Effect Measure

TB but not the TB they thought

It now turns out that the XDR-TB case which caused such an uproar last month (see our posts here) wasn’t XDR-TB at all but MDR-TB, a treatable form of the disease:

Andrew Speaker was diagnosed in May with extensively drug resistant TB, based on an analysis of a sample taken in March by the U.S. Centers for Disease Control and Prevention. The XDR-TB, as it is called, is considered dangerously difficult to treat.

But three later tests have all shown Speaker’s TB to be a milder form of the disease, multidrug-resistant TB, a federal health official said on condition of anonymity before a news conference in Denver. (Washington Post)

Just to be clear. His TB isn’t milder. MDR stands for “multiple drug resistant” while XDR is “extensively drug resistant” (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). MDR-TB isn’t a good thing to have, but it is treatable. XDR-TB often isn’t. So getting the diagnosis right is not just important, it’s a matter of life and death. He was diagnosed with MDR-TB, for which he was under treatment, before he left for Europe. The “discovery” that it was the XDR form came after he was there. At that point there is evidence of confusion if not panic at CDC, where the supposed diagnosis was made on the basis of laboratory tests.

But three later tests have all shown Speaker’s TB to be a milder form of the disease, multidrug-resistant TB, a federal health official said on condition of anonymity before a news conference in Denver.

[snip]

“Laboratory tests conducted at National Jewish Medical and Research Center indicate that patient Andrew Speaker’s tuberculosis is susceptible to some of the medication previously thought ineffective against his disease,” the hospital said in a written statement.

An about-face on the XDR diagnosis would be a major embarrassment for the CDC. The diagnosis was a key factor in issuing a quarantine order on Speaker, who had traveled to Greece to be married in May despite warnings from health officials that he shouldn’t travel.

On Tuesday, the CDC did not immediately clarify whether they were wrong in the earlier diagnosis or whether there are two conflicting results.

The failure to allow attribution by the unnamed “federal health official” suggests this is a CDC screw-up and they know it. Maybe not. Information and transparency from CDC would be useful. It is more evidence that things are not well at the agency, however. CDC has a powerful brand name as the most expert “disease detectives” in the country, if not the world. But under Director Gerberding much of that expertise has left, leaving a remnant and beleaguered cadre of dedicated professionals to fend for themselves amidst an institution crumbling around them.

What a pity.

Comments

  1. #1 Path Forward
    July 4, 2007

    Here is a feeble effort to fine-tune some of the excellent comments in your post, “TB but not the TB they thought.”

    Although you later clarify your first statement (“a treatable form of the disease”), that statement and much of the current media coverage may contribute to an impression that MDR-TB is more treatable than it actually is. Here is what CDC Director Julie Gerberding said about MDR and XDR cure rates in her March 7 testimony to Congress:

    “The [MDR-TB] cure rate is 70-80 percent under optimal conditions, but is usually closer to 50 percent. Among non-HIV infected persons, reports indicate that less than 30 percent of [XDR-TB] patients can be cured, and more than half of those with XDR die within five years of diagnosis.” –quote from Julie Gerberding testifying to the House Committee on Foreign Affairs at a March 7, 2007 hearing entitled “Extensively Drug Resistant TB: CDC’s Public Health Response” [link: http://tinyurl.com/ypefns

    You also define XDR TB as "in addition [to resistance to isoniazid and rifampicin], XDR-TB is resistant to at least one of three injectable second line drugs (capreomycin, kanamycin, and amikacin)”.

    Please note that by definition XDR-TB is also resistant to any fluoroquinolone (the class of drugs to which Cipro belongs), an important class of drugs for treating MDR-TB.

    You state that Speaker was “under treatment for MDR-TB before he left for Europe.”

    Actually, although he was told on May 10 that he had MDR-TB, treatment was not started until he arrived at National Jewish Hospital in late May. At the time he was told he had MDR-TB on May 10, drug-susceptibility testing of his TB culture sample was still not complete — it was known that his strain was resistant to the first line drugs he’d previously been on, but it was not yet known what drugs would kill his strain.

    You write: “An about-face on the XDR diagnosis would be a major embarrassment for the CDC. The diagnosis was a key factor in issuing a quarantine order on Speaker”.

