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MDR & XDR TB - A Case of Bacterial Evolution

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Mefiante
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« on: October 11, 2006, 11:45:03 AM »

Yesterday's episode of e-tv's 3rd Degree discussed the case of 60+ deaths in KZN resulting from infection by extremely drug resistant tuberculosis (XDR-TB).  Apart from being yet another very black mark against SA's health ministry (for its much-delayed reaction to timely and ample warnings), it is also an object lesson in just how critical a proper understanding of evolutionary processes can be.

But first, a little background information and a few comments: Tuberculosis is a contagious but curable disease of the lungs that worldwide currently kills about 1.7 million people a year.  It spreads through the air, much like the common cold.  The infective agent of TB is the Tubercole, or TB, Bacillus, which is a type of mycobacterium rather than a virus, as is the case with the common cold.  At present, South-East Asia has the highest number of TB cases - about 33% of the world total - with an annual new infection rate of 182 per 100,000.  However, sub-Saharan Africa's annual new infection rate is almost twice as high at 356 per 100,000.

Treatment in the form of antibiotics was first developed about 50 years ago, and TB incidence, prevalence and mortality rates declined sharply, to the point where it was felt that TB was about to become a thing of the past, much like smallpox.  Treatments were therefore not developed any further.  However, the normal treatment regimen is lengthy, taking six to eight months to complete, and is often accompanied by unpleasant side effects.  The discipline required to see the treatment to completion is often lacking, especially in poor countries and rural areas where TB is most common.  The discipline problem is aggravated by the fact that improvements are noted soon after treatment begins, and patients wrongly assume that their full recovery requires no further medication.  Some TB bacilli survive the curtailed treatment, and the patient is almost guaranteed to suffer a relapse in the near future.

The salient facts of the treatment, such as its length, the possibility of unpleasant side effects and the necessity for completing it, are carefully explained to patients at its commencement, so it is a little spurious of 3rd Degree to attempt to blame the Dept. of Health alone.  At least some of the responsibility must be apportioned to the patients themselves.  Also, 3rd Degree did not spell out the full facts about TB treatment, which are central to the whole issue.  The emergence of mmultiple drug resistant TB (MDR-TB) and XDR-TB was barely given the attention it deserved: one medical doctor was permitted to say that they resulted from "sub-optimal treatment."

Though truthful, that description is hardly complete, and explains nothing useful.  The emergence of MDR-TB and XDR-TB is a direct consequence of incomplete treatment and evolutionary processes, and is exactly what evolutionary theory predicts will happen.  In any population of TB bacilli, the available genetic variety will ensure that some bacilli are more resistant, and some less so, to the presence of a given antibiotic.  The less susceptible ones will tend to survive, and pass on their antibiotic resistance to their offspring.  Again, some of the new generation will be more, and some less, resistant, but on average, each new generation of bacilli will have a greater resistance than the previous one, provided that the antibiotic is present.

The antibiotic thus exerts a selection pressure on the bacilli, driving the entire bacillus population towards greater resistance.  The few random genetic mutations that increase resistance in this regard - most will be neutral, and some negative - will be better adapted to their antibiotic environment and therefore survive preferentially, while the neutral and negative variations will quickly succumb to the antibiotic and die.

The way to cure TB then is to keep the TB bacillus population small by taking the appropriate medication for a lengthy period and allowing the body's immune system to mop up the surviving bacilli.  If treatment is stopped too early, the immune system will not be able to cope and the more resistant TB strain will flourish.  As has frequently occurred, repeating this cycle of relapse and incomplete treatment will amount to a selective breeding exercise where the relevant TB strain is effectively bred to be resistant to different types and potencies of antibiotics.

It is doubtful that new antibiotics can be developed quickly enough that effectively treat MDR-TB and, especially, XDR-TB.  So we're basically left once again with the problem of implementing prevention and containment protocols, which, as has ever been the case, are considerably more problematic to administer than effective treatment management.

If nothing else, the above facts do, however, graphically illustrate the dangers and costs of ignoring good science.

'Luthon64
« Last Edit: October 11, 2006, 11:47:25 AM by Anacoluthon64 » Logged
qrios
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« Reply #1 on: October 11, 2006, 12:43:00 PM »

Interesting post 'Luthon.... and I could not agree more on your comment..
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black mark against SA's health ministry (for its much-delayed reaction to timely and ample warnings), it is also an object lesson in just how critical a proper understanding of evolutionary processes can be.

