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TB Virus

The Dilemma of a Positive TB Test

Image Source: CDC/ Dr. Roger Feldman

You have been told by your doctor or your employer’s medical department that your tuberculosis (TB) test is positive. What does that mean? Do you have TB? Are co-workers and family at risk because they have been around you?  Should you be on medication? All of these questions are natural reactions to this report.

Tuberculosis is a serious infection, usually located in the lungs, but possibly anywhere in the body. However, it is also possible that the positive test is the result of underlying TB-like germs that do not have the disease-causing potential of Mycobacterium tuberculosis (MTb), the agent of TB disease. Active TB disease is the tissue-destructive interaction between the multiplying TB germ invaders and the host’s immune system. However, screening TB tests do NOT usually indicate disease.

About Screening TB Tests

TB tests can include the Mantoux and PPD skin tests, which are less used because they can be difficult to apply properly and even to interpret.

Now, doctors are using a relatively new blood test, Quantiferon TB IF (or T-Spot TB IF), which is an indirect immune system test for the presence of MTb, the agent of TB disease, as opposed to a direct culture or stain of tissues for the organism. In that regard, the Quantiferon TB (QTB) test is similar to the old TB skin tests.

These tests have been used in the past to screen high-risk populations – people who are likely to be or to have been exposed to others with active TB disease – to evaluate them for  the potential for active disease early on, before they become a public health risk for spreading TB, or to consider starting preventive treatment with isoniazid (INH) to kill any hibernating TB organisms before they have a chance to activate to cause disease.

So, it is possible for QTB to be positive when no disease or risk of TB transmission is present.

Context is an Important Factor in TB Risk

Another important point is made by the Bayesian Theorem of conditional probability. Simply stated, any test done and positive in the context of low probability for a disease is likely a false positive and not indicative of the disease or risk of disease.

For instance, if a 6-month old boy’s blood or urine were subjected by a laboratory mistake to a pregnancy test and were found to be positive, would it be reasonable to then conclude the 6-month old boy was pregnant?

If a QTB test were positive in a high-level U.S.-based executive who had never traveled outside the United States and had minimal exposure to sick people, is it likely to be a true positive for the TB organism? Perhaps if he had immigrant workers in his home and around him frequently. Otherwise, likely it is a false positive.

On the other hand, what about a Nigerian national sponsored by an international energy company who is training in the United States? A positive QTB here is much more likely to represent the presence of MTb, a true positive.

Because of the context-driven nature of the validity of any biological test, the U.S. Centers for Disease Control and Prevention has recommended QTB (and for that matter TB skin testing) not be done in low-risk populations, because the percentage of false positive tests will rise dramatically and lead to unnecessary anxiety and further medical actions, some costly and some with risk, and unlikely indicated or productive.

However, many companies with overseas operations have chosen to do the test as part of routine pre-work assignment or post-exposure medical screening protocols. In many cases, the QTB has replaced skin testing. The test is extremely sensitive, highly specific and bypasses the problems with skin testing, which, in addition to false positives and difficulty with reading a positive, requires expert placement and reading technique and several days for interpretation.

What do you do if you have a positive result on a TB test?

Deciding what to do with the result, especially in TB low-risk patients can be problematic. Many times, physicians will respond by placing a patient on INH prophylaxis. However, this medication can have side-effects such as peripheral neuropathy (nerve dysfunction), chemical hepatitis (liver inflammation, and rarely liver failure and/or death), and other reactions. Giving this medicine to prevent TB disease that may never happen is a complex risk-benefit decision analysis. It should never be an automatic reflex to a positive test.

First widely available for about 5 years, the QTB test has not been around long enough for the CDC or other public health agencies to correlate a positive QTB test in either TB low or high-risk populations with the likelihood of progression to disease. So, clinicians are somewhat on their own in considering a number of factors and the known science on them in creating a rational, reasonable response to a QTB positive.

IMC’s QTB Solution

At International Medicine Center, we have done just that. We have developed an analytical model for a responding to QTB positives based on current science. We are referred many QTB-positive patients, both from referring physicians and corporate clients. We review all the information on the specific case, and arrive at an action plan that makes sense and assures the patient that we will not miss active disease in them and that they will not be putting others at risk for TB. We are focused on not over-treating since most of the patients referred to us are truly low-risk for TB disease or activation.

Obviously, how to deal with a positive QTB will continue to be a work in progress. The complex issues of considering a positive QTB and responding to it, not too little and not to much, are truly expert functions to be handled by a qualified, experienced specialist.

Edward R. Rensimer, MD, FACP