The dis-ease of disease

Timothy Holtz ('91 MD), works around the world to control 'XDR TB,' a drug resistant form of tuberculosis

2 years ago, I was standing outside my office at the Centers for Disease Control and Prevention (CDC) with a colleague discussing how to classify an emerging phenomenon we were seeing in Eastern Europe and Asia ' tuberculosis that was resistant to multiple anti-TB drugs. I blurted out 'XDR TB' ' an acronym that would soon become well-known when a man named Andrew Speaker got on a plane and traveled halfway around the world and back with this dangerous form of the disease.

As a medical epidemiologist assigned to the International Research and Programs Branch of the CDC's Division of Tuberculosis Elimination, I focus on multidrug-resistant TB (MDR TB), which is TB caused by an isolate resistant to isoniazid and rifampin. A large part of my team's work has been in the Baltic States, where our division has partnered with national TB programs since the 1990s to control MDR TB.

After the fall of the Soviet Union in 1991, the health systems in the Baltics collapsed; it only took five or six years for drug-resistant TB to develop in this area. Latvia's MDR TB rate has been one of the highest in the world, with Estonia and Lithuania close behind.

In Latvia I work with physicians to evaluate their TB treatment program, which is how we found that many patients were resistant to up to eight different drugs. That day in the CDC hallway, we thought that if there was a way to classify these patients as a special population, we might be able to call attention to the problem and help design new treatment methods for them.

Ensuing discussion led to the acronym XDR TB. The 'X' stands for 'extensive,' and means the disease is resistant to four or more critical anti-TB drugs. My analysis in Latvia has shown that TB patients with resistance to these four drugs have less than a 40 percent chance of survival; if infected with HIV, their chances were even worse.

We've been accused of trying to 'sex up' the name, while others said, 'Can't you spell? It should be an 'E'!' In truth, we wanted something catchy so that people would pay attention to this global health threat. For better or worse, I think it worked.

XDR TB is prevalent not only in Eastern Europe but also East Asia, Latin America and Southern Africa, where economic distress and widespread poverty have led to poor health care access. TB programs disintegrate when underfunded, leading to unregulated markets for second-line drugs. Those factors, along with poor infection control in health care settings, a high burden of TB in the population, and a high prevalence of HIV/AIDS are all converging to form what we are calling 'the perfect storm.' AIDS patients exposed to MDR TB and XDR TB are much more likely to progress toward disease and spread it to others, including health care workers, who are at high risk of being exposed.

When we first heard about the patient from Atlanta, I realized that the existence of XDR TB in a young, healthy lawyer is proof that the world needs to improve TB control in the poorer areas of the world, which are proving to be perfect incubators for more and more dangerous forms of the disease. It was strange to see this new classification, an acronym I just coined on a whim a couple of years ago, splashed across the news, but it was also gratifying to see the world recognizing this emerging health threat. TB is still a disease of mass destruction, infecting nine million people and killing nearly two million people each year. For a disease we've known how to diagnose since 1882, that's unacceptable. That's what keeps me going in my job.