized by erythema (redness) and swelling and induration (raised and hard).
False positive tests usually manifest themselves as lesser reactions [ indicate prior
exposure or infection with other mycobacteria or vaccination with BCG].
False negatives are more rare than false positives but are especially common in AIDS
patients, malnutrition, steroids, etc.,

Administering the Mantoux test
Pulmonary tuberculosis.
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Ziehl-Neelsen acid-fast staining

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.

Pewarnaan BTA [Ziehl-Nelsen]
Badan kuman berwarna merah, dihitung jumlas sel
bakteri untuk menetapkan derajat patogenitas
MTB complexes are always found in the well-
aerated upper lobes of the lungs. ich is an agar
based medium and Lowenstein-Jensen
medium which is an egg based medium. MTB
colonies are small and buff colored when
grown on either medium. Both

Colonies of Mycobacterium tuberculosis on
Lowenstein-Jensen medium
Pengeraman minimal 2 minggu pada suhu 37
Figure 29-2 Mycobacterium tuberculosis colonies on Löwenstein-
Jensen agar after 8 weeks of incubation. (From Baron EJ, Peterson LR,
Finegold SM: Bailey and Scott's diagnostic microbiology, ed 9, St Louis,
1994, Mosby.)
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Mycobacterium kansasii colonies on Middlebrook agar 1 day after
exposure to light.
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2005 Elsevier
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.

Stages of the Disease

Disease progression depends on:
Strain of MTB
Prior exposure
Infectious dose
Immune status of the host

stage 1: Droplet nuclei are inhaled. One droplet
nuclei contains no more than 3 bacilli, so small [5
micrometers] that they can remain air-borne for
extended periods of time. The most effective
(infective) droplet nuclei tend to have a diameter of.
Droplet nuclei are generated by during talking [for 5
minutes generates 3000 droplet nuclei], coughing
[about 3000 droplet nuclei] and sneezing [generates
the most droplet nuclei by far, which can spread to
individuals up to 10 feet away] .

Spread of droplet nuclei from one individual to another. After droplet
nuclei are inhaled, the bacteria are nonspecifically taken up by alveolar
macrophages. However, the macrophages are not activated and are unable
to destroy the intracellular organisms.
Tuberculosis begins when droplet nuclei reach the alveoli. When a person
inhales air that contains droplets most of the larger droplets become lodged
in the upper respiratory tract (the nose and throat), where infection is
unlikely to develop. However, the smaller droplet nuclei may reach the small
air sacs of the lung (the alveoli), where infection begins.

Stage 2
Begins 7-21 days after initial infection. MTB
multiplies virtually unrestricted within
unactivated macrophages until the
macrophages burst. Other macrophages begin
to extravasate from peripheral blood. These
macrophages also phagocytose MTB, but they
are also unactivated and hence can not
destroy the bacteria.

Stage 3
At this stage lymphocytes specifically T-cells begin to
infiltrate,recognize processed and presented MTB antigen in
context of MHC molecules. This results in T-cell activation and
the liberation of cytokines including gamma interferon (IFN).
The liberation of IFN causes in the activation of macrophages.
These activated macrophages are now capable of destroying
It is at this stage that the individual becomes tuberculin-
The secondary lesions caused by milliary TB can occur at almost
any anatomical location, but usually involve the genitourinary
system, bones, joints, lymph nodes and peritoneum. These
lesions are of two types:
1. Exudative lesions result from the accumulation of PMN's
around MTB. Here the bacteria replicate with virtually no
resistance. This situation gives rise to the formation of a "soft
2. Productive or granulomatous lesions occur when the host
becomes hypersensitive to tuberculoproteins. This situation
gives rise to the formation of a "hard tubercle".

Stage 4
Although many activated macrophages can be found
surrounding the tubercles, many other macrophages present
remain unactivated or poorly activated. MTB uses these
macrophages to replicate, and hence, the tubercle grows.
The growing tubercle may invade a bronchus MTB infection
can spread to other parts of the lung. Similarly the tubercle may
invade an artery or other blood supply line. The hematogenous
spread of MTB may result in extrapulmonary tuberculosis
otherwise known as milliary tuberculosis.

Stage 5
For unknown reasons, the caseous centers of the tubercles
liquefy. This liquid is very conducive to MTB growth, and the
organism begins to rapidly multiply extracellularly. After time,
the large antigen load causes the walls of nearby bronchi to
become necrotic and rupture. This results in cavity formation.
This also allows MTB to spill into other airways and rapidly
spread to other parts of the lung.
Only a very small percent of MTB infections result in disease,
When the primary lesion heals, it becomes fibrous and calcifies
Ghon complex.
Depending on the size and severity is readily visible upon chest X-ray.
Small metastatic foci containing low numbers of MTB may also
calcify. However, in many cases these foci will contain viable
organisms. These foci are referred to Simon foci.
Depending on the size and severity is readily visible upon chest X-ray.
Small metastatic foci containing low numbers of MTB may also
calcify. However, in many cases these foci will contain viable
organisms. These foci are referred to Simon foci. The Simon foci are
also visible upon chest X-ray and are often the site of disease

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.

The first effective treatment for TB was developed in
the 1940s streptomycin.TB is currently treated by
means of combination therapy, using cocktails of 3-4
drugs with different properties:
Antibacterial activity: e.g. isoniazid, rifampin,
Inhibiting the development of resistance: e.g.
isoniazid, rifampin, ethambutol

How is TB treated?

Jenis, sifat dan dosis OAT

Jenis OAT

Dosis yang direkomendasikan [mg/kg]

Harian 3x seminggu

Isoniazid (H) Bakterisid


10 (8-12)

Rifampicin (R) Bakterisid 10(8-12)


Pyrazinamide (Z) Bakterisid 25 (20-30) 35 (30-40)

Streptomycin (S) Bakterisid 15 (12-18)

15 (12-18)

Ethambutol (E) Bakteriostatik 15 (15-20)

30 (20-35)