Even her new medical tariff proposals for next year is ludicrous.

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Antibiotic resistance, like insecticide resistance, is not evolution as proved by the fact that both are reversible and soon disappear when the challenging molecules are no longer present. Like ontogeny is now, evolution WAS never reversible.

“At most, the environment plays a similar role with regard to organisms; IT CAN ONLY PROVOKE AND SET IN MOTION SOME POTENTIAL THAT IS ALREADY PRESENT.”
Otto Schindewolf, Basic Questions in Paleontolog, page 313, his emphasis.

Hence the Prescribed Evolutionary Hypothesis.
 

http://www.uncommondescent.com/archives/1675#more-1675

I was also reading on the development of antibiotics, and the ability to "evolve" into resistant strains, but unfortunately I gave not had the time to finish it all and conclude... Embarrassed
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Mefiante
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« Reply #2 on: October 11, 2006, 13:07:18 PM »

Quote
Antibiotic resistance, like insecticide resistance, is not evolution as proved by the fact that both are reversible and soon disappear when the challenging molecules are no longer present. Like ontogeny is now, evolution WAS never reversible.
Hogswill and bilgewater.  This response is typical creationist subterfuge: it deliberately misrepresents what evolution is.  The fact is that antibiotic resistance is indeed reversible over generations in a given population.  However, individual bacilli with enhanced resistance have to die off and be replaced by less resistant progeny so that the average population resistance decreases.  You can't magically somehow make a given individual bacillus less resistant.  The fact of reversibility is, in point of fact, entirely in line with evolutionary theory because removing the antibiotic again changes the selection pressures on the population and thus the environment it is in, so that increased resistance no longer matters, and therefore less resistant mutations survive and dilute the overall population resistance over time.

'Luthon64
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« Reply #3 on: October 11, 2006, 13:37:26 PM »

I wanted to add this to my previous post, but the edit period had expired.

There are certain species of fish that live entirely in dark caves.  Their eye structures are gradually receding.  By the creationist argument cited earlier, that shouldn't happen at all.  Nevertheless, it does, and for the same essential reasons I gave before.  In fact, eyes are detrimental in a perpetually dark setting because they are easily injured by bumping into things.  Thus, such creatures with normal eyes are actually more vulnerable, and selection pressure is in favour of those specimens that have less easily injured (e.g. a thicker cornea or nictitating membrane) or smaller eyes.  There's no selection pressure to maintain the eyes' ability to see because sight itself doesn't matter in the dark.

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« Reply #4 on: October 11, 2006, 14:43:29 PM »

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Hogswill and bilgewater.
THE RECIPE FOR EVOLUTION!!!!!  Grin - Sorry couldn't resist - Still can't believe that you find it plausible that the universe created itself Huh?

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You can't magically somehow make a given individual bacillus less resistant.
Do you imply that the opposite is somehow exceptable?

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The fact of reversibility is, in point of fact, entirely in line with evolutionary theory because removing the antibiotic again changes the selection pressures on the population and thus the environment it is in, so that increased resistance no longer matters, and therefore less resistant mutations survive and dilute the overall population resistance over time.

Quote
Biological evolution ... is change in the properties of populations of organisms that transcend the lifetime of a single individual. The ontogeny of an individual is not considered evolution; individual organisms do not evolve. The changes in populations that are considered evolutionary are those that are inheritable via the genetic material from one generation to the next. Biological evolution may be slight or substantial; it embraces everything from slight changes in the proportion of different alleles within a population (such as those determining blood types) to the successive alterations that led from the earliest protoorganism to snails, bees, giraffes, and dandelions."

-- Douglas J. Futuyma in Evolutionary Biology, Sinauer Associates 1986

My argument is not against micro-evolution. I do believe it is possible as a creationary process. I am mainly anti-Darwinism...
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Mefiante
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« Reply #5 on: October 11, 2006, 15:15:51 PM »

Still can't believe that you find it plausible that the universe created itself Huh?
The origin of the universe is a question of physics, not one of biology.  Apart from the fact that your statement above assumes the existence of a universe before it "created itself," I find it hard to believe that you reject wholesale the lessons of cosmology and quantum mechanics.  In particular, the universe may be the ultimate free lunch, having a nett energy content that is zero, and having started as a quantum fluctuation as allowed by Heisenberg's Uncertainty Principle.  The fact that we don't know how things came about doesn't mean that we cannot know, and a naturalistic explanation has hitherto always been vastly more fruitful than a supernatural one.  The latter always raises more questions than it manages to answer.


