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Tuberculosis

LatentTB: Regular Monitoring vs INH Treatment

01/07/2008

Question:

I have a positive skin test for TB. I have not taken the INH treatment due to:

1. Confirmation that the exposure is not an infection. I have been regularly monitoring this with Chest X-Ray and discussions / tests by my physician.

2. BCG vaccination during Childhood (Well, now it has been atleast 32 years after that fact!)

3. I did not understand how we can be assured that the INH treatment has successfully killed the latent bacteria. In other words, is there a test available to "measure" the success?

4. INH treatment doesn’t guard against any future "exposures". If at all future exposure happens, there is no way to even identify such exposure through skin test etc. In these cases identifying the TB happen through Chest X-Ray and other tests when it has already become an infection - we could potentially be spreading TB already at that point.

5. INH treatment might affect the liver function in certain cases. Once this is identified and INH is discontinued, the TB bacteria become immune to that medication and cannot be treated with that.

With all these said, when I cannot make sure that the INH treatment worked OR identify any future TB exposures, is it really helpful to go through the INH treatment for the latent TB given the potential impacts and risks? Can`t we just be cautious with regular chest X-Rays and other symptoms to monitor the situation on an ongoing basis?

Answer:

These are excellent questions that are often asked by patients with positive tuberculin skin tests (TST) and latent TB infection (LTBI). We will review some general facts about tuberculosis (TB) and then address each one of your concerns.

TB is a disease caused by a germ called Mycobacterium tuberculosis that is spread from person to person through the air. When a person with infectious TB of the lungs coughs or sneezes, he expels droplets with M. tuberculosis into the air. When another person breathes in the infected air droplets, he or she may become infected. Approximately 90 to 95% of people who are infected with M. tuberculosis do not develop active TB disease, they do not feel sick. Their body is able to fight the bacteria to stop them from growing. The bacteria become inactive, but they remain alive in the body and can become active later. These people have LTBI.

Even though people with LTBI are not infectious and cannot spread TB infections to others. They should receive treatment for LTBI to prevent development of active TB disease. About 10% of persons with LTBI will develop active TB disease at some time in the future. The general symptoms of active TB include unexplained weight loss, weakness, fatigue, loss of appetite, fever, chills, and night sweats. The symptoms for TB of the lungs include a bad cough that lasts 3 weeks or longer, pain in the chest, and coughing up blood or sputum (phlegm from deep inside the lungs). Risks of developing active TB disease are higher in patients who are recent contacts of someone with active pulmonary TB (within the first two years of infection) and persons whose immune systems are weak (HIV infection, young children, elderly, and patients with other medical illnesses). As long as the TB germ is in your body, it can begin to multiply and cause active TB disease. Scientific studies have shown that completing latent TB treatment can reduce the risk of developing active TB disease by up to 90%.

Now to answer your specific questions.

1. "Confirmation that the exposure is not an infection. I have been regularly monitoring this with Chest X-Ray and discussions / tests by my physician."

A positive TST means that you are infected with the TB bacillus. Once your doctor has evaluated you and made sure that you do not have any evidence of “active” TB disease (including a normal CXR) you are diagnosed with latent TB infection (LTBI). Persons with latent TB infection should take the medication to prevent them from developing active TB disease.

Because TB can spread to any part of the body and not just the lungs, we do not recommend getting frequent CXRs as a method to monitor for TB disease for people with no symptoms of active TB disease. I am not sure what other tests your physician is regularly performing to monitor for active TB disease. Currently, there is no single test available to monitor patients with LTBI to see when they develop active TB disease. Instead, medical evaluation and work up should depend on symptom reviews.

2. "BCG vaccination during Childhood (Well, now it has been at least 32 years after that fact!)"

Bacille Calmette-Guérin (BCG) is a vaccine for TB disease. This vaccine is often given to infants and young children in countries where TB is common; it not generally used in the United States. The BCG vaccine does not always protect people from getting TB. It can sometimes cause a false positive TST, but usually in those who received the BCG vaccine recently or after age 5. If your BCG vaccine was 32 years ago, your positive TST is unlikely to be due to the BCG vaccine. The fact that you received the BCG vaccine indicates that you were probably born in a country with high rates of TB and that you were probably exposed and infected as a child with the TB bacteria.

There is a new blood test for TB screening that is not affected by the previous BCG vaccine (QuantiFERON-TB Blood Test). This blood test measures the response to TB proteins (antigens) when they are mixed with a small amount of blood. Some health departments and hospitals may offer this blood test.

3. "I did not understand how we can be assured that the INH treatment has successfully killed the latent bacteria."

