New Weapon Targets Ancient Foe

Microscopic image of a long, thin, rod-like bacteria

Colorized scanning electron micrograph of Mycobacterium tuberculosis. Source: Clifton E. Barry III, Ph.D., NIAID, NIH.

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

6 thoughts on “New Weapon Targets Ancient Foe

  1. Why would you blog on TB Today and not the Stem Cell Victory clearing the way for the additional lines pending?

  2. Hi, Jana,

    You’re quite right to point out that today’s action by the U.S. Supreme Court represents a major victory for NIH-supported stem cell research.

    In fact, the news is so important that the NIH Director chose to address it on his main web page, http://www.nih.gov/about/director/, which is where he issues statements on matters of widespread significance for biomedical research.

    For the convenience of blog readers who’ve not seen that statement, we’re also posting it here:

    Statement by NIH Director Francis S. Collins, M.D., Ph.D., on Supreme Court’s decision regarding stem cell case

    I am very pleased with today’s decision by the U.S. Supreme Court to decline to review the Sherley v. Sebelius U.S. Court of Appeals ruling. This decision allows the ruling to stand, and enables NIH to continue conducting and funding stem cell research, following the strict ethical guidelines put in place in 2009. Patients and their families who look forward to new therapies to replace cells lost by disease or injury, or who may benefit from new drugs identified by screening using stem cells, should be reassured that NIH will continue supporting this promising research.

    • While it has been nice to see the NIH approving more embryonic stem cell lines to help advance research, the field had remained in much controversy, as evidenced by the ongoing lawsuit Sherley vs Sebelius challenging federal funding of embryonic stem cell research. Has this caused the NIH to NOT move forward with the redefinition of the embryo, which would allow more lines to be approved for federal funding… and move the entire field forward?

      As you know, several lines pending NIH review will only qualify after the redefinition is adopted by the NIH.

      These lines were derived without the destruction of the embryo, and offer the NIH and the United States a clear path to assume a leadership position on ethical hESC research and therapies.

      Why isn’t the NIH leading on this issue?

      Why does the NIH refuse to act on the redefinition and let 2 people who filed a lawsuit to derail a very promising and ethical path to hESC research and cures?

      When will the NIH assume a leadership position on this issue and act on the redefinition so that the lines are considered for federal funding?

      As the Director of the NIH, I ask you lead on this issue and move us forward by approving the redefinition now!

      5 Years Ago my Grandfather could see through a toilet paper roll.
      Now my Grandfather can see through a drinking straw.
      He will never get to see any of his grandchildren.

      Dr Francis has done nothing on this pending item for 3 years! 3 Wasted Years!

      We get comments like “stay tuned”

      Please give the people some sort of update as some go blinder by the day!

  3. Hello

    Can we please amend the definition of hesc now!

    I know you guys have read the comments, please let’s change the definition today!

  4. Russian scientists reported success in treating antibiotic-resistant TB with ozone gas infusions a PubMed-cited article reported. (Belianin  et al, Blood Ozonation in the Treatment of Patients with Progressive Pulmonary Tuberculosis Concurrent with Diabetes Mellitus. Russia Probl Tuberk. 1998. PMID: 9553431)  

  5. The site was absolutely fantastic! Lots of great information and inspiration, both of which we all need!Keep ’em coming… can’t tell you how much I, for one, appreciate all you do!

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