TB's Global Resurgence Amplifies U.S. Risk
Maria Jimenez contracted TB in San Antonio; complications made her drug-resistant.
NASHVILLE, Tenn.—Natalie Skipper started feeling under the weather a few weeks after returning home from volunteering at a South Africa hospital. "The worst flu I had ever had in my life," she said.
Her temperature hit 105 degrees. She had trouble walking.
She didn't have the flu.
Ms. Skipper, a 34-year-old physical therapist with a love of travel, was infected with tuberculosis. And not just any tuberculosis. She brought to Tennessee a strain that can't be cured with the most potent and common drugs used against the deadly disease. Multidrug-resistant TB is at epidemic proportions in some parts of the world—a growing problem the U.S. is surprisingly unprepared for.
Natalie Skipper caught a dangerous strain of tuberculosis while volunteering in South Africa and brought it to Tennessee. JOSH ANDERSON FOR THE WALL STREET JOURNAL
The U.S. beat back multidrug-resistant tuberculosis in the 1990s. Today, however, a new threat is emerging as drug resistance worsens abroad and far more dangerous strains develop and spread, including some that are all but untreatable with standard drugs.
In the U.S., rates of multidrug-resistant tuberculosis remain low, but are starting to inch back up, as hundreds of millions of American citizens and foreigners alike travel to the U.S. from abroad every year. At the same time, funding and expertise are in decline.
"What's worrying me personally is that I'm seeing a resurgence of complacency," in the U.S. health-care community says Kenneth Castro, director of the division of tuberculosis elimination at the Centers for Disease Control and Prevention.
Ms. Skipper's infection took doctors more than a year to properly diagnose. First, they thought she had an nasty intestinal bug from Africa. Then they suspected pneumonia—a common misdiagnosis.
Finally, the doctors discovered she carried drug-resistant TB. That set off a scramble to trace and test everyone around her hometown of Paris, Tenn., and elsewhere with whom she might have had close contact with while contagious. Ms. Skipper had, in fact, infected someone else.
IN-DEPTH: A KILLER QUIETLY GAINS STRENGTH
The Wall Street Journal is chronicling the world's imperfect response to the rise of drug-resistant tuberculosis, an ancient disease that modern medicine, until recently, could defeat.
A selection of reports:
- Deadly unintended consequences: The global TB-fighting strategy helped allow the spread of new, all-but-untreatable strains. (11/23/2012)
- Exclusive numbers suggest more than 25% of patients at one Indian TB clinic don't respond to the primary treatment. (11/23/2012)
- One woman's case of nearly incurable tuberculosis echoes around the world. (9/8/12)
- India's slow reaction appears to be nurturing an all-but-untreatable strain of TB, raising the prospect of a global health hazard. (6/20/12)
- A top doctor in Mumbai reports finding 12 cases of tuberculosis that are all but untreatable by current methods. (1/19/12)
"We cannot be safe in the U.S." while drug-resistant TB is an "epidemic in the rest of the world," said Barbara Seaworth, medical director of the Heartland National TB Center in San Antonio. Outbreaks are "absolutely" possible in the U.S., said Dr. Seaworth, who has treated hundreds of patients with drug-resistant strains.
Tuberculosis, an airborne disease characterized by the coughing of blood, is one of the world's great killers. In some developing countries, drug-resistant strains are rampant. A doctor in India this year startled the global health community by finding patients carrying a particularly dangerous strain—one all but incurable. The Wall Street Journal in November detailed how long-standing global strategies for fighting TB have unintentionally helped make the disease harder to cure.
Most drug-resistant cases are imported into the U.S. by foreigners arriving from places where the disease rages. Of 124 multidrug-resistant cases in 2011, 106 were in foreign-born individuals, the CDC says. Most cases are in California and Texas, many along the border with Mexico. Cases come from Mexico, Vietnam, and India, among others. The U.S. doesn't vaccinate against TB because there is no vaccine considered widely effective for adults.
In parts of Mexico, drug-resistant TB flourishes. Treatment of regular TB isn't always vigilant, and medicines that can tackle drug-resistant TB became available there only recently.
Complicating matters is Mexico's gang violence, which prevents U.S. public-health experts from visiting many nearby areas to train medical teams. "We have not crossed the border in three years," said Brian Smith, regional director for the Texas Department of State Health Services in Harlingen, Texas. His people get around that by talking on the phone with Mexican counterparts, and meeting in the U.S.
