Tuberculosis: a growing threat

8 April, 2010, Lux Fatimathas

Drug resistance – the new frontline in the war against TB.

I have seen the effects of tuberculosis close up. It is not a pretty story.

TB, short for Tubercles Bacilles, is caused by Mycobacterium tuberculosis – an organism no bigger than a few microns in size. The most common form of infection presented is that of open TB. The onslaught of symptoms that ensue include; weight loss, congested lungs, night sweats and a productive cough. The less often presented form of TB, which I have witnessed, is closed TB. This is what took hold in my mother.
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It surreptitiously invades the bones of the spinal column and here it resides as it gradually digests away the vertebrae. Over the course of a year, I saw my mother go from upright, mobile and working to bed ridden, in constant pain and unable to take care of her most basic needs. A diagnosis eventually came resulting in the removal of a large tuberculoma that had eaten away two of her vertebrae. Two months lying horizontal twenty four hours a day, twelve hours worth of surgery, two titanium bars to reinforce the spine, a spinal brace to be worn whenever upright and nine months of physical therapy. It took all of this for my mother to recover the ability to walk again. The key to her recovery however was the cocktail of drugs she diligently took every day, several times a day, for nine months.

Isoniazid, Rifampicin, Pyrazinamide and Ethambutol. It is this astounding combination of drugs that rid my mother of her TB.

However a new threat looms of the lives of over 400,000 TB infected people worldwide, according to figures released by the World Health Organisation in 2008.

These individuals are infected with multiple drug resistant TB (MDR-TB), a form of TB resistant to Isoniazid and Rifampicin. An even more foreboding strain of TB was identified in 2006 in South Africa, killing 52 of the 53 patients who contracted it – extensively drug resistant TB (XDR-TB). This form is even more deadly, as not only is it unresponsive to Isoniazid and Rifampicin, but also to a host of second line antibiotics such as fluoroquinolone and capreomycin. XDR-TB sprung out of Africa in communities already plagued by HIV and AIDS.

Quite surprisingly, a third of the global population is infected with the TB causing bacteria. However the infection is able to lay dormant until the immune system of the host individual drops; perhaps due to another infection, fatigue, aging or as is sadly often the case in Africa due to HIV and AIDS.

Age-old remedies for neutralizing the threat of TB are no longer effective?

What hope is there for the future when it seems that age-old remedies for neutralizing the threat of TB are no longer effective? The BCG vaccine, initially created in the early twentieth century at the Pasteur Institute in France, is to this day still administered in well over 150 countries worldwide. Although the protection conferred by this vaccine in children is considered to be highly significant, its usefulness in protecting adults from open TB is debatable. This has spurred on the development of several new incarnations of the BCG vaccine such as MVA85A, developed by the McShane lab at the University of Oxford in the UK. This vaccine is already in Phase II clinical trials and appears to enhance and extend the immune response to TB, particularly when used in conjunction with the old BCG vaccine.

Image: Janice Carr, Centre for Disease Control An electron microscopy image of TB. Small and seemingly simple in design, yet these cylindrical packages wreak havoc on our immune systems.

Whilst efforts are being made to bolster preventative approaches in combating TB, it is still vitally important to address the current needs of those already infected. The race is on to create new drugs targeting MDR-TB, drugs like TMC207. TMC207 was published last year, by the New England Journal of Medicine (Volume 360:2397-2405), to be effective against MDR-TB and to exert its effect in a more timely manner than previous drug treatments. This time factor is a significant hurdle in the treatment of TB. Implementing multiple drug regimes is problematic enough, but ensuring that this complicated course of treatment is maintained over a period of 12 to 24 months in the case of MDR-TB, is near impossible in resource poor regions of Africa and South America.

The fight against TB will require a multi-pronged approach; improved vaccines and drug treatments, coupled with increased financial backing and multinational support for the effective implementation of healthcare.

Image: Centre for Disease Control TB infected sputum. A single cough from a TB infected individual releases micro-droplets of this sputum into the air, containing thousands of TB particles (shown here in red).

TB is not an incurable disease yet it kills approximately 5000 people every day. My mother was lucky enough to be living in England, a country where TB is not a death sentence. This stark contrast comes down to the incredible inequality still present in the accessibility to decent healthcare.

This situation is not insurmountable.

World TB Day came to pass again this year on March 24th. The World Health Organisation took this opportunity to once again highlight the aim of the Global Plan to Stop TB – halve the number of deaths due to TB by 2015 from what they were in 1990. This is not impossible, nor implausible. This is challenging. The challenge is to save 14 million lives that will otherwise be lost to TB.

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