Hey Doc, Is Tuberculosis Making a Comeback in Drug Resistant Form?

When it comes to diseases like tuberculosis, many people think of days gone long by about a disease that killed the likes of famous gunslinger and gambler Doc Holliday and poet John Keats at a young age. Of course, back in those days, there wasn’t any formidable treatment for the disease.  While immunizations, drugs and a tectonic shift in overall healthcare and preventative measures in most countries have greatly curbed the prevalence of former mass killer, it’s still around…and some wonder if drug resistant strains will spark a comeback if not addressed now.

The World Health Organization reported in its “Global tuberculosis report 2013” released on Wednesday that the number of people with TB dropped to 8.6 million in 2012 (from 8.7 million in 2011) and deaths from TB declined to 1.3 million (from 1.4 million in 2011). On the positive front, WHO added that the world is on pace to meeting the 2015 goal of reducing the mortality rate of TB by 50 percent compared to 1990.

Meanwhile, the report estimates that only about three-quarters of the global cases were actually diagnosed, with three million people being “missed” by health systems.  WHO reported that 75 percent of the three million undiagnosed cases were in just 12 countries, including India, Pakistan and South Africa.

TB is caused by bacteria (Mycobacterium tuberculosis) and spread from person to person through the air.  When people with lung TB cough, sneeze or spit, they propel TB germs into the air, exposing others that only need to inhale a few of the germs to become infected.  Everyone is at risk, but children and people with compromised immune systems, such as people infected with HIV, stand the greatest chance of falling ill.  About one-third of the world’s population, or 2.4 billion people, has latent TB, meaning that they carry the bacteria, but aren’t sick and can’t transmit it to others.

People may think of TB as a killer of the past, but it still ranks second behind only HIV as a top killer in the infectious disease category.

The decreased incidence rate is encouraging, but as Geneva-based WHO notes, “Standard anti-TB drugs have been used for decades, and resistance to the medicines is growing. Disease strains that are resistant to a single anti-TB drug have been documented in every country surveyed.”  WHO studies cover nearly 200 countries and territories, canvasing essentially every TB case reported.

WHO estimates that 450,000 people were infected with multi-drug resistant TB (MDR-TB) in 2012, with India, China and Russia reporting more than 50 percent of the cases.  Nearly 40 percent of those people (170,000) died from the disease.  MDR-TB patients do not respond to treatment with isoniazid or rifampicin, the two strongest, first-line defenses for TB.  About 45,000 of the MDR-TB cases demonstrated more severe drug resistance, known as extensively drug-resistant tuberculosis, or XDR-TB.  In these cases, patients don’t respond to first-line drugs or the most effective second-line of anti-TB drugs.

As explained by The Scripps Research Institute, the tuberculosis bacteria is extremely adept at persisting in humans, frequently reverting to a dormant, non-replicating state and creating attack-resistant cell colonies.  “Compared to ordinary, fast-replicating TB, these other forms of TB are much less susceptible to existing drugs. Effective TB therapy thus requires months to years of regular dosing. But many patients quit before completing such long courses of treatment and end up incubating drug-resistant TB strains.”

In December 2012, the FDA approved Sirturo (bedaquline), a product of Johnson & Johnson’s (JNJ) subsidiary Janssen Therapeutics, as part of a combination therapy for adults with MDR-TB.  It was the first anti-TB drug approved in 40 years.  In developed countries, a six-month treatment of Sirturo costs about $30,000.

In general, WHO says it is facing about a $2 billion annual shortfall in the $7 billion to $8 billion that it requires for a full response to the global TB epidemic.

According to WHO, there are 10 other new or repurposed TB drugs in late stage clinical development.  Also, there are 10 TB vaccines and two immunotherapeutic vaccines for TB coming down the regulatory pathway.  Relative to other diseases, this is a paltry number for such a prominent disease and represents an area of great unmet medical need that doesn’t draw much attention, especially considering drug-resistant forms are hitting heavily populated countries like China and India.