Ila 4 Tuberculosis Final Compilation

8/3/2019 Ila 4 Tuberculosis Final Compilation

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ILA 4: TUBERCULOSIS

Definition

Tuberculosis:

-contagious infectioncaused by the bacterium called

-Mycobacterium tuberculosis. Abbreviated TB. Tubercles (tinylumps) are a characteristic finding in TB.

Diagnosis may be made by skin test, which if positive should will be followed by a chest X-ray to

determine the status (active or dormant) of the infection.

Tuberculosis is more common in people with immune systemproblems, such as AIDS, than in the general population.

Treatment of active tuberculosis is mandatory by law in the US, and should be available at no

cost to the patient through the public health system. It involves a course of antibiotics and

vitamins that lasts about six months. It is important to finish the entire treatment, both to

prevent reoccurrence and to prevent the development of antibiotic-resistant tuberculosis. Most

patients with tuberculosis do not need to be quarantined, but it is sometimes necessary.

Although there are millions of new cases of TB each year, not everyone exposed to the

bacterium becomes infected nor does everybody infected with it develop clinical symptoms ofTB.

A genetic regionhas been discovered to be associated with clinical TB. Peoplewith at least one high-risk copy of this genetic region are ten times more likely to develop TB

than normal. The genetic region contains a gene, NRAMP1, that is known to be involved inthe susceptibility to leprosy, which is caused by a bacterium related to TB
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Types of Tuberculosis

Tuberculosis is divided into three clinically important categories:

Primary TB

Secondary Reactivated TB Disseminated/Milliary TB

Primary Tuberculosis

Primary tuberculosis refers to the infection process which eventually eliminates the pathogen

or results in a stalemate between the Mycobacteria and the immune system. With most TB

infections, the immune system is able to restrain, although not eliminate,

the Mycobacteria within the tubercle, preventing the spread of

bacteria and progression of the disease. M. tuberculosis can remain in thisimpasse of dormant infection for many years.

Tubercles in the lungs develop as a result of infection by theMycobacterium

tuberculosisbacterium.Granulomasform in the infected tissue and undergonecrosisin the centre.

Tubercles are also known as tuberculous nodules. For more information seeTuberculosis.

Dormant-inactive

Impasse-a position or situation from which there is no escape

Tubercle-such a swelling as the characteristic lesion oftuberculosis.

Stalemate

any position or situation in which no action can be taken orprogress made; deadlock

Secondary or Reactivated Tuberculosis

The infection can become reactivated if the Mycobacteria are able to

rupture the tubercle and spread through the lungs. This reactivation

typically happens to those with a weakened or suppressed immune

system.
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Disseminated/Milliary Tuberculosis

The spread of the disease within the body may result if infected macrophages moving through

the blood and lymph transport the bacteria to other sites. Once infected, symptoms of

disseminated TB correspond to the locations infected. The antiquated term "consumption"

arose from the myriad of symptoms associated with disseminated tuberculosis, when thoseinfected seemed to slowly waste away

Signs and Symptoms

Transmission

Tuberculosis spreads by droplet infection. This type of transmission means that when a TB

patient exhales, coughs, or sneezes, tiny droplets of fluid containing tubercle bacilli are released

into the air. This mist, or aerosol as it is often called, can be taken into the nasal passages and

lungs of a susceptible person nearby. Tuberculosis is not, however, highly contagious comparedto some other infectious diseases. Only about one in three close contacts of a TB patient, and

fewer than 15% of more remote contacts, are likely to become infected. As a rule, close,

frequent, or prolonged contact is needed to spread the disease. Of course, if a severely infected

patient emits huge numbers of bacilli, the chance of transmitting infection is much greater.

Unlike many other infections, TB is not passed on by contact with a patient's clothing, bed

linens, or dishes and cooking utensils. The most important exception ispregnancy. The fetus of

an infected mother may contract TB by inhaling or swallowing the bacilli in the amniotic fluid.

Progression

Once inhaled, tubercle bacilli may reach the small breathing sacs in the lungs (the alveoli),

where they are taken up by cells called macrophages. The bacilli multiply within these cells and

then spread through the lymph vessels to nearby lymph nodes. Sometimes the bacilli move

through blood vessels to distant organs. At this point they may either remain alive but inactive

(quiescent), or they may cause active disease. Actual tissue damage is not caused directly by

the tubercle bacillus, but by the reaction of the person's tissues to its presence. In a matter of

weeks the host develops an immune response to the bacillus. Cells attack the bacilli, permit the

initial damage to heal, and prevent future disease permanently.

