TUBERCULOSIS

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INTRODUCTION-

Tuberculosis (TB) is a potentially serious infectious disease that mainly affects your lungs. The bacteria that cause tuberculosis are spread from one person to another through tiny droplets released into the air via coughs and sneezes.

Once rare in developed countries, tuberculosis infections began increasing in 1985, partly because of the emergence of HIV, the virus that causes AIDS. HIV weakens a person’s immune system so it can’t fight the TB germs. In the United States, because of stronger control programs, tuberculosis began to decrease again in 1993, but remains a concern.

Many strains of tuberculosis resist the drugs most used to treat the disease. People with active tuberculosis must take several types of medications for many months to eradicate the infection and prevent development of antibiotic resistance.

CAUSES-

Tuberculosis is caused by bacteria that spread from person to person through microscopic droplets released into the air. This can happen when someone with the untreated, active form of tuberculosis coughs, speaks, sneezes, spits, laughs or sings.

Although tuberculosis is contagious, it’s not easy to catch. You’re much more likely to get tuberculosis from someone you live with or work with than from a stranger. Most people with active TB who’ve had appropriate drug treatment for at least two weeks are no longer contagious.

HIV and TB

Since the 1980s, the number of cases of tuberculosis has increased dramatically because of the spread of HIV, the virus that causes AIDS. Infection with HIV suppresses the immune system, making it difficult for the body to control TB bacteria. As a result, people with HIV are many times more likely to get TB and to progress from latent to active disease than are people who aren’t HIV positive.

Drug-resistant TB

Another reason tuberculosis remains a major killer is the increase in drug-resistant strains of the bacterium. Since the first antibiotics were used to fight tuberculosis more than 60 years ago, some TB germs have developed the ability to survive despite medications, and that ability gets passed on to their descendants.

Drug-resistant strains of tuberculosis emerge when an antibiotic fails to kill all of the bacteria it targets. The surviving bacteria become resistant to that particular drug and frequently other antibiotics as well. Some TB bacteria have developed resistance to the most commonly used treatments, such as isoniazid and rifampin.

Some strains of TB have also developed resistance to drugs less commonly used in TB treatment, such as the antibiotics known as fluoroquinolones, and injectable medications including amikacin and capreomycin (Capastat). These medications are often used to treat infections that are resistant to the more commonly used drugs.

Tuberculosis Types

A TB infection doesn’t always mean you’ll get sick. There are two forms of the disease:

• Latent TB. You have the germs in your body, but your immune system keeps them from spreading. You don’t have any symptoms, and you’re not contagious. But the infection is still alive and can one day become active. If you’re at high risk for re-activation — for instance, if you have HIV, you had an infection in the past 2 years, your chest X-ray is unusual, or your immune system is weakened — your doctor will give you medications to prevent active TB.  
• Active TB. The germs multiply and make you sick. You can spread the disease to others. Ninety percent of active cases in adults come from a latent TB infection.

A latent or active TB infection can also be drug-resistant, meaning certain medications don’t work against the bacteria.

SYMPTOM-

Although your body may harbor the bacteria that cause tuberculosis (TB), your immune system usually can prevent you from becoming sick. For this reason, doctors make a distinction between:

• Latent TB. In this condition, you have a TB infection, but the bacteria remain in your body in an inactive state and cause no symptoms. Latent TB, also called inactive TB or TB infection, isn’t contagious. It can turn into active TB, so treatment is important for the person with latent TB and to help control the spread of TB. An estimated 2 billion people have latent TB.
• Active TB. This condition makes you sick and in most cases can spread to others. It can occur in the first few weeks after infection with the TB bacteria, or it might occur years later.

Signs and symptoms of active TB include:

• Coughing that lasts three or more weeks
• Coughing up blood
• Chest pain, or pain with breathing or coughing
• Unintentional weight loss
• Fatigue
• Fever
• Night sweats
• Chills
• Loss of appetite

Tuberculosis can also affect other parts of your body, including your kidneys, spine or brain. When TB occurs outside your lungs, signs and symptoms vary according to the organs involved. For example, tuberculosis of the spine may give you back pain, and tuberculosis in your kidneys might cause blood in your urine.

When to see a doctor

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See your doctor if you have a fever, unexplained weight loss, drenching night sweats or a persistent cough. These are often signs of TB, but they can also result from other medical problems. Your doctor can perform tests to help determine the cause.

