TB Alliance: Putting science to work for a faster TB cure

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MDR-TB has emerged and spread due to the inadequacy of treatment. Today, treatment for drug-resistant TB can take up to two years, and is so complex, expensive, and toxic that many patients are unable to access treatment. Of those who do, more than a third will die.

Drug-resistant TB is the man-made result of interrupted, erratic, or inadequate TB therapy, and its spread is undermining efforts to control the global TB epidemic. MDR-TB and XDR-TB develop when the long, complex, decades-old TB drug regimen is improperly administered, or when people with TB stop taking their medicines before the disease has been fully eradicated from their body. Once a drug-resistant strain has developed, it can be transmitted directly to others just like drug-susceptible TB. Today, it is believed that direct transmission is the most common way drug-resistant TB is spread, and augments this emerging global health threat.

Multidrug-resistant TB (MDR-TB)

Multidrug-resistant TB (MDR-TB) is defined by resistance to the two most commonly used drugs in the current four-drug (or first-line) regimen, isoniazid and rifampin. WHO treatment standards require that at least four drugs be used to treat TB in order to avoid the development of further resistance. The stories of those living with drug-resistant TB are harrowing.

Novel regimens are
needed to treat MDR-TB
on a global scale

According to the WHO, Eastern Europe's rates of MDR-TB are the highest, where MDR-TB makes up 14 percent of all new TB cases. In some parts of the former Soviet Union, up to 35 percent of new TB cases are multidrug-resistant. Among previously treated cases in the same region, reported rates of drug resistance are commonly above 50 percent and as high as 62 percent. During the late 1980s and early 1990s, outbreaks of MDR-TB in North America and Europe killed more than 80% of those who contracted the disease. During a major TB outbreak in New York City in the early 1990s, one in 10 cases proved to be drug-resistant.

Today, drug-resistant TB is also quite common in India and China — the two countries with the highest MDR-TB burdens.

Treatment for MDR-TB consists of what are called second-line drugs. These drugs are administered when first-line drugs fail. Treatment for MDR-TB is commonly administered for 2 years or longer and involves daily injections for six months. Many second-line drugs are toxic and have severe side effects. Further, the cost of curing MDR-TB can be staggering — literally thousands of times as expensive as that of regular treatment in some regions — posing a significant challenge to governments, health systems, and other payers.

The complexity and prohibitive cost of MDR-TB treatment means that few of the world's MDR-TB patients receive proper treatment. Without a significantly simpler, faster, cheaper, oral treatment for MDR-TB, countries cannot scale up treatment to serve their populations.

Extensively drug-resistant TB (XDR-TB)

Extensively drug-resistant TB (XDR-TB), also known as Extremely Drug-Resistant TB, is emerging as an even more ominous threat. XDR-TB is defined as TB that is resistant to any fluoroquinolone, and at least one of three injectable second-line drugs (capreomycin, kanamycin, and amikacin), in addition to isoniazid and rifampin. This makes XDR-TB treatment extremely complicated, if not impossible, in resource-limited settings.

In a 2006 XDR-TB outbreak in KwaZulu-Natal, South Africa, 52 of 53 people who contracted the disease died within months. It is estimated that 70% of XDR-TB patients die within a month of diagnosis.

The most recent drug-resistance surveillance data issued by the WHO estimates that an average of roughly 9 percent of MDR-TB cases are XDR-TB. Estimating the incidence of XDR-TB is extremely difficult because most laboratories are ill-equipped to detect and diagnose it; it is thought that the majority of XDR-TB cases go undocumented.