Infection does not always mean disease; in fact, it usually does not. At least nine of ten patients

who harbor M. tuberculosis do not develop symptoms or physical evidence of active disease,

and their x-rays remain negative. They are not contagious; however, they do form a pool of

infected patients who may get sick at a later date and then pass on TB to others. It is thoughtthat more than 90% of cases of active tuberculosis come from this pool. In the United States

this group numbers 10-15 million persons. Whether or not a particular infected person will

become ill is impossible to predict with certainty. An estimated 5% of infected persons get sick

within 12-24 months of being infected. Another 5% heal initially but, after years or decades,

develop active tuberculosis either in the lungs or elsewhere in the body. This form of the

disease is called reactivation TB, or post-primary disease. On rare occasions a previously

infected person gets sick again after a later exposure to the tubercle bacillus.
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Pulmonary tuberculosis

Pulmonary tuberculosis is TB that affects the lungs. Its initial symptoms are easily confused with

those of other diseases. An infected person may at first feel vaguely unwell or develop

acoughblamed onsmokingor a cold. A small amount of greenish or yellow sputum may be

coughed up when the person gets up in the morning. In time, more sputum is produced that is

streaked with blood. Persons with pulmonary TB do not run a highfever, but they often have alow-grade one. They may wake up in the night drenched with cold sweat when the fever

breaks. The patient often loses interest in food and may lose weight. Chestpainis sometimes

present. If the infection allows air to escape from the lungs into the chest cavity

(pneumothorax) or if fluid collects in the pleural space (pleural effusion), the patient may have

difficulty breathing. If a young adult develops a pleural effusion, the chance of tubercular

infection being the cause is very high. The TB bacilli may travel from the lungs to lymph nodes

in the sides and back of the neck. Infection in these areas can break through the skin and

discharge pus. Before the development of effective antibiotics, many patients became

chronically ill with increasingly severe lung symptoms. They lost a great deal of weight and

developed a wasted appearance. This outcome is uncommon today

at least where moderntreatment methods are available.

Extrapulmonary tuberculosis

Although the lungs are the major site of damage caused by tuberculosis, many other organs and

tissues in the body may be affected. The usual progression is for the disease to spread from the

lungs to locations outside the lungs (extrapulmonary sites). In some cases, however, the first

sign of disease appears outside the lungs. The many tissues or organs that tuberculosis may

affect include:

Bones. TB is particularly likely to attack the spine and the ends of the long bones.

Children are especially prone to spinal tuberculosis. If not treated, the spinalsegments (vertebrae) may collapse and causeparalysisin one or both legs.

Kidneys. Along with the bones, the kidneys are probably the commonest site of

extrapulmonary TB. There may, however, be few symptoms even though part of a

kidney is destroyed. TB may spread to the bladder. In men, it may spread to the

prostate gland and nearby structures.

Female reproductive organs. The ovaries in women may be infected; TB can spread

from them to the peritoneum, which is the membrane lining the abdominal cavity.

Abdominal cavity. Tuberculousperitonitismay cause pain ranging from the vague

discomfort of stomach cramps to intense pain that may mimic the symptoms ofappendicitis.

Joints. Tubercular infection of joints causes a form of arthritis that most often affects

the hips and knees. The wrist, hand, and elbow joints also may become painful and

inflamed.

Meninges. The meninges are tissues that cover the brain and the spinal cord.

Infection of the meninges by the TB bacillus causes tuberculousmeningitis, a

condition that is most common in young children but is especially dangerous in the
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elderly. Patients develop headaches, become drowsy, and eventually comatose.

Permanent brain damage is the rule unless prompt treatment is given. Some patients

with tuberculous meningitis develop a tumor-like brain mass called a tuberculoma

that can cause stroke-like symptoms.

Skin, intestines, adrenal glands, and blood vessels. All these parts of the body can be

infected by M. tuberculosis. Infection of the wall of the body's main artery (theaorta), can cause it to rupture with catastrophic results.

Tuberculouspericarditisoccurs when the membrane surrounding the heart (the

pericardium) is infected and fills up with fluid that interferes with the heart's ability

to pump blood.

