News — Researchers found that a new, more sensitive blood test can detect latent tuberculosis (TB) more effectively than the traditional tuberculin skin test, especially in foreign individuals, according to a new study published in the first issue of the November 2005 American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.
The new test may prove to be an important tool in controlling TB in the developing world. According to the World Health Organization, TB kills more Africans than HIV and malaria combined. Worldwide, TB infection is spreading at the rate of one newly infected person each second.
In collaboration with seven associates, Peter F. Barnes, M.D., of the Center for Pulmonary and Infectious Disease Control at the University of Texas Health Center in Tyler, Texas, studied 413 individuals who have had contact with patients diagnosed with TB. After administering both tests to the group, the researchers found that the standard skin test returned positive results for exactly half of the subjects, while ELISPOT, the new blood test, only found TB in 39 percent.
The investigators argued that the blood test proved more accurate in TB diagnosis because it reduces the risk of error in test administration and interpretation, especially in developing nations. The authors also noted that certain types of vaccinations can trigger erroneous results from the skin test.
"Unfortunately, the standard method of diagnosing latent TB infection is the tuberculin skin test, which has many shortcomings," said Dr. Barnes. "Two visits are required and skilled personnel are essential for proper placement and interpretation of the test. In addition, because purified protein derivative of tuberculin contains many antigens that are shared with other mycobacteria, the skin test does not reliably distinguish latent TB infection from prior immunization with bacilli Calmette-Guérin, or BCG vaccination, or from infection with environmental mycobacteria."
"This is a major problem in most developed countries because a growing proportion of those with latent infection are foreign-born persons from high-incidence countries, most of whom received BCG vaccination during childhood," Dr. Barnes continued. "A more accurate and convenient test to diagnosis latent TB infection would greatly enhance tuberculosis control efforts."
Of the study cohort, 185 individuals (45 percent) were born in the United States, while 228 were foreign-born. Among the foreign-born persons in the study, 201 (88 percent) were BCG-vaccinated. Of those born in the United States, only 3 had received the BCG vaccine.
During the study, six subjects developed TB. Five had positive blood tests and four had positive tuberculin skin tests. The investigators developed a formula to calculate a "contact score" for each TB case, which quantified the extent of exposure to a TB patient, as well as the degree of infectiousness.
Since the risk of acquiring latent TB infection is proportional to the closeness of the person's relationship to the patient, the infectivity of the patient and the extent of exposure, the contact score is calculated by multiplying an individual's relationship (a household contact had increased weight) by infectivity (positive acid-fast sputum smears were weighted four times higher) and the extent of exposure (time spent indoors, within three feet of patient, type of room, etc.).
"Persons born in the United States and those who were not vaccinated with BCG were at relatively low risk for preexisting latent TB infection, and their principal risk was from recent exposure to a patient with tuberculosis," said Dr. Barnes. "In this setting, higher contact scores were significantly associated with both positive ELISPOT and tuberculin skin test results. However, the contact score was more strongly related to the ELISPOT than the tuberculin skin test results, although this difference was not statistically significant."
According to the authors, both ELISPOT and tuberculin skin test results were positive in 133 persons and both were negative in 175 contacts. The tuberculin skin test alone was positive in 75 cases (18 percent) and the ELISPOT test alone was positive in 30 cases (7 percent).
ELISPOT, approved for use in Europe, is being evaluated by the U.S. Food and Drug Administration.
For more information on tuberculosis, visit the American Thoracic Society's website at to read "Treatment of Tuberculosis," a statement produced in 2003 by the ATS, the Centers for Disease Prevention and Control and the Infectious Disease Society of America.
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American Journal of Respiratory and Critical Care Medicine (Nov-2005)