Effect Measure

A hundred years ago Sir William Osler described acute pneumonia as “The Captain of the Men of Death,” a phrase he remembered from John Bunyan’s The Life and Death of Mr. Badman (the actual phrase is “Captain Consumption, with all his men of death”). In 17th century England it was indeed “consumption,” an older term for tuberculosis, which deserved the rank in Death’s Legion, and the day may come again when it will come out of retirement to lead a new regiment against us. Beginning in the late 1940s tuberculosis began to recede from the consciousness of the industrialized West, and now it is an infrequent but manageable disease. Mostly. But it still ravages the developing world and WHO estimates 8.8 million new cases a year (2005 data), 1.6 million deaths (about one person every 20 seconds). 195,000 also had HIV infection. None of that is good news, but if there was any good news it was that we did have drugs that could manage and control the disease. Did.

Because now we have drug resistant TB. Yes, we’ve had TB resistant to many of our first line drugs for a long time. That was multidrug resistant (MDR- TB). Now we have TB resistant to our second line drugs. That’s Extensively Drug Resistant TB, or XDR-TB. (The technical definitions: MDR-TB is resistant to isoniazid and rifampicin; in addition, XDR-TB is resistant to at least one of three injectable second line drugs (capreomycin, kanamycin, and amikacin). Of the 8.8 milliion new cases how many are XDR-TB we don’t know because most places where it occurs don’t have the laboratory capacity to diagnose it. We know it has been reported in 37 countries, including the US, and WHO’s estimate is about 27,000 new cases a year. Even when treatable, the drugs are expensive and treatment lasts up to two years requiring constant compliance.

WHO’s estimate of XDR-TB’s case fatality ratio is 50%, but when combined with HIV it is almost always fatal (CFR greater than 90%).

“The global concern is . . . we will face untreatable TB,” [Dr. Karin Weyer, of the tuberculosis research and policy unit of South Africa’s Medical Research Council] said.

“It’s like TB in the ’20s,” [Emory University’s Dr. Ruth] Berkelman said of that possibility, though she admitted with increased population density, global travel and HIV-AIDS, the problem of untreatable TB would actually be more complex in the 21st century. (Helen Branswell reporting for Canadian Press)

Our interest here in bird flu has been to use it as a lens for looking at public health. We could as easily have used XDR-TB wbich has been likened to bird flu in slow motion. Which is worse, bird flu or XDR-TB?

They are both bad. Really, really bad.


  1. #1 Mathematician
    May 25, 2007

    Could you talk about vaccination and XDR-TB (either now, or some time)? I’m puzzled about it. Q11 in the WHO FAQ list:
    dismisses BCG (with a bogus “therefore” by the way). OK, so BCG isn’t good enough. But doesn’t TB, unlike flu, change rather slowly – witness the fact that we only expect to vaccinate once, not every year? And doesn’t it follow that developing better vaccines, which would protect against XDR-TB (at least if given in childhood), should be relatively straightforward, at least compared to the flu pandemic vaccine problem? If not, why not? What’s going on in the TB vaccination field?

  2. #2 revere
    May 25, 2007

    I think the main question is how effective BCG vaccination is, i.e., does it protect the person. There is controversey about one of the main objections, that BCG prevents later easy diagnosis via skin testing. I haven’t reviewed this for ages. Maybe someone else wants to weigh in?

  3. #3 dmk
    May 25, 2007

    Many countries either did or still do give BCG to infants/children. The only use in this country has been with infants in the specific situation of living with someone (mother, etc) who has active TB. There isn’t a belief in the efficacy of BCG in this country (which makes the above administration interesting). According to the CDC, the vaccine wanes. So if a TB skin test is given to someone who received the vaccine years before and the results are positive, that person is treated (CXR with meds depending on result). Please note that this is according to the CDC.

  4. #4 anon
    May 26, 2007

    > 8.8 million new cases a year (2005 data),
    > 1.6 million deaths
    > Our interest here in bird flu has been to use
    > it as a lens for looking at public health.
    > We could as easily have used XDR-TB wbich
    > has been likened to bird flu in slow motion.
    > Which is worse, bird flu or XDR-TB?
    > They are both bad. Really, really bad.

    I calculate that you estimate the probability of a
    1918-like (or worse) pandemic as less than 2% per year.

  5. #5 revere
    May 26, 2007

    anon: No. I don’t estimate a 1918 pandemic as less than 2% per year. I don’t have an estimate. I don’t know. You are mistaken.

  6. #6 Marissa
    May 26, 2007

    Revere, being English I had the BCG in my early teen years. About 25 years later had a routine test for TB–can’t think why–and the test came up ositive. Was started on isoniazid before I remember having the shot, so in my opinion the vaccine till has some effect. Whether it will give protection against XDR is anyone’s guess.

  7. #7 wenchacha
    May 27, 2007

    La la la. I’m not worried in the least. I’m just going to have some nursing wallabies on hand Crikey.


  8. #8 revere
    May 27, 2007

    Ah, yes. I saw this a few weeks ago. Of course the key word in all this is “preclinical.” Until it’s tested and shown to work in humans, I will use wallabees as shoes.

  9. #9 Melanie
    May 27, 2007

    Also note that the article says that the milk compound is anti-bacterial, not anti-viral.

  10. #10 wenchacha
    May 27, 2007

    Preclinical? Anti-viral???? Drat!

    I will have to rethink my grand opening of the Miracle Wallabee Ice Cream stand. And it was such a sure winner.

  11. #11 Kristjan Wager
    May 28, 2007

    I wrote a little about the same subject back in march.

    One thing I think is worth noting is that there haven’t been any new approvals of TB drugs in 40 years, and the tests used are the same tests used in 1882. New research on the disease is desperately needed.

  12. #12 Machi
    May 28, 2007

    TB is a most insidious and patient enemy. It holds an immense army in reserve: A key number not mentioned above is that ONE-THIRD of the world’s population is latently harboring the bacilus. It silently waits for other diseases or conditions to weaken the immune system and then it kicks you while you’re down.
    Important to remember also that MDR-TB and XDR-TB are creations of our inept medical systems, which see no profit in the poor and destitute who make up most of TB’s victims. I’ve seen physicians prescribe monotherapy, simply add another drug to a failing regime, call into doubt laboratory findings and stop therapy, etc. We often talk about ‘patients abandoning treatment’ when what we really mean is that the ‘treaters abandon patients’.
    Important progress has been made by proactively instituting directly observed therapy with a creative array of community participants, fixed dose combined therapies for regular TB, national protocols backed up with enforcement, and competent labs with quick and easy access & reporting.
    Skin testing is essentially useless in developing countries (first- most everybody is positive anyway, and, second- its requirements for timing and technology are more of a challenge than simple sputum microbacteriology), but the BCG at birth does prevent disseminated forms of TB that would otherwise kill many children.
    A great infusion of money for TB has taken place over the last 15 years. Perhaps it will come up with a faster lab test, capable of use in the field, that will identify the bug AND its resistance profile at the same time.
    But even that will be useless unless our medical systems can mount their own army of patient, consistent and dedicated workers.