Miliary tuberculosis. Miliary TB is a life-threatening condition that occurs when large

numbers of tubercle bacilli spread throughout the body. Huge numbers of tiny

tubercular lesions develop that cause marked weakness and weight loss, severe

anemia, and gradual wasting of the body.

Diseases similar to tuberculosis

There are many forms of mycobacteria other than M. tuberculosis, the tubercle bacillus. Some

cause infections that may closely resemble tuberculosis, but they usually do so only when an

infected person's immune system is defective. People who are HIV-positive are a prime

example. The most common mycobacteria that infect AIDS patients are a group known

as Mycobacterium avium complex (MAC). People infected by MAC are not contagious, but they

may develop a serious lung infection that is highly resistant to antibiotics. MAC infections

typically start with the patient coughing up mucus. The infection progresses slowly, but

eventually blood is brought up and the patient has trouble breathing. In AIDS patients, MAC

disease can spread throughout the body, with anemia,diarrhea, and stomach pain as common

features. Often these patients die unless their immune system can be strengthened. Other

mycobacteria grow in swimming pools and may cause skin infection. Some of theminfectwoundsand artificial body parts such as a breast implant or mechanical heart valve.

Causative Agent

Causative agent for tuberculosis is Mycobacterium tuberculosis. Mycobacteria are slender rods that are acid fast stain.

These organism are aerobic, non motile, non capsulated and non sporing.

There are four species ; M. tuberculosis, M. bovis, M. microti,M. africanum Mycobacteria tuberculosis hominis is responsible for most cases of TB ; the reservoir of

infection is usually found in humans with active pulmonary disease.

Transmission is usually inhalation of airborne organisms in aerosols generated by

expectoration or by exposure to contaminated secretion of infected persons.

Mycobacteria Tuberculosis is not classified as either Gram-positive or Gram-negative

because it does not have the chemical characteristics of either, although the bacteria do
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contain peptidoglycan (murein) in their cell wall. If a Gram stain is performed, it stains

very weakly Gram-positive or not at all.

The cell wall structure ofMycobacterium tuberculosis

contain high concentration of lipid. The high concentration of lipids inthe cell wall of Mycobacterium tuberculosis have been associated with these properties

of the bacterium:

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 macrophages

Morphology of Mycobacterium Tuberculosis

Mycobacteria are Gram-positive (no outer cell membrane), 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, M. microti, and M. canettii. all cause the disease known as tuberculosis

(TB) and are members of the tuberculosis species complex. Each member of theTB complex is pathogenic, but M. tuberculosis is pathogenic for humans while M.

bovis is usually pathogenic for animals.

M. tuberculosis is an obligate aerobe mycobacterium (Gram positive) that divides

every 15 to 20 hours. This is extremely slow compared to other bacteria, which

tend to have division times measured in minutes. It is a small, rod-like bacillus that

can withstand weak disinfectants and can survive in a dry state for weeks but

can grow only within a host organism.

M. tuberculosis is identified microscopically by its staining characteristics: it retains

certain stains after being treated with acidic solution, and is thus classified as an

"acid-fast bacillus". Acid-fast bacilli can be visualized by fluorescent microscopy,

and by auramine-rhodamine stain. The reason for the acid-fast staining seen in

mycobacteria is because of its thick waxy cell wall.

Species Common name


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M. tuberculosisHuman tubercle

bacillus

M. bovis

Bovine tubercle

bacillus

M. africanumAfrican tubercle

bacillus

M. microti Vole tubercle bacillus

[Image link] :

1. Colonial morphology ofMycobacterium tuberculosis(Wikipedia)

2. Mycobacterium tuberculosis, 1000x (click)

The Acid-Fast Stain

Bacteria with an acid-fast cell wall when stained by the acid-fast procedure, resist

decolorization with acid-alcohol and stain red, the color of the initial stain, carbol

fuchsin. The genusMycobacterium and the genus Nocardia are acid-fast. All other

bacteria will be decolorized and stain blue, the color of the counterstain

methylene blue.

The acid-fast stain is an especially important test for the genus Mycobacterium.

