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Charles: This is Charles Prober. Morgan: And I'm Morgan Theis. Charles: And we're going to talk about the prevention of tuberculosis. There are I's, four I's to consider in preventing TB infections. One I stands for "Intensified case finding." We'll come back to that, but finding cases of TB. When we talk about that, we'll talk about finding cases of latent TB and what we can do about it and finding cases of active infection and what we can do about it. Morgan: OK. Charles: The second of the four I's is "Isoniazid" or INH, an important anti-tuberculose drug that, in the context of this video, we're going to talk about its use in the treatment of latent TB. Morgan: OK. Charles: The third I is "Isolation," and that we're going to talk about in the context of an actively infected patient, a patient that may be infectious to others and how we can prevent the spread of their TB to other people. Morgan: This is a very good infectious disease principle, right? Charles: Right. you want to isolate the person from spreading it. Charles: For many, that is absolutely true. And then the fourth I is "Immunization." Morgan: OK. Charles: What vaccine we currently have available for the prevention of TB and perhaps what's on the horizon. Morgan: OK. Charles: Starting with the first I, "Intensified case finding," mentioned at the onset that we're either looking for latently infected people, people with a positive TB skin test, for example, or looking for cases of active TB. First of all, thinking about those who may be latently infected with TB or actively infected, there are certain high-risk populations that we always have to keep in mind. For example, persons immigrating, moving from a country that's got a high level of infection with TB, such as in many of the countries in Sub-Saharan Africa, moving to another part of the world that has a low level of TB infection, such as North America, the United States or Canada. Another high-risk population, similar, are migrant workers from highly endemic areas. Another high-risk population are prisoners, especially in the United States. The homeless population have a high risk of tuberculosis. Individuals who abuse drugs intravenously, IVDU, intravenous drug-using individuals, have a high risk of TB. And those co-infected or infected with HIV have a high risk. These would be individuals that we would be screening with a tuberculose skin test, for example, on a regular basis. If we find them to be positive on that test, that is, to be latently infected with TB, this leads us to the second I, which is "INH." Treating these latently infected individuals with isoniazid is a very effective way of reducing the likelihood that the latent infection will become an active infection. INH is about 90% effective in reducing infection. The prescription of INH is for a 9-12 month period. Morgan: Whew! Charles: It is a long time, that's correct. But with that 9-12 months of treatment, you reduce infection developing. There are some alternatives to INH alone, but the alternatives tend to be a little bit more toxic, have more side effects. One example of an alternative is to give INH with rifampin for 4 months or rifampin with pyrazinamide (PZA) for 2-3 months. These combined therapies seem to be almost as effective as INH alone for 9-12 months but not quite, and they also are more toxic. Morgan: OK. Charles: So again, the second I is INH. Morgan: Now, once you start treating someone who has latent TB with INH, how long before they stop being infectious? Charles: They're not infectious to begin with, so if they have latent TB, they're not infectious. The idea of treating them is so that they don't develop active TB. Morgan: Which would be infectious. Morgan: OK. Charles: And in fact, let's stay with this intensive case finding and go down the active TB pathway. Many persons with active TB are infectious for other individuals. There are some that are much more infectious than others. For example, if you've got pulmonary TB, the most common site of infection with TB, and that pulmonary TB is cavitary, so there is a big cavity on the chest X-ray, the likelihood is that that's teeming with TB organisms, that is, there is a lot of them, and they may spread to other individuals quite readily. With those kinds of infectious individuals, they must be isolated, which is our third I. Morgan: Right. Charles: They must be isolated so they cannot spread infection to others. What isolation typically means is they're put into a single hospital room with protected airflow, and any visitor to that hospital room wears a mask that filters out TB organisms, typically called an N95 mask. And then of course, the person with active TB is treated for their infection, and usually, in about 2 weeks, 3 weeks, or 4 weeks, they become non-infectious. That is, their anti-tuberculose therapy reduces the amount of TB organisms they have present, so they're not infectious anymore. So then they can come out of isolation and go back into their regular home life. Morgan: And is this treatment just going to be the same, just using INH, or that's a more intensive regimen? Charles: It's a more intensive regimen, and we're going to have a video or two about different treatment options. The other thing to say about those with active TB in terms of the intensified case finding is when you find somebody with active TB, you must do contact evaluation as well. You want to look to all the individuals that they may have been in contact with before they were diagnosed because in doing so, you may discover other cases of active tuberculosis that also need to be managed with treatment, isolation, and so forth. Morgan: So you're looking for their contacts for evaluating? Charles: Exactly. You're looking for where they got the infection potentially or to whom they already spread the infection. That's a very important public health effort to reduce the continued spread of tuberculosis. The fourth and final I with TB prevention is "Immunization." Morgan: OK. That would be great. Why don't we just immunize everybody against TB and we won't have a problem? Charles: And that would be great if the vaccine were highly effective, which unfortunately, the current vaccine available worldwide has some effectiveness, but it's limited. That vaccine is called BCG, all capitals, and it's a live attenuated vaccine derived from Mycobacterium bovis, which is another kind of tuberculose agent, M.bovis. It's a vaccine which is administered in many parts of the world that have high rates of tuberculosis to try and prevent the spread, to try to prevent the individuals from acquiring TB and then spreading it. The immunization is typically given around the time of birth, with BCG. The degree of effectiveness of the vaccine varies widely from study to study, ranging from a low of 0% to a high of about 80%. Most use the estimated protective effectiveness of about 50%. It turns out that the vaccine is especially effective, when it's effective, when given to children, and that's why it's administered around the time of birth. Morgan: OK. Charles: And the reduction in TB is especially evident for severe disease. It seems to reduce the likelihood of getting very severe disease, including TB meningitis and miliary TB. That's important because that's the worst kind of tuberculosis. But again, its effectiveness is limited, as I had mentioned. Now, because this vaccine is live and attenuated, there are also some risks that you can get from vaccinating a large number of individuals. If you inadvertently vaccinate somebody who's got an immunodeficiency, their immune system isn't working very well, their vaccine site can become quite necrotic, and they can even disseminate the BCG. You can have an infection arising from the vaccination. That's fortunately not way common, but it does occur. In just normal individuals, that is, those who do not have any immunodeficiency, it's estimated that somewhere between 1 and 10% will get a little ulcer at the vaccine site, and you can see this little crater in their arm over a long term, and that sort of says, "Oh, this person's had BCG vaccine." Less commonly, beyond the ulcer, you can get some local adenopathy, lymph node swelling around the area where the vaccine's been given, for example, in the armpit, and very rarely, maybe one in a million cases, you can get osteomyelitis, a bone infection, from the BCG vaccine. These are all quite uncommon and unbalanced. BCG vaccine is more useful than not, and that's why it's given. Then the final thing I mention about immunization is there is a lot of interest and work in developing new vaccines for tuberculosis that would be more effective, of course, and with less side effects. There are probably about 30 new vaccines under development, but unfortunately, at this point, none of them have been found to be so beneficial as to be licensed for widespread use. But stay tuned. We hope to have a vaccine against tuberculosis that's more effective sometime in the future.