Tuberculosis: the problem

People went on red alert about SARS, where the fatality rate was approximately 10%. Bird flu doesn’t even spread between people (yet), but we’re on red alert about bird flu. Don’t get me wrong. Prevention is way better than cure. But it would make sense to deal with actual current threats before panicking about possible ones.

Tuberculosis is a much bigger problem than SARS, and it’s here, now, and killing millions. Untreated TB has a fatality rate of around 55%. TB treatment in the days before drugs reduced that rate to around 30%. In developed countries, with anti-TB drugs, the fatality rate was around 7%. (TB stats from the CDC.) Most of the current fatalities worldwide are people who had ordinary TB and couldn’t afford the cure. From a callous perspective, that’s not a problem in developed countries. But the drug-resistant strains that evolve in people who can’t or don’t take the full course of treatment is everybody’s problem.

As if that wasn’t bad enough, drug-resistant TB just took a turn for the worse.

There are three different factors to keep in mind with bacteria and viruses: virulence (the severity of the symptoms caused by that specific strain), infectivity (how likely you are to catch it), and drug resistance. These are not correlated. A disease can be virulent, but not highly infective or drug resistant, or totally resistant to drugs, but not virulent, and so on.

So far, drug resistant TB has been rather low on infectivity. (Even bacteria have a hard time being good at everything all at once.) The guy I will always think of as The TB Lawyer had an extremely drug resistant strain (XDR, worse than the MDR, multiply drug resistant, strains you commonly hear about). But it was a strain with low infectivity. I guess, when they told him that, he heard only the good news, and figured he was good to go. [Update: Turns out he has MDR TB. See footnote for a bit more detail.] I haven’t seen anything about where he picked it up, which seems like an interesting question, or how virulent it is. They say he has a 30% chance of succumbing, which is what you’d expect for “normally” virulent TB when drugs aren’t — or as in this case — can’t be used.

Well, now comes news from South Africa of a hyper-virulent, extremely drug resistant strain. When these medical types say hyper-virulent, they mean it. Fifty two out of the 53 people with confirmed diagnoses died. Average survival after the diagnostic samples were taken was 25 days. Median survival (i.e. the length of time the largest number of people survived) was 16 days.

Now, these particular people also had AIDS, which doesn’t help, but this is not the way AIDS patients react to “normal” TB. There is no reason to think the hyper-virulence would be different in people without AIDS. It’s also not an experiment where I’d like to be the guinea pig.

The strain is not, from what I see, hyper-infective. If it’s like “normal” TB, it spreads rather like a cold.

Great, huh?

The World Health Organization is so freaked out by this combination of characteristics, they’d like to see people go on a SARS-type alert to prevent global transmission. They also want South Africa to receive as much aid as is necessary to make sure all cases are identified, isolated, and treated. See the excellent PLoS article for that and many other links.

(Factoid via CDC, March 2006: “XDR TB was identified in all regions but was most common in South Korea … and countries of eastern Europe/western Asia.” These strains are not (yet) hyper-virulent.)

Following the steps indicated by the WHO would be the intelligent thing to do. Not to panic. Not to hoard (probably useless) drugs, not to join Cheney in a bunker and shoot all comers. No, just to address the issue and do what it takes.

Instead, the reaction in the developed world could be summarized as, “Another disease in Africa?” *Yawn*

We won’t be yawning when (it’s when, not if) the strain gets here. Then we’ll be flapping around in a useless panic, probably with fascist overtones, if past experience is any guide.

(Next: TB: The Solution?)

(MDR TB: resistant to the two main TB drugs (rifampicin and isoniazid). XDR TB is resistant to those as well as the quinolone class of antibiotics, and at least one of the second-line antibiotics (kanamycin, capreomycin, or amikacin). (These drugs are more toxic to the patient and usually(?) or always(?) have to be given by IV.) The older definition of XDR TB was resistance to three or more of the second-line drugs. (From Wikipedia) The definitions are clearly divided, but the bacteria are not. Resistance is not all or nothing. So a TB infection could be 100% resistant to the two main drugs, 90% resistant to one of the second-line drugs, 80% to another one, 65% to another one, and so on. What are you going to call that? MDR? XDR? I suspect this is the problem the CDC was having. They tested the diagnostic samples, found plenty of resistance, and tried to find the guy. Further tests showed some susceptibility, so now they’re calling it MDR.)