    I agree that there is much for CDC to be embarrassed about — including CDC’s unconscionable scapegoating of Speaker, when much of the blame for Speaker’s behavior should be placed on the Fulton County Department of Health (blame which CDC is surely placing behind the scenes), and on the way CDC handled contacts with Speaker when he was in Rome.

    But it is not true that “the [XDR] diagnosis was a key factor in issuing a quarantine order…”

    The quarantine order was primarily based on CDC’s fear that Speaker might be more infectious than the Fulton County Health Department thought he was. Note that Speaker was isolated by New York City; he was and still is isolated by National Jewish Hospital; but he was not isolated in any shape or form (advice, suggestion, recommendation, order) by the Fulton County Department of Health, despite unchanging clinical and smear status (and unrelated to the issue of “MDR vs XDR”).

    Isolation policies do not distinguish between MDR and XDR TB, as far as I can tell. But they are usually much more stringent than for “regular” TB with similar clinical and smear status — in some states, requiring negative cultures for release of MDR patients from isolation, for instance.

    CDC wanted to stop Speaker from traveling home from Rome because such a flight would trigger twice as much contact tracing responsibility (and additional embarrassment) for CDC under the WHO air travel recommendations (http://tinyurl.com/yv2g2m).

    The WHO recommendations do not mention the term “XDR-TB”. XDR-TB is a subcategory of MDR-TB, for the purpose of interpreting the WHO recommendations, which include algorithms for contact tracing in a situation presented by a traveler like Andrew Speaker, with culture-positive MDR-TB:

    “People known to have infectious TB must not travel by
    public air transportation until at least two weeks of
    adequate treatment have been completed. Patients with
    MDR-TB should not travel until they have been proved to
    be non-infectious (i.e. culture-negative).”
    From: WHO Tuberculosis and Air Travel: Guidelines for Prevention and Control, 2006.

  2. #2 revere
    July 4, 2007

    PF: Thanks for the helpful clarifications and corrections (some of which pertain to the not very good WaPo pull quote; there was a lot there that needed comment and I didn’t do a thorough job so I’m glad you did). My def. of XDR and MDR was verbatim from CDC. WaPo reported (not me) that the XDR diagnosis was the linchpin of the isolation order, and I don’t have any other info on that but I know you do, so it is useful to have your input. The idea he was already under treatment for MDR TB, however, came from me and from what you say this is incorrect, which I accept. No TB infection is good, as I noted. With drug sensitive and MDR TB, at least, there is a decent chance of bringing it under control. But it is still a lousy disease. But even MDR TB has to be kept in perspective because it is too easy to react to it in a way that is socially destructive and inhumane. This means it is a trade-off. Locking up every TB case would be the safest thing to do jsut on the basis of preventing disease transmission, but the costs of all kinds are prohibitive. So the treatability differences between MDR and XDR start to become very important, at least that is how I see it. It is a subject that needs much more discussion, however, and I have an open mind about it — I think.

    The CDC issue to me is that they were confused, issued mixed messages and seemed to panic. This is an agency that no longer has its act together. I recognize that in a fast breaking situation mistakes can happen. If this were an agency running smoothly at the top of its form one would be more likely to say just that. But it isn’t.

  3. #3 Path Forward
    July 4, 2007

    Hi again.

    I think you are using an older CDC definition of XDR-TB.

    The CDC cites the March 2006 definition (which you use above) — and then updates it — in the November 3 2006 edition of the MMWR: http://tinyurl.com/2zmh3c

    CDC’s November 2006 definition of XDR-TB is:

    “Accordingly, the new agreed-upon definition of XDR TB is the occurrence of TB in persons whose M. tuberculosis isolates are resistant to isoniazid and rifampin plus resistant to any fluoroquinolone and at least one of three injectable second-line drugs (i.e., amikacin, kanamycin, or capreomycin).”

    Obviously, these types of issues are moving targets (surprise, surprise) — which should be acknowledged regularly to minimize the kind of pendular journalism we are seeing now.

  4. #4 revere
    July 4, 2007

    PF: Ahhh. Got it. Thanks.

