Tuberculosis (TB)

Description

• Tuberculosis, or TB, is a chronic infectious disease caused by a bacterium called Mycobacterium tuberculosis.
• It usually affects the lungs, but can attack other parts of the body.
• TB is a global problem, although undeveloped countries usually have much higher incidences than developed countries.
• South Africa has one of the highest reported TB infection rates in the world.
• TB is mainly spread by breathing in air-borne bacteria from people with active infectious TB disease.
• A person can be infected by the TB organism for years without getting sick or spreading the disease to others.
• If your immune system is weakened for some reason, latent TB infection can develop into active disease.
• Although TB can be treated, the minimum period required for successful treatment is six months, and medication must be taken exactly as prescribed.
• Failure to complete the treatment regimen may result in the emergence of drug resistant strains of TB.
• In some parts of the world, such as South Africa, TB is the most important opportunistic infection of people with HIV.

Tuberculosis, or TB, is a chronic infectious disease caused by bacteria, which usually manifests in the lungs (pulmonary TB). The bacteria can destroy parts of the lungs, making it difficult to breathe. Bacteria can spread to and damage other parts of the body, such as the digestive and urogenital tracts, bones, joints, nervous system, lymph nodes and skin. This is called extrapulmonary TB, and is far less common. The disease is characterized by the development of granulomas or tubercles in infected tissues.

Prevalence

Worldwide prevalence

• According to the World Health Organization, tuberculosis (TB) is second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent.

• In 2012, 8.6 million people fell ill with TB and 1.3 million died from TB.
  

• Over 95% of TB deaths occur in low- and middle-income countries, and it is among the top three causes of death for women aged 15 to 44.

• People of all ages, nationalities and socio-economic groups can get TB.
• Every country is vulnerable to the consequences of poor TB treatment practices in others.
• People with untreated TB disease could infect another 10 to 15 people each year.
• TB is the leading infectious killer of people with HIV/Aids, accounting for almost one in four Aids deaths. HIV and TB each speed the other's progress.
• 80% of TB sufferers are in their most economically productive years.
• 5% to 10% of people infected with TB become sick or infectious during their lifetime.
• Factors that contribute to the increase in global TB prevalence are:
  • Increasing number of HIV/Aids cases.
  • Drug-resistant TB strains.
  • Population mobility. Global trade and air travel have increased greatly since 1960. Numbers of refugees and displaced people have increased nine-fold in 20 years. TB spreads quickly in crowded refugee camps and shelters. It is difficult to treat mobile populations. Other displaced people such as homeless people in industrialised countries are at risk.

Prevalence in South Africa

• TB has reached epidemic proportions in South Africa: the WHO has confirmed that we have one of the world's worst TB epidemics.
• TB disease rates are up to 60 times higher than in the USA or Western Europe. In 2007 about 336 000 South Africans had TB disease, from which 112 000 died.
• SA ranked third in the world in terms of total numbers of incident cases of TB in 2008. In the Western Cape the incidence of TB is about 800 cases per 100 000 people.
• More than half of all TB patients are HIV-positive.
• TB is the leading infectious killer of youths and adults.
• About two thirds of the population are infected with TB, although most will not get TB disease.

Cause

TB is caused by the bacterium Mycobacterium tuberculosis. TB in the lungs or throat can be infectious i.e. the bacteria can be spread to other people. TB in other parts of the body is usually not infectious. TB is spread mainly through the air. When infectious people cough, sneeze, talk, laugh or spit, droplets containing bacteria are sprayed into the air. People nearby may inhale these bacteria and become infected. Bacteria can stay air-borne for a long time, and can remain active in house dust for weeks. However, transmission usually occurs only after substantial exposure to someone with active TB. People with TB disease are most likely to spread it to those they spend time with daily, such as family members and co-workers. You are unlikely to get TB from someone coughing in a public place. You cannot get TB from handshakes, toilet seats, or sharing eating utensils, bedclothes or clothing with people who have TB.

