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The Threat of Drug-Resistant Tuberculosis
Dr. Neil W. Schluger's main area of academic interest has been in tuberculosis, including clinical trials, molecular epidemiology, development and evaluation of diagnostics, and human host immune responses. He is the principal investigator at Columbia University for the Tuberculosis Trials Consortium, a CDC-funded collaboration in clinical trials in which patients are enrolled in trials of treatment of latent tuberculosis infection and active tuberculosis disease. In addition, Dr. Schluger has led studies examining the transmission dynamics of tuberculosis in New York City, using tools of molecular epidemiology. He has a long standing interest in the development and evaluation of new tools for the diagnosis of tuberculosis.
More recently, in addition to his studies in tuberculosis, he has led clinical trials for the use of retinoids in the treatment of emphysema and for the use of interferon gamma in the treatment of idiopathic pulmonary fibrosis.
Question: What is XDR-TB?
Neil Schluger: So the really frightening thing about multidrug-resistant TB and extremely or extensively drug-resistant TB, XDR, I think is that we don’t really know how prevalent it is. We know that drug-resistant tuberculosis now has been seen in all regions of the world and these extensively drug-resistant cases have also been observed in most parts of the world. We have a patient we’re treating in our clinic in New York who has that sort of an unusual case. In general, in New York and in the United States extensively drug-resistant tuberculosis is not much of a problem. In New York City last year there were only nine cases of multidrug-resistant TB, much less extensively drug-resistant TB, so at the moment it’s not much of a problem in the U.S. but around the world it clearly is. In Russia and countries in the former Soviet Union as many as ten, 15 or 20% of cases can be multidrug resistant and then some of those are extensively drug resistant. In Africa we have very little idea because most African countries don’t have enough money to do cultures of TB and do drug-susceptibility testing on a routine basis so we don’t really know. If you look at the WHO’s map of XDR-TB, most of Africa is just this big blank because we don’t know, and to me that’s one of the most frightening things. Our inability to get sophisticated diagnostic testing in to places where TB is most common really prevents us from knowing exactly how bad this situation is so that’s worrisome. And then of course the other worrisome aspect is for people with XDR-TB essentially we have no treatment. Drug development for economic reasons as I mentioned earlier has really lagged and if someone comes in with XDR-TB it’s sort of throw the kitchen sink at them and hope something works.
Question: How did tuberculosis become drug-resistant?
Neil Schluger: So drug resistance in tuberculosis usually comes about because of erratic administration of medicine or erratic use of medicine. Tuberculosis has to be treated with multiple antibiotics and they really have to be taken all together in a very precise schedule and if that falls apart, if patients don’t take their medicine just the way they need to, then drug-resistant strains will predominate. They’ll sort of out-compete the drug-sensitive strains and you’ll develop drug-resistant TB so most of the time when we see drug-resistant TB it’s a reflection that the local TB control program somehow is not doing a great job of getting the right patients to the- the right medicines to the patient and getting the patients to take them in the right way. Once you’ve sort of created this reservoir of drug-resistant cases though then they just spread in the usual way that TB spreads. Someone with drug-resistant TB starts coughing next to someone who is healthy and the next thing you know that person’s infected with drug-resistant TB. So it starts because of sort of poorly functioning TB control programs where patients somehow are not getting the message that they need to take their medicine in a particular way, and then it just starts to spread around to vulnerable people.
Question: How big of a threat is it in the U.S.?
Neil Schluger: So multidrug-resistant tuberculosis cases in the United States have been pretty steady at about 1% of the most of all TB cases for the last several years and in fact in New York City in 1992 about 16% of all cases of TB were multidrug resistant and as I mentioned last year that went down from 400 cases to nine. So at the moment we’re doing quite well I think in MDR-TB. The danger is that as budgets everywhere are being cut people will say, “Oh, TB’s not much of a problem anymore. We don’t need to fund the TB control program nearly as much as we’ve been funding it,” and clinics will close and TB services will be dismantled and then we’ll get behind the eight ball. That’s what all of us are worried about. That’s what happened in the ‘70s and early ‘80s. People thought TB had went away, the money was taken out of TB control programs, and the next thing you know, “boom,” there’s a huge TB epidemic. So I think in the United States at the moment we’re doing well with drug-resistant TB by and large. The cases that come in mostly come in from outside the United States. We have the capacity to diagnose them and treat them but we need to be vigilant about our TB control program budgets.
Recorded on: 04/25/2008
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