The **** hits the fan regarding antibiotic-resistant tuberculosis

Drug-Resistant TB in South Africa Draws Attention From U.N.

The World Health Organization will hold an urgent meeting this week to seek ways to deal with deadly strains of tuberculosis that are virtually untreatable with standard drugs.

The meeting, in Johannesburg on Thursday and Friday, comes in response to recent reports from a number of the world’s regions about a small but growing number of cases of the deadly strains, known as extreme drug-resistant tuberculosis, or XDR-TB.

“XDR-TB poses a grave public health threat, especially in populations with high rates of H.I.V.” and few health care facilities, the health organization, a United Nations agency, said Tuesday.

More below…

This strain of TB already has worldwide distribution (including the United States, but it’s been a relatively small percentage of cases. What’s brought it to attention currently is a highly deadly outbreak in South Africa [bonus points to whoever spots the giant gaffe in the article]:

A new, deadly strain of tuberculosis has killed 52 of 53 people infected in the last year in South Africa, the World Health Organisation said on Friday, calling for improved measures to treat and diagnose the bacteria.

The strain was discovered in Kwazulu-Natal, and is classified as extremely drug-resistant. Drugs from three of the six second-line medicines, used as a last line of defence against TB, proved useless against the new strain.

“We are extremely worried about the issue of extreme drug resistance,” said Paul Nunn, coordinator of the WHO’s drug resistance department. “If countries don’t have the diagnostic capacity to find these patients, they will die without proper treatment.”

And it certainly has killed quickly:

Drug resistance is a common problem in TB treatment, but the new strain appears particularly virulent: 52 of the 53 patients infected all died within about three weeks of being tested for drug resistance.

Of course, the fear is that, if this strain spreads more widely and becomes increasingly common (overtaking even the MDR-TB strains), this could essentially send us back to the pre-antibiotic era as far as treatment for TB goes:

The lack of effective drugs brings doctors back to the era before antibiotics, when the limited treatment measures included chest surgery. For patients whose tuberculosis was confined to one lung, surgeons could remove a portion or whole lung, but without assurance of cure.

If the strain keeps spreading, it could exceed by “hundreds of times” the outbreak of drug-resistant tuberculosis in New York City in the 1990’s, Dr. Raviglione said. That outbreak was brought under control by adopting strong measures, including observation of infected patients to make sure they took their drugs properly.

Over at Time’s Global Health blog, they note that new TB drugs may be on the horizon, but of course, that just keeps us one step ahead of the game, and only lying in wait for the bacteria to develop resistance to the new drugs as well. This is a strategy we can’t win in the long term.

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25 Replies to “The **** hits the fan regarding antibiotic-resistant tuberculosis”

  1. Is there anything out there that isn’t going to kill us! What with bird flu, new strains of TB and so on, I have decided that blissful ignorance is the way forward!

  2. Don’t forget stingrays.

    This strain is still quite rare in the US–and the average healthy person with access to good health care is unlikely to contract TB. However, in a country like South Africa with such a large percentage of the population infected with HIV, this has the potential to be a real nightmare. What both this and “bird flu” show, however, is that we’re still largely slaves to the microbial life on earth–and it doesn’t take much on their part to really mess us up.

  3. ding ding ding. The 2 billion number is actually pretty well accepted, but it’s tough to know exactly because most of the cases are asymptomatic. The “TB viruses,” though, obviously is just shoddy writing/editing (especially since they say bacteria in the bold heading).

  4. I also caught the viruses comment. Interestingly enough, there was a House, MD episode about TB. A patient had TB plus other symptoms. They had to treat his TB to determine the underlying problem. It was very interesting.

  5. The 2 billion figure is generally accepted as it’s thought (very roughly) that 1/3 people have the bacterium in one way or another. The vast majority of cases of TB, even those in animals, is that the infected animal never shows any symptoms or even gets affected by disease. It’s only a certain subset of the total infected individuals that progress to disease.

    They’ve derived the 2 billion people thing from the generally accepted estimate of 1/3 people having TB in one form or another. ~6 billion people and divide by 3 you get 2 billion.

    I thought them calling a bacterium a virus was more of a gaffe.

  6. I found some poor sentence structure funny. They said

    “…to treat and diagnose the bacteria.”

    They probably really want to treat and diagnose the disease caused by the bacteria. Or even better diagnose then treat the disease.


  7. I’ll play….The article says “drugs from three of the six second-line medicines, used as a last line of defence against TB, proved useless against the new strain”. Aren’t three of the six drugs useless against MDR-TB. I believe all drugs are useless against XDR-TB.

  8. OK, if “this is a strategy we can’t win in the long term” then what strategy will win? Surveillance and quarantine? Those plus stepped-up development of new treatments? It almost sounds like you don’t think it’s worth it to develop new treatments, but that just can’t be right. It seems to me that we should use all of the weapons at our disposal, not abandon some in favor of others. What am I missing?