Besides the many saprophytic forms of mycobacteria, there are two distinct

pathogens in this group: M. tuberculosis, the causative organism of tuberculosis,

and M. leprae, the causative agent of leprosy.Mycobacterium tuberculosis (the

tubercle bacillus) causes tuberculosis, although atypical species

ofMycobacterium may occasionally cause tuberculosis-like infections, especially in

the debilitated or immunosuppressed host. Mycobacterium avium-

intracellulare complex (MAC), for example, frequently causes systemic infections

in people with HIV/AIDS.
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Pathogenesis

About 90% of those infected with Mycobacterium tuberculosis have asymptomatic,

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

of alveolar macrophages.

The primary site of infection in the lungs is called the Ghon focus, and is generally

located in either the upper part of the lower lobe, or the lower part of the upper lobe.

Bacteria are picked up by dendritic cells, which do not allow replication, although these

cells can transport the bacilli to local (mediastinal) 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.

Dendritic cells(DCs) areimmune cellsforming part of themammalianimmune system. Their main

function is to process antigen material and present it on the surface to other cells of the immune system.

That is, they function asantigen-presenting cells.

All parts of the body can be affected by the disease, though it rarely affects the heart,

skeletal muscles, pancreas and thyroid.

Tuberculosis is classified as one of the granulomatous

inflammatory conditions.Macrophages, Tlymphocytes, B lymphocytes, and fibroblasts are among the cells that

aggregate to form granulomas, with lymphocytes surrounding the infected

macrophages.

The granuloma prevents dissemination of the

mycobacteriaand provides a local environment for interaction ofcells of the immune system.
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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) in the center of tubercles.

To the naked eye this has the texture ofsoft white cheese and is termed caseous

necrosis.

Chain of Transmission of TB

Etiologic Agent

The etiologic agent is any microorganism that causes infection. For TB, it's Mycobacteriumtuberculosis. The better its ability to grow, invade tissue, and cause disease, the greater the

possibility of the bacterium causing an infection.

Reservoir

The reservoir of infection might be human, animal or objects such as countertops and

doorknobs. This gives the microorganism a place to thrive and reproduce. The only reservoir for

TB is the human.

Portal of Exit

This is where the microorgansim leaves the reservoir. TB's portal of exit is via the mouth and

nose. When someone with TB sneezes or coughs, they release large numbers of the TB

microbacterium.

Mode of Transmission


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The mode of transportation is how the bacterium moves from one place

to another. Many bacterium are transported by unwashed hands that transmit the

bacterium to other surfaces. With TB, however, the mode of transmission is the cough

or sneeze that releases TB bacterium into the air. Itcan then be inhaled by another person in the room.

Portal of Entry

Many portals of entry exist for microorganisms, including breaks in the skin, mucus membranes

(the nose and mouth) and orifices in the body. TB's portal of entry is also its portal

of exit--the human respiratory system. Just as the TB bacterium can be expelled

by sneezing, it can be inhaled by the nose and mouth.Susceptible Host

Microorganisms look for a host who can easily be

invaded, such as someone who is already sick or has a

low immune system.An older person with HIV or AIDS will have a much hardertime surviving TB than a young, healthy 25-year-old.

Epidemiology of tuberculosis

Chronic Inflammation

What is chronic inflammation?

Inflammation that has a slow onset and persists for weeks or more

Symptoms are not as severe as with acute inflammation, but the condition is

insidious and persistent.

May:

o follow on from acute inflammation

o Due to recurrent acute inflammation

o Chronic inflammation itself from beginning without any acute phase

Characteristics

1. Mononuclear cells infiltration

Lymphocyte Tissue macrophage


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Macrophage , lymphocyte, plasma cells

indicates persistent reaction to injury

2. Damage to tissue

Necrosis Done by way of inflammatory cells

3. Repairing process (Angiogenesis and fibrosis)

Attempt to replace lost tissue

Causes

1. Persistence of microbiological agent

Bacteria, Virus, Fungi which are unresponsive to treatment and etc.

2. Excessive and unnecessary immune response

Auto antigens

Ex: rheumatoid arthritis. Multiple sclerosis Allergic diseases like Bronchial

asthma

3. Prolonged exposure to exo /endogenous toxic agent.

Ex: Silicosis ,Atherosclerosis

Systemic effects of chronic inflammation

Fever with loss of weight and weakness

Anaemia

Leucocytosis (generally lymphocytosis)

Raised ESR

Amyloidosis (in long term chronic suppurative inflammation.)