The Centers for Disease Control and Prevention recommends that people who have an increased risk of tuberculosis be screened for latent TB infection. This recommendation includes people who:

• Have HIV/AIDS
• Use IV drugs
• Are in contact with infected individuals
• Are from a country where TB is common, such as several countries in Latin America, Africa and Asia
• Live or work in areas where TB is common, such as prisons or nursing homes
• Work in health care and treat people with a high risk of TB
• Are children and are exposed to adults at risk of TB

Risk factors

Anyone can get tuberculosis, but certain factors can increase your risk of the disease. These factors include:

Weakened immune system

A healthy immune system often successfully fights TB bacteria, but your body can’t mount an effective defense if your resistance is low. A number of diseases, conditions and medications can weaken your immune system, including:

• HIV/AIDS
• Diabetes
• Severe kidney disease
• Certain cancers
• Cancer treatment, such as chemotherapy
• Drugs to prevent rejection of transplanted organs
• Some drugs used to treat rheumatoid arthritis, Crohn’s disease and psoriasis
• Malnutrition
• Very young or advanced age

Traveling or living in certain areas

The risk of contracting tuberculosis is higher for people who live in or travel to areas that have high rates of tuberculosis and drug-resistant tuberculosis, including:

• Africa
• Eastern Europe
• Asia
• Russia
• Latin America
• Caribbean Islands

Poverty and substance use

• Lack of medical care. If you receive a low or fixed income, live in a remote area, have recently immigrated to the United States, or are homeless, you may lack access to the medical care needed to diagnose and treat TB.
• Substance use. Use of IV drugs or excessive alcohol weakens your immune system and makes you more vulnerable to tuberculosis.
• Tobacco use. Using tobacco greatly increases the risk of getting TB and dying of it.

Where you work or live

• Health care work. Regular contact with people who are ill increases your chances of exposure to TB bacteria. Wearing a mask and frequent hand-washing greatly reduce your risk.
• Living or working in a residential care facility. People who live or work in prisons, homeless shelters, psychiatric hospitals or nursing homes are all at a higher risk of tuberculosis. That’s because the risk of the disease is higher anywhere there is overcrowding and poor ventilation.
• Living in or emigrating from a country where TB is common. People from a country where TB is common may be at high risk of tuberculosis infection.
• Living with someone infected with TB. Living with someone who has TB increases your risk.

Complications

Without treatment, tuberculosis can be fatal. Untreated active disease typically affects your lungs, but it can spread to other parts of your body through your bloodstream. Examples of tuberculosis complications include:

• Spinal pain. Back pain and stiffness are common complications of tuberculosis.
• Joint damage. Tuberculous arthritis usually affects the hips and knees.
• Swelling of the membranes that cover your brain (meningitis). This can cause a lasting or intermittent headache that occurs for weeks. Mental changes also are possible.
• Liver or kidney problems. 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 disorders. Rarely, 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.

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Prevention

If you test positive for latent TB infection, your doctor may advise you to take medications to reduce your risk of developing active tuberculosis. The only type of tuberculosis that is contagious is the active variety, when it affects the lungs. So if you can prevent your latent tuberculosis from becoming active, you won’t transmit tuberculosis to anyone else.

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.

Finish your entire course of medication

This is the most important step you can take to protect yourself and others from tuberculosis. When you stop treatment early or skip doses, TB bacteria have a chance to develop mutations that allow them to survive the most potent TB drugs. The resulting drug-resistant strains are much more deadly and difficult to treat.

Vaccinations

In countries where tuberculosis is more common, infants often are vaccinated with bacillus Calmette-Guerin (BCG) vaccine because it can prevent severe tuberculosis in children. The BCG vaccine isn’t recommended for general use in the United States because it isn’t very effective in adults. Dozens of new TB vaccines are in various stages of development and testing.

TRANSMISSION-

When someone who has TB coughs, sneezes, talks, laughs, or sings, they release tiny droplets that contain the germs. If you breathe in these germs, you can get it.

TB isn’t easy to catch. You usually have to spend a long time around someone who has a lot of the bacteria in their lungs. You’re most likely to catch it from co-workers, friends, and family members.

Tuberculosis germs don’t thrive on surfaces. You can’t get it from shaking hands with someone who has it or by sharing their food or drink. 

Tuberculosis Tests and Diagnosis

There are two common tests for tuberculosis:

• Skin test. This is also known as the Mantoux tuberculin skin test. A technician injects a small amount of fluid into the skin of your lower arm. After 2 or 3 days, they’ll check for swelling in your arm. If your results are positive, you probably have TB bacteria. But you could also get a false positive. If you’ve gotten a tuberculosis vaccine called bacillus Calmette-Guerin (BCG), the test could say that you have TB when you really don’t. The results can also be false negative, saying that you don’t have TB when you really do, if you have a very new infection. You might get this test more than once.
• Blood test. These tests, also called interferon-gamma release assays (IGRAs), measure the response when TB proteins are mixed with a small amount of your blood.

