New Weapon Targets Ancient Foe

Posted on January 7th, 2013 by Dr. Francis Collins

Tuberculosis is an ancient scourge that has evolved in lockstep with humans for more than ten millennia. It infected residents of ancient Egypt; remnants of Mycobacterium tuberculosis, the deadly bacterium that ravages the lungs and other organs of its victims, have been found in Egyptian mummies dating back 3,000 years. It is considered one of the world’s deadliest diseases.

I’ve had my own experience with TB. As a medical resident in the intensive care unit in North Carolina in 1977, I was exposed to the bacterium during emergency care of a young migrant worker who arrived at our hospital in extremis from internal bleeding. Only after the hemorrhaging was stopped did we discover his advanced tuberculosis. But I’m happy to say we treated him successfully with a battery of drugs, and he walked out of the hospital. My own TB skin test tested positive a few months later, and so I had to take a year’s worth of therapy with isoniazid to wipe out those little microbial invaders. That was all it took.

For the most part, TB cases have been reduced to a trickle in the Western world—thanks to antibiotics—and relegated to the history books with descriptions of ‘consumption’ in nineteen-century England and tales of jail-like sanatoria where those consumptives were quarantined and often died.

But it may surprise you to learn that this highly infectious, often lethal disease is once again a growing menace in the developing world. In 2011 there were about 9 million new TB cases and 1.4 million deaths, according to the World Health Organization [1]. That same year in the US, 10,528 people were diagnosed with TB. Treatments can prove effective, but they are long, expensive, and difficult to enforce: a cure requires that patients adhere to a strict six-month regimen of several different antibiotics. When patients stop taking the medications, or use them improperly, the bacteria become resistant to the drugs, making them more difficult to kill. This is exactly what is happening across the globe, from Brazil, Russia, and South Africa to India and China, [2] where many people cannot or will not comply with the treatment regimen. These resistant strains are thriving and spreading widely, particularly in people with HIV and others with suppressed immunity. About one third of the TB deaths now occur in individuals with HIV [1]. I saw this scourge in all of its frightening dimensions when I recently visited South Africa.

Worldwide, public health experts are now detecting rising numbers of TB strains that are resistant to our most powerful anti-TB drugs. And with international travel and commerce, these highly contagious strains present a threat to the entire world. Last year, an estimated 630,000 people were infected with multi-drug resistant TB (MDR-TB), with 98 of those cases here in the US. The WHO estimates the global caseload of MDR-TB could mushroom to about 2 million within three years.

But today I’ve got some potentially excellent news. The FDA just approved [3] a new drug to fight these treacherous MDR-TB strains. Sirturo (bedaquiline) is the first innovative TB drug in over 40 years. The drug, which was developed by scientists at Janssen (the pharmaceutical arm of Johnson and Johnson), uses a novel killing mechanism to defeat the bacterium. It enters the Mycobacterium tuberculosis cell and blocks its ability to produce energy, essentially starving the cell from inside out. What’s even more impressive is that it doesn’t harm human cells.

The FDA approval of Sirturo was fast-tracked because it is a “drug of last resort.” It carries some significant risks, and still requires further testing and larger trials that will reveal its promise and perils. The NIH is collaborating with Janssen to see how best to use Sirturo in combination with AIDS drugs in places like South Africa to curb the rise of MDR-TB in this vulnerable population.

Although total TB cases continue to decline in the US [4], it’s critical that we continue to develop and test new approaches to kill these resistant strains. Sirturo’s approval was the culmination of Janssen’s decade long program that brought together the NIH, FDA, The Bill and Melinda Gates Foundation, The TB Alliance, and the Critical Path to TB Drug Regimens (CPTR) Initiative. Without all of these players it wouldn’t have happened. This is a very promising first step, but we will need many more novel anti-TB drugs in the future.

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REFS:

[1] WHO: How many TB cases and deaths are there?
http://www.who.int/gho/tb/epidemic/cases_deaths/en/

[2] WHO: Multidrug-resistant tuberculosis 2012 Update
http://www.who.int/tb/publications/MDRFactSheet2012.pdf

[3] FDA press release
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm333695.htm

[4] Reported Tuberculosis in the United States, 2011
http://www.cdc.gov/tb/statistics/reports/2011/executivecommentary.htm