COMPLICATION

1. Military or generalize TB: Untreated active disease typically affects your lungs, but it

can spread to other parts of the body through your bloodstream. Examples include:

Plasma cell


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Bones: Spinal pain and joint destruction may result from TB that infects your

bones. In many cases, the ribs are affected.

Brain: Tuberculosis in your brain can cause meningitis, a sometimes fatal

swelling of the membranes that cover your brain and spinal cord.

Liver or kidneys: Your liver and kidneys help filter waste and impurities from your

bloodstream. These functions become impaired if the liver or kidneys are

affected by tuberculosis.

Heart: Tuberculosis can infect the tissues that surround your heart, causing

inflammation and fluid collections that may interfere with your heart's ability to

pump effectively. This condition, called cardiac tamponade, can be fatal.

2. Adult respiratory distress syndrome A type of lung (pulmonary) failure that may result from any disease that causes

large amounts of fluid to collect in the lungs.

ARDS is not itself a specific disease, but a syndrome, a group of symptoms and

signs that make up one of the most important forms of lung or respiratory

failure.

It can develop quite suddenly in persons whose lungs have been perfectly

normal. Very often ARDS is a true medical emergency.

The basic fault is a breakdown of the barrier, or membrane that normally keeps

fluid from leaking out of the small blood vessels of the lung into the breathing

sacs (the alveoli).

3. Pleural effusion A pleural effusion is a buildup of fluid between the layers of tissue that line the

lungs and chest cavity.

Your body produces pleural fluid in small amounts to lubricate the surfaces of

the pleura, the thin tissue that lines the chest cavity and surrounds the lungs. A

pleural effusion is an abnormal, excessive collection of this fluid.

Two different types of effusions can develop:

i. Transudative pleural effusions are caused by fluid leaking into the pleural

space. This is caused by increased pressure in, or low protein content in,

the blood vessels. Congestive heart failure is the most common cause.

ii. Exudative effusions are caused by blocked blood vessels, inflammation,

lung injury, and drug reactions.

4. Respiratory failure
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5. Antibiotic-resistant tuberculosis (TB)

Tuberculosis (TB) that develops a resistance to one type of antibiotic is not

usually a concern because alternative antibiotics are available.

However, in an increasing number of cases:

o TB develops a resistance to two antibiotics - this is known as multi-drugresistance tuberculosis (MDR-TB)

o TB develops a resistance to three or more antibiotics - this is known as

extensive multi-drug resistance tuberculosis (XDR-TB)

6. Relapse of disease

7. Death

Virulence factor

Adhesion. Many bacteria must first bind to host cell surfaces. Many bacterial and host

molecules that are involved in the adhesion of bacteria to host cells have been identified.

Often, the host cell receptors for bacteria are essential proteins for other functions.

Colonization. Some virulent bacteria produce special proteins that allow them to colonize

parts of the host body.Helicobacter pyloriis able to survive in the acidic environment of the

human stomach by producing the enzyme urease. Colonization of the stomach lining by this

bacterium can lead to Gastric ulcer and cancer. The virulence of various strains

ofHelicobacter pyloritends to correlate with the level of production of urease.

Invasion. Some virulent bacteria produce proteins that either disrupt host cell membranesor stimulate endocytosis into host cells. These virulence factors allow the bacteria to enter

host cells and facilitate entry into the body across epithelial tissue layers at the body

surface.

Immune response inhibitors. Many bacteria produce virulence factors that inhibit the

host's immune system defenses. For example, a common bacterial strategy is to produce

proteins that bind host antibodies. The polysaccharide capsule ofStreptococcus

pneumoniaeinhibits phagocytosis of the bacterium by host immune cells.

Toxins. Many virulence factors are proteins made by bacteria that poison host cells and

cause tissue damage. For example, there are many food poisoning toxins produced by

bacteria that can contaminate human foods. Some of these can remain in "spoiled" food

even after cooking and cause illness when the contaminated food is consumed. Some

