Twenty Years of Global Surveillance of Antituberculosis-Drug Resistance

The Global Project on Anti-Tuberculosis Drug Resistance has been gathering data since 1994. This study provides the latest data on the extent of drug resistance worldwide. Data for drug susceptibility were gathered from 90 726 patients in 83 countries and territories between 2002 and 2007. Standardised collection of results enabled comparison both between and within countries. Where possible, data for HIV status and resistance to second-line drugs were also obtained. Laboratory data were quality assured by the Supranational Tuberculosis Reference Laboratory Network. The median prevalence of resistance to any drug in new cases of tuberculosis was 11.1% (IQR 7.0-22.3). The prevalence of multidrug resistance in new tuberculosis cases ranged from 0% in eight countries to 7% in two provinces in China, 11.1% in Northern Mariana Islands (although reporting only two cases), and between 6.8% and 22.3% in nine countries of the former Soviet Union, including 19.4% in Moldova and 22.3% in Baku, Azerbaijan (median for countries surveyed 1.6%, IQR 0.6-3.9). Trend analysis showed that between 1994 and 2007, the prevalence of multidrug-resistant (MDR) tuberculosis in new cases increased substantially in South Korea and in Tomsk Oblast and Orel Oblast, Russia, but was stable in Estonia and Latvia. The prevalence of MDR tuberculosis in all tuberculosis cases decreased in Hong Kong and the USA. 37 countries and territories reported representative data on extensively drug-resistant (XDR) tuberculosis. Five countries, all from the former Soviet Union, reported 25 cases or more of XDR tuberculosis each, with prevalence among MDR-tuberculosis cases ranging between 6.6% and 23.7%. MDR tuberculosis remains a threat to tuberculosis control in provinces in China and countries of the former Soviet Union. Data on drug resistance are unavailable in many countries, especially in Africa, emphasising the need to develop easier methods for surveillance of resistance in tuberculosis. Global Project: United States Agency for International Development and Eli Lilly and Company. Drug resistance surveys: national tuberculosis programmes, the Government of the Netherlands, the Global Fund to Fight AIDS, Tuberculosis and Malaria, Japan International Cooperation Agency, and Kreditanstalt für Wiederaufbau.

Data on global trends in resistance to antituberculosis drugs are lacking. We expanded the survey conducted by the World Health Organization and the International Union against Tuberculosis and Lung Disease to assess trends in resistance to antituberculosis drugs in countries on six continents. We obtained data using standard protocols from ongoing surveillance or from surveys of representative samples of all patients with tuberculosis. The standard sampling techniques distinguished between new and previously treated patients, and laboratory performance was checked by means of an international program of quality assurance. Between 1996 and 1999, patients in 58 geographic sites were surveyed; 28 sites provided data for at least two years. For patients with newly diagnosed tuberculosis, the frequency of resistance to at least one antituberculosis drug ranged from 1.7 percent in Uruguay to 36.9 percent in Estonia (median, 10.7 percent). The prevalence increased in Estonia, from 28.2 percent in 1994 to 36.9 percent in 1998 (P=0.01), and in Denmark, from 9.9 percent in 1995 to 13.1 percent in 1998 (P=0.04). The median prevalence of multidrug resistance among new cases of tuberculosis was only 1.0 percent, but the prevalence was much higherin Estonia (14.1 percent), Henan Province in China (10.8 percent), Latvia (9.0 percent), the Russian oblasts of Ivanovo (9.0 percent) and Tomsk (6.5 percent), Iran (5.0 percent), and Zhejiang Province in China (4.5 percent). There were significant decreases in multidrug resistance in France and the United States. In Estonia, the prevalence in all cases increased from 11.7 percent in 1994 to 18.1 percent in 1998 (P<0.001). Multidrug-resistant tuberculosis continues to be a serious problem, particularly among some countries of eastern Europe. Our survey also identified areas with a high prevalence of multidrug-resistant tuberculosis in such countries as China and Iran.

In the past decade the incidence of tuberculosis has increased nationwide and more than doubled in New York City, where there have been recent nosocomial outbreaks of multidrug-resistant tuberculosis. We collected information on every patient in New York City with a positive culture for Mycobacterium tuberculosis during April 1991. Drug-susceptibility testing was performed at the Centers for Disease Control and Prevention. Of the 518 patients with positive cultures, 466 (90 percent) had isolates available for testing. Overall, 33 percent of these patients had isolates resistant to one or more antituberculosis drugs, 26 percent had isolates resistant to at least isoniazid, and 19 percent had isolates resistant to both isoniazid and rifampin. Of the 239 patients who had received antituberculosis therapy, 44 percent had isolates resistant to one or more drugs and 30 percent had isolates resistant to both isoniazid and rifampin. Among the patients who had never been treated, the proportion with resistance to one or more drugs increased from 10 percent in 1982 through 1984 to 23 percent in 1991 (P = 0.003). Patients who had never been treated and who were infected with the human immunodeficiency virus (HIV) or reported injection-drug use were more likely to have resistant isolates. Among patients with the acquired immunodeficiency syndrome, those with resistant isolates were more likely to die during follow-up through January 1992 (80 percent vs. 47 percent, P = 0.02). A history of antituberculosis therapy was the strongest predictor of the presence of resistant organisms (odds ratio, 2.7; P < 0.001). There has been a marked increase in drug-resistant tuberculosis in New York City. Previously treated patients, those infected with HIV, and injection-drug users are at increased risk for drug resistance. Measures to control and prevent drug-resistant tuberculosis are urgently needed.