Infection can also be acquired from contact with an infected cow or through drinking contaminated milk. However, this is an extremely rare way of getting TB. Most milk is pasteurized, and dairy herds are usually kept under veterinary control.

Symptoms

Symptoms of TB may include the following:

• A cough that starts out dry but later produces sputum (thick liquid from deep inside the lungs) or blood
• Coughing for longer than a month
• Chest pain
• Breathing difficulty e.g. shortness of breath
• Weakness or fatigue
• Loss of weight and appetite
• Chills and fevers (the fever may be low, and may be intermittent)
• Joint pain
• Wheezing
• Rales (additional sounds made to those of normal breathing)
• Excessive sweating, including sweating at night
• Hearing loss
• Diarrhoea
• A persistent lump or lesion
• Clubbing of fingers or toes - the nails become swollen and feel slightly "pulpy".

Some people have mild symptoms or none at all. People may therefore spread bacteria without knowing they have TB.

Course

After inhaling the TB bacteria from the air, they can settle in your lungs. The bacteria enter via the respiratory mucous membranes and multiply to form a primary lesion. The main infection site is the lung, but any organ can become infected if the bacteria spread. They can enter the bloodstream and lymphatic system and travel to other parts of the body.

The majority of TB cases are pulmonary. However, TB can also break down bones and vertebrae, causing sufferers to become hump-backed. A rare form called 'lupus vulgaris' attacks and disfigures the soft tissue of the face. TB can also attack the brain as a deadly form of meningitis. Incidence of TB in parts of the body other than the lungs is higher among people infected with HIV.

Once you are infected by the TB bacteria, there are essentially two things that can happen: you may develop active disease; or your body may control the bacteria - you will be infected, but will not have active TB.

TB Infection (Latency)

It is very important to realise that most people who are infected with the TB bacteria do not develop active TB. These people therefore have no symptoms and are not infectious. The immune system controls the infection by forming walls around the bacteria. This inactivates the bacteria, but does not kill them. They can lie dormant inside these walls for years. In many people, TB bacteria remain inactive for a lifetime, but in others, especially those with weak immune systems, the bacteria may become active and cause active TB disease.

People with latent TB infection:

• Have no symptoms
• Do not feel sick
• Cannot spread TB to others
• Usually have a positive skin test reaction (see later)
• Can develop TB disease later if they receive no preventive therapy

TB Disease

TB disease is a serious illness caused by active TB bacteria. It can either develop when you are first exposed to the TB bacteria, especially if you have a weak immune system, or it can develop as reactivation disease in people who have been previously infected. Some people develop TB disease within weeks of becoming infected: their immune systems are too weak to stop bacterial growth. Other people may get sick later, when their immune systems become weak for some reason such as drug abuse, poor nutrition, immune suppression, old age or ill health. Babies and children often have weak immune systems. TB bacteria become active if the immune system can't stop their growth; they multiply and cause disease.

People with TB disease can be cured if they have proper medical treatment. Without the correct treatment, however, they may become seriously ill and even die.

Risk factors

At high risk for developing active TB include:

• People with HIV infection.
  • Because HIV weakens the immune system, people with both TB and HIV infection are at high risk of developing TB disease.
  • If you are HIV-positive, you are 30 times more likely to get active TB once infected than someone infected with TB who is HIV-negative.
  • People with HIV should be TB tested and those with a positive skin test should get HIV tested. This way someone with both infections can take medicine to reduce the chance of developing TB disease.
  • Treatment is more difficult and the infecting bacteria are often resistant to therapy. However, of diseases associated with HIV, TB is relatively preventable and curable.
• Patients receiving certain medical treatments, such as corticosteroid treatment, anti-cancer chemotherapy, or transplant anti-rejection medication.
• People who have been in close contact with someone who has infectious TB.
• People who became infected with TB in the last two years.
• Babies and young children.
• People who inject drugs.
• People with other conditions that weaken the immune system, especially
  • Diabetes mellitus
  • Silicosis
  • Cancer of the head or neck
  • Leukaemia or Hodgkin's disease
  • Severe kidney disease
  • Low body weight
  • Substance abuse
• Elderly people
• People born where TB is common, such as Africa, Asia or Latin America.
• Low-income groups with poor health care access.
• People in residential facilities such as nursing homes and correctional facilities.
• People exposed to TB through their work, such as health care workers.

