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. If you don't, 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
- Yellowish skin or eyes
- Fever for three or more days
- Abdominal pain
- Tingling fingers or toes
- Skin rash
- Easy bleeding
- Aching joints
- 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 tuberculosis strains 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 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 Centres 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 (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.
Reviewed by Dr AW Dreyer, Pathologist and Clinical Microbiologist, Centre for Tuberculosis, National Institute for Communicable Diseases February 2015.
Previously 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.