ILA 4: TUBERCULOSIS Definition

Tuberculosis:

-contagious infection caused by the bacterium called

-

Mycobacterium tuberculosis. Abbreviated TB. Tubercles (tiny

lumps) 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 system problems, 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 of TB. A has been discovered to be associated with clinical TB. People with 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 in the susceptibility to leprosy, which is caused by a bacterium related to TB

genetic region

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 this
impasse of dormant infection for many years.
Tubercles in the lungs develop as a result of infection by the Mycobacterium tuberculosis bacterium. Granulomas form in the infected tissue and undergo necrosis in the centre. Tubercles are also known as tuberculous nodules. For more information see Tuberculosis.

Dormant-inactive
Impasse-a position or situation from which there is no escape Tubercle-such a swelling as the characteristic lesion of tuberculosis. 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.

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 those infected 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 compared to 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 is pregnancy. 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 thought that 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.

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 a cough blamed on smoking or 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 high fever, but they often have a low-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. Chest pain is 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 todayat least where modern treatment 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 spinal segments (vertebrae) may collapse and cause paralysis in 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. Tuberculous peritonitis may cause pain ranging from the vague discomfort of stomach cramps to intense pain that may mimic the symptoms of appendicitis. 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

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 (the aorta), can cause it to rupture with catastrophic results. Tuberculous pericarditis occurs 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 them infect wounds and 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

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 of Mycobacterium tuberculosis contain high concentration of lipid. The high concentration of lipids in
the 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 the TB 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

M. tuberculosis M. bovis M. africanum M. microti

Human tubercle bacillus Bovine tubercle bacillus African tubercle bacillus Vole tubercle bacillus

[Image link] : 1. Colonial morphology of Mycobacterium 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 of Mycobacterium may occasionally cause tuberculosis-like infections, especially in the debilitated or immunosuppressed host. Mycobacterium aviumintracellulare complex (MAC), for example, frequently causes systemic infections in people with HIV/AIDS.

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) are immune cells forming part of the mammalian immune 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 as antigen-presenting cells.

All parts of the body can be affected by the disease, though it rarely affects the heart, skeletal muscles, pancreas and thyroid.

granulomatous inflammatory conditions. Macrophages, T

Tuberculosis is classified as one of the

lymphocytes, 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

mycobacteria and provides a local environment for interaction of

cells of the immune system.

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 of soft 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 Mycobacterium tuberculosis. 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

The mode of transportation is how

the bacterium moves from one place

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

cough or sneeze that releases TB bacterium into the air. It

bacterium to other surfaces. With TB, however, the mode of transmission is the can 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 Susceptible Host

inhaled by the nose and mouth.

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 harder
time 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

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

Plasma cell

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:

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

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-drug resistance 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 pylori is 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 of Helicobacter pylori tends to correlate with the level of production of urease.

Invasion. Some virulent bacteria produce proteins that either disrupt host cell membranes or 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 of Streptococcus 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.

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 -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.

Antigen 85 complex

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 LAM at cell wall - also scavenge oxygen radicals, in vitro, and inhibits the host protein (lipoarabinommannan) 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

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 causes tuberculosis infection.

tuberculosis,

the bacterium which

The test is done by putting a small amount of TB protein (antigens) under the top layer of skin 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 1 Giving the Mantoux tuberculin skin test.

Figure 2a The induration (raised area) is what is measured. NOT the erythema (red area).

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 TB The FDA has approved two interferon-gamma release assay (IGRA) tests for TB infection. The two tests are:

QuantiFERON-TB Gold In-Tube test (GFT-GIT) T-SPOT.TB.

The IGRA tests identify the presence of Mycobacterium 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.

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 to collect 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 like Nocardia. 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

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, can lie 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.

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 SouthEast 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 increasing globally in the WHO regions of Africa, the Eastern Mediterranean and South-East Asia.

Preventing Tuberculosis: An Overview

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

preventable disease.
symptoms of

Preventive treatment in people who have a positive TB test without

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.

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 prevent tuberculosis 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

Malaysia

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 take advantage 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