When to see a doctor

Call a health professional if:

• You have been exposed to TB, or if symptoms develop.
• Symptoms persist despite treatment.
• New symptoms develop.

Diagnosis

You should get tested for TB if you:

• Have spent time with someone with infectious TB
• Have HIV infection or another condition that puts you at high risk for TB disease
• Think you might have TB disease
• Are from a country where TB disease is very common i.e. Africa, Latin America, the Caribbean and Asia (excluding Japan)
• Inject drugs
• Live where TB disease is common (homeless shelters, hostels, prisons, some nursing homes)

Tuberculin skin test

A small amount of testing fluid, called tuberculin or PPD, is injected beneath the skin of your lower arm. Do not rub the injection site. (An immediate, local inflammatory type reaction may occur. Cold packs or topical glucocorticoid ointment may relieve discomfort. Allergic reactions have been reported. Rarely, swelling of lymph nodes may occur. If given to patients with TB, a severe reaction may occur.)

You are told within three days whether the test reaction was positive. A small lump at the injection site is a positive reaction and usually indicates TB infection. However, remember that infection with TB does not necessarily mean you have active, infectious TB. Most people with positive tuberculin tests do not have active TB.

People exposed to TB should be skin tested immediately. If you have recently become infected, your first skin test may show up negative. You may need a second test 10 to 12 weeks after the last time you were with the infectious person: it can take several weeks after infection for your immune system to react to the test. If your reaction to the second test is negative, you are probably not infected.

Because older people may have a poorer immune response, a two-step test method is used: if the test is negative, it is repeated in seven to ten days.

If you have a positive reaction, your doctor may perform other tests to check for TB disease, such as chest x-rays and sputum tests. As bacteria may be found elsewhere besides your lungs, blood or urine may also be tested. If your test is positive, close family members should also be tested.

Skin testing for TB is done during routine well-baby exams. Infants are usually screened at one year and children at five.

Reactivity to the test may be poor if you have advanced TB disease, viral infection (including immunisation with live viral vaccine during the previous 14 days), or bacterial infection. Patients receiving corticosteroids or other immunosuppressive agents, or who are suffering from malignant conditions, may also react poorly to the test.

On the other hand, people who have received the BCG vaccine (see later) may develop a positive reaction even if they have not been infected with TB bacteria. Generally speaking, the stronger the skin reaction, the more likely that you have been infected with TB, or you may even have active TB. However, you can see that interpreting a positive or a negative skin test can be difficult. The skin test therefore should ideally not be used as the only means of diagnosis of TB.

Chest X-ray

If you inhaled TB bacteria but fought off the infection, your lungs may be undamaged and your chest X-ray normal. If bacteria have attacked your lungs, your chest X-ray will be abnormal. Unfortunately, other conditions (lung cancer, for example) can also give people symptoms similar to those of TB, and also result in an abnormal chest X-Ray. Other tests are thus also often required to make a diagnosis of TB.

Sputum test

A sputum sample is examined under a microscope for TB bacteria. In some circumstances, the sputum may also be cultured to see if there are TB bacteria present. However, it may take up to six to eight weeks for a sputum culture to yield definite results. In an endemic area, TB can be diagnosed on the basis of a positive sputum smear alone. In fact, any patient with symptoms suggestive of TB who has a positive sputum smear should be started on anti-TB therapy, even if a culture is going to be done.

If a doctor suspects that the patient has extra-pulmonary TB (such as in the abdomen, uro-genital system or brain) it is also possible to examine fluids from these sites under a microscope and to culture them for TB.

In some situations, neither the microscopic examination nor the culture will indicate the presence of any TB bacteria, and doctors may sometimes decide to treat for TB based on the patient's history of exposure to TB, symptoms, X-Ray examination and any other evidence (e.g. skin test). You can see, though, that the diagnosis of TB is not always easy to make.