In other words, is there a test available to "measure" the success? Unlike some other infectious diseases, there is no test available to “measure” the success of treatment for LTBI or active TB disease. However, there are several scientific studies that have shown that patients who received treatment for LTBI were much less likely to develop active TB disease than those who did not receive LTBI treatment. Because patients with LTBI do not have as many organisms in their body as those with active TB disease, one drug instead of many drugs is used for treatment and because the TB bacteria is a very slow growing organism, several months of antibiotic treatment are needed to ensure “killing” of all of the organisms (9 months of INH). Completing the entire course of LTBI treatment as directed will increase your likelihood of successful treatment.

4. “INH treatment doesn’t guard against any future "exposures". If at all future exposure happens, there is no way to even identify such exposure through skin test etc. In these cases identifying the TB happen through Chest X-Ray and other tests when it has already become an infection - we could potentially be spreading TB already at that point.”

You are correct, treatment of LTBI does not guard against any future “exposures”. The reason for treatment of LTBI is to kill the TB organisms that are in your body now and prevent you from developing active TB disease. The majority of TB cases in the United States are reactivation of TB and one of the goals of controlling TB is to treat patients with LTBI, especially those who are at increased risk of developing active TB disease. This will decrease the risk of spreading TB to others later.

Currently, if a person is diagnosed with active TB of the lung, the public health department will conduct a contact investigation. TB screening is done on anyone who has had an extended contact with the infectious person such as those who live or work with him or her. The close contacts are asked about symptoms of active TB and either a TST or TB blood test is performed. For those with previous positive TSTs, a symptom review is done. A CXR and additional diagnostic tests are done for anyone with a positive TB screening test or review of symptoms. We always advise those with a history of TB infection to receive treatment for LTBI if they have not done so already.

We also advise everyone, including those who have completed LTBI treatment, to seek medical evaluation as soon as possible if they develop any symptoms of active TB disease as outlined above and to always let the doctor know that they have a history of TB exposure. By getting evaluated early, the diagnosis and treatment can be started sooner which will decrease the likelihood of spreading the TB bacteria to others.

5. "INH treatment might affect the liver function in certain cases. Once this is identified and INH is discontinued, the TB bacteria become immune to that medication and cannot be treated with that."

As with any drug, there is a potential for side effects. INH can affect the liver; however, recent studies have shown that patients who do not have underlying liver disease have a very low risk of developing liver problems during LTBI treatment. Studies have also shown that if someone stops the TB medication as soon as any liver problem develops, there is usually no permanent damage to the liver. The symptoms of liver problems are loss of appetite, nausea, vomiting, abdominal pain, fever, yellowing of the skin, and darkening of the urine. We educate patients that if they are experiencing any of these symptoms to stop the medication right away and come into the clinic for blood tests.

Frequent liver blood tests can be checked to monitor patients who are at increased risk of developing liver problems. Alcohol and other drugs or over the counter products that affect the liver can increase the risk of liver problems. Your doctor can review your current medications and risks with you. For some patients who do not tolerate INH another drug called Rifampin can be used.

Drug resistance is a very big concern. Patients with drug resistance have either acquired drug resistant strains of TB or developed resistant strains during their treatment. Most drug resistance occurs when medications are not taken as directed and many doses are missed. By taking and completing the medication as directed you are less likely to develop drug resistance. If a person develops active TB disease, typical tests that are done are a culture and drug susceptibility testing. The drug testing will let your doctor know which antibiotic works best for your strain of the TB bacillus. Your doctor will choose a combination of drugs that is most effective and has the least side effects. Both latent and active TB are treatable and curable.

In summary, LTBI treatment has been shown to markedly decrease the chance of developing active TB disease and proper monitoring during treatment will decrease the risk of drug side effects. A discussion with your doctor to determine if you are at high risk for developing active TB disease should be done along with a discussion of the benefits and risks of treatment.

References:

Treatment of Tuberculosis, American Thoracic Society (ATS) and Centers for Disease Control, and Infectious Disease Society of America, 2003.

Targeted Tuberculin Testing and Treatment of Latent Tuberculosis infection, Centers for Disease Control, 2000

Questions and Answers About TB, Centers for Disease Control, 2005.

Tuberculosis: General Information, Centers for Disease Control, 2007

Treatment of Latent TB Infection: Maximizing Adherence, Centers for Disease Control, 2005.

The Difference Between Latent TB Infection and Active TB Disease, Centers for Disease Control, 2007.

QuantiFERON-TB Gold Test, Centers for Disease Control, 2007.

For more information:

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Response by:

Shu-Hua   Wang, MD, MPH&TM Shu-Hua Wang, MD, MPH&TM
Clinical Assistant Professor of Infectious Diseases
Clinical Assistant Professor of The Division of Epidemiology
College of Medicine
The Ohio State University

Larry S Schlesinger, MD Larry S Schlesinger, MD
Professor:
Molecular Virology, Immunology and Medical Genetics
Microbiology Administration
Environmental Health Sciences
College of Medicine
The Ohio State University