(Survival Manual/ 6. Medical/b) Disease/Tuberculosis)

 The global epidemic of tuberculosis (TB)
It is estimated that approximately 1.7 million people died of tuberculosis in 2009. There were an estimated 9.4 million new cases of tuberculosis in 2009 of which the majority were in Asia and Africa. It is thought that the rates of new tuberculosis infections and deaths per capita have probably been falling globally for several years now. However, the total number of new tuberculosis cases is still slowly rising due to population growth.

One-third of the world’s population is currently infected with TB or tuberculosis.
24 Mar 2012
The World Health Organization says TB remains a leading cause of death from infectious diseases worldwide, second only to HIV/AIDS. Last year alone, 8.4 million people contracted TB and 1.4 million died from the disease.

Control of Tuberculosis (TB)
In the 1950s the US and many European countries introduced immunization programs. As a result the incidence of TB fell dramatically. In the late 1980s there was a resurgence of TB cases in the large cities of the US and in Europe. There have been for a number of reasons for the increase, among them: Homelessness; overcrowding in shelters, prisons and in homes for the poor; increased immigration from countries with a high incidence of TB; drug abuse; HIV/AIDS.

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

Tuberculosis was once rare in developed countries, but the number of TB cases began increasing in 1985. Part of the increase was caused by the emergence of HIV, the virus that causes AIDS. HIV weakens a person’s immune system so it can’t fight the TB germs.
Many strains of tuberculosis can resist the effects of the drugs most commonly used to treat the disease. People who have active tuberculosis must take several different types of medications together for many months to eradicate the infection and prevent development of antibiotic resistance.

A.  Symptoms
Although your body may harbor the bacteria that cause tuberculosis, 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.
•  Active TB. This condition makes you sick and can spread to others. It can occur in the first few weeks after infection with the TB bacteria, or it might occur years later. Most people infected with TB germs never develop active TB.

Signs and symptoms of active TB include:
•  Cough
•  Unexplained weight loss
•  Fatigue
•  Fever
•  Night sweats
•  Chills
•  Loss of appetite

What organs are affected?
Tuberculosis usually attacks your lungs. Signs and symptoms of TB of the lungs include:
•  Coughing that lasts three or more weeks
•  Coughing up blood
•  Chest pain, or pain with breathing or coughing

But tuberculosis can also affect other parts of your body, including your kidneys, spine or brain. When TB occurs outside your lungs, 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
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.

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 especially 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. Tuberculosis and HIV have a deadly relationship — each drives the progress of the other.
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. Ever since the first antibiotics were used to fight tuberculosis 60 years ago, the germ has developed the ability to survive attack, and that ability gets passed on to its 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.

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 can often successfully fight TB bacteria, but your body can’t mount an effective defense if your resistance is low. A number of diseases and medications can weaken your immune system, including:
•  Diabetes
•  End-stage kidney disease
•  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
•  Advanced age
International connections
TB risk is higher for people who live in or travel to countries that have high rates of tuberculosis, such as:
•  Sub-Saharan Africa
•  India
•  China
•  Mexico
•  The islands of Southeast Asia and Micronesia
•  Parts of the former Soviet Union

Poverty and substance abuse
Lack of medical care:
If you are on 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 abuse: Long-term drug or alcohol use weakens your immune system and makes you more vulnerable to tuberculosis.

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, immigration centers or nursing homes are all at risk of tuberculosis. That’s because the risk of the disease is higher anywhere there is overcrowding and poor ventilation.
_ Living in a refugee camp or shelter: Weakened by poor nutrition and ill health and living in crowded, unsanitary conditions, refugees are at especially high risk of tuberculosis infection.

Without treatment, tuberculosis can be fatal. 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.

Tests and diagnosis
During the physical exam, your doctor will check your lymph nodes for swelling and use a stethoscope to listen carefully to the sounds your lungs make when you breathe.
The most commonly used diagnostic tool for tuberculosis is a simple skin test. A small amount of a substance called PPD tuberculin is injected just below the skin of your inside forearm. You should feel only a slight needle prick. Within 48 to 72 hours, a health care professional will check your arm for swelling at the injection site. A hard, raised red bump means you’re likely to have TB infection. The size of the bump determines whether the test results are significant.