bacterial toxins are chemically altered and inactivated by the heat of cooking.
http://en.wikipedia.org/wiki/Transmembrane_receptorhttp://en.wikipedia.org/wiki/Helicobacter_pylorihttp://en.wikipedia.org/wiki/Helicobacter_pylorihttp://en.wikipedia.org/wiki/Helicobacter_pylorihttp://en.wikipedia.org/wiki/Enzymehttp://en.wikipedia.org/wiki/Ureasehttp://en.wikipedia.org/wiki/Gastric_ulcerhttp://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Capsule_(microbiology)http://en.wikipedia.org/wiki/Streptococcus_pneumoniaehttp://en.wikipedia.org/wiki/Streptococcus_pneumoniaehttp://en.wikipedia.org/wiki/Streptococcus_pneumoniaehttp://en.wikipedia.org/wiki/Streptococcus_pneumoniaehttp://en.wikipedia.org/wiki/Phagocytosishttp://en.wikipedia.org/wiki/Food_poisoninghttp://en.wikipedia.org/wiki/Toxinhttp://en.wikipedia.org/wiki/Toxinhttp://en.wikipedia.org/wiki/Food_poisoninghttp://en.wikipedia.org/wiki/Phagocytosishttp://en.wikipedia.org/wiki/Streptococcus_pneumoniaehttp://en.wikipedia.org/wiki/Streptococcus_pneumoniaehttp://en.wikipedia.org/wiki/Capsule_(microbiology)http://en.wikipedia.org/wiki/Cancerhttp://en.wikipedia.org/wiki/Gastric_ulcerhttp://en.wikipedia.org/wiki/Ureasehttp://en.wikipedia.org/wiki/Enzymehttp://en.wikipedia.org/wiki/Helicobacter_pylorihttp://en.wikipedia.org/wiki/Transmembrane_receptor


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Virulence factor of mycobacterium tubercolosis

Cell wall -contains peptidoglycan

- it is composed of complex lipids

- protect extracellular mycobacteria from complement deposition in serum-accounts for impermeability and resistance to antimicrobial agents,

-resistance to killing by acidic and alkaline compounds in both the

intracellular and extracellular environment,

-resistance to osmotic lysis via complement deposition and attack by

lysozyme.

Adherence -produces pili during human infection, which could be involved in initial

colonization of the host

Antigen 85 complex -this complex is composed of a group of proteins secreted by MTB that are

known to bind fibronectin.

-These proteins may aid in enclosed the bacteria from the immune system

and may facilitate tubercle formation.

Slow generation time. -the immune system may not readily recognize the bacteria or may not be

triggered sufficiently to eliminate them.

Intracellular growth -an effective means of evading the immune system.

-In particular, antibodies and complement are ineffective. Once MTB is

phagocytosed, it can inhibit phagosome-lysosome fusion by secretion of a

protein that modifies the phagosome membrane.-It may remain in the phagosome or escape from the phagosome, in either

case, finding a protected environment for growth in the macrophage.

Cord factor -It is primarily associated with virulent strains of MTB. It is known to be

toxic to mammalian cells and to be an inhibitor of PMN migration.

Nitrate reductase - using NO3 as a final electron acceptor

- the existence of nitrate reductase could be a significant factor in

sustaining growth in anaerobic condition.

UreC gene - prevents acidification of the phagosome

- The bacteria also evade macrophage-killing by neutralizing reactive

nitrogen intermediates

LAMat cell wall

(lipoarabinommannan)

- also scavenge oxygen radicals, in vitro, and inhibits the host protein

kinase C

- to down regulate host immune responses to M. tuberculosis infection, to

protect the bacterium from potentially lethal mechanisms like the

respiratory burst.

- an immunomodulator analogous to the 19-kDa protein.

-Addition of LAM to murine macrophages depresses IFN-gamma


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production

Investigations

Laboratory Tests

Laboratory tests are conducted when a patient is diagnosed with TB. Examples of the tests are:

1) Mantoux / Tuberculin Skin Test A Mantoux Test is a skin test which is used to test someone for signs of

exposure to Mycobacterium tuberculosis, the bacterium which

causes tuberculosis infection.

The test is done by putting a small amount of TB protein (antigens) under the top layerofskin on your inner forearm

If you have ever been exposed to the TB bacteria (Mycobacteriumtuberculosis), your

skin will react to the antigens by developing a firm red bump at the site within 2 days.

The TB antigens used in a tuberculin skin test are called purified protein derivative

(PPD).

A measured amount of PPD in a shot is put under the top layer of skin on your forearm.

This is a good test for finding a TB infection. It is often used when symptoms, screening,

or testing, such as a chest X-ray, show that a person may have TB.

Figure 1Giving the Mantoux tuberculin skin test.

Figure 2a

The induration (raised area) is what is measured.

NOT the erythema (red area).
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Figure 2b

Only the induration is being measured. This is CORRECT.

