Tuberculosis -- a disease far from the minds of most Americans -- is making a comeback around the world. Not only is TB infecting more people, it's taking a form that is alarming health experts from Moscow to San Francisco. As the World Health Organization reported in February 2008, the disease is becoming more and more resistant to the types of antibiotics that used to be a sure-fire cure. The WHO estimates that as many as 500,000 people worldwide are newly infected each year with multi-drug resistant TB, also known as MDR TB. Still more disturbing, the number of cases of this virulent strain of tuberculosis has nearly doubled since 2000.

As the name suggests, multidrug-resistant tuberculosis is a strain of the disease that doesn't respond well to at least two medicines commonly used to treat TB. The germ's ability to resist powerful drugs -- including the once-reliable antibiotics isoniazid (brand name Nydrazid) and rifampin (brand name Rifadin) --greatly complicates treatment and increases the threat of an already dangerous disease.

Like regular TB, MDR TB spreads through the air (not through kisses, handshakes, or shared food), and it moves most quickly in crowded places, such as prisons, schools, or homeless shelters. Only people with active infections can pass the infection to someone else.

For now, MDR TB is most common in Russia, India, China, and some Eastern European and Southeast Asian countries. Experts also believe that there are major, undetected outbreaks of MDR TB occurring in parts of Africa, where the equipment and personnel needed to identify and treat the illness are generally unavailable. And while it's still relatively rare in the U.S. -- the Centers for Disease Control and Prevention reported just over 2,600 cases between 1993 and 2004 -- any spread of the disease overseas means trouble here. "With the world as it is, we can't keep it out," says Masae Kawamura, MD, director of San Francisco's Tuberculosis Control Center. "It's going to keep coming here in waves." With its large population of residents who were born in Asian countries having some of the highest rates of MDR TB, California has the highest proportion of MDR TB cases, according to Kawamura.

You certainly don't have to go overseas to find the frontlines in the battle against the disease, either. Public health workers in San Francisco's Tenderloin District, a low-income neighborhood of immigrants, the homeless, and the indigent, have long been dealing with the regular type of tuberculosis that is responsive to first-line medications. Workers often walk into cramped apartments, and, after a little small talk with residents, they will pull out a handful of antibiotics and watch the patients swallow the pills.

The same scene is repeated on a daily basis in 2008, and with good reason. When it comes to treating tuberculosis, taking every pill is crucial, Kawamura says. Treatment for TB can take at least six months. Doctors can't just give patients a prescription and hope for the best. In San Francisco and other major cities, health departments rely on "directly observed therapy" or DOT. Workers hand pills to patients and watch to make sure that every pill is actually taken as directed. Proper treatment of tuberculosis not only cures individual patients, Kawamura says, it also helps prevent the emergence of drug-resistant strains of the disease.

As Kawamura explains, MDR TB gets its start when TB patients don't have enough medications or don't take their pills exactly as prescribed. When a patient with TB or any other bacterial infection takes an antibiotic, many of the germs quickly die. Naturally, the germs that are most sensitive to the medication are the first ones to go, and the germs that are less sensitive hang around a bit longer.

If the patient stops taking the medication before all the germs die, the extra-tough germs that remain have a chance to multiply, passing along their drug-fighting powers to entirely new generations of bacteria. (This is the same process that created methicillin-resistant staph infections, also known as MRSA, that are spreading rapidly across the country.) Tuberculosis, however is more easily transmitted than MRSA, and treatment for TB lasts a lot longer.

The most alarming aspect of MDR TB is that worldwide only 2 percent of people identified as having it are getting the treatment they need to cure it. "If only a small percent are being treated, the rest are spreading TB," says Kawamura.

All of the pieces are in place for a rapid increase of MDR TB cases around the world. According to the World Health Organization, more than 50 million people worldwide carry tuberculosis germs that are already resistant to at least one drug. It's a small step from there to MDR TB. And that's not even the worst-case scenario. An unknown number of people -- maybe about 10 percent of all those with MDR TB -- have germs that can withstand just about any drug, making their illness extremely difficult to treat.

