Slow Elimination of Multidrug-Resistant Tuberculosis

The spread of drug-resistant tuberculosis may be halted and reversed through appropriate use of drugs and diagnostics. Vive la Résistance? Study says “Non” Headlines routinely report the bad news about tuberculosis—the causative agent, Mycobacterium tuberculosis, causes about 9 million new cases a year, the disease kills more than a million people a year, and multidrug-resistant bacterial strains are springing up at alarming rates all over the world, particularly in southeast Asia and the western Pacific region, especially China. Now, Dye and Williams report some good news about a bad bacteria—analysis of trend data reveals that superior treatment practices can stem the current spread of multidrug-resistant strains. Only 5 to 10% of people infected with M. tuberculosis develop the coughing, weakness, and fever characteristic of active disease. Healthy people can contain the bacteria in a harmless state, whereas AIDS patients are particularly susceptible to the bacterium. Tuberculosis has been treated successfully for more than 50 years with 6-month courses of drug combinations including isoniazid, and later rifampicin, which was introduced about 35 years ago. But if treatment is terminated too early or the drugs are in short supply, isoniazid- and rifampicin-resistant bacteria emerge, and more expensive toxic drugs must be administered for up to 2 years. A global endeavor to eliminate tuberculosis by midcentury (<1 case per million by 2050) is showing signs of success, with per capita incidence stable or falling in most countries. But the emergence of drug-resistant disease may imperil this effort. The tuberculosis bacterium spreads in droplets expelled by a coughing, infected person and is usually transmitted, traditionally said, to about 10 people a year—but some recent estimates put it in the range of 5 to 10 people a year. This number of secondary cases arising from each primary case—a value called the case reproduction number, R—determines how fast tuberculosis spreads through a population. If R can be kept to less than 1 by proper diagnosis and treatment, the disease will eventually die out. To accurately predict the course of tuberculosis spread, it is critical to know the value of R for multidrug-resistant M. tuberculosis. With this information, ongoing eradication efforts can be adjusted to keep R at less than 1 and on track for disease elimination. Dye and Williams used data reported to the World Health Organization from 1996–2008 (though the years differ among countries) from European countries (Estonia, Germany, Latvia, Lithuania, United Kingdom, and others), Russia, Hong Kong, and the United States to estimate the values of R for bacterial strains resistant to rifampicin, isoniazid, or both drugs. When analyzed with a model of disease spreading, the data indicate that the R for each of the drug-resistant strains tested in each country is less than 1, with the exception of Russia where there may be regions in which drug-resistant strains are self-sustaining. Thus, present efforts at eradication, focused on public health surveillance and treatment, seem to be achieving effective control of multidrug-resistant tuberculosis, at least in the countries reporting data used in this study. The less good news is that, at the present slow rates of decline, elimination is a long way off. Further analysis of statistics gathered from other countries, including those with higher incidence of AIDS, is necessary to extend these conclusions globally. The growing number of reports of antibiotic resistance worldwide has led to fears that some lethal human pathogens, such as Mycobacterium tuberculosis, will soon become untreatable. Here, we show that, although this is possible, it is not inevitable. The World Health Organization has recently reported more cases of multidrug-resistant tuberculosis than ever before, but a new analysis of trend data for 10 groups of countries shows how and why the spread of multidrug-resistant tuberculosis can be reversed by good treatment practices. We find that multidrug-resistant tuberculosis is not self-sustaining in 9 out of the 10 settings and conclude that multidrug-resistant tuberculosis can be set on a path—albeit a slow path—to elimination. This result applies even to countries such as Estonia and Latvia, which have exceptionally high prevalence rates of multidrug-resistant tuberculosis.