Tuberculosis: Growing Problem at Home and Abroad

It was honeymooner Andrew Speaker, an attorney from Atlanta, who touched off an international health scare last May when he flew to Europe knowing he had a drug-resistant form of tuberculosis.

But TB has been a worldwide problem for centuries. The disease has long plagued U.S. prisons. In the past week, two high school students in Pennsylvania and one in Ohio tested positive for tuberculosis. A woman in Sunnyvale, Calif., is accused of spreading TB to another passenger on a recent flight to New Delhi.

And Daniel Roberts, a patient with drug-resistant tuberculosis who was locked up in a Phoenix hospital for more than a year, was recently indicted on charges that he exposed the public to the disease. The Russian-born man left the U.S. to go back to Russia last year to avoid possible prosecution by Maricopa County Sheriff Joe Arpaio.

The announcement of Roberts' indictment coincided with World Tuberculosis Day on March 24, which marks the day in 1882 when Robert Koch heralded his discovery of the bacterium that causes the infection.

These days, there is little to celebrate. This airborne disease is on the verge of being a failure of modern health practices. One out of three people worldwide is currently infected with tuberculosis.

Despite its low profile, tuberculosis is not a relic from the days of Charles Dickens. It is estimated that 8 million people throughout the world will contract TB this year alone. Fifteen years after being declared a health emergency by the World Health Organization, it is still thriving around the globe. In too many places, it is out of control.

Drug-resistant strains have been found in more than 80 countries, and that’s only in places where health officials are looking. A virtually untreatable form of drug-resistant TB has appeared in 45 countries. Although a co-infection with HIV can kill a patient in as little as two weeks, the resources to fight TB are limited -- even in Western countries. Recently, it has been garnering more attention and funds, but many health officials warn the response is barely enough to curb the spread of this disease.

“I feel like I’m working with a chisel and hammer to deal with tuberculosis while everyone else around me is using power tools,” said Dr. Kenneth Castro, director of U.S. Centers for Disease Control and Prevention’s Division of TB Elimination.

Castro is not alone. The problems with reigning in TB, both in the U.S. and abroad, are complicated. For starters, the most common way to look for regular TB is a skin test that was developed more than a century ago. Compound that with the growing rates of multi-drug resistant and extensively drug-resistant tuberculosis -- known as MDR and XDR-TB respectively -- and the task of controlling this epidemic seems daunting. With insufficient labs and a lack of political will, tuberculosis, especially drug-resistant strains, will continue to spread.

But many health experts say that does not have to be the case.

The Threat of Drug Resistance

Tuberculosis needs better diagnostic tests, much better drugs, and a whole lot more money. The WHO estimates it will take more than $50 billion to meet their goal of saving 1.2 million TB patients by 2015.

The disease is spread by mycobacterium tuberculosis, a tube-shaped bacterium that hangs in the air after a person with active TB coughs, spits or even sings. A person can be infected but show no symptoms and not be contagious, which is known as latent TB. When a patient has a compromised immune system or has been infected for a long time, the bacteria can multiply and the disease becomes active. It often infects the lungs, leading to breathing problems and coughing up blood, a trademark of the disease.

Therein lies one of the largest problems with treating tuberculosis. It can take days or months to get test results using current testing methods. Ideally, microscopic tests would be done along with liquid cultures, which are much more complicated. In the case of Andrew Speaker, he was trotting the globe while those tests were being evaluated. “I’m pretty frustrated by the global situation of investment and resources in TB,” Raviglione said.

When medications are not taken through for the prescribed duration of time, or the wrong medications are administered, the bacteria can grow resistant and morph into MDR-TB, the most powerful strand.

“Once you’re off the first-line drugs, the other drugs are weaker. They are toxic to the liver. You can get mental disorders,” said Dr. Mario Raviglione, the director of the WHO’s Stop TB Department. “It’s a completely different set of circumstances.”

