Drug Resistant TB an Urgent Threat

Spread of Drug Resistance More Widespread Than Thought

The more drug resistance, the more money must be spent on treatment, diverting funds and staff from addressing rampant, but run-of-the-mill TB. That means the conditions creating drug resistance — when treatable cases go unnoticed or patients receive bad medicine — could get worse.

“I’ve seen the resistance pattern changing,” says [Dr.] Udwadia. Basically, we’re screwed.”

By we, he means all of us.

TIME, March 4, 2013

So far, 2013 has been a good year for Mycobacterium tuberculosis, the bacterium that causes tuberculosis. Consider its headline-grabbing performance this year (see TB in the News):

In Los Angeles, public health officials are battling an outbreak of TB among the homeless, and are attempting to track down 4,500 people who have been exposed to the disease. Health departments across the U.S. are contending with TB drug shortages; a new survey found that of the departments that treat drug-resistant TB, 80 percent have trouble finding the drugs they need.

World TB Day: March 24

World TB Day marks the date in 1882 when German physician Dr. Robert Koch announced the discovery of the bacterium that causes TB. He was awarded the Nobel Prize in 1905 for this discovery.

Globally, there are even more challenges. In South Africa, where TB and HIV have teamed up to become more deadly, doctors have identified a case of totally drug-resistant (TDR) TB, which they describe as “virtually untreatable.” In India and Eastern Europe, doctors are struggling to accurately detect drug-resistant strains of TB and treat them with the appropriate drugs. And in the largest study of its kind, conducted in in 17 countries, researchers found that TB drugs purchased from local pharmacies are too often of poor quality or fake.

And finally, these global and domestic storylines converge in the case of a Nepalese man with extensively drug-resistant (XDR) TB who was detained by immigration officials, but not before traveling through 13 countries on his way to the U.S.

TB is getting smarter, more dangerous, and more difficult to treat. This World TB Day marks 131 years since the bacterium was first discovered—it is clear we need a renewed global effort to defeat this disease. The Global Fund to Fight AIDS, Tuberculosis and Malaria, which provides 90 percent of international financing for TB control, must be central to this response.

The Global Threat of Drug-Resistant TB

Although usually treatable with a course of inexpensive drugs ($22–50), TB kills 1.4 million people every year, making it the most deadly curable infectious disease in the world. One-third of the global population carries the bacterium that causes TB, and nearly 9 million will become sick with active TB in a year. TB continues to be the biggest killer of people with HIV, taking one in four lives of those who die of AIDS-related causes.

Drug-Resistant TB:
From Bad to Worse

Multidrug-resistant (MDR) TB is resistant to the two most widely used and effective first-line drugs, rifampin and isoniazid.

Extensively drug-resistant (XDR) TB is also resistant to first-line drugs, and at least three second-line drugs.

Totally drug-resistant (TDR) TB is resistant to all available treatments.

When TB is treated improperly or inconsistently, the disease develops resistance to the limited number of effective drugs available. Though overall TB death rates have dropped by 41 percent since 1990, hard-to-treat drug-resistant TB is surging because of poor or incomplete treatment. And those with active drug-resistant TB transmit the drug-resistant TB strain to others.

A paper published last August in The Lancet reported that worldwide rates of multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB are higher than previously thought. MDR-TB has been found in 135 countries, while XDR has been found in 84 countries. Since drug resistance is difficult to detect, the number of countries reporting drug-resistant TB may in fact be much higher.

The World Health Organization (WHO) estimates there will be more than 2 million new cases of MDR-TB from 2011 to 2015. Yet, because drug-resistance is hard to detect and drugs are often scarce, only 10 percent of new MDR-TB cases get proper treatment. Those who do not receive treatment inevitably spread the disease: a person with untreated active TB can infect up to 15 others in a year.

The Centers for Disease Control and Prevention (CDC) reported 124 cases of multidrug-resistant TB (MDR-TB) in the U.S. in 2011, up from 107 cases in 2010. Although the total number of TB cases in the U.S. is decreasing, this masks the toll of drug resistant cases, which are more difficult and expensive to treat. A single case of drug-resistant TB in the U.S. can cost $200,000 to $1 million to treat. In 1991 an outbreak of MDR-TB in a New York City hospital among about 200 people cost the state and federal government over $1 billion to contain, proving that the U.S. is not immune to expensive, dangerous drug-resistant TB outbreaks.

