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- [00:00]
Host 1
Welcome back to Run the List, a medical education podcast in internal medicine. As a quick disclaimer, this podcast is made for educational and informational purposes only and should not be understood as medical advice under any circumstances. Before we get to the show, a quick word on the sponsors for today's episode.
- [00:16]
Sponsor Representative
This episode is brought to you by Open Evidence. Open Evidence is a really incredible resource for people in medicine. It's an AI powered medical information platform that can help you answer clinical questions, provide high quality literature and and so much more. You can ask questions like what are the classic imaging findings for gout? Or tell me about the landmark trials in lupus nephritis. They recently partnered with the New England Journal of Medicine so they have access to their text, figures and tables within Open Evidence. It's free and unlimited for healthcare professionals, so I highly encourage you to go check it out. Go to openevidence.com to learn more. Welcome back to Run the List.
- [01:04]
Emily Gutowski
My name is Emily Gutowski and I have with us today Dr. Malika Madova, a hospitalist at Bellevue Hospital and clinical Assistant professor at NYU Langone. She completed a Global Health Fellowship and has a Diploma in Tropical Medicine from the Gorgas course in Peru. Malika, thank you so much for joining us today.
- [01:21]
Dr. Malika Madova
Thank you so much for having me.
- [01:23]
Emily Gutowski
Today we will be talking about the inpatient logistics of suspension, suspected tb, when to isolate, how to test, and next steps after someone tests positive. So this is a super important topic that comes up all the time, both in inpatient and outpatient medicine that I think generates a lot of confusion and could definitely benefit from some clarity. So let's get into our case. We have a 55 year old gentleman who presents to the ED with several weeks of fever, night sweats, malaise, cough and shortness of breath. He has a history of type 2 diabetes and he was recently treated at urgent care for presumed community acquired pneumonia in the ED. His vitals are a temperature of 100.8, heart rate of 102, blood pressure 128 over 82, respiratory rate 22 and his O2 set is 94% on room air. They get a chest X ray which shows an opacity in the left upper lobe and the ED team suspects non resolving community acquired pneumonia. They get a CT chest which shows that left upper lobe consolidation though with a few areas of cavitation. So Dr. Madhava, what about this case makes you think that it could actually be TB and not just run of the mill pneumonia?
- [02:34]
Dr. Malika Madova
Yeah. Thank you for the case. There's several features of this case that make me think that there might be something more than just your run of the mill community acquired pneumonia? The first is the duration of symptoms. He's been having symptoms for several weeks now, and the fact that it didn't resolve with typical CAP treatment makes me think that there might be something else. The factors of this case that make me think specifically about tb, or at least bring about some of the alarm bells for TB is the fact that he has left upper lobe consolidations with areas of cavitation. TB really does like the upper lobes because of how well they're aerated. And I would want to know more about exposures or histories in order to see if TB might be on the differential with his travel or background.
- [03:25]
Emily Gutowski
In general, thinking about risk factors for TB outside of this patient, what might some other features of a case be that should sound the alarms that this could be possible?
- [03:33]
Host 1
Tb?
- [03:34]
Dr. Malika Madova
So the exposure history is often the biggest factor. So if someone is from an endemic area, so a country where TB is endemic, or settings where there is a high burden of tb, like prisons or healthcare exposures, the other important factors in someone's history would be if they're immunocompromised. So particularly if they have HIV or they're on medication, medications that increase the risk of tb, like TNF alpha inhibitors. And then the other kind of category of things that I'm looking for are those more consumptive features on the clinical history. So constitutional symptoms, the duration. So often TB is a lot more indolent than other forms of pneumonia. And also some of the imaging findings like we already talked about, so the predilection for the upper lobes and potentially things like cavitation that might lead to hemoptysis.
- [04:25]
Emily Gutowski
So we learn a little bit more about this patient and his background. And he tells us that he recently spent a couple months in India with his family where a cousin of his had a persistent cough. He also mentions that he's lost a couple pounds over the past month or so, but he didn't really think much of this. He did have a positive PPD many years ago, but he was told that this was probably from his BCG vaccine as a child and never got further evaluation for it. So. So we have a reasonable degree of suspicion here based on his clinical history and his presentation as the admitting provider on the inpatient team receiving this patient. What are your initial steps here?
- [05:03]
Dr. Malika Madova
So anytime I'm suspicious for tb, one of the first steps is to place the patient on airborne isolation, basically because we're suspicious that tuberculosis might Play a role in this patient's presentation. We wanna protect both ourselves and other patients from potentially being exposed to tb. So if you have somewhat of a degree of suspicion, even if it's not high, the right thing to do is always to place them on precautions. And that way you are protecting everyone, taking care of the patient and around the patient.