This condition is called extensively drug resistant TB, or XDR TB, and it could be the next worldwide health crisis. For a few weeks in the summer of 2007, it was certainly the biggest health story in the country. Andrew Speaker, a young Atlanta attorney who had been diagnosed with XDR TB, flew to Europe and back for a wedding, a move that alarmed the CDC and frayed the nerves of his fellow travelers.

Fortunately, the story ended well: Speaker, then a 31-year-old living in Atlanta, received treatment to control his disease, and he apparently didn't infect anyone on his airplane (or anywhere else). It was later determined that he had MDR TB, not the XDR variety. (Because Andrew Speaker's case was inactive at the time of his flight, the people sitting near him were never in any serious danger.)

For now, only a tiny fraction of TB cases in this country qualify as XDR TB. The CDC counted a total of 49 cases between 1993 and 2006. But in San Francisco, Kawamura has seen cases of TB take an alarming move toward that direction. "Since 2000, we've seen a pattern of increased resistance," she says. New strains are not only resistant to isoniazid and rifampin, they're also gaining strength against injected antibiotics that are the second line of defense. "When you lose those injected antibiotics, then you're really in trouble," she says.

The germs that cause MDR TB still have their weaknesses -- for now. In the United States, up to 70 percent of patients with MDR TB will respond well to treatments. Even so, this more pernicious form of TB takes the lives of 35 percent of those it strikes worldwide, according to the WHO's Stop TB program. For U.S. patients whose immune system has also been weakened by HIV/AIDS, the survival rate drops to 50 percent.

The first step to treating MDR TB is to recognize the danger. Doctors should suspect drug resistance any time first-line drugs don't seem to be working or any time a person who has previously taken medications for TB comes down with a new case. Every TB culture is tested for resistance, but it can take up to 12 weeks to get the final results. In other words, some patients with overlooked cases of MDR TB could go three months without the treatment they really need to fight the disease. Too often, that's enough time for the disease to spread to someone else.

For now, California and New York are the only states in the country that have the technology to rapidly diagnose MDR TB by examining the DNA of cultures. Unfortunately, California is likely to lose this tool in the next round of across-the-board state budget cuts. "In public health, you can't have across-the-board cuts. You have to let experts decide, and this diagnostic test is the single most important technological advance we've had in decades," says Kawamura. (She and colleagues have sent a letter to California Governor Arnold Schwarzenegger protesting the cut.)

It takes a barrage of medications to bring MDR TB under control. At a minimum, patients should take at least five drugs every day until cultures from their lungs no longer show any signs of the germ. Even then, they'll need to take at least three drugs every day for at least another nine months to maximize their chances of beating the infection. The treatment for XDR TB requires at least 18 months of antibiotics, perhaps along with surgery to remove the affected part of the lung. This is serious business, both medically and economically. Curing a single case of MDR TB can cost more than $100,000.

Doctors worry that people with active, untreated cases of MDR TB could eventually infect others. But the bigger risk is that the millions of standard TB cases out there could become resistant to drugs. For this reason, both patients and doctors must take precautions to treat TB right the first time. If every patient diagnosed with the disease took every pill on schedule, new cases of MDR TB would plummet.

The WHO estimates that it will take $1 billion in 2008 to control MDR TB and XDR TB throughout the world. If countries can't or won't make that investment, the impact could reverberate on the streets of San Francisco and beyond.

-- Chris Woolston, MS, is a contributing editor to Consumer Health Interactive. A former staff writer for Hippocrates magazine, he has written for Health, Prevention, and other journals. He writes The Healthy Skeptic, a biweekly column in the Los Angeles Times. He is also the co-author of Generation Extra Large: Rescuing Our Children from the Epidemic of Obesity (Perseus paperback, 2006).

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First published March 21, 2008
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