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The standard regimens to treat tuberculosis (TB) are inadequate in countries with high rates of multi-drug resistant (MDR) TB. In countries with high rates of MDR-TB, patients are nearly twice as likely to fail their initial treatment than those in countries with low rates, according to a new analysis of World Health Organization (WHO) data. This finding suggests strongly that current TB treatment regimens need to updated and revised to address the shifting landscape of public health in the face of MDR-TB.
"In countries with low prevalence of initial multi-drug resistance, the standardized treatment regimens for new case appear to be adequate, wrote Dick Menzies, MD, lead author of the study and director of the respiratory division at McGillUniversity. "However, in countries where the prevalence of initial drug resistance exceeds three percent, we believe it is urgent to strengthen capacity to perform drug sensitivity testing, or to reevaluate these standard treatment regimens, given the unacceptably high rates of failure and relapse."
The study appeared in the first issue for August of the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.
When the current public health strategies to contain TB were conceived, MDR-TB was much less common. "We hypothesized that, in countries using standardized initial and retreatment regimens, the proportion of patients with poor treatment outcomes would be correlated with prevalence of initial and acquired multi-drug resistance," wrote Menzies.
To determine if that were the case, Menzies and co-investigators reviewed the WHO's data from 2003 and 2004 for a total of 155 countries, 121 of which reported at least 250 cases annually. They assessed dropout, failure, relapse and death rates with initial treatment, as well as dropout, failure and death rates for retreatment. All rates were analyzed with respect to the prevalence of MDR-TB in each country.
They were right: rates of failed treatment were dramatically higher with increasing prevalence of MDR-TB (p<0.0001). In fact, after accounting for age, HIV prevalence, per capita income and treatment regimen, for every one-percent increase in MDR TB prevalence, they saw a 0.30 percent rise in treatment failure among new cases, a 1.1 percent increase in failure rate among RE-treatment cases, and a one percent increase in relapse. "This is striking evidence that MDR-TB is directly linked to the increased failure rates of our current treatment regimens," said Menzies.
Overall, the proportion of patients requiring retreatment nearly doubled between countries with low and high prevalence of MDR-TB, from 11.9 percent in countries with initial MDR prevalence of less than one percent, to 21.4 percent in countries with MDR prevalence of more than three percent. "In the short term, the higher the failure and relapse rates mean greater morbidity and mortality for patients, with greater social and economic harm for their families and communities. In the long term, these standardized regimens may be contributing to amplification of multi-drug resistance in these countries," wrote Menzies.
The concern is that with current treatment regimens, many patients fail treatment or relapse later, and by continuing to use those regimens, researchers and public health officials may be unwittingly increasing the problem of drug resistance and multiplying the problem for other future patients. "Unless those with the responsibility to boost control and research efforts increase their commitments and their financial investments by several fold, we may never see elimination of this major scourge in the decades to come," wrote Marcos Espinal, MD, and Mario C. Raviglione, MD, both of the WHO, in an accompanying editorial in the same issue of the journal.