Those tests don’t tell you if your infection is latent or active. If you get a positive skin or blood test, your doctor will learn which type you have with:

• A chest X-ray or CT scan to look for changes in your lungs
• Acid-fast bacillus (AFB) tests for TB bacteria in your sputum, the mucus that comes up when you cough

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Tuberculosis Treatment

Your treatment will depend on your infection.

• If you have latent TB, your doctor will give you medication to kill the bacteria so the infection doesn’t become active. You might get isoniazid, rifapentine, or rifampin, either alone or combined. You’ll have to take the drugs for up to 9 months. If you see any signs of active TB, call your doctor right away.
• A combination of medicines also treats active TB. The most common are ethambutol, isoniazid, pyrazinamide, and rifampin. You’ll take them for 6 to 12 months.
• If you have drug-resistant TB, your doctor might give you one or more different medicines. You may have to take them for much longer, up to 30 months, and they can cause more side effects.

Whatever kind of infection you have, it’s important to finish taking all of your medications, even when you feel better. If you quit too soon, the bacteria can become resistant to the drugs.

Tuberculosis Medication Side Effects

Like any medication, TB drugs can have side effects–

Common isoniazid side effects include:

• Numbness and tingling in your hands and feet
• Upset stomach, nausea, and vomiting
• Loss of appetite
• Weakness

Ethambutol side effects may include:

• Chills
• Painful or swollen joints
• Belly pain, nausea, and vomiting
• Loss of appetite
• Headache
• Confusion

Some pyrazinamide side effects include:

• Lack of energy
• Nausea and vomiting
• Loss of appetite
• Muscle or joint pain

Common rifampin side effects include:

• Skin rash
• Upset stomach, nausea, and vomiting
• Diarrhea
• Loss of appetite
• Inflamed pancreas

Tuberculosis Complications

Tuberculosis infection can cause complications such as:

• Joint damage
• Lung damage
• Infection or damage of your bones, spinal cord, brain, or lymph nodes
• Liver or kidney problems
• Inflammation of the tissues around your heart

Global commitments and the WHO response

On 26 September 2018, the United Nations (UN) held its first- ever high-level meeting on TB, elevating discussion about the status of the TB epidemic and how to end it to the level of heads of state and government. It followed the first global ministerial conference on TB hosted by WHO and the Russian government in November 2017. The outcome was a political declaration agreed by all UN Member States, in which existing commitments to the Sustainable Development Goals (SDGs) and WHO’s End TB Strategy were reaffirmed, and new ones added.

SDG Target 3.3 includes ending the TB epidemic by 2030. The End TB Strategy defines milestones (for 2020 and 2025) and targets (for 2030 and 2035) for reductions in TB cases and deaths. The targets for 2030 are a 90% reduction in the number of TB deaths and an 80% reduction in the TB incidence rate (new cases per 100 000 population per year) compared with levels in 2015. The milestones for 2020 are a 35% reduction in the number of TB deaths and a 20% reduction in the TB incidence rate. The strategy also includes a 2020 milestone that no TB patients and their households face catastrophic costs as a result of TB disease.

The political declaration of the UN high-level meeting included four new global targets:

• treat 40 million people for TB disease in the 5-year period 2018–2022;
• reach at least 30 million people with TB preventive treatment for a latent TB infection in the 5-year period 2018–2022;
• mobilize at least US$ 13 billion annually for universal access to TB diagnosis, treatment and care by 2022;
• mobilize at least US$ 2 billion annually for TB research.

The political declaration also requested the UN Secretary-General, with support from WHO, to provide a report in 2020 to the General Assembly on global and national progress, as the basis for a comprehensive review at a high-level meeting in 2023. The Director-General of WHO was requested to continue to develop a multisectoral accountability framework for TB (MAF-TB) and to ensure its timely implementation.

