XDR-TB: Deadlier and more mysterious than ever

November 06, 2008

New research has found that XDR-TB is increasingly common and more deadly than previously known. Extensively drug-resistant tuberculosis (XDR-TB) is a growing public health threat that is only just beginning to be understood by medical and public health officials.

Patients with XDR-TB are four times as likely to fail treatment and three times more likely to die than patients with other forms of multi-drug-resistant TB (MDR-TB), according to a recent study that directly compared patients with XDR-TB to individuals with other types of MDR-TB to determine the differences in treatment outcomes and long-term survival rates. Researchers also found that MDR-TB was "a major threat to public health," representing 2.7 percent of new TB cases in South Korea in 2004, up from 1.6 percent in 1994.

The results were published in the second issue for November of the American Journal of Respiratory and Critical Care Medicine, a journal of the American Thoracic Society.

Since it appeared on the public health radar in 2006, XDR-TB rekindled an urgent interest in preventing, fighting and containing TB. But at the same time, little was known about how XDR-TB changed the face of combating TB on all fronts, from the perspective of the patient, the clinician and the public health official.

"Treatment outcomes [of XDR-TB] have varied among studies, and data on long-term survival are still scarce," wrote Tae Sun Shim, M.D., an associate professor at Asan Medical Center in Seoul, South Korea, and a principal investigator of the study. "[This] is the largest report that we know of that compares patients with XDR-TB with other patients with MDR-TB to determine the impact of XDR-TB on treatment outcomes and long-term survival in mostly HIV-negative patients with MDR-TB."

The study reviewed the medical records of more than 1,400 patients in South Korea with MDR-TB (which includes XDR-TB) from all national hospitals, Korean National TB Association chest clinics and select university hospitals. In addition to the patients' demographic information, their history of TB and previous treatments were noted with regard to outcome. In this study, XDR-TB was defined as MDR-TB resistant to both ofloxacin and at least one second-line injectable drug.

The researchers found that patients with XDR-TB were significantly older than MDR-TB patients, were more likely to have a history of treatment with second-line TB drugs, and more likely to have a history of being treated for TB two or more times.

Among this population, treatment failure was, not surprisingly, much more common when compared to other patients with MDR-TB. While relapse rate among "cured" patients also tended to be higher among patients with XDR-TB, the difference was not statistically significant.

"[Having] XDR-TB was the strongest predictor of both all-cause and TB-related mortality, and survival curves showed higher cumulative mortality among patients with XDR-TB than in other patients with MDR-TB," wrote Dr. Shim. Over the three to seven years that the study's patient population was monitored, approximately 50 percent of those identified with XDR-TB died, which was a mortality rate similar to untreated TB patients in South India, and one that becomes even worse with HIV co-infection.

Perhaps the biggest public health threat associated with XDR-TB, however, is not its particular virulence, but the lack of information and treatment options that medical and public health officials have on which to draw. The collective dearth of knowledge was likened by Giovanni Battista Migliori, M.D., Morgan Richardson, R.N., P.H.N., and Christopher Lange, M.D., Ph.D., co-authors of the accompanying editorial, to the proverbial blind men trying to describe an elephant-too big a task to accomplish with too little information.

The risks of this lack of information are clear. "Regrettably, a new drug [to treat TB] has not been licensed in decades," they wrote, saying that only further research and concerted effort to understand and quantify the effects of the disease can really prevent MDR- and XDR-TB from becoming pandemic health crises.

"As we wait for new diagnostics and drugs that can meet the challenge of XDR-TB, we must work with what we presently have to create the optimal conditions for success and thus seize the opportunity we have to eliminate tuberculosis," they concluded.

American Thoracic Society

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