Wednesday, May 30, 2007

Tuberculosis Scare



Today in the New York Times I came across an article on an intercontinental medical crisis. The way the story unfolded was nearly cinematic, chasing down passengers on international flights and quarantining parties that have suspected contact with this one carrier of a grave illness. It would seem that an American man has recently been found with an extensively drug resistant (XDR) form of tuberculosis, and had possibly been infectious earlier in the month when he was travelling internationally.

This is the latest outbreak scare in only a handful of years; this type of event appears to be getting more and more common. SARS was traced from a single source through several countries and across an ocean, the West Nile virus came to the United States from what was thought to be a single mosquito on a ship traversing the Atlantic, and fears of the Bird Flu remain in the public eye. Clearly with our new global community, disease control has to be handled in a different way.

With this current tuberculosis outbreak, the concern lies in spreading an extremely resistant form of the bacteria through several countries, since the ill man recently visited Paris, Prague, and Montreal. It could very well become an international health crisis if the people on the flight and in contact with the infected American also become ill or carriers of the disease.

On this same day that news spread of the XDR TB scare, we learned about tuberculosis infection in class. It is caused by Mycobacterium tuberculosis, a type of bacteria that has a waxy coat instead of the normal bacterial cell walls. If you look at my previous entry, I discuss what makes up a cell wall; in mycobacteria, unlike gram negative and gram positive bacteria, they have Mycolic acids linked to arabinogalactin. This basically makes the bacterial surface somewhat protected from your body's immune response. It also means that instead of staining with gram stain or safranin, these bacteria are acid fast, and a sample will stain in the presence of acid.

What I mean when I say that these bacteria are protected from your immune response is that they actually go on to live inside the very cells trying to kill them, the macrophages. When your body notices it is infected, the macrophage cells try to respond by surrounding and swallowing the bacteria. Normally, they would then kill the bacteria; however, because of the waxy coat, the fact that mycobacteria love oxygen, and for other reasons, many of the pathogens survive inside their macrophage assassins.

When the macrophage realizes it has found a pathogen, it releases a large burst of signals, cytokines and chemokines, that attract other immune responders. These form a large cluster around the original pathogen, called a granuloma. The granuloma walls off the infection inside, and with such cellular response the center of the granuloma will begin to die, leaving a lesion that in normal, healthy people becomes fibrous or calcified. The granuloma is the infection being contained by your immune system, and this group of 91% of the infected population fail to show disease.

However, of the other 9%, two-thirds have clinical TB and one-third with go on to have progressive systemic disease and death. It is this 9% that is of greatest concern, not only because they suffer from the disease, but also because these active cases of TB are what can spread the pathogen. Which is why the CDC is so concerned with the current outbreak. With active cases of TB, there are several treatment options, but the pathogen over time has become more resistant to the few drugs available for treatment. There are first line and second line drugs, based on how effective they are for treatment. There are guidelines for treatment of course, but as you would expect it is worse when the bacteria is resistant to the first line of medications.

XDR Tuberculosis, or extensively drug resistant TB, doesn't respond to any of the first-line drugs nor 3 of the 6 second line drugs, making it very evasive of our current medical arsenal. We aren't facing a disease as dangerous as the subject of the film Outbreak, but there is concern. TB is spread through droplets in the air, which only reach those in close proximity, and only active TB infections are spread by coughing. Moreover, you need a high dose of the bacteria in order to get a productive infection; just a few mycobacteria will be non-infectious to nearly any normal host. This TB scare is not frightening because of its ability to spread rapidly or its high host fatality, but rather because modern medicine isn't equipped to deal with large numbers of cases of this disease.

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