Newer tests

A lot of work is being done to find tests that are more reliable or quicker than the currently available tests. These new tests include:

Tests to detect the DNA of the TB bacterium in sputum samples.There are currently tests licensed for use in the diagnosis of TB. However, they are very expensive, and would not be practical for use in a high incidence population such as SA.

Immune based tests to see if the patient has antibodies, or some other immune response to TB that can be measured. A number of promising antibodies and methods have been investigated, but nothing is so far well enough established to be used as a routine diagnostic test.

Treatment

Medicine for Preventive Therapy

Preventive therapy (PT) against TB involves people at high-risk for infection taking anti-TB drugs to prevent progression to active disease. If you are infected and/or in a high-risk group, you can take medicine to help avoid developing active TB disease. Sometimes people receive PT even with a negative skin test, for example infants, children, and HIV-infected people who have recently spent time with someone with infectious TB disease, as they are at very high risk of developing TB disease soon after infection.

The drug isoniazid, or INH, is usually used for PT. INH kills inactive TB bacteria, and may keep you from developing TB disease if taken as prescribed. Most people take INH for at least six to nine months; children and HIV-infected people for longer.

While taking INH, see your doctor regularly and do not drink alcohol.

If you have a positive tuberculin skin test but have not received PT, you should have routine medical checkups to detect if TB is becoming active, in order to treat it at an early stage. Know the TB disease symptoms, and see a doctor immediately should any develop. It is important to make sure that people do not have active TB before they are given PT. If someone has active TB he or she needs to be treated differently (see below).

Medicine for Active TB Disease

People with active TB are usually treated with several anti-TB drugs: this is more effective in killing all the bacteria and preventing them from becoming drug resistant. Daily oral doses are continued for six months. Most commonly used drugs used are:

• Isoniazid (INH)
• Rifampin (RIF)
• Pyrazinamide (PZN)
• Ethambutol (EMB)
• Streptomycin (STR)

The standard treatment regimen involves taking INH, rifampicin, pyrazinamide and ethambutol for two months, and then INH and rifampicin for the next four months.

The drugs listed above sometimes cannot kill atypical TB infections, or drug-resistant strains, and new treatments must be found.

Over 95% of people properly treated for TB are cured. The main reason treatments fail is that people do not take their medications properly. Medicines given to people with TB disease usually stop them from spreading TB bacteria within a few weeks. Most TB patients live at home and can continue normal activities if they take their medicine. TB of the lungs or throat means you are probably infectious and should stay home from work or school. Your doctor will tell you when you can return to work. When you are no longer infectious or feeling sick, you can resume normal activities, but you must continue to take your medication for the prescribed time.

Hospitalisation may be advised to prevent spread of bacteria until the infectious period is over, usually two to four weeks after starting therapy. Once treatment has started, the amount of coughing is reduced and results in fewer droplet nuclei. This factor, and that of coughing into a tissue, reduce the number of droplet nuclei generated during early treatment, thus reducing infectivity.   

It takes at least six months for the medicine to kill the bacteria. You will probably start feeling well after only a few weeks of treatment, but it is VERY important that you take the medicine regularly, and take it for the full six months even though you have no symptoms. Otherwise, the bacteria will regrow, and may also become resistant to the drugs. If this happens, you will need new, different drugs, which must be taken for longer and usually have more serious side effects. If you become infectious again, you could give bacteria to others.

Anti-TB medications are relatively safe, although all have some toxicity. Rifampin and isoniazid may cause non-infectious hepatitis. Other complications include drug resistance to certain TB strains and relapse of the disease. Occasionally, the drugs cause side effects. If you have any of these serious side effects, call your doctor immediately:

• No appetite
• Nausea
• Vomiting
• Yellowish skin or eyes
• Fever for three or more days
• Abdominal pain
• Tingling fingers or toes
• Skin rash
• Easy bleeding
• Aching joints
• Dizziness
• Tingling or numbness around the mouth
• Easy bruising
• Blurred or changed vision
• Ringing in the ears

If you have any of the following minor side effects, continue taking your medicine:

• Rifampin can turn urine, saliva, or tears orange or brown, and may stain contact lenses.
• Rifampin can make you more sun-sensitive.
• Rifampin makes birth control pills and implants less effective. Use another birth control method while taking rifampin.
• If you are taking rifampin and methadone (to treat drug addiction), you may have withdrawal symptoms and your methadone dosage need adjustment.