- [05:35]
Emily Gutowski
Okay, so this patient is put on airborne precautions and now we start with diagnostic testing. So I think this is where a lot of confusion will often come up. I know there's sputum, there's blood tests, there's quant gold. How do we fit all of this together? What are our first steps in testing?
- [05:53]
Dr. Malika Madova
Yeah, great question. I have to admit, I was also confused about this when I was a trainee. And it took a lot of experience testing for TB in settings where it's much more endemic for me to become more comfortable with this. Basically, when someone comes in and you're suspicious of tb, I like to think about it as a TB workup as opposed to a TB rule out. Since we are suspicious and do want to try to identify the mycobacteria, there's a couple ways to identify whether mycobacteria is present or the cause of someone's pneumonia. The most common thing that we hear about is AFB smears. So basically what these are is it looks directly for the bacilli under a microscope and we basically have the patient expectorate. Sometimes it's hard to get them to produce sputum. So we can induce a sputum using hypertonic saline. And then once we get a sputum sample, we can stain it specifically for afb and then someone actually looks under the microscope to see if they see the acid fast bacilli. It's worth mentioning that the AFB smears are only about 60% sensitive for actual tuberculosis causing disease. And so it is by far not our most sensitive test. The more sensitive rapid test that gets you an answer relatively quickly is the gnat or nucleic acid amplification testing. It is another test that is run on the sputum sample that the patient expectorated. And this looks specifically for genetic material from tuberculosis. So what they do is they put it into a machine that makes millions of copies of any TB DNA that might be present in the sample until it's detectable. This is a really great way to tell if someone might have tb, because it also not only tells you if TB is present, but also if there is rifampin resistance, which can clue you into whether there's any drug resistance. In that TB sample. It also is relatively fast. It takes a few hours to run. But this might be dependent on the hospital or the system because sometimes it's a send out test and sometimes they only run it on certain days. Finally, the last test that we use to look for TB is the TB culture. This is much slower and I find pretty rarely actually leads to our TB diagnosis here in the States. Because it can take weeks for mycobacteria to grow on culture, it requires a specialized media. Often the Lowenstein Jensen media is what's used. This process of culturing often comes back once the patients have already been identified to have TB and started on TB treatment.
- [08:36]
Emily Gutowski
Thank you for taking us through that. That's very helpful. I think I mentioned before quantgold, maybe the word T spot sounds familiar as well. How do those tests fit in with active TB diagnostics?
- [08:47]
Dr. Malika Madova
Great question. Both the quant gold and the T spot are known as IGRA tests, which are basically interferon gamma release assays. And they're looking for the body's response to tb. So it's not actually looking for the mycobacteria or TB DNA, it's looking at whether our immune system has ever been exposed to TB in the past. It's worth mentioning that these tests are about 80% sensitive and 80% specific. So for every 100 patients with active TB, 20% of them will have a negative quant gold or T spot. And so it really is not sensitive enough for us to use in active TB or in suspicions for active TB because a negative test does not rule it out.
- [09:33]
Emily Gutowski
And just going back to what the patient told us, he had mentioned having a positive PPD many years ago. How do we understand that in this scenario?
- [09:42]
Dr. Malika Madova
So the PPD also looks for our body's response to the tuberculin antigen. The PPD stands for a purified protein derivative, and it's done by placing a little bit of tuberculin antigen under the skin and seeing how strongly we react to that antigen. Interestingly, the BCG vaccine can confound this because it acts as a similar sort of antigen as the actual TB mycobacteria does. And our body will create a very similar response to both. So the fact that the patient has had a positive PPD in the past does not help us distinguish whether he has actually been exposed to TV since he also was vaccinated.
- [10:25]
Emily Gutowski
Just a little bit more on the BCG vaccine. I know it's not routinely given in the United States, but where is it given and why in those countries? And not here.
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Dr. Malika Madova
The BCG vaccine is a preventative vaccine used to protect against tb, and it's recommended by the WHO in endemic settings for healthy infants shortly after birth. It is often used to help decrease the incidence of tuberculosis and tuberculous meningitis in kids. But it does tend to wear off as we get older, and it loses its protective properties over time.
- [10:57]
Emily Gutowski
Okay, so getting back to this patient's diagnostics, we've ordered three sputums for him to produce. What if a patient is unable to expectorate or produce these sputum samples naturally?
