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Author Topic: Why is TB so hard to treat?  (Read 12913 times)

Gaurav

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Why is TB so hard to treat?
« on: 11/03/2011 11:30:03 »
Gaurav asked the Naked Scientists:
   
Hi my question is - why is TB so hard to treat - are there many forms and are there any new therapies on the horizon? Can it affect other parts of the body as well as the lungs?

Many Thanks,

What do you think?
« Last Edit: 11/03/2011 11:30:03 by _system »


 

Offline lab monkey

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Why is TB so hard to treat?
« Reply #1 on: 16/03/2011 12:47:37 »
TB is hard to treat for several reasons.  One is that the bacterium which causes the disease (Mycobacterium tuberculosis) lives inside cells of the immune system called macrophages and actively subverts them.

The basic job of a macrophage is to swallow up invading bugs into the cell itself where it then kills the bug.  TB gets swallowed up but then interferes with the killing process of the macrophage and escapes.  The macrophage, knowing it's swallowed a bug, sneds out signals calling in lots more macrophages, all of which will start swallowing up the M. tuberculosis bugs, all of which signal more macrophages.  It's like fanning a fire with more and more macrophage activation and recruitment to the site of infection.
Eventually, the immune system walls off this site with fibrous tissue and a granuloma forms.  It is these which you see as spots on a lung X-ray.

From a treatment point of view, it's pretty difficult to target drugs into these granulomata.  They're walled off pretty tightly from the rest of the lung and, if you can get drugs into them the bugs are often inside the macrophages inside the granuloma.

Another reason why treatment is so difficult is that the bug itself has a very very complicated cell wall and getting drugs through that wall is tough to say the least.

A third factor is the very slow growth rate of TB.  Most bacteria will grow and show visible colonies overnight in a lab (given the right nutrients, temperature, oxygen levels and so on).  TB can take weeks and weeks to grow to visible colonies.  Because it's such a slow grower you have to treat for a long time.

There are more reasons, and thats ignoring drug resistance and co-infection with things like HIV, but the main factors are:

The fact it actively subverts the immune system which makes treating it without damaging the immune system very tricky
It's complicated cell wall and metabolism
 

Offline yor_on

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Why is TB so hard to treat?
« Reply #2 on: 24/03/2011 23:49:43 »
Interesting.

How do the bug escapes the macrophage?
Do you mean it irritate it and then leave, or that it corrupts it into doing something different than what it is expected to do?
 

Offline lab monkey

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Why is TB so hard to treat?
« Reply #3 on: 29/03/2011 14:11:43 »
How do the bug escapes the macrophage?
Do you mean it irritate it and then leave, or that it corrupts it into doing something different than what it is expected to do?

This is the topic of a lot of research at the moment.  What seems to happen is this:

In a normal macrophage, the bacteria are swallowed up into a vesicle called a phagosome.  This then undergoes a maturation process.  Lots of things happen here but ultimately 2 major events normally occur.  Firstly, the pH of the phagosome drops and the interior gets more acidic and secondly the phagosome fuses with another vesicle called a lysosome.  The lysosome contains lots of enzymes that help to destroy and degrade pathogens.

The TB bacterium actively slows, and maybe stops, the acidification of the phagosome and it also blocks the fusion of the phagosome and the lysosome.  It then escapes the relatively comfortable phagosome into the main body of the macrophage.  The detail of how this happens is unclear and there is loads of cutting edge research into this area at the moment.
 

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Why is TB so hard to treat?
« Reply #3 on: 29/03/2011 14:11:43 »

 

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