Symptoms may improve in two to three weeks.

See your health professional regularly and have regular blood tests while taking these drugs. Rest, a healthy environment (clean dry air), stress reduction and a healthy diet high in vitamin C improve treatment response. Joining a support group where members share common experiences may alleviate the stress of illness.

Multidrug-Resistant TB (MDR-TB)

Mycobacterium tuberculosisstrains resistant to one or more anti-TB drugs have emerged. Multidrug-resistant TB (MDR TB) is when bacteria become resistant to at least the two first-line drugs, isoniazid and rifampin. When people fail to complete treatment regimens or receive incorrect treatment, they may remain infectious. Bacteria in their lungs may develop resistance to certain anti-TB drugs, which then can no longer kill the bacteria. People they infect will acquire the same drug-resistant strain. When drug treatment stops, the resistant bacteria will being to multiply and cause active disease again, for which treatment options are limited.

The end result is drug-resistant TB, a form of TB that doesn't respond to treatment. Drug-resistant Mycobacterium tuberculosis strains may emerge due to inconsistent or partial treatment, when patients do not take all their medicines regularly for the required period because they start to feel better, health workers prescribe the wrong drugs or the wrong combination of drugs, or the drug supply is unreliable.

Drug resistance is more common in people who:

• Have spent time with someone with drug-resistant TB disease
• Do not take their prescribed medicine regularly
• Do not take all their medicine
• Develop TB disease again, after having taken TB medicine previously
• Come from areas where drug-resistant TB is common (South East Asia, Latin America, Haiti and the Philippines)

People with MDR-TB disease must be treated with special drugs, which are not as effective as the usual anti-TB drugs and often cause severe side effects. People with MDR-TB disease must consult a TB specialist to observe their treatment to check its effectiveness. MDR-TB is at least 100 times more expensive to cure than non-resistant TB. At best, only half those infected with new strains can be cured. There is no cure affordable to some developing countries for MDR strains.

People who have spent time with someone with MDR-TB disease can become infected with MDR-TB bacteria. If they have a positive skin test reaction, preventive therapy is important for those at high risk of developing MDR-TB disease, such as children and HIV-infected people.

In 2008 an estimates 440 000 cases of MDR-TB emerged globally. MDR-TB comprises about 2% of new cases and 7% of previously treated cases of TB in South Africa.

The worst scenario is that TB will become untreatable due to the emergence of MDR-TB strains with additional resistance to other drugs available for the treatment of TB.

XDR-TB

XDR-TB stands for Extensively Drug Resistant TB (also referred to as Extreme Drug Resistance). This is MDR-TB that has also become resistant to three or more of the six classes of second-line drugs.

This description of XDR-TB was first used earlier in 2006, after a survey by the World Health Organisation and the US Centers for Disease Control and Prevention.

XDR-TB is a serious global concern as there are limited treatment options available for people infected with these strains. An outbreak of XDR-TB in KwaZulu Natal in 2006 killed 52 out of 53 people infected. XDR-TB is of particular concern in areas where the HIV prevalence is high, and is especially difficult to treat in HIV-positive people.

 DOTS

DOTS (Directly Observed Treatment, Short-course) is a strategy used by primary health services to detect and cure TB patients. DOTS combines five elements: political commitment, microscopy services, drug supplies, monitoring systems and direct observation of treatment.