WHO is working closely with countries, partners and civil society in scaling up

the TB response. Six core functions are being pursued by WHO to contribute to achieving the targets of the UN high-level meeting political declaration, SDGs, End TB Strategy and WHO strategic priorities:

• Providing global leadership to end TB through strategy development, political and multisectoral engagement, strengthening review and accountability, advocacy, and partnerships, including with civil society;

• Shaping the TB research and innovation agenda and stimulating the generation, translation and dissemination of knowledge;
• Setting norms and standards on TB prevention and care and promoting and facilitating their implementation;
• Developing and promoting ethical and evidence-based policy options for TB prevention and care;
• Ensuring the provision of specialized technical support to Member States and partners jointly with WHO regional and country offices, catalyzing change, and building sustainable capacity;
• Monitoring and reporting on the status of the TB epidemic and progress in financing and implementation of the response at global, regional and country levels.

Mycobacterium tuberculosis

Mycobacterium tuberculosis is the etiologic agent of tuberculosis  in humans. Humans are the only reservoir for the bacterium.

Mycobacterium bovis is the etiologic agent of TB in cows and rarely in humans. Both cows and humans can serve as reservoirs. Humans can also be infected by the consumption of unpasteurized milk. This route of transmission can lead to the development of extrapulmonary TB, exemplified in history by bone infections that led to hunched backs.

Other human pathogens belonging to the Mycobacterium genus include Mycobacterium avium which causes a TB-like disease especially prevalent in AIDS patients, and Mycobacterium leprae, the causative agent of leprosy.

History and Present Day Importance

Mycobacterium tuberculosis (MTB) was the cause of the “White Plague” of the 17th and 18th centuries in Europe. During this period nearly 100 percent  of the European population was infected with MTB, and 25 percent of all adult deaths were caused by MTB (Note: The White Plague is not to be confused with the “Black Plague”, which was caused by Yersinia pestis and occurred about 3 centuries earlier).

General Characteristics

Mycobacterium tuberculosis is a fairly large nonmotile rod-shaped bacterium distantly related to the Actinomycetes. Many non pathogenic mycobacteria are components of the normal flora of humans, found most often in dry and oily locales. The rods are 2-4 micrometers in length and 0.2-0.5 um in width.

Mycobacterium tuberculosis is an obligate aerobe. For this reason, in the classic case of tuberculosis, MTB complexes are always found in the well-aerated upper lobes of the lungs. The bacterium is a facultative intracellular parasite, usually of macrophages, and has a slow generation time, 15-20 hours, a physiological characteristic that may contribute to its virulence.

Two media are used to grow MTB Middlebrook’s medium which 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 types of media contain inhibitors to keep contaminants from out-growing MT. It takes 4-6 weeks to get visual colonies on either type of media.

Chains of cells in smears made from in vitro-grown colonies often form distinctive serpentine cords. This observation was first made by Robert Koch who associated cord factor with virulent strains of the bacterium.

MTB 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 on MTB, it stains very weakly Gram-positive or not at all (cells referred to as “ghosts”).

Mycobacterium species, along with members of a related genus Nocardia, are classified as acid-fast bacteria due to their impermeability by certain dyes and stains. Despite this, once stained, acid-fast bacteria will retain dyes when heated and treated with acidified organic compounds. One acid-fast staining method for Mycobacterium tuberculosis is the Ziehl-Neelsen stain. When this method is used, the MTB. smear is fixed, stained with carbol-fuchsin (a pink dye), and decolorized with acid-alcohol. The smear is counterstained with methylene-blue or certain other dyes. Acid-fast bacilli appear pink in a contrasting background.

In order to detect Mycobacterium tuberculosis in a sputum sample, an excess of 10,000 organisms per ml of sputum are needed to visualize the bacilli with a 100X microscope objective (1000X mag). One acid-fast bacillus/slide is regarded as “suspicious” of an MTB infection.

The Disease Tuberculosis

TB infection means that MTB is in the body, but the immune system is keeping the bacteria under control. The immune system does this by producing macrophages that surround the tubercle bacilli. The cells form a hard shell that keeps the bacilli contained and under control. Most people with TB infection have a positive reaction to the tuberculin skin test.  People who have TB infection but not TB disease are NOT infectious, i.e., they cannot spread the infection to other people. These people usually have a normal  chest x-ray. TB infection is not considered a case of TB disease. Major similarities and differences between TB infection and TB disease are given in the table below.
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

Predisposing factors for TB infection include:
– Close contact with large populations of people, i.e., schools, nursing homes, dormitories, prisons, etc.
– Poor nutrition
– iv drug use
– Alcoholism
– HIV infection is the #1 predisposing factor for MTB infection. 10 percent of all HIV-positive individuals harbor MTB. This is 400-times the rate associated with the general public

Only 3-4% of infected individuals will develop active disease upon initial infection, 5-10% within one year. These percentages are much higher if the individual is HIV+.

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