KEYSTONE, COLO. — Epidemiologic trends indicate that American physicians will increasingly encounter extensively drug-resistant tuberculosis in coming years, Dr. Charles L. Daley said at a meeting on allergy and respiratory disease sponsored by the National Jewish Medical and Research Center, Denver.
In the mid-1990s, TB in the United States occurred chiefly in U.S.-born persons. Indeed, U.S.-born patients with TB outnumbered foreign-born patients with TB 2:1. Since then, however, the annual number of TB cases among U.S.-born individuals has declined sharply, while the number of cases arising in the foreign born has remained constant. In each year since 2001 foreign-born persons have accounted for more than half of all TB cases in the United States.
“That's an important epidemiologic factor, because most of the XDR [extensively drug-resistant]-TB that's been reported has been outside the United States. With more cases here coming from those areas, no surprise, we're going to see more MDR [multidrug-resistant]- and XDR-TB,” said Dr. Daley, head of the division of mycobacterial and respiratory infections at the center and professor of medicine at the University of Colorado, Denver.
The No. 1 risk factor for MDR and XDR is foreign birth in areas where TB is endemic and TB control practices are poor. Russia and many of its neighboring former Soviet republics constitute the biggest problem area worldwide. In those regions, more than 40% of people who've previously been treated for TB have MDR-TB.
Drug resistance in Russia was created mainly in the prisons—and recent mass pardons have put many convicts with MDR-TB back into the community. A lot of transmission also took place in the country's hospitals because of the lack of infection control protocols. In Russia, 14% of MDR-TB strains are XDR, compared with 6% in the United States and Western Europe. South Africa is another hotbed of XDR, though there is little TB drug resistance elsewhere on the continent.
Suspect MDR-TB in a patient with TB symptoms and who is from or has traveled to an endemic area, Dr. Daley advised.
Globally each year, there are more than 400,000 new cases of MDR-TB and 40,000 of XDR-TB. “The XDR strains aren't real virulent, so far as we know, but they're almost untreatable,” according to Dr. Daley.
A handful of published reports show cure rates of about 30% in U.S. patients with XDR-TB, compared with what's being reported elsewhere. In contrast, treatment success rates of 60%–80% are reported with systematic treatment for MDR-TB.
A Centers for Disease Control and Prevention case series reported last year highlighted the changing epidemiology of XDR-TB in the United States during 1993–2006.
In 1993–1999, 72% of cases in the series were men, 38% were foreign born, and 44% were HIV positive. In contrast, in 2000–2006, only 47% were men, 76% were foreign born, and just 12% were HIV infected.
“You might say, 'Well, this doesn't matter to my practice,'” Dr. Daley said, adding that in the past year and a half, there has been a handful of documented cases of MDR-TB diagnosed in Rocky Mountain states where TB hasn't historically been much of a problem. All involved foreign-born individuals.
Current treatment regimens for XDR-TB virtually always require utilization of third-line drugs that aren't very potent against Mycobacterium tuberculosis, such as amoxicillin/clavulanate, clofazimine, linezolid, and the macrolides. With cure rates for XDR-TB hovering around 30%, new drugs are clearly needed, Dr. Daley said.
Multidrug-resistantTB has emerged in Rocky Mountain states where TB hasn't historically been much of a problem. DR. DALEY