Figure 3

The erythema is being measured. This is INCORRECT.

2) Blood Test for TBThe FDA has approved two interferon-gamma release assay (IGRA) testsfor TB

infection. The two tests are:

QuantiFERON-TB Gold In-Tube test (GFT-GIT)

T-SPOT.TB.


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The IGRA tests identify the presence ofMycobacterium tuberculosis infection by measuring the

immune response to the TB bacteria in whole blood. These tests cannot determine if a person

has latent TB infection or active TB disease. Additional tests are needed to diagnose TB disease.

The IGRA process:

Blood is collected by a health care provider and sent to a laboratory for processing. The lab

must begin processing the blood in 8-30 hours after collection (depending on which test is

used). The test results are generally available in 24 hours.

The possible test results are:

Positive: There has been an immune response indicating the presence of TB bacteria.

Negative: There has not been an immune response indicating the presence of TB

bacteria.

Indeterminate: Results unclear. Possible testing error or the results are not conclusive.

Borderline (T-SPOT.TB only): Results in a borderline zone and cannot tell if truly positive

or negative.

ALL test results should be discussed with a trained health care provider. It is important to note

that TB blood tests are part of a larger toolkit used to diagnose TB infection. A negative result

does not necessarily mean that a person does not have latent TB infection or TB disease.

only one visit is required to draw blood for the test.

Centers for Disease Control (CDC) has released its new TB guidelines which allows

medical practitioners to use a TB blood test called QuantiFERON-TB Gold. (2010)

TB blood tests are preferred for persons who have received the BCG vaccine

However World Health Organization(WHO) urges on the banning of TB blood test due to

its high potency for false positive results. This article has just been posted on Medsape

recently around 20th July 2011.

3) Sputum Culture (AFB Smear and Culture)

Testing mucus from the lungs (sputum culture) is the best way to diagnose active TB. For

suspected cases of tuberculosis lung infections, three sputum samples are collected

early in the morning on different days.

An acid-fast bacillus (AFB) smear is used to look for AFB in a sample from the site of

suspected infection.
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For the smear, the sample is spread thinly onto a glass slide, treated with a special stain,

and examined under a microscope. This is a relatively quick way to determine if an

infection may be due to one of the acid-fast bacilli, the most common of which is M.

tuberculosis.

If the affected person is unable to produce sputum, a bronchoscope may be used tocollect fluid during a procedure called a bronchoscopy.

If TB bacteria grows from the samples, sensitivity testingis done on the bacteria. These

tests will show which medicines will kill the bacteria. Results of sensitivity tests can take

between 1 and 6 weeks because TB-causing bacteria grow very slowly.

In children, gastric washings/aspirates may be collected. Depending on symptoms,

urine, an aspirate from the site of suspected infection, cerebrospinal fluid (CSF), other

body fluids, or biopsied tissue samples may be submitted for AFB smear and culture.

Staining Method

Ziehl Neelson stain is a special bacteriological stain used to identify acid-fast organisms,

mainly Mycobacteria.

It is helpful in diagnosing Mycobacterium tuberculosis since its lipid rich cell wall makes

it resistant to Gram stain.

It can also be used to stain few other bacteria likeNocardia. The reagents used are

ZiehlNeelsen carbolfuchsin, acid alcohol and methylene blue. Acid-fast bacilli will be

bright red after staining.

Procedure:

Prepare smear

2. Air dry and heat fix it

3. Rinse in carbol fuchsin

4. Light a cotton swab and hold it underneath until steam appears

5. Wash with dilute hydrochloric acid until a faint pink color remains.

6. Counterstain with Methylene Blue Chloride for a minute 7. Wash with gentle water till violet becomes faint

8. Blot dry

9. View under oil immersion lens
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Studies have shown that an AFB stain without a culture has a poor negative predictive

value. An AFB Culture should be performed along with an AFB stain; this has a much higher

predictive value.

3) Molecular Method-The majority of molecular tests have been focused on detection of nucleic acids,both DNA and

RNA that are specific to mycobacterium tuberculosis by amplification techniques such as

Polymerase Chain Reaction.