Shortages of TB drugs in the U.S. have become acute enough that the government is in talks with the World Health Organization to tap a service that more commonly helps poorer countries obtain drugs. The goal would be to arrange for the importation of drugs produced in other countries, he said. He called the move "unusual." "But the public-health nature of this problem merits a renewed look," Dr. Castro said.
Some 64% of state and local officials in charge of TB control reported difficulties obtaining drugs for multidrug-resistant TB, according to a 2010 survey by the National TB Controllers Association.
Over the past 15 years, the purchasing power of the U.S.'s TB-control budget has dropped about 45%, according to the CDC. Further cuts could be coming: President Barack Obama's next proposed budget included a $4.6 million cut for TB control, from $140.3 million previously.
The U.S. boasts some of the most rigorous methods for diagnosing and treating tuberculosis. Nevertheless, it faces a fundamental problem that affects all nations, rich or poor: Everyone must use the same decades-old drugs and diagnostic techniques. The Food and Drug Administration is reviewing one new medication, bedaquiline, to treat drug-resistant TB. Developed by a Johnson & Johnson unit, it would be the first significantly new TB drug to be approved in more than 40 years.
Meanwhile, the U.S. lags on other technologies. A new machine, GeneXpert, that can diagnose a common form of drug resistance in just hours—rather than days or weeks required by traditional tests—is rolling out in countries including India and South Africa. It hasn't received FDA approval here for tuberculosis.
GeneXpert's maker, Cepheid, expects to have the TB test available in the U.S. in mid-2013, a spokesman said. The FDA declined to comment.
TB drugs' toxicity can be a big obstacle to treatment. Maria Jimenez of San Antonio was infected with regular tuberculosis in 2011 by an ex-boyfriend. Once she was infected, though, the disease became drug-resistant inside her body.
One reason: The drugs she was taking made her so sick—she would vomit them back up—that basically she was being undermedicated, according to Dr. Seaworth, who treated her. Undermedication is dangerous because this is how the TB bacteria develop resistance to drugs.
Ms. Jimenez, 37 years old, began coughing up blood. "I had no energy," she said. She gave up her housecleaning work and eventually became bedridden.
Further complicating her treatment was the fact that Ms. Jimenez is diabetic, making it harder for her to absorb one medicine. Rising diabetes rates amplify the TB risk. Diabetics who are infected with TB become ill with the disease at three times the ratio of the general population because their immune systems are compromised, said Dr. Seaworth, who is also a professor of medicine at the University of Texas Health Science Center-Tyler. "Diabetes may be a more important driver of the TB epidemic globally than HIV," she said.
At the urging of her doctors, Ms. Jimenez agreed in May to be hospitalized at the Texas Center for Infectious Disease, a specialized facility in San Antonio. The hospital treats especially difficult TB cases like hers.
There, she gradually improved. Her doses were split up over the course of the day so she didn't get as nauseated. A nutritionist designed a diet for her diabetes.
Today, Ms. Jimenez says she feels better and can stick to her treatment, though she is still "grossed out" by the pills. She left the hospital in October in part, she said, because she was worried about her 15 year-old daughter, who was skipping school.
During a recent interview in San Antonio, as Ms. Jimenez received a TB-drug infusion at the TB hospital, she described how all five of her children living with her became infected as well, stirring up resentments. "My 13-year-old said, 'You have to take your drugs,'" Ms. Jimenez said, because "we also had to fight this."
The next day, at a different clinic, she showed up for a checkup to take 12 different pills. Washing them down with water and grimacing at the taste, she said to a nurse, "At the hospital, they give me juice."
Ms. Jimenez is lucky in an important respect. The kind of specialized TB clinic that treated her is becoming increasingly rare. They are an echo of the early 20th century, when TB was widespread and sanitariums dotted the nation. Today, only a few remain. In Florida this year a similar facility closed.
For doctors who don't specialize in TB, treatment of resistant strains gets tricky. Not even cancer patients require "as much work in terms of coordinating experts and resources," said Jonathan Fine, a pulmonologist in Norwalk, Conn., with one multidrug-resistant patient. To devise a regimen, Dr. Fine said he consulted experts at several institutions and ultimately needed special approval to prescribe a drug normally used for leprosy, which is caused by similar bacteria.
