Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders With Dr. Avindra Nath
Show notes
Advances in immunotherapies for multiple sclerosis and related disorders have increased the risk of infections and raised important questions about vaccination efficacy. This episode reviews infection risks across treatment classes, emphasizes the importance of monitoring and patient education, and discusses optimal vaccine timing to preserve protective immune responses.
In this episode, Aaron L. Berkowitz, MD, PhD, FAAN, speaks with Avindra Nath, MBBS, FAAN, coauthor of the article "Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders" in the Continuum® April 2026 Multiple Sclerosis and Related Disorders issue.
Dr. Berkowitz is a Continuum® Audio interviewer and a professor of neurology in the Department of Neurology at the University of California, San Francisco, in San Francisco, California.
Dr. Nath is the chief of the Section of Infections of the Nervous System at the National Institute of Neurological Disorders and Stroke, National Institutes of Health, in Bethesda, Maryland
Additional Resources
Read the article: Infection Risk and Vaccine Considerations in Multiple Sclerosis and Related Disorders
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Social Media
Host: @AaronLBerkowitz
Full episode transcript available here
Dr Berkowitz: Over the last decades, there has been a revolution in the treatment of multiple sclerosis, neuromyelitis optica spectrum disorder, and other immune-mediated neurologic conditions with countless new, highly effective medications. However, with every new treatment comes new risks; and in the case of immunomodulatory therapy, many of those risks relate to infection. Today, I have the privilege of talking with an expert on this topic, Dr Avindra Nath, about the infectious risks of treatments for multiple sclerosis and other immune-mediated neurologic disorders.
Dr Jones: This is Dr Lyell Jones, Editor-in-Chief of Continuum. Thank you for listening to Continuum Audio. Be sure to visit the links in the episode notes for information about earning CME, subscribing to the journal, and exclusive access to interviews not featured on the podcast.
Dr Berkowitz: This is Dr Aaron Berkowitz, and today I'm interviewing Dr Avi Nath about his article on vaccine considerations and infection risk in multiple sclerosis and related disorders, which he coauthored with Dr Amit Bar-Or. This article appears in the April 2026 Continuum issue on multiple sclerosis. Welcome to the podcast, Dr Nath, and could you please introduce yourself to our audience?
Dr Nath: Thanks very much for inviting me to this podcast. I'm absolutely delighted to have the opportunity to discuss our areas of interest and expertise related to infections and vaccinations for MS patients. My area has been studying the infections of the nervous system since the beginning of the AIDS pandemic, and over the years and decades, we've developed expertise related to various types of CNS infections. That includes ones that are developing in individuals who have immune compromise due to a variety of different reasons.
Dr Berkowitz: Fantastic. Well, glad to have the opportunity to speak with you today. When I was in medical school---and you were my attending, actually, we were just reminiscing, which we probably think was not that long ago, but is now over twenty years ago---there were just two medications for MS, right? Beta interferon and glatiramer acetate. And now we have over a dozen, and it's amazing to think of all the progress in these last two decades, as well as for related diseases like NMO. I don't think we even had the aquaporin-four biomarker, right, when I was working with you as a med student in the early 2000s.
Dr Nath: And that certainly dates me a lot.
Dr Berkowitz: Both of us.
Dr Nath: Yeah.
Dr Berkowitz: Of course, with all these new treatments, these have been amazing advances for our patients, right? But these come with new treatment-related risks to monitor for with the immunomodulatory medications for MS and related disorders. And one of those most important risks is that of infection. So, your article reviews the potential infectious complications of medications used to treat MS, NMO, etc, and also covers considerations related to thinking about vaccines in this patient population. So, as the MS treatment landscape grows, I can say as a general neurologist, keeping up with all these medications and what to screen for and what to worry about and when to vaccinate just becomes more challenging every year. And your article has so many helpful tables, some organized by medicine, some organized by- sorry, medication, some organized by infection, some by vaccines. So, this is gonna be a great resource for our providers to print out and tape up in their clinic rooms. We won't be able to get into all the depth and detail that you have in this article today, but I do want to focus on some of the key points here related to the common medications we use for MS and which infections to think about and which vaccine considerations we might need to keep in mind for these medications. But before we delve into the drugs, I just wanna ask you more broadly, you talk in the article about the challenge of patients with immune-mediated diseases who are on immunomodulatory therapy being at risk for both flares of their disease and for infections; and these infections can present somewhat atypically, right, in immunomodulated hosts, to maybe coin a term you can correct me on, because they can't mount the full inflammatory response. So how do you approach new symptoms in patients on these immunomodulatory medicines as far as distinguishing disease flare from a treatment-related infection?
Dr Nath: So, I have to say that although a lot of new treatments have come along for MS, and they've really, you know, improved the outcome tremendously and there are so many different options, it has also kept people like me relevant because they cause a lot of various types of infections, and so keeps me in business all the same. But just as you mentioned, there's so many of them, even I have difficulty keeping track of what does what. So, you do need to be able to refer back to published literature, and the tables, I hope, will be quite useful in that regard. You're absolutely right, and you can get new infections, you can get reactivation of existing infections, and you can get atypical presentations of various types of infections that you may not normally think of. So that presents multiple challenges to the treating physician. The other interesting thing about MS is, just as you mentioned, that you already have CNS lesions to begin with. Now, on top of it, you have an infection, so now how to sort out what is the existing disease and what is the infection, it can again become challenging. But one thing is for sure: all these infections are caused by an organism. So, what you really need to do is, the underlying diagnostic is to demonstrate the presence of the organism. Whether you demonstrate it depending on the infection in the spinal fluid or in the brain or, you know, some peripheral organ system, that is going to be key to making the diagnosis. So, all your clinical acumen is good, but that alone may not be sufficient.