- [11:11]
Dr. Malika Madova
Yeah, great question. This is a clinical scenario we run into, not infrequently. The most common way that we get patients to produce sputum is actually through induction, which we already discussed. But if that's not working, or you have a patient who can't produce sputum, this comes up frequently in our pediatric populations as well. There's two main options. The first is to do a bronchoscopy with bronchoalveolar lavage and then test that sample both for AFB and nucleic acid amplification testing. The other main way that we get samples is through gastric aspirates. This is something that's used much more commonly in children because they tend to swallow their sputum. And this is a common way, even in low resource settings, that samples are obtained for AFB testing. So though it is worth saying that gastric aspirates have a much lower sensitivity than sputum samples do.
- [12:08]
Emily Gutowski
When, in the course of this diagnostic testing, would you notify various parties, including infection prevention at the hospital, maybe consulting id, maybe consulting polem. And I know at some point you also have to loop in the public health department. When do all those things happen?
- [12:25]
Dr. Malika Madova
Yeah, so usually as soon as there's concern for tb, having more teams involved is better. Usually the moment you put someone on isolation, the hospitals infection prevention and control department is notified. And so they should be involved. Right. As soon as you have suspicion for tb. Infectious disease is often also involved right from the beginning. Whenever there's a suspicion for tb, I find it really useful to loop them in in order to guide further testing and whether someone should be empirically treated if the testing ends up coming back negative. Since the whole idea with this is that we're working them up for TB because we do have suspicion for it. Involvement from PALM tends to be pretty institution independent. Here at Bellevue, our pulmonologists are very closely involved in our management of TB versus at other institutions. Sometimes they get more involved if someone actually needs a bronchoscopy or pulmonary assistance in obtaining the diagnosis, or if there's other things that are on the differential, that might also involve closer look from the pulmonologists. And then finally, as far as the public health department, this is very state dependent here in New York. Technically, any patient who has been placed on isolation for TB should be reported to the state department, because of course, again, we're suspicious for it, but in other states they are interested in knowing once TB is confirmed.
- [13:46]
Emily Gutowski
Okay, great. So we do all of these things and the first two sputum samples that the patient provides come back negative. The patient's family is asking if all of these isolation precautions can be loosened, what would you tell them?
- [14:00]
Dr. Malika Madova
This is something that comes up in clinical contexts often where even though the sputum comes back negative, that's often not enough for us to say that TB is not a causative factor. Here, again, especially in this patient, he has enough of a exposure history and a clinical course that makes us think that TB could be playing a role here. And so even if our sputums are initially negative, we do really have to take into consideration all of the information we have thus far. And here our suspicion is high enough that we would inform the family that the isolation precautions are here to stay in patients where the suspicion is lower. The policies for discontinuing isolation precautions are very hospital dependent. Typically you need three negative AFB smears. And again, these smears are only about 60% sensitive for tuberculosis. And so just having a couple negative smears doesn't mean that TB isn't what's causing our patient's symptoms. And then in most hospitals, you also need a couple of negative PCR tests as well. And again, these are actually more sensitive, about 90% sensitive. So the combination of having a number of negative smears and a few negative PCR tests can often point us away from TB being the diagnosis. But of course, if TB is still on, the differential, airborne precautions should be continued.
- [15:27]
Emily Gutowski
The family understands and they are fine with continuing precautions. So while we're waiting for his third sputum to result, can you briefly explain the difference between active and latent tb? Yeah.
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Dr. Malika Madova
So latent TB is basically the form of tuberculosis, where after someone is infected, their immune system does a good job of controlling it. By definition, patients with blatant TB don't have any active symptoms. The infection is completely contained, so it's not at all transmissible. This often comes up in our clinical scenarios. As an outpatient, when someone has a positive quant gold T Spot test or ppd, and then it's on the provider to determine whether or not there are any signs or symptoms of active tb. If there's no active tb. Determined to be playing a role here. So often we look for pulmonary disease on a chest X ray, but also you want to do a full review of systems, because only about 80% of active TB is actually pulmonary TB. And if they are completely asymptomatic and there's nothing on the chest X ray, then we would classify the patient as having latent TB. And if left untreated, latent TB has about a 5 to 10% conversion rate to active tuberculosis over a lifetime.
- [16:47]
Emily Gutowski
In my world as a rheumatologist, we often think about reactivation of TB whenever we're starting a patient on immunosuppressive medication. So we'll check a quant gold before starting anything like a TNF inhibitor or other biologics. But I know some other scenarios can also make latent TB reactivate. Basically anything that might immunosuppress the patient. Is that right?
- [17:08]
Dr. Malika Madova
Exactly.
- [17:09]
Emily Gutowski
Okay, so you were starting to get into this a little bit. But what forms of active TB are contagious?
