10% of new TB cases involve drug resistance

Ten percent of new tuberculosis cases involve resistance to a first-line anti-tuberculosis drug, according to a large international study published in the December 16^th edition of The Lancet. The study also revealed that 1% of new tuberculosis cases are multi-drug resistant, and that three countries – Russia, China and India – all of which have growing HIV epidemics, account for the majority of cases of multi-drug resistant tuberculosis.

It is estimated that a third of the world’s population is infected with tuberculosis and that there are almost 9 million new cases of the disease with 2 million deaths a year. Tuberculosis is a serious health concern in the context of HIV, with the infection being the leading cause of death amongst HIV-positive individuals worldwide.

Since the middle of the 20th century antimicrobial drugs have been available and when used correctly can completely cure tuberculosis. However, inappropriate use and poor patient adherence has lead to the emergence of drug resistant strains of the microbacterium. In addition, multi-drug resistant tuberculosis (MDR-TB)– tuberculosis that is resistant to two key first-line drugs, isoniazid and rifampicin – is becoming an increasing concern. The cure rate for MDR-TB is much lower than that for wild-type tuberculosis, involves more drugs with a greater side-effects profile, and costs significantly more.

Since 1994, the Global Project on Anti-tuberculosis Drug Resistance Surveillance has been monitoring the prevalence, patterns, and trends of drug-resistant tuberculosis around the world. The project involves key international organistations including the World Health Organization and the International Union Against Lung Disease and Tuberculosis.

In the latest round of surveillance, conducted between 1999 and 2002, data were gathered from 79 countries and setting. The prevalence of resistance to any first line tuberculosis drug ranged from 0% in Andorra, Iceland, and Malta to 57% in Kazakhstan, with the median being 10%. The median prevalence of MDR-TB was 1%. Although nine countries reported no MDR-TB, Kazakhstan, Israel, Tomsk Oblast in Russia, Karakalpakstan in Uzbekistan, Estonia, the Lianoning and Henan provinces of China and Lithuania had a prevalence of MDR-TB of almost 8%.

The investigators then looked at trends in resistance. They found that although the prevalence of resistance to any drug fell in Cuba (p < 0.017) and Hong Kong (p = 0.023), it increased significantly in Botswana (p < 0.001) and the Tomsk Oblast region of Russia (p = 0.005). A significant increase in the prevalence of MDR-TB was also observed in Tomsk Oblast, whereas MDR-TB prevalence fell significantly in the US (p = 0.002), and Hong Kong (p = 0.01).

Data were also analysed on resistance amongst individuals who had received previous tuberculosis therapy. Significantly increased trends in MDR-TB in such patients were observed in Estona (p < 0.001), Lithuania (p = 0.007) and Tomsk Oblast (p = 0.002).

“Antituberculosis drug resistance has been identified in virtually all the countries surveyed, reaching especially high levels in areas of the former Soviet Union and some provinces in China”, write the investigators.

The investigators stress that although the overall burden of MDR-TB may appear low, they stress that “absolute numbers” as well as absolute percentages should be considered. They comment, “one can estimate that 424,000 cases of MDR-TB emerged worldwide in 2004 – ie 4.3% of all new and previously treated tuberculosis cases globally. Three countries – China, India, and Russia – account for 261,362 cases of MDR-TB, or 62% of the global burden. Ultimately, the burden of MDR-TB must be placed in the context of the ability of the country to address the problem.”

Increased prevalence of MDR-TB in Botswana particularly worried the investigators, given the country's high HIV prevalence. The investigators also note with concern the recent emergence of extensively drug resistant tuberculosis (XDR-TB) – strains of the mycobacterium that are resistant to three or more second-line drugs. They write, “all means should be put in place urgently to control these deadly strains.”