"The most important aspect of this is that we get the patient cured the first time around," Weyer says. "Every time a patient has to get treated again, you run the risk of amplifying resistance."
That has led to the cases of totally drug-resistant tuberculosis (TDR) described in the Emerging Infectious Diseases journal. Paul van Helden, director of South Africa's Centre of Excellence for Biomedical TB Research and one of the authors of the study, says it was only a matter of time before tuberculosis developed resistances to the last remaining effective antibiotics. TDR has previously been found in India, Iran, and Italy, but appears to be most prevalent in South Africa.
"How long it's been out there is anyone's guess. We found nine cases in one small area; obviously it's something that's been out there for a while," he says.
Patients are rarely tested for a particular strain of tuberculosis, so it's unclear how prevalent TDR is worldwide. Major health organizations have yet to even define the parameters necessary for a case of tuberculosis to be considered TDR.
Bishai says van Helden's paper suggests that "TDR is extensive in South Africa."
"It's gone relatively unrecognized," he says. "This is evidence that it's emerged and is spreading—we're playing with fire here."
Drug-resistant TB isn't just a South African problem. In the early '90s, there was an outbreak of MDR in a New York City hospital. During that outbreak, 32 patients caught MDR over the course of a few months and 29 of them died. That outbreak was eventually controlled, but more than 100 cases of MDR have been detected in the United States over the past eight years, and there have been high-profile outbreaks in Peru, Russia, and India over the past decade.
Despite the high death rate during the New York City outbreak, public health officials were able to keep MDR from escaping into the general population, a task that took a concerted effort and many millions of dollars, van Helden says. South Africa, doesn't have that luxury.
"The fact that New York City managed the outbreak suggests we can contain it, but the cost was phenomenal," van Helden says. "We don't have the same resources as the U.S. South Africa is going to go through a lot of strain trying to combat this problem."
But while tuberculosis appears to be getting more nefarious by the year, Bishai and other experts are more optimistic about humanity's chances for fighting TB than they are about some other drug-resistant bacteria. Global TB rates have been declining for years, and in the most developed countries, there are very few tuberculosis deaths. In the United States, 529 people died of TB in 2009 (the most recent year for which data is available from the CDC). About 10,000 Americans contract the disease each year.
Today, 22 "high burden" countries (including South Africa) account for 80 percent of the world's TB cases, according to WHO. But the organization's most recent report notes that the "global burden of TB remains enormous." The disease killed 1.4 million people in 2011.Because of that burden, pharmaceutical companies are working on new drugs to treat it—which can't be said for some more innocuous bacteria that have developed drug resistances, such as gonorrhea.
In December, the FDA approved bedaquiline, the first new class of TB drug to be developed in more than 40 years. The drug will likely be approved in South Africa sometime this year. It's unclear whether the new drug will be effective against TDR, but scientists are optimistic.
Weyer says bedaquiline is a good start, but if more new drugs aren't quickly developed, TB will develop resistance to that drug as well.
"The only game-changing effects will happen once we have enough drugs to put completely new treatment regiments into use," she says. "It's encouraging we have a few drugs in the pipeline, but we need several new ones, with new mechanisms of action, to protect against new resistances."