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14 Comments

Filed under 13_quixote

14 responses to “Tuberculosis: the problem

  1. oddjob

    Here’s a technical quibble. Isn’t your definition of “median” survival actually the definition of the “mode”? Wouldn’t “median” survival be the number of survival days that splits the sample in half (ie., 50% of the sample population survived longer than 16 days and 50% survived fewer than 16 days)?

    On a historical note, before the advent of modern antibiotics TB was known as “the white plague” (as opposed to “the black plague”). It’s a killer and has been for a very long time. Many strains of it are slow acting and fairly difficult to get, but even though they’re slow some of the them were relentless once they got going.

  2. Tricia(now there's more than one)

    (Obviously hearsay, but in case it helps in any way) TB Lawyer is a friend of my boss’s brother and he was told that TBL caught TB while in Vietnam. So the wedding/honeymoon trip to Europe was actually the second time he “traveled while contagious.”

    Nice, huh.

  3. Melissa McEwan

    We won’t be yawning when (it’s when, not if) the strain gets here. Then we’ll be flapping around in a useless panic, probably with fascist overtones, if past experience is any guide.

    Oy. Too true.

  4. Oddjob: yes, you’re right. In this case, median and mode are in pretty much the same part of the graph. It’s not a bimodal distribution. The average is skewed because there were a few, long-surviving outliers. Long in this case being around 50 days.

    All the numbers in this topic are just, “read ’em and weep.”

  5. These super virulent forms of XDR TB are indeed very worrying. I keep singing the same old song of more funding for better diagnostics, antibiotics and a vaccine. However with NIH’s budget being plundered to pay for overseas military adventures I fear that things wont happen quickly…

  6. Kate Harding

    Ugh. I don’t know if I’m glad to have this information or not.

  7. Kelley

    Even better: TB lawyer now thinks the CDC owes him an apology for confining him, and treating him with drugs he might not have needed. I don’t even know where to start with this asshole.

    Regardless of what strain he has, IT’S STILL FUCKING COMMUNICABLE. When the CDC tells you not to get on a plane with a communicable disease, don’t get on the fucking plane. But, oh no, this selfish little snot-nosed, overprivileged white asshole thought his wedding/honeymoon was more important that NOT spreading a dangeous disease. Now is his sorry ass wants an apology??? Not until he apologizes to each and every person on the the plane during any and all flights he undertook, and to each and every person he came in contact with along the way.

    Plus, now he’s bitching about the drugs he was given. Boo-fucking-hoo. Tell that to the millions of people in this country who can’t get any treatment for anything. Say, all the uninsured folks out there who couldn’t afford treatment after having contracted the TB-virus this selfish fucker spread.

    The only thing TB lawyer deserves is disbarrment and a boot up his ass.

  8. evilchemistry

    I love this sentence: Moreover, while the diagnosis of MDR-TB may take weeks or months, new technologies, including liquid culture and PCR probes, can reduce this time.

    One of my rotations in grad school was through a mycobacteriology lab and one of the ways the lab made money was diagnostic tests for zoos and the like. The tools for diagnosing mycobacteria are ancient and all are growth dependent. The most complex diagnostic assay in use at the time was an ELISA!

    Do you have any idea how difficult mycobacteria are to grow? Very difficult, they are extremely fastidious as well as slow growing…well the pathogens, which I think derives from their lifestyle as intracellular pathogens. All this complicates quantifying drug resistance, immensely.

    The important part of all this is the CDC was correct in their actions whether they identified strain correctly or not.

    If it’s like “normal” TB, it spreads rather like a cold.

    I don’t think the infectivity is anywhere near as high as a cold virus. That would be frightening.

    Kelley,
    TB-virus
    Tuberculosis is a mycobacterial disease, not viral.

  9. Brynn

    I don’t think the infectivity is anywhere near as high as a cold virus. That would be frightening.

    From what I know about TB, and that’s a fair amount because I wrote my thesis in graduate school about its resurgence back in 1992 when experts first began warning Americans that the de-funding of their public health system did not bode well for the prevention of treatable infectious diseases, TB is extremely contagious. Anyone on an airplane, bus, elevator or in a room with a contagious TB sufferer for any length of time can be infected. I’d say the cold analogy is spot on.

