This article is from the In-Depth Report The Crisis of Antibiotic Resistance

Fear-Resistance: How Worried Should We Be about "Totally Drug-Resistant" Tuberculosis?

An Indian clinic's claim of totally untreatable TB ignited public fears, but experts say poor disease management is the real threat

Courtesy Wikimedia Commons

A few weeks ago a clinic in Mumbai claimed to have identified a dozen patients with a strain of tuberculosis (TB) resistant to all known treatments. TB is a highly contagious lung infection that kills about 1.5 million people each year worldwide, according to the World Health Organization (WHO), so the development of a totally untreatable form of the disease would be cause for alarm. "It conveys that there is no hope, that not a single drug works," says Madhukar Pai, a tuberculosis researcher at McGill University in Montreal.

Fortunately, it does not appear that the Mumbai cases are completely untreatable. After evaluating the cases last week, India's Ministry of Health and Family Welfare reported that the patients actually had "extensively drug-resistant" tuberculosis, a form of the disease that is difficult to treat, but not incurable. Although three of the 12 patients have died, the other nine are reportedly being treated with antibiotics used to treat extensively drug-resistant TB, such as clofazimine and rifabutin.

Still, the case has prompted WHO to schedule a meeting in March to discuss the merits of creating a new "totally drug-resistant” category of tuberculosis. Most likely, "extensively drug-resistant," or XDR, will remain the top level of tuberculosis threat. For one thing, current laboratory tests for determining drug-resistant TB are not reliable enough to rule out all TB drugs conclusively, particularly three of the six classes of second-line drugs. "The tests aren't highly reproducible," says Peter Cegielski, head of the U.S. Centers for Disease Control and Prevention's drug-resistant TB program. "You can even get different results from the same patient specimen."

WHO cannot designate a new disease category without clear, quantifiable diagnostic criteria. For example, XDR-TB is defined as tuberculosis that is resistant to the main first-line TB drugs—rifampin and isoniazid—and to two or more of the second-line drugs for which there are reliable susceptibility tests.

There are also new tuberculosis drugs on the horizon, including two that will likely be available to patients in the next few years, making the timing of adding a "totally drug-resistant" TB category impractical.

That doesn't mean, however, that it is impossible for an untreatable form of TB to exist. "It's reasonable to discuss it," Cegielski says. It also does not mean that public health workers can rest easy. Drug-resistant TB remains a huge problem worldwide. Not only does it take months or, in some cases, years to treat, but once drug-resistant strains develop, they can be passed from person to person.

What the recent Indian case really highlights, rather than the potential for total drug-resistance, is the need for consistent tuberculosis management worldwide, says Carole Mitnick, a public health researcher at Harvard University who specializes in the treatment of drug-resistant TB. "It reflects the lack of equal access to quality care and treatment," she says.

For example, tuberculosis medications are highly restricted in some countries, such as Brazil, but are more freely available in others. In India, where there are about two million new TB cases a year, it is possible to get some TB drugs from pharmacies without a prescription, says McGill's Pai, who is from India and has studied TB treatment there. "A lot of patients won't take the full course [of antibiotics], and then they start a new drug. That's the pattern that leads to drug resistance," he says. A study published in PLoS One last year found excessive private market sales of TB drugs in several countries, including India and Indonesia, implying misuse.

The new, soon-to-be-released TB drugs have been specifically developed to address drug-resistant strains, but experts warn that without proper disease management, patients will become resistant to the new treatments before they can do much good.

Some Indian news reports have criticized the Mumbai clinic for causing unnecessary panic, but the fact that it is identifying and reporting such cases is a good sign, Cegielski says. "In the past 10 years, there has been this tidal wave of developing countries discovering drug-resistant TB cases," he adds. The problem itself is not new, but now it is better documented thanks to increased awareness and improved access to drug-resistant screening technologies. "There are still probably more cases of highly drug-resistant tuberculosis than we know about," Cegielski says.

Tuberculosis may not be as pressing a concern in the U.S., where in 100,000 people there are only about 3.6 cases (pdf), compared with 280 in Southeast Asia and 450 in Africa, according to WHO. But in the age of drug-resistant TB, every nation is vulnerable. As the nonprofit Stop TB Partnership said in a recent campaign, "TB anywhere is TB everywhere."

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