-Molecular methods for drug resistance:

1. Pyrazinamide

2.Ethambutol

3.Rifampin

4.Isoniazid

5.Streptomycin (IV)

Epidemiology

World

Infection and transmission

Tuberculosis (TB) is a contagious disease. Like the common cold, it spreads through the air. Only

people who are sick with TB in their lungs are infectious. When infectious people cough,

sneeze, talk or spit, they propel TB germs, known as bacilli, into the air. A person needs only to

inhale a small number of these to be infected.

Left untreated, each person with active TB disease will infect on average between 10 and 15

people every year. But people infected with TB bacilli will not necessarily become sick with the

disease. The immune system "walls off" the TB bacilli which, protected by a thick waxy coat, canlie dormant for years. When someone's immune system is weakened, the chances of becoming

sick are greater.

Overall, one-third of the world's population is currently infected with the TB bacillus.

5-10% of people who are infected with TB bacilli (but who are not infected with HIV) become

sick or infectious at some time during their life. People with HIV and TB infection are much

more likely to develop TB.


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Global and regional incidence

WHO estimates that the largest number of new TB cases in 2008 occurred in

the South-East Asia Region,which accounted for 35% of incident cases globally.However, the estimated incidence rate in sub-Saharan Africa is nearly twice that of the South-

East Asia Region with over 350 cases per 100 000 population.

An estimated 1.7 million people died from TB in 2009. The highest

number of deaths was in the Africa Region.

In 2008, the estimated per capita TB incidence was stable or falling in all six WHO regions.

However, the slow decline in incidence rates per capita is offset by population growth.

Consequently, the number of new cases arising each year is still increasingglobally in the WHO regions of Africa, the Eastern Mediterranean and South-East Asia.

Preventing Tuberculosis: An Overview

Generally,tuberculosis(TB) is a preventable disease.Prevention measures focus on:

Preventive treatment in people who have a positive TB test withoutsymptoms of

tuberculosis(latent tuberculosis)

Precautions at hospitals and clinics

BCG vaccine

Reducing exposures when a person is infectious.

Protect your family and friends

If you have active TB, keep your germs to yourself. It generally takes a few weeks of treatment

with TB medications before you're not contagious anymore. Follow these tips to help keep your

friends and family from getting sick:

Stay home. Don't go to work or school or sleep in a room with other people during the first few

weeks of treatment for active tuberculosis.

Ventilate the room. Tuberculosis germs spread more easily in small closed spaces where air

doesn't move. If it's not too cold outdoors, open the windows and use a fan to blow indoor air

outside.
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Cover your mouth. Use a tissue to cover your mouth anytime you laugh, sneeze or cough. Put

the dirty tissue in a bag, seal it and throw it away.

Wear a mask. Wearing a surgical mask when you're around other people during the first three

weeks of treatment may help lessen the risk of transmission.

Hospitals and Clinic Precautions

Hospitals and clinics take precautions to preventtuberculosis transmission, which include using

ultraviolet light to sterilize the air, special filters, and special respirators and masks. In hospitals,

people with TB are isolated in special rooms with controlled ventilation and airflow until they

can no longer spread tuberculosis.

Estimated TB incidence, prevalence and mortality, 2009

Uncertainty bounds for the table below are available in the Global tuberculosis control 2010
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Malaysia


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What is the relationship between tuberculosis and HIV?

People who are co-infected with both HIV and latent TB have

an up to 50 times greater risk of developing active

tuberculosis disease and becoming infectious compared to

people not infected with HIV.. HIV attacks and weakens the immune system,leaving the body vulnerable to TB. So once the bacteria that cause TB enter the body of

someone with HIV, usually through the lungs, the bacteria are able to multiply, invade, and

cause full-blown tuberculosis, rather than being contained by a healthy immune system. For

people with HIV, the body just can't fight the tuberculosis infection.

People with advanced HIV infection are vulnerable to a wide range of infections and

malignancies that are called 'opportunistic infections' because they takeadvantage of the opportunity offered by a weakened immune system.

Tuberculosis is an HIV related opportunistic infection. A person that has both HIV and active

tuberculosis has an AIDS defining illness.

There are several important associations between the epidemics of HIV and tuberculosis:

Tuberculosis is harder to diagnose in HIV positive people

Tuberculosis progresses faster in HIV-infected people

Tuberculosis in HIV positive people is more likely to be fatal

if undiagnosed or left untreated

Tuberculosis occurs earlier in the course of HIV infection

than other opportunistic infections

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Ila 4 Tuberculosis Final Compilation

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