Health officials concerned about possible global spread of XDR-TB

November 2006

Health officials have expressed concern about the emergence of virulent drug-resistant strains of tuberculosis that are virtually untreatable with standard drugs, and have called for actions to prevent the global spread of the deadly strains.

Recent research from multiple national and international sources has identified cases of extensive drug-resistant TB (XDR-TB) that leaves patients (including many living with HIV) untreatable using available anti-TB drugs. Multidrug-resistant TB is described as strains of TB that are resistant to at least the two main first-line drugs — isoniazid and rifampicin. XDR-TB is multidrug-resistant TB that is also resistant to three or more of the six classes of second-line drugs.

“XDR-TB has emerged worldwide as a threat to public health and TB control, raising concerns of a future epidemic of virtually untreatable TB. New anti-TB drug regimens, better diagnostic tests, and international standards for second line drug-susceptibility testing are needed for effective detection and treatment of drug-resistant TB,” WHO and CDC health officials wrote in Morbidity and Mortality Weekly Report.

Globally, about 8 to 10 million people contract TB each year and about 1.7 million of those die, according to WHO. There are about 425,000 cases of multidrug-resistant TB each year. Although most strains of drug-resistant TB are treatable, fighting them requires prolonged and expensive doses of medication. The time required to treat TB can vary from six months to two years, putting huge pressure on the health infrastructure of developing countries.

XDR-TB emerging

WHO and CDC researchers detected XDR-TB in all regions of the world, but most frequently in countries in Eastern Europe and Asia. Findings from their international survey of TB laboratories, conducted from November 2000 through 2004 among 17,690 TB samples, indicated that 20% of isolates were multidrug-resistant and 2% were XDR-TB.

In the United States, 4% of multidrug-resistant TB cases met the criteria for XDR-TB. In South Korea, 15% of multidrug-resistant TB cases met the criteria and in Latvia, a country with one of the highest rates of multidrug-resistant TB, 19% of the cases met the XDR-TB criteria. Sixty people have already died in South Africa due to XDR-TB, and the disease is threatening to spread across the region.

Experts fear that South Africa’s high rates of HIV/AIDS could quickly lead to a global epidemic of XDR-TB. The particularly virulent strain has already surfaced in two South African provinces and is suspected in the Gauteng province, the country’s economic hub, which recently reported a batch of new cases.

Separate data from an outbreak of XDR-TB in a population of people with HIV in the South African province of KwaZulu Natal showed alarmingly high mortality rates, according to research presented at the XVI International AIDS Conference. From January 2005 through March 2006, researchers evaluated 536 patients and found that 41% (221 patients) had multidrug-resistant TB, of which 53 were cases of XDR-TB. Forty-seven of the patients with XDR-TB had HIV. Within about 25 days, all but one of the patients died, despite treatment with antiretroviral therapy.

“Increased surveillance in rural South Africa revealed a markedly greater multidrug-resistant TB prevalence than previously recognized, with evidence of recent nosocomial and community transmission of XDR-TB in HIV co-infected patients,” the researchers wrote in their abstract. “The convergence of the TB/HIV epidemic with multidrug-resistance and XDR-TB in resource poor settings is a deadly threat to gains in survival achieved by TB DOTS and antiretroviral therapy.”

HIV infection rates are similarly high in the neighboring countries of Botswana, Lesotho, Mozambique, Swaziland and Zimbabwe, which have yet to report any XDR-TB cases.

Another study, conducted in Tehran, Iran, between 2003 and 2005, indicated that 11% of patients with multidrug-resistant TB had XDR-TB. Researchers analyzed sputum samples from 2,030 TB patients, of which 1,284 had positive Mycobacterium tuberculosis cultures and found that 12% had multidrug-resistant TB. Further drug sensitivity testing on 113 patients with multidrug-resistance showed evidence of XDR-TB among 12 participants for all eight second-line drugs. The researchers also found that XDR-TB in this locale was transmitted to individuals in two family clusters, and people with HIV were most at risk, according to the data published Clinical Infectious Diseases.

TB, especially the XDR-TB strain, poses an acute threat in Africa and other less-developed regions because the disease is easy to contract, but problematic and expensive to treat. Scarce drug resistance data available from Africa indicate that although population prevalence of drug-resistant TB appears to be low compared to Eastern Europe and Asia, drug resistance in the region is on the rise. Because of the underlying HIV epidemic in Africa, drug-resistant TB could have a severe effect and requires urgent preventive action, WHO suggested.

Resistance to anti-TB drugs in populations is a phenomenon that occurs primarily because of poorly managed TB care. Problems include incorrect drug prescription practices by providers, poor quality drugs or erratic supply of drugs and also lack of patient adherence to treatment.

For more information:

• CDC. Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs — worldwide, 2000-2004. MMWR. 2006;55:301-305.
• Gandhi NR, Moll A, Pawinski R, et al. High prevelance and mortality from extensively-drug resistant (XDR) TB in TB/HIV coinfected patients in rural South Africa. Late Breaker Abstract THLB0210. Presented at: XVI International AIDS Conference; Aug. 13-18, 2006; Toronto.
• Masjedi MR, Famia P, Sorooch S, et al. Extensively drug-resistance tuberculosis: 2 years surveillance in Iran. Clin Infect Dis. 2006;43:841-847.