 Results can be wrong
The TB skin test isn’t perfect. Sometimes, it suggests that people have TB when they really don’t. It can also indicate that people don’t have TB when they really do. A false-positive test may happen if you’ve been vaccinated with the bacillus Calmette-Guerin (BCG) vaccine. This tuberculosis vaccine is seldom used in the United States but is widely used in countries with high TB infection rates. False-negative results may occur in certain populations — including children, older people and people with AIDS — who sometimes don’t respond to the TB skin test. A false-negative result can also occur in people who’ve recently been infected with TB but their immune system hasn’t had time to react to the bacteria yet.

Blood tests
Blood tests may be used to confirm or rule out latent or active tuberculosis. These tests use sophisticated technology to measure your immune system’s reaction to TB bacteria. These tests may be useful if you’re at high risk of TB infection but have a negative response to the skin test, or if you received the BCG vaccine.

Chest X-ray
If you’ve had a positive skin test, your doctor is likely to order a chest X-ray. This may show white spots in your lungs where your immune system has walled off TB bacteria, or it may reveal changes in your lungs caused by active tuberculosis.

Sputum tests
If your chest X-ray shows signs of tuberculosis, your doctor may take a sample of your sputum — the mucus that comes up when you cough. The samples are tested for TB bacteria. These bacteria can also be tested to see if they are resistant to the effects of medications commonly used to treat tuberculosis. This helps your doctor choose the medications that are most likely to work.

Treatments and drugs
Medications are the cornerstone of tuberculosis treatment. But treating TB takes much longer than treating other types of bacterial infections. With tuberculosis, you must take antibiotics for at least six to nine months. The exact drugs and length of treatment depend on your age, overall health, possible drug resistance, the form of TB (latent or active) and its location in the body.

Most common TB drugs
If you have latent tuberculosis, you may need to take just one type of TB drug. Active tuberculosis, particularly if it’s a drug-resistant strain, will require several drugs at once. The most common medications used to treat tuberculosis include:
•  Isoniazid
•  Rifampin (Rifadin, Rimactane)
•  Ethambutol (Myambutol)
•  Pyrazinamide

Medication side effects
Side effects of TB drugs aren’t common but can be serious when they do occur. All tuberculosis medications can be highly toxic to your liver. When taking these medications, call your doctor immediately if you experience any of the following:
•  Nausea or vomiting
•  Loss of appetite
•  A yellow color to your skin (jaundice)
•  Dark urine
•  A fever that lasts three or more days and has no obvious cause

Completing treatment is essential
After a few weeks, you won’t be contagious and you may start to feel better. It might be tempting to stop taking your TB drugs. But it is crucial that you finish the full course of therapy and take the medications exactly as prescribed by your doctor. Stopping treatment too soon or skipping doses can allow the bacteria that are still alive to become resistant to those drugs, leading to TB that is much more dangerous and difficult to treat.
To help people stick with their treatment, a program called directly observed therapy (DOT) is sometimes recommended. In this approach, a health care worker administers your medication so that you don’t have to remember to take it on your own.

B.  TB Medical Advisory Board Statement on the Treatment of Active Tuberculosis in Adults
1. Recommended Treatment Regimens
Unless there are contraindications, patients with active tuberculosis should be treated initially with four drugs: isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), and ethambutol (EMB). Four drugs are recommended because (1) EMB helps to prevent the emergence of RIF-resistant organisms when primary resistance to INH may be present; (2) INH resistance continues to occur in our state, (3) foreign-borne persons from countries with high rates of drug resistance make up a growing number of TB cases in Indiana, and (4) six-month treatment regimens are not possible without the use of PZA.