Do you imply that the opposite is somehow exceptable?
What is this supposed to mean?  Evolution is concerned with populations, not individuals, just as the Futuyama quote says and I have written in this thread.


My argument is not against micro-evolution. I do believe it is possible as a creationary process. I am mainly anti-Darwinism...
Is this supposed to mean that you reject macroevolution and speciation?

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« Reply #6 on: October 11, 2006, 16:14:40 PM »


The origin of the universe is a question of physics, not one of biology.  Apart from the fact that your statement above assumes the existence of a universe before it "created itself," I find it hard to believe that you reject wholesale the lessons of cosmology and quantum mechanics.  In particular, the universe may be the ultimate free lunch, having a nett energy content that is zero, and having started as a quantum fluctuation as allowed by Heisenberg's Uncertainty Principle.  The fact that we don't know how things came about doesn't mean that we cannot know, and a naturalistic explanation has hitherto always been vastly more fruitful than a supernatural one.  The latter always raises more questions than it manages to answer.
We are as much a part of the universe as any free lunch...
The problem I have with quantum mechanics and string theories and the likes, is the fact that as science and technology advances, the theories and rules and ideas change... forcing a change in beliefs if that was the basis to start of with. Like you said in a previous post, one should not ignore good science, and I am a big fan of Stephen Hawking and other the great scientists. If what I believe should proof to be in error, I will gladly change to what is in evidence proven to be right.

Do you imply that the opposite is somehow exceptable?
Quote
What is this supposed to mean?  Evolution is concerned with populations, not individuals, just as the Futuyama quote says and I have written in this thread.
I most probably do not have enough knowledge on the topic, or I misread your statement that...
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You can't magically somehow make a given individual bacillus less resistant
If there is MORE resistance in an given individual bacillus, how does that happen? Futuyma refers to
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genetic material from one generation to the next
Does a generation not consist of individuals? Something somehere must change, and the change must start at a certain bacillus or group of bacillus?


My argument is not against micro-evolution. I do believe it is possible as a creationary process. I am mainly anti-Darwinism...
Quote
Is this supposed to mean that you reject macroevolution and speciation?
It is supposed to mean that I accept micro-evolution, but have yet too be convinced that man, all animals and life descended from the same gene.
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« Reply #7 on: October 11, 2006, 17:13:50 PM »

The problem I have with quantum mechanics and string theories and the likes, is the fact that as science and technology advances, the theories and rules and ideas change... forcing a change in beliefs if that was the basis to start of with. Like you said in a previous post, one should not ignore good science, and I am a big fan of Stephen Hawking and other the great scientists. If what I believe should proof to be in error, I will gladly change to what is in evidence proven to be right.
Science does not, and never has, promised absolute and/or eternal answers.  It is a process, not a destination.  A bit more than a hundred years ago a jumped up patent clerk in Berne, Switzerland, overturned the Newtonian conception of the world.  His name was Einstein.  The Newtonian conception was held to be virtually unassailable (in fact, even today there are still people who reject Einstein in favour of Newton).  It is possible that Einstein and Hawking/Penrose will one day be superseded by even greater intellectual accomplishments.  If you want eternal, static and absolute answers, science is not for you.


If there is MORE resistance in an given individual bacillus, how does that happen?
As I tried repeatedly to explain, this specific bacillus' resistance cannot easily be changed except possibly by some skillful interference from outside.  However, when it produces offspring, there is a small chance of a random genetic mutation occurring that determines that the offspring's resistance will be different.  If this descendant then has a different antibiotic resistance to its progenitor, it is either better or worse off for it when the antibiotic is present, and its survival to further reproduce is correspondingly affected.

Futuyama says it three times in the quote you cited - I have taken the liberty of emphasising important bits:
  • "Biological evolution ... is change in the properties of populations of organisms that transcend the lifetime of a single individual"
  • "... individual organisms do not evolve."
  • "The changes in populations that are considered evolutionary are those that are inheritable via the genetic material from one generation to the next."