- [17:16]
Dr. Malika Madova
Whenever we put someone on airborne precautions for tb, it's because we're worried that the tuberculosis or mycobacteria might spread from aerosolized particles. This really only happens in pulmonary or laryngeal tb. Laryngeal TB is worth a mention because it's extremely contagious when someone speaks. And TB can involve truly any organ. When people have other forms of tb, such as TB meningitis, TB lymphadenitis, or Potts disease, those actually are not in and of themselves contagious, but they are developed from hematogenous spread, often from pulmonary tb. And so in any patient where they have tuberculosis, we really want to make sure that they don't have pulmonary TB as well, since pulmonary TB is contagious and how TB is spread. And so in these cases, you would still isolate the patient and have them produce sputums and test the sputum for both AFB and pcr. But in those cases, if there's truly no signs of pulmonary tuberculosis, often we can discontinue the airborne precautions and treat them separately for tuberculosis where they do have disease.
- [18:30]
Emily Gutowski
One more question as we're waiting for our final result here. Oftentimes this is more in the outpatient setting, but sometimes we'll send a quant gold and it will come back indeterminate. So I know there's kind of two reasons why this could happen. Can you help us understand what to do with an indeterminate quant gold and why that could be.
- [18:49]
Dr. Malika Madova
Yeah. So the quantiferon gold test basically looks at the interferon gamma activity to the tuberculosis exposure. There's two reasons why the quantiferon gold might be an indeterminate. The first is if the patient's actual interferon gamma activity is high at baseline, the test cannot differentiate between the background interferon gamma activity and the response to tuberculosis. The opposite can also be true if someone just doesn't produce an interferon gamma response. And often this can happen in patients who are immunosuppressed. The test cannot identify any sort of response to tuberculosis.
- [19:29]
Emily Gutowski
So in those cases, I know sometimes we'll repeat a quant gold, sometimes it will be more definitive that second time around. And if it's indeterminate, again, you can send a T spot or sometimes use a PPD if the T spot is not definitive. Would you say that's correct?
- [19:43]
Dr. Malika Madova
Yeah, that's correct. The T spot actually uses a slightly different way of measuring interferon gamma, and so often it has far fewer indeterminate results than the quantiferon gold does. If your institution has the ability to send a T spot test as opposed to a quant gold, that could be an excellent next step. Otherwise you could consider using a ppd. But again, the PPD tends to cross react with other antigens.
- [20:08]
Emily Gutowski
Okay, so back to our case. Our patient's third AFB smear does indeed come back positive. What are our next steps here?
- [20:17]
Dr. Malika Madova
So in this patient, we already had a fairly high suspicion for active tb, and this would actually be a case where you were probably discussing already with ID whether or not we wanted to start empiric treatment. In light of the first few AFB smears coming back negative, the fact that his third AFB came back positive just cinches the diagnosis. And our next steps here are to make sure that everything up until this point has been done correctly, that the patient is in isolation, that the DoH has been notified, and that we are starting treatment even while we're waiting for more information about susceptibilities.
- [20:56]
Emily Gutowski
We're not going to get into the weed zone treatment on this episode, but can you kind of just give us a very, very rough overview of things to keep in mind when it comes to treatment?
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Dr. Malika Madova
Hopefully, if this patient's smear is coming back positive, we'll also have PCR testing coming back, and that can give us an early sense of whether or not this patient's tuberculosis is drug resistant. If he is drug susceptible tuberculosis, then classic treatment with ripe, which is rifampin, isoniazid, pyrazinamide and ethambutol would be a good starting point. This would be a decision that we make in conjunction with our infectious disease colleagues.
- [21:32]
Emily Gutowski
Got it. Okay. The patient also wants to know when can he tell his friends and family that he's no longer infectious?
- [21:39]
Dr. Malika Madova
Yeah. So this is very dependent on the case. This patient actually has cavitary disease which tends to have a much higher infectious burden than non cavitary disease. Often, at the very minimum, we need patients to be on two weeks of therapy before they can be taken off of isolation. But likely in this patient, we'll be repeating AFB sputums and PCR testing in order to see when he stops producing AFB in the sputum. And at that point we might consider discontinuing isolation.
- [22:11]
Sponsor Representative
Okay.
- [22:11]
Emily Gutowski
Dr. Madhava, you have been so incredibly helpful in teaching us how to understand in whom to suspect tb, what are first step should be and getting patients started with diagnostics and treatment, if appropriate. So thank you so very much for joining us today.
- [22:27]
Dr. Malika Madova
Thank you so much for having me.