 2. Drug Administration
The preferred regimen in our state is the ‘Denver Regimen.’ In this regimen, the patient is treated with daily medication for the first two weeks, followed by twice-weekly dosing until a total of 26 weeks of therapy are completed. This regimen must be given using directly observed therapy (DOT), meaning that a public health worker delivers medication to the patient and observes the patient ingest the medication. Completion of treatment is defined by the total number of doses ingested as well as the duration of treatment. Note: twice-weekly therapy is contraindicated for HIV-infected patients with CD4+ lymphocyte counts < 100 cells/µl. An overview of the ‘Denver Regimen’ is provided in Table 2 as “Option 1.” Doses for anti-tuberculosis medications are as follows:

Table 1

Table 2

Daily dosing for 5 rather than 7 days per week is an option for the daily portion of treatment options 1 and 2, but should only be used if dosing 7 days per week is not feasible. DOT must be used with this option.

INH, rifampin and pyrazinamide should be continued for the entire first two months. Ethambutol may be discontinued after the drug susceptibility test shows that the patient’s organism is susceptible to both INH and RIF.

3. Major Adverse Effects
All patients should be counseled to watch for symptoms of hepatotoxicity.  If hepatotoxicity develops (ALT or AST greater than five times the upper limit of normal, elevated bilirubin, or symptoms of hepatotoxicity), all drugs should be discontinued, and ISDH should be consulted immediately. The ISDH TB Medical Advisory Board has published guidelines on the management of hepatotoxicity. Other significant adverse reactions are listed in the table below:

Table 3

Drug Major Adverse Effects
Isoniazid Hepatitis, peripheral neuropathy
Rifampin Drug nteractions, hepatitis
Pyrazinamide Hepatitis, GI upset, hyperuricemia
Ethambutol Optic neuritis

4. Drug Dosages and Toxicity

The ISDH TB Medical Advisory Board does not recommend prescribing anything other than standard therapeutic doses (Table 1). Prior to treatment, measure CBC with platelets, liver enzymes, uric acid, visual acuity, and perform color vision screening. Then, assess monthly for side effects and order laboratory tests as indicated.

[What is hepatotoxicity? Hepatotoxicity is a general term for liver damage.
The signs and symptoms of hepatotoxicity vary depending on how badly the liver is damaged. Symptoms of liver damage include: nausea, vomiting, abdominal, pain, loss of appetite, diarrhea, feeling tired or weak, jaundice (yellowing of the skin and eyes), hepatomegaly (liver enlargement)
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5. Use of Drugs Other Than INH, RIF, PZA, or EMB
There are no substitutes for any of the first-line agents. Before rifampin was available, TB patients had to take medication for 18-24 months. The combination of INH and rifampin allowed completion of therapy within 9 months. Routine addition of PZA during the first two months has shortened duration of therapy to 6 months for most cases. Ethambutol is known as a ‘companion drug,’ and has bacteriostatic activity. Its primary purpose is to suppress the further development of resistance in situations where INH resistance is already present at diagnosis. Ethambutol can be discontinued as soon as the organism is known to be susceptible to both INH and RIF.

The drugs are not interchangeable. Second-line agents must be used when patients cannot take first-line drugs because of resistance or intolerance. These second-line agents are substantially less active, and not without risks of toxicity. Patients taking second-line drugs in lieu of both INH and RIF require treatment durations of up to 2 years with frequent monitoring for side effects.

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 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 and it causes a false-positive result on a TB skin test. Researchers are working on developing a more effective TB vaccine.

Coping and support
Undergoing treatment for tuberculosis is a complicated and lengthy process. But the only way to cure the disease is to stick with your treatment. You may find it helpful to have your medication given by a nurse or other health care professional so that you don’t have to remember to take it on your own. In addition, try to maintain your normal activities and hobbies, and stay connected with family and friends.
Keep in mind that your physical health can affect your mental health. Denial, anger and frustration are normal when you must deal with something difficult and unexpected. At times, you may need more tools to deal with these or other emotions. Professionals, such as therapists or behavioral psychologists, can help you develop positive coping strategies.

[End of article]

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