  5. #5 M. Randolph Kruger
    July 4, 2007

    So boys, PF and Revere. Is Speaker infectious or not? Those are CDC guidelines you a citing PF and straight from the book no less. I dont think they have the authority except under the Surgeon General’s laws that date back I think to the 1900′s to detain him.

    So the question was and is did the dummy get onto a plane knowing that he was infectious, or was it that “I dont recall Senator” stuff we have been getting? Certainly he knew he had TB before he left and common sense said uh, no cant, aint, wont, go because I “might” endanger other people. Thats my big rub with this guy. I would have gotten onto a plane with him if he was masked up.

  6. #6 revere
    July 4, 2007

    I’ll await a more in depth treatment. Right now there are conflicting reports. My impression is that he was given the idea he wasn’t a danger to others (which is the most likely thing, although I’m not sure anyone could say this one way or another with great confidence) and I gather that is what the recording shows but I may be wrong. It appears this was a cock up from the get go, probably with plenty of blame to go around. But CDC isn’t supposed to make mistakes like that and it isn’t supposed to be unconscionably scapegoating, as PF put it. No one is going to look good from this. That’s a change, though. Before it it was only Speaker that looked bad. Now he has company.

  7. #7 Paul Todd
    July 4, 2007

    The man has a wife and a child, and he was not advised to avoid close contact with them, so why would anyone think he would be more of a danger to someone in an airplane, sitting next to his wife, especially when he had no symptoms of the disease.

    Active TB is a relatively low infectious disease as is, but if you are not coughing and have a negative sputim test, as Speaker was, infectiousness is even lower if not nil.

    From CDCs yellow book:

    “The risk of TB transmission on commercial aircraft remains low (6). The number of air exchanges per hour in airplanes exceeds the number recommended for hospital isolation rooms. Contact investigations for persons exposed to TB during air travel are limited to situations in which the index case is believed to have been highly infectious (e.g., AFB smear-positive with cavitary or laryngeal TB) during travel AND when other passengers have had >8 hours of exposure to the index case, have taken more than one trip with the index case, or when ventilation on the aircraft has been restricted (7).”

    Speaker was X-Rayed in January for a rib injury, and TB diagnosed by the end of the month, at which point he was started on the standard drug regime. He had no symptoms of disease, and his sputim smears were negative. They had to do a bronchoscopy to get any of the bugs to culture and run drug resistance tests on. Again, all indications are he was not very infectious.

    By May he was told his TB was resistant to some of the drugs, and was told this in a meeting with his physicians and his wife and no one was wearing a mask, another clue as to how infectious his doctors thought he was. He was told it would take another 2-3 weeks for additional test results, and was not asked to restrain or limit his contacts with anyone, but was advised not to travel, presumably because patients diagnosed with TB are at highest risk from going on to have active TB in the first 2 years. His chest X-Rays from January through May actually showed improvement, suggesting either his immune system was holding it in check and/or some of the 4 drugs he was on were working.

    This information is from the transcripts of his interview with Larry King.

    The question is, what prompted the CDC to intervene in this case. Couple of facts:

    The US had 13,767 cases of TB in 2006. The lowest rate since records have been kept (1953). TB rates have been in decline every year since 1993. Only 5-10% of those with TB go on to get active TB, the highest risk is in the first 2 years of infection and later in life when your immune system is compromised due to age, disease, etc.

    Most of those diagnosed are either foreign born, black or hispanic. For American black or hispanic I suppose this is due to they live in an urban environment and may be less well off. They do not say what percentage are illegal immigrants, but the leading country of foreign born TB in the US is Mexico.

    So why is it that the CDC chooses this case among the 13,000 plus cases per year, and uses it to exercise their isolation powers for the first time in over 40 years for a healthy, asymptomatic, medically insured white male diagnosed with TB that was certainly not very infectious, if infectious at all?.

    Certainly the XDR diagnosis was a factor, but XDR TB is not anymore infectious than regular TB, and any TB is an undesirable outcome.

    Dunno, but one week after the Speaker case became news legislation was introduced to fight TB and give the CDC up to 300 million, replacing some of the the CDC budget cuts in the Bush years.