Study eyes NTMs effect on PPD false-positives
Up top half in 10- to 14-mm range
TB experts have long believed that nontuberculous mycobacteria (NTMs) are responsible for a certain proportion of positive reactions to the PPD skin test. A new study1 helps delineate exactly how much the NTMs may be muddying the PPD waters. Using side-by-side tests for M. avium and M. TB on healthy hospital workers with no history of exposure to TB, researchers found that half of positive reactions in the 10- to 14-mm range were due to NTMs. By comparison, only about 20% of positive reactions that measured more than 15 mm were found to be due to NTMs.
The data underscore why it makes sense to use 15 mm as the cutoff for what’s considered positive, at least in healthy adults with no known exposures to TB, says Fordham von Reyn, MD, lead researcher for the study, and professor of medicine and chair of the infectious diseases section at Dartmouth-Hitchcock Medical Center in Hanover, NH.
Von Reyn’s study also adds urgency to the quest for a better diagnostic test for latent TB — whether Quantiferon, or something else. (von Reyn says he’s not convinced Quantiferon has the capability to weed out false-positives from atypicals.) "This study further illustrates the limits of skin-testing in assessing health care worker infection with TB," says Ed Nardell, MD, professor of pulmonary medicine at the Cambridge Hospital. "It also suggests that testing should be limited to places where there’s significant risk for TB."
Sorting out an old assumption
The aim of the study was to see how many skin tests below 15 mm actually were due to NTMs, says von Reyn (whose research interests include AIDS, the PPD skin test, and atypical mycobacteria). "We already knew from previous work that false-positives are more common when you get below the 15-mm cutoff," he adds.
To begin sorting out the issue, the first step was to validate a diagnostic test for NTMs. To that end, von Reyn rounded up patients from various sources — including Emory University in Atlanta, the Rochester, MN-based Mayo Clinic, and the National Jewish Hospital in Denver — who’d already been diagnosed with M. avium complex (MAC) disease. Then, using a skin test containing M. avium sensitin (developed and manufactured by the State Serum Institute of Copenhagen, Denmark), researchers did side-by-side comparisons of the PPD and the M. avium skin test. The Copenhagen test performed as von Reyn had predicted: "We were able to show quite nicely that people with culture-positive MAC lung disease had bigger skin-test reactions to M. avium than to the PPD," he says.
Next, researchers did the same side-by-side comparisons on a group of healthy U.S. health care workers. This second group was recruited from around the country and included health care workers at varying levels of risk for TB exposure. This time, researchers compared reactions to both skin tests, looking to see which induration was bigger. "We infer you’ll have a reaction to an M. avium infection you’ve had in the past, in the same way a PPD skin test elicits the positive reaction for a latent TB infection," von Reyn explains — though strictly speaking, atypicals don’t persist in a latent stage the way M. TB does.
North vs. South: Little difference
Though NTMs are widely supposed to be more prevalent in the southern United States, von Reyn says he didn’t find much evidence to support that belief. "I think the difference may have been overestimated in the past," he says. "The difference between North and South may be on the order of 30% vs. 40%; not, say, 5% vs. 50%." If you look at environmental sources for NTMs, he adds, the highest-ever rates cultured in the environment turn out to have been reported from Finland — not exactly a tropical paradise.
That brings up the next question — namely, whether von Reyn’s findings also lend weight to the widespread presumption that NTMs are on the rise. "There’s convincing evidence that’s so, both from adults with pulmonary disease and children with cervical adenitis," he says.
As to why the increase, there are many schools of thought on that subject. von Reyn, like several other experts in the field, believes institutional sources of hot water are one of the culprits, at least as far as adults in developed countries are concerned. "In the late 1970s, many hospitals lowered their hot-water temperature by about 20°, taking it from a temperature the bugs couldn’t tolerate, to one where they were quite comfortable," he says. Using molecular fingerprinting techniques, and working with colleague Robert Arbeit, MD, he showed several years ago that a group of AIDS patients with MAC disease had all become infected with the same strain of M. avium from the same hot-water source.
Kids, on the other hand, probably don’t pick up atypical infections the same way. "Many of those NTMS are probably acquired in childhood," von Reyn believes. "Children at play probably get soil and water contamination in their mouths — most likely when they’re cutting teeth."
As rates of TB go down and those of NTMS apparently rise, implications for TB controllers are clear, von Reyn believes. "We’ve got to become increasingly concerned about false-positives in low-risk people," he says.
1. von Reyn CF, et al. Skin test reactions to Mycobacteria tuberculosis-purified protein derivative and Mycobacterium avium sensitin among health care workers and medical students in the United States. Int J Tuberc Lung Dis 2001; 5:1,122-1,128.
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