TB-control officials are often stretched for resources. "I've transported people many times in my own car," said Jon Warkentin, Tennessee's statewide tuberculosis-control officer. He puts the patient in the back seat of his Honda Civic wearing a surgical mask, rolls down the windows—"even during the winter," he says—and wears a respirator of his own while he drives.
The U.S. has strengthened TB screening of immigrant applicants in recent years and tightened travel restrictions for people with infectious TB. But visitors to the U.S. aren't checked by the government. The case of Ms. Skipper, the Tennessean who contracted TB while volunteering in a small hospital in South Africa, shows how difficult it is to keep the disease outside U.S. borders.
Ms. Skipper volunteered for five months of 2007 in a shantytown about 40 minutes outside Capetown. She originally connected with the hospital through her Presbyterian church in Nashville.
A physical therapist, she worked with HIV and TB patients both in the hospital and in their tiny homes. She helped people do bed exercises. She taught a man without a leg how to use a walker.
Before returning to her hometown hospital in Paris, Tenn., Ms. Skipper had to take a TB test. It came back negative, which can happen with people infected only recently.
Her early symptoms—upset stomach and a bloody stool—didn't cause doctors to suspect TB. Knowing she had been to Africa, they thought it was "a bad parasite she had caught," said her primary-care doctor, Walter "Bo" Griffey III. In fact, those symptoms might have been unrelated to TB; it's still not clear.
In early 2009, after Ms. Skipper had been sick for a year, she developed tightness in her chest. Dr. Griffey first diagnosed pneumonia, but his thoughts turned to TB when a follow-up X-ray showed a dense spot on her lung.
"Being a small-town doctor in Tennessee, TB is not really on your radar screen," Dr. Griffey said. But with so many people traveling the world, "you just have to always be aware of it."
It took three more tests, including a lung-tissue biopsy, to nail it down as TB. It was the first case Dr. Griffey had seen since his residency in Alabama in the '90s.
Still, it wasn't clear yet that Ms. Skipper carried the drug-resistant strain. She began taking a standard regimen of four drugs for regular TB.
When word of her case reached the state department of health, "I immediately saw red flags," said Dr. Warkentin, the state official. "She had been working where MDR is common," he said, using shorthand for multidrug-resistant TB. New tests showed she was resistant to seven drugs, including the four she was taking. Hers was an unusual strain not previously seen in the U.S., Dr. Warkentin said.
The diagnosis triggered a sort of "Typhoid Mary" scramble to find and test everyone who might have been in close contact with Ms. Skipper. They identified 110 people, including family and patients in the U.S. hospital where she worked.
Fortunately, she hadn't been coughing much, so the disease hadn't spread widely. She did infect one person who was treated for latent tuberculosis. Out of caution, Ms. Skipper's two toddler nieces were also briefly treated, until tests showed they hadn't been infected.
Ms. Skipper's new regimen came with painful, toxic side effects. Unable to work, she left her job and grew depressed. "Here I was, 30-something. All my friends were working, and my job became taking drugs every day," she said.
She spent 90 days in isolation at home, until she was no longer infectious. When she went to see the doctor, she had to wear a mask. People would give her strange looks. "I'm a people person," she said. "I wanted to see my friends so much, but it was against the law to see them."
She worried that she would die. One of her drugs, cycloserine, is dubbed "psychoserine" by some doctors and patients. She started forgetting to pay her bills, and would get lost while driving to familiar places. "I became socially awkward," she said. "I was constantly dropping things."
Her insurance ran out about a year and a half into treatment. The state picked up the tab, which it does in TB cases to make sure a patient completes treatment and to protect the public, Dr. Warkentin said.
Ms. Skipper said she believes her treatment cost hundreds of thousands of dollars, but neither she nor Dr. Warkentin has a total cost. A recent study led by a CDC researcher found that the average total direct cost to treat a patient in the U.S. with multidrug-resistant TB is $131,000.
Today, Ms. Skipper is considered cured. Still, recovery continues. She suffers kidney stones from one drug, and is susceptible to illnesses. "I catch everything that goes around," she said.
Despite everything, she is eager to get healthy enough to go back to South Africa, where she has many friends from her first trip. And because of her own experience, she shares a new empathy. "I can't wait to return," she said.
She and her new husband, whom she met in the later months of her cure, have talked about heading back once her strength rebuilds. "I was able to have the best health care, the best doctors, and the best treatment," Ms. Skipper said. "It upsets me they're not able to have the same kind of treatment."
Write to Betsy McKay at betsy.mckay@wsj.com
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