Something somehere must change, and the change must start at a certain bacillus or group of bacillus?
The source of change is twofold: random genetic mutation and extant genetic variety in a population (no two individuals will have exactly the same genetic make-up).  The word "random" must not be equated with "spontaneous" because mutations can be induced by external factors; it merely means that any mutations that do occur are not directed at any specific goal.  They occur without any regard for whether the mutation is good, bad or indifferent for the survival of the offspring.


It is supposed to mean that I accept micro-evolution, but have yet too be convinced that man, all animals and life descended from the same gene.
This is merely an argument from incredulity.  You once correctly argued that merely because I believe something to be the case, does not make that thing true.  By the same token, just because you don't or can't believe it to be true, doesn't make it false.  Besides, there is a deeply puzzling amount of genetic overlap among the most apparently diverse species.  How do you explain that?

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« Reply #8 on: February 05, 2007, 07:28:56 AM »

On Saturday evening, e News reported that there are currently two confirmed cases of XDR TB in the Western Cape.  The word "containment" featured prominently in the Health Department's spin of the issue.  The word "spreading" didn't quite make it.

In other news, it seems that a potentially promising new antibiotic, one that interferes with the ability of a bacterium to form a cell membrane and thus procreate, has been identified in soil from South Africa that accompanied plants exported to the US.  It will be a few years before a viable drug will be available - such things as dosages, manufacturing methods, clinical trials and indications will need careful research.

Of course, South African officials will "dimand" a share of the profits (and probably get them too), despite having absolutely nothing in any way novel to do with the new drug, should it prove viable.

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« Reply #9 on: February 05, 2007, 16:33:33 PM »

Quote
Diagnosed cases of XDR-TB likely represent a small proportion of the true extent of the problem. The number of persons harbouring latent infections is unknown (and likely unknowable at present). Official statistics also likely underestimate the true prevalence of XDR-TB, as the current national TB guidelines prescribe the conditions under which M. tuberculosis susceptibility testing should be done.

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XDR-TB is a serious global health threat. It has the potential to derail the global efforts to contain HIV/AIDS, as broadly disseminated XDR-TB will prove to be a much more serious public health threat owing to its mode of transmission.

Extracts from a journal article published 23 January 2007.

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« Reply #10 on: February 13, 2007, 11:40:54 AM »

from: iafrica.com - Killer TB needs drastic steps
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Drastic new measures have been proposed to stop the spread of the virulent strain of TB that has claimed at least five lives in the Eastern Cape.

Dispatch Online reported on Monday that the suggested steps included infection monitoring at airports and border posts and the isolation of patients — even against their will.

The recommendations were made in a report published by the Johannesburg-based Public Library of Science (PLS).

Hopefully they will implement it.

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Figures released by the Johannesburg-based National TB Control Unit last week put the death toll from XDR-TB at 183 nationally since it was identified in September last year.

The unit said some 328 cases of XDR-TB had been identified and added that its own figure showed that some 18 people have died from the disease in the Eastern Cape.
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« Reply #11 on: February 26, 2007, 12:19:52 PM »

From a Mail & Guardian report:
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Health Minister Manto Tshabalala-Msimang told a news conference that drug-resistant mutations of the virus were emerging because TB patients were failing to complete the required course of drug treatment.
(Emphasis added.)

Is this the M&G's mistake, or is Tshabalala-Msimang just careless ("Uninformed?"  Nooooooo, never!!!) when making statements?

TB isn't caused by a virus.

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« Reply #12 on: February 26, 2007, 12:52:03 PM »

TB is and AIDS isn't.  Wink
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« Reply #13 on: April 26, 2007, 11:49:42 AM »

According to this news report, KZN's TB incidence is currently over 1,000 cases per 100,000 persons, and the disease is thus officially an epidemic.  By a factor of 5!  Apparently, many of the afflicted actively resist completing their treatment so as to remain ill for the purpose of claiming a temporary disability grant that is suspended once the patient is cured.  This habit plays a sizeable part in the rapid growth and spread of MDR- and XDR-TB.

Unfortunately, the article doesn't give any details about what remedial action is envisaged, other than possibly trying to suffocate the bacilli in money.

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« Reply #14 on: September 03, 2007, 19:32:37 PM »

This evening's e News Prime Time broadcast reports that SA is currently in 5th place of the top 22 countries with a TB problem, according to WHO statistics.  This ignores particular TB strains, i.e. treatable, MDR or XDR.

Call me alarmist, but I think we're witnessing the early stages of a disaster.

'Luthon64
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