Treating MDR and XDR, both of which are resistant to at least three second-line drugs, emphasizes the need for labs that can quickly identify the disease so people in need receive the correct treatment. But in many cases, especially in HIV and AIDS patients, the bacteria may not show up under the microscope even though the person is sick.

There are not enough well equipped laboratories around the world to carry out sputum analysis -- a test that analyzes matter discharged from the air passages in diseases of the lungs, bronchi, or upper respiratory tract -- using liquid cultures. Many patients continue to spread these virulent strains, most often dying, while waiting for results. “We have 5,000 deaths a day," Castro said.

Even in the best-equipped labs in the U.S., problems persist. In the case of Speaker and Daniels, while they were first identified as having XDR, after more tests were done at National Jewish Medical and Research Center in Denver, a leading laboratory and hospital for treating tuberculosis, both men were reclassified as having MDR.

“The barrier is [that] even in the best lab it takes too long, so we need a more accurate and rapid test,” said Dr. Charles Daley, head of the infectious disease unit at Denver's National Jewish Medical Center.

It turns out, this happens all the time. Daley said he hears of discordant results between labs on a monthly basis, and in the CDC's -- Centers for Disease Control and Prevention --, Castro confirmed that the problem lies in the lack of standards for analyzing tuberculosis. Even the best labs in the world know the mutations for only some, but not all, of the drugs. Many of the new diagnostic tests are being developed by the Foundation for Innovative New Diagnostics, or FIND. “I think that within the next year, we could have some new and useful tests,” Castro said.

While FIND is spearheading new tests for TB, new drugs are harder to come by. Dr. Salmaan Keshavjee, a professor at Harvard Medical School and co-chair of the WHO’s Green Light Committee, which secures low-cost TB drugs for developing nations, said that new drugs are at least seven to 10 years away. With rates of MDR higher than 20 percent in places like Baku, the capital of Azerbaijan, that is simply too long.

MDR can cost 100 times as much to treat as drug-susceptible tuberculosis, and it takes least two years of twice-daily medications. “I think we’re at a tipping point, where in many places, MDR will become the majority of cases,” Keshavjee said.

Derailing AIDS Efforts

A new pilot project in Maseru, Lesotho — a small country bordered by South Africa — hopes to be a model of how a little investment can go a long way to curb tuberculosis.

“Out of the 60 or so patients [in the clinic], about 70 or 80 percent are alive,” Keshavjee said. “They are surviving.”

While AIDS is a superstar epidemic, with money pouring in from around the globe, tuberculosis kills about 2 million people a year without fanfare, many of them also infected by HIV and AIDS.

This means that the billions of dollars spent by countries, including the U.S., to curb the AIDS epidemic are being sabotaged by the epidemic of tuberculosis. President Bush’s Emergency Plan for AIDS relief committed more than $130 million in funding specifically for tuberculosis in 2007, an important step in controlling these dual epidemics. But Raviglione at the WHO estimated that even in the best scenarios, TB is only getting about one-twentieth of the funding that AIDS receives.

But Keshavjee said the Partners in Health clinic in Lesotho, where 25 percent of the country is HIV infected, shows that TB can be controlled in countries with high rates of HIV/AIDS infections and little resources. The Soros Foundation provided $3 million for a brand new laboratory and training. “Everyone said ‘oh my God, you’ll never be able to do this in Lesotho,’” he said. “It’s shown me that this stuff can happen in Africa.”

Lesotho is a bright light in the fight against TB. But Lesotho represents only about 1,200 of the nearly half-million reported cases of MDR in 2006. With only six African nations reporting, experts agree things are going to get worse before they get better.

“There is no alternative. If you don’t invest, then you see the disaster that is happening in some parts of the world” Raviglione said. “We’re going to have more death, we’re going to have more drug resistance.”

Although the situation is grim, Raviglione is hopeful that the international community will respond. The WHO is drafting new guidelines about air travel. Other African countries have approached Partners in Health about facilities like the one in Lesotho. And although authorities in Arizona are indicting Daniels, he is actually a success story in the world of drug-resistant tuberculosis. He is surviving.