  10. Chromosome Crawl

    “The tools for diagnosing mycobacteria are ancient and all are growth dependent”

    Don’t mean to be a pain and contradict you EC, but I am a Specialist in clinical & public health micro/virology, and I can assure you that detection, identification & susceptibility (drug sensitivity) methods have changed quite a bit recently.

    PCR can be done on bronchial wash material and render a ‘yes/no’ answer in a matter of hours (enabling respiratory precautions to be set in place if need be). Drug susceptibility results can be sped along via the use of molecular detection of resistance genes. Relatedness typing for epi purposes can be done within a week of receipt of the sample in a PH lab, also via molecular methods.

    The fly in the ointment is the state of staffing of PH labs, which often get to use some really cool technologies as mandated by the folks at CDC, but are so underfunded that they can’t afford to attract & retain the proper number of people to staff the lab.

    (steps off soapbox…)

  11. evilchemistry

    Brynn,

    Yah, I get it. I wasn’t thinking of someone walking around with active TB, shedding all over the place. Those people are supposed to be quarantined and are in desperate need of medical attention. My bad. I was thinking of those considered to be in a latent phase.

    CC,

    Sure you can detect the presence of an antibiotic gene from some sample, which has its positives and negatives. That doesn’t tell you anything about the organism(s) carrying that gene. I was speaking specifically to mycobacteria and the difficulties in diagnosing a mycobacterial infection and quantifying it’s level of resistance to antibiotics.
    The tools for diagnosing mycobacteria are advancing but aren’t much farther than when Koch first developed them. That is why I love that sentence I referred to earlier.

    new technologies, including liquid culture and PCR probes

    Liquid culturing would be a new technology in aiding the identification of MDR-TB. In other words, it would be nice to be able to get enough of the cells to extract enough DNA so we could actually do some molecular biology. You know, provided you can even get an isolate. I know people like to think that all bacteria grow like E. coli from their undergrad laboratory in microbiology but its just not true.

    Like one of those articles above says, we could have wiped TB out a long time ago before it evolved multiple drug resistance.

    Cheers

  12. The TB Lawyer is talking about suing? !!!! Where is that goddamn fainting couch when I need it? I hope everybody on all those planes sues him for massive pain and suffering damages, and GETS THEM. Then, and only then, should the law even touch any papers he cares to file. What a stupendous jerk.

    evilchemist: TB infectivity is complex, as you also pointed out in your second comment. There’s not only the infectivity of the strain itself (which may indeed be a lot lower than a cold), there’s also individual susceptibility. Some people never get symptoms, even though they’re carriers. Some people seem to catch it just from one breath.

    The crucial thing, for me, is that I don’t want to find out the hard way which group I’m in! If it’s a very infective strain and/or I’m highly susceptible, I would catch it like a cold. I think it’s that which freaks everyone out, including public health officials.

    The newer molecular techniques can indeed make diagnosis swift and sure, but, as you point out, public health isn’t a priority. The technicians who can do that kind of thing don’t come cheap.

  13. Chromosome Crawl

    EC-

    I know where you are coming from on the “growing” versus “presence of gene” issue – much of my career has been spent explaining the difference to Residents & the like. I started working with molecular techniques in the mid-80’s when thermocyclers were still branded by Cetus, and the lab I’m in today has 20 of the current buggers as well as about a dozen sequencers. Our company does both phenotypic (growing) and genotypic (sequence – based) drug susceptibility testing of HIV, and I have long held that for bacteria, the good old fashioned phenotypic resistance test will never go out of style.

    I also worked in the late 90’s on developing a PCR-based assay that can be used on sputum or bronch wash samples to rule out M. Tb on the same day that the sample is taken. It’s just a matter of how important it is to a facility to get these results in a timely manner – another healthcare decision with the beancounter component!

    I’m pretty sure the quote you reference is talking about things like the Bactec or Trek culture bottles, and the probes commonly used by local hospitals to tell the difference between M. Tb and things like M. avium.

    The only good thing about the XDR cases is that hopefully they will help continue to keep pressure on the feds to actually LISTEN to the people with the experience and finally shore up the PH system. I’m not going to hold my breath, tho b/c TB is not a sexy disease like SARS or the Flu.

    I always find it funny that people freak out about the latest drug resistant infectious disease, and yet can’t seem to make the connection and finish their full prescription. Le sigh!

  14. Pingback: Tuberculosis: the solution? at Shakesville

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