Do you shudder when you hear the word 'tuberculosis'? Not anymore? You should.
A new form of incurable TB showed up in India in 2011-2012 and they call it totally drug-resistant tuberculosis (TDR-TB). This form is deadlier than the already highly resistant forms of TB, variously called multidrug-resistant TB (MDR-TB) or extensively drug-resistant TB (XDR-TB).
These unnerving acronyms tell you just about all you need to know about the progression of TB going on before our very eyes. An old disease feared for generations as a death sentence is coming back to haunt us. Currently, there are about 9.4 million TB cases per year worldwide and approximately 440,000 are multidrug-resistant forms of TB.
And if you think resistant forms of TB are not a problem for us to worry about in the U.S., you need only consider that a highly drug-resistant strain of TB, called strain W, was responsible for TB outbreaks in New York in the early 1990s. Most of the patients were HIV positive and death rates exceeded 80%. From January 1992 through February 1997, cases were diagnosed in nine states and Puerto Rico.
Why is this happening?
Therapy compliance has always been an issue for TB because it typically needs to be treated for six months. But drug resistance is becoming another big problem.
Current drug therapy just doesn't work all the time anymore and the result is Multidrug-resistant TB (MDR-TB), Extensively drug-resistant TB (XDR-TB), and now Totally drug-resistant TB (TDR-TB). This makes some sense when you consider the well-known and discussed problem of antibiotic resistance doctors tell us about whenever we want an antibiotic for a virus.
Furthermore, most of us are aware of antibiotic resistance for common infections like strep throat, which are now routinely treated with newer antibiotics because tetracycline, once a mainstay for strep throat, no longer works very well.
But here we're talking about TB, a very dangerous infection, and treatment options are becoming more and more limited, as evidenced by the appearance of MDR, XDR, and TDR-TB.
Ruth McNerney, a TB researcher at the London School of Hygiene and Tropical Medicine says, "It's very worrying, but kind of inevitable, given the gradual emergence of resistance. It's like watching a slow-motion horror movie unfold." As unfold it did when in 2006 XDR-TB strains emerged in many countries, followed by TDR-TB strains in Italy in 2007, and more in Iran in 2009.
Now India is the third country reporting TDR-TB cases in 2011-12. As of now, TDR-TB does not represent the bulk of TB cases worldwide, and does not appear to be as great a threat in the U.S. because immigration regulations require screening for TB infection. Nevertheless, it remains much on the minds of health officials and TB experts everywhere, who are waiting for the other shoe to drop.
The emergence of HIV has also been a factor in the increase of drug resistance to TB treatment. The World Health Organization (WHO) estimates approximately 13% of TB cases arise in patients infected with HIV.
In fact, TB is second only to HIV as the world's leading cause of death from infectious disease. There are many reasons for the continued prevalence of TB, especially in poverty-stricken countries. TB testing, for example, often still uses a standard WHO-recommended diagnostic test developed more than 100 years ago. But although it's inexpensive, it's also prone to false negatives, doesn't provide drug susceptibility evidence, and results can take weeks.
This poses a real problem if patients get drugs that don't work and then transmit the infection to others. While TB is often described as a disease of poverty, the drug-resistant varieties seen today are considered more a problem of untimely or inappropriate treatment.
Fortunately, in 2010 the WHO approved a new test that can gauge resistance to the most often used first-line drug, rifampicin, that is fully automated. As of July 2011, more than 25 countries use this test and nearly 150 are eligible to purchase kits at a reduced price.
Another issue, which might surprise you in the era of modern pharmacology, is that no new first-line drugs for TB have been developed in over 50 years! Fortunately, more than ten new or repurposed TB drugs are in clinical trials now and have the potential to be useful in treating the drug-resistant forms of TB emerging.
Some of these drugs may shorten the duration of TB treatment (from 6 months to 4 months). This alone is great news because long-term therapy too often leads people to quit taking their drugs before they are 'cured' and no longer able to spread TB. Poor drug compliance has long been known to enhance the cycle of resistance and lead to the development of drug resistant forms of TB.
Brand new drugs are being investigated too that are specifically designed for drug-resistant TB. In some cases these drugs are benefiting from public-private partnerships in research, such as late-stage studies with pharmaceutical companies and the Global Alliance for TB Drug Development (TB Alliance).
New drug therapies, either in the form of repurposed ways of using older drugs or the development of completely novel drugs, will hopefully be able to address Totally Drug Resistant-TB before it becomes a global problem of epic proportions. I certainly don't want to watch the horror movie of TB coming back to haunt us as TDR-TB, do you?
Dorian Paul founded a company providing cutting edge science writing to clients in Biotech and big Pharma. Paul's thriller, Risking the World, is about a rapidly fatal bioengineered form of TB used as a bioweapon and is available from Amazon.com
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