An Opportunity for a Global Response

Drug resistance threatens to undermine much of the progress we have made against TB. But new tools in the fight against the disease provide an opportunity to get ahead of drug resistance before it becomes impossible to contain.

The Global Fund to Fight AIDS, Tuberculosis and Malaria

The Global Fund is an international partnership dedicated to raising resources to fight three of the world's most devastating diseases and directing those resources to the people who need them most. Since its establishment in 2002, the Global Fund has supported more than 1,000 programs in 151 countries, providing AIDS treatment for 4.2 million people, anti-tuberculosis treatment for 9.7 million people, and 310 million insecticide-treated nets for the prevention of malaria.

One the key challenges in fighting drug-resistant TB is obtaining an accurate diagnosis. In most poor countries, TB is diagnosed by examining sputum from a patient under a microscope. The process is not only time consuming, but is unable to detect whether the TB strain is drug resistant. A new rapid TB diagnostic test (called “Xpert”) has the potential to revolutionize the fight against TB. Developed by an American company, Xpert dramatically reduces the time it takes to obtain an accurate diagnosis from days — or even weeks or months — to just two hours. And critically, it can detect resistance to one of the primary TB drugs, which helps patients get the proper treatment instead of ineffective drugs that will strengthen TB’s resistance.

New drugs are also becoming available to fight TB. In December 2012, the Food and Drug Administration (FDA) approved a new drug for treatment of MDR-TB (Sirturo, also known as bedaquiline). This was the first new TB drug approved by the FDA in 40 years. Researchers are also searching for a more effective TB vaccine, with more than a dozen candidates in clinical trials.

We need U.S. leadership and a renewed global effort to put these tools to work to stop the spread of drug-resistant TB.

U.S. Leadership Is Essential

Just as the U.S. should be leading other donors to support the Global Fund to fight TB, the shortsighted budget debate in Washington could hamper our response. The AIDS research foundation, amfAR, estimates that sequestration budget cuts to the U.S contribution to the Global Fund will result in 57,000 fewer TB patients receiving treatment, leading to 6,800 more TB deaths. President Obama and Congress should work to ensure that we’re leading at the Global Fund, not retreating from the threat of drug-resistant TB. The Global Fund is a “best buy” in global health, since every $1 the U.S. contributes to the Global Fund is matched with $2 from other donors.

U.S. leadership in funding for the Global Fund to Fight AIDS, Tuberculosis, and Malaria (Global Fund) must be a centerpiece of an effective global response. For many poor countries, the Global Fund is the only source of external support in their fight against TB. The Global Fund currently provides nearly 90 percent of the global investment in TB control, supporting treatment for over 9.7 million people since its creation in 2002. The Global Fund is our best bet to address the TB threat at a scale commensurate with the enormous challenge.

TB in the News

XDR-TB Patient in Texas

A Nepalese man is in medical isolation in South Texas — the first person to cross and be held in detention while infected with XDR-TB.

L.A. Tuberculosis Outbreak

Public health officials have launched a coordinated attack to contain a persistent outbreak of tuberculosis on downtown Los Angeles’ skid row, including a search for more than 4,500 people who may have been exposed to the disease.

Substandard Drugs

In a study published in the International Journal of Tuberculosis and Lung Disease, it was found that fake and poorly made antibiotics are being widely used to treat tuberculosis — almost certainly making the disease more resistant to drugs.

TB Drug Shortages in the U.S.

According to a recently released national survey, more than 80 percent of health departments in the U.S. that treat drug-resistant TB have trouble obtaining the drugs they need to cure the disease.

Drug-Resistant TB in India

India, where about two people die every three minutes from TB, is on the front line of the global battle against TB and drug-resistant TB. Global progress to control and end TB weighs heavily on how India deals with this epidemic.

Drug-Resistant TB in South Africa

A recently published paper in the Centers for Disease Control and Prevention’s Emerging Infectious Diseases journal warns that the first cases of “totally drug-resistant” tuberculosis have been found in South Africa and that the disease is “'virtually untreatable.”

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