The biggest obstacle to curing TB was patient non-compliance i.e. failure of patients to complete treatment - often because of distance from a clinic. With the DOTS system, patients take medicine under supervision of a community worker, thus making the health system responsible for achieving a cure. Resources are first directed toward identifying sputum smear positive cases for treatment, as these people are the sources of infection. Once infectious cases are detected using microscopy services, health workers counsel, observe and record patients taking the correct dosage of anti-TB drugs for six to eight months.

Most patients start to feel better after a few weeks of medication and are often tempted to stop taking it. The health system monitors patients' progress, ensures all TB bacteria are gone, and documents when patients are cured. This is especially important during the first two months of treatment when patients may be seriously ill, at risk of acquiring drug resistance, and infectious.

The correct combination and dosage of anti-TB medicines - short-course chemotherapy - must be used for the right length of time. These drugs provide a knockout punch to kill TB bacteria.

After two months sputum smear testing is repeated, to check progress, and again at the end of treatment to ensure patients are free of TB.

DOTS produces cure rates of up to 85 percent even in the poorest countries, and helps prevent new infections and the development of MDR-TB. The World Bank rates DOTS as one of the most cost-effective health interventions.

Through analysis of each group of patients, this system allows health services to quickly identify districts not achieving 85 percent cure rates, and to provide additional support and training.

Establishing a dependable, high-quality supply of anti-TB drugs throughout the health system is essential to ensure uninterrupted treatment.

Prevention

Most important in TB prevention is for people with infectious TB to take their medicine as prescribed. If you are taking medication, you need regular check-ups and possibly additional chest X-rays or sputum tests to show whether the medicine is working, and whether you are still infectious. If the tests show that you still have the bacteria in your sputum even after a few months of treatment, you may need to take some extra drugs, or change the drugs you are taking.

Detection of early cases and prompt treatment are crucial in controlling the spread of TB. The local health department may need to test people who have spent time with you for TB infection.

If you are sick enough to go to hospital, you may be put in a special room with air vents that keep TB bacteria from spreading. People working in these rooms wear facemasks to protect themselves from bacteria. You must stay in the room to prevent spreading bacteria.

If you are infectious while at home, protect yourself and others as follows:

• Wash your hands after sneezing, coughing or holding your hands near your mouth or nose.
• Cover your mouth with a tissue when you cough, sneeze or laugh. Discard used tissues in a plastic bag, then seal and throw it away.
• Do not attend work or school.
• Avoid close contact with others.
• Sleep in a room away from other family members.
• Ventilate your room regularly. TB spreads in small closed spaces. Put a fan in your window to blow out air that may contain bacteria.

TB Vaccine (BCG)

The TB vaccine, BCG, is often given to babies and children in countries where TB is common, although its protective value is debatable. However, it is thought that BCG does offer increased protection against developing TB in parts of the body apart from the lungs (i.e. extra-pulmonary TB). The vaccine's efficacy varies throughout the world from 0 to 80%, but it is only effective in children, not adults. In South Africa efficacy is about 60% against pulmonary TB.

In some countries, BCG is no longer given routinely, since the incidence of TB in those countries is very low. In other parts of the world where there is a high prevalence of TB, BCG is given to children at birth as part of the routine vaccine schedule. It may also be given at three months, on entering school, and on leaving high school. BCG must not be given to a person with active TB. If you were vaccinated with BCG, you may have a positive reaction to a TB skin test, due to the BCG vaccine itself or to a real TB infection.

A positive reaction probably means that you have TB infection if:

• Your skin test reaction is large
• You were vaccinated many years before (the BCG reaction lessens over time)
• You have ever spent time with someone with infectious TB
• Someone in your family has had TB
• You are from a country where TB disease is common such as South Africa

BCG vaccination should not be given to tuberculin-positive individuals, patients on corticosteroid or immunosuppressive therapy, and other causes of immune deficiency.

Adverse effects are rare, however, the vaccine may cause a local reaction in sensitive people, lasting about three days.

Children visiting areas with a high risk of TB infection should be offered tuberculin skin testing, and BCG vaccination if the test is negative.

 - Reviewed by Joanna Evans, PhD, Molecular Mycobacteriology Research Unit, Division of Medical Microbiology
Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, February 2011