  9. Platypus, what we need is prevention. Ideally, a highly protective and widely available vaccine. There is a vaccine currently for TB, but it’s not very effective and immunity wanes (and there are other problems with it as well), and we need to do better. I don’t think we should abandon anything, and certainly new treatments are needed, but simply throwing new drugs at bacteria is like running on a treadmill: it works for awhile but you never really get anywhere.

  10. Accroding to Danish media, there is currently one treatment that takes two years, and which is not particularly succesful. However, as one of the Danish experts explained, that doesn’t mean that people should panic, since it’s very hard to get infected, and even if you are infected, there is only a 10% lifetime risk of actually getting sick.

    Does this sound right to you Tara?

    (oh, and we have a Danish case as well, which is why the expert was quick to try to reassure people – and the media thankfully made sure to include his remarks).

  11. Sam, absolutely. In fact, there’s at least one group looking at phage as a TB treatment, though I don’t know if they’re effective against XDR-TB. Mycobacterium tuberculosis as a species has very limited genetic diversity, but I don’t know if a single phage could be enough to kill all of them or if they’d still need multiple phage types.

    Kristjan, I don’t know all the details about treatment, but that sounds in the ballpark. TB is a very slow-growing bacterium (like its cousin that causes leprosy) and so must be treated for an extended period of time in order to clear the infection. And yes, most people who harbor the bacterium remain asymptomatic.

  12. My understanding is that the current first line therapeutic, isoniazid (INH) is actually very effective in controlling and clearing the infection. The problem is that you have to take the drug for 6-9 months or more. Resistant MTB arises in those that do not complete to treatment. To help solve this problem many NGOs use Directly Observable Treatment (DOTs) programs to make sure everyone takes their meds.

    My question is how will you ethically run a clinical trial for new therapeutics (or vaccines) when current ones work pretty well when used correctly? For instance, although there are a 10-14 thousand TB cases each year in the US (mostly in recent immigrants, HIV positives, IV drug users etc.) as far as I can find the mortality rate for TB in the US is zero.

    A strategy that will be effective in the long run is better diagnostics coupled with effective treatments or vaccines for HIV and a higher standard of living for those who live in underdeveloped countries.

  13. Kristjan and DDS, you’re both in the ballpark. 6-9 months of INH is now the standard therapy for ‘latent TB’, meaning that the person has been exposed to TB and carries the bacterium but doesn’t have an active infection. I suspect that’s the 2 billion referred to above. A much smaller number (10% sounds in the ballpark) develop ‘active TB’ which requires treatment with a 3 or 4 drug regimen for 4-6 months. That’s what requires DOT because TB develops resistance pretty easily, which is also why one drug is not reliably effective. (Interestingly enough, one drug seems to be sufficient for latent TB, but not active TB.) The big problem is that persons with the active form get under-treated, the bug develops resistance, and it is then spread around. Hence you get multidrug resistant TB strains becoming more common in some areas of the world.

    More info on US TB trends here. Don’t know about deaths, but there must be some.

  14. Carpus,
    I looked quite hard through the CDC and WHO websites and pubs for US deaths from TB. I couldn’t find any reported deaths, which does seem a little strange. I did find one note that people who have AIDs/HIV and die from TB are classified as AIDS deaths. I’ll try to find the reference again if anyone cares.


  15. phage, schmage.

    Is there really anyone serious in putting credence in a phage therapy for M.tb.?

    What’s the plan, aerosolized phage?
    and they get into to macrophages….how?
    and caseating tubercles….how?
    and then into lymph nodes….how?
    and the phage does what to metabolically inactive dormant cells in calcified nodules?


    IV therapy? and after two weeks, when IgG
    increases….you boost them with MORE? phage
    and exponentially increase Ab’s against the
    phage capsid proteins? then….what?

    Granted, phage therapy may find a use when sprayed on a cutaneous infection (i.e. – anti-Pseudomonal phage for infected burns) but this idea – at least 75 years old – is still a “breakthrough” in search of a verifiable cure. The Russians have been flogging the phage therapy horse forever – and it’s still in the barn.

    As for the “throwing drugs at them” antibiotic problems – the mutation rate to phage resistance is the same as the rate for abx. Might as well throw phage too, for all the good it will do.

    Ask the cheese industry about lactococci phages…. they are running on the phage resistance treadmill just as fast as those who fight antibiotic resistance.
    Every time they select a phage resistant starter culture, a new phage comes along that can turn 100,000 gallons of fermenting milk into cattle feed. Or their previously resistant strain becomes re-susceptible to a phage mutant – that turns another 100,000 gallons into hog-slop.

    nasty, slipperies, mutansy evolutions!

  16. DDS – TB infection is reportable, but I wonder if deaths from it are? I don’t know. The CDC may not have numbers on it for that reason. It might be in databases listing causes of death. I’ll try to take a look sometime.

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