Dr Berkowitz: Very good. So, when you see a, a patient now who has a new neurologic symptom in the context of an immune-mediated disease who's on immunomodulatory therapy, what goes through your mind? Are you thinking this disease and this drug, and sort of what are the infections, and does the syndrome match? Or are you thinking, you know, you can't always rely on the imaging to distinguish between, say, a flare of an MS and PML because white matter lesions could look similar? How do you sort of approach this scenario when it comes up?
Dr Nath: So, you're right. You have to keep an open mind so that even though you know some infections are more likely to occur with certain types of medications, that doesn't mean that others cannot occur. So, I think when you first see the patient, you should not jump to conclusions, but rather have an open mind. But yes, for example, your patient is on natalizumab, the chances of PML are going to be high. It's a very interesting drug. It does not cause immune compromise in the periphery, but what it's doing is preventing these cells from getting into the brain. So, because then it's acting at the blood-brain barrier. So that means that organisms that are already present in the brain have an opportunity to get reactivated. Turns out you don't have a lot of organisms in the brain, except JC virus seems to be one of them that does somehow, in some individuals, manage to reside out there. And so that can get reactivated. It can get reactivated in the periphery and then enter the brain, too. So, where the very specific mutations have to occur in that virus in order to take residence in the brain. That would be a suspicion that you might have, and MRI can be useful in, again, helping you think about that possibility. If you have typical lesions involving the U fibers, they're demyelinating, usually you do not have much edema around them because patient is immune compromised, but certainly within the brain in these individuals. And so, then you need to demonstrate the organism. The demonstration of the organism should be in the spinal fluid and not in the blood because in the virus, it can-- is reservoir in the kidneys and in the lymph nodes, and periodically it'll shed into the blood. Detection of the organism in the blood can be a false positive, but in the spinal fluid, it shouldn't be there unless you have an infection. Or if you cause a traumatic tap, I guess, if a patient is viremic, that's a possibility, but those are extremely rare. So at least for PML, that's the way that you would diagnose it. Now, you can develop, for example, if an individual is on fingolimod, you can get a wide variety of infections. Here it's a totally different type of mechanism of action. Here the cells are trapped within the lymph nodes, so that means now your entire periphery is immune compromised, right? So here you can get viral infections, bacterial infections, fungal infections. So here, if a patient presents with new neurological symptoms, you have to have a really open mind for all these possibilities. Now, let's say a patient was on dimethyl fumarate, and dimethyl fumarate causes neutropenia early on. So here you have to worry about an individual developing bacterial infections, so latent tuberculosis or bacterial meningitis can occur in these individuals. That's something to keep in mind. It's not that other infections cannot occur with dimethyl fumarate, you can see PML and other things too, but the chances of bacterial infections are greater. So, you got to make sure that you draw all the cultures for that purpose. Similarly, if you're on a complement inhibitor, like a C5 inhibitor or the thing that I could use in NMO, there are the chances of meningococcal meningitis. So, these patients, you need to prevaccinate them before you start these kinds of treatments and look for that possibility. When you suspect bacterial infections, particularly acute bacterial meningitis, there time is of essence. Also, in some of the acute viral infections, for example---herpes encephalitis is another one---you have to be so careful, and if you suspect any of them, even if they're with possibly atypical manifestations, you treat first and then diagnose later, and draw all your cultures, whatever you need to, and just treat them. And these infections can also cause cerebral edema, so one has to be careful about doing spinal taps in these individuals. You want some kind of neuroimaging before you do them. In the days when we didn't have neuroimaging, we used to say, "Okay, if your patient has focal neurological signs or is comatose, you don't do it." But these days, you can get imaging very quickly and very easily. All the-- Because of our stroke management, we've learned how to do them so quickly. So, I think there's little excuse not to do imaging and prevent herniation from occurring.
Dr Berkowitz: That's very helpful. So, using the information we know about the drug, and we're going to rapid-fire review some of that in a bit to know what infections the patient is susceptible to, but acknowledging that any patient can get any infection, right? Whether they're on particular medications or not. And then if you're not sure, based on the neuroimaging, which as you said, is helpful, but not always helpful in distinguishing between infections and flares or, as you said, in the case of meningitis, encephalitis, early on at least, especially in immunocompromised or immunomodulated, quote unquote, patient might not see the typical imaging. So really, when safe, getting CSF or cultures, PCRs, and other infectious studies too is really gonna be the definitive diagnostic maneuver here. Is that fair summary across the board?
Dr Nath: I think you said that absolutely right. And you summarized that correctly. And, you know, thing about infection, a lot of neurological diseases are, you know, diagnosed by clinical acumen, like your Parkinson's and Alzheimer's and others. Think about infections is caused by an organism, demonstrate the organism, right? That should be your goal. It doesn't mean that clinical acumen is not important, but here you have an opportunity to demonstrate the organism, so you should depend upon that.
Dr Berkowitz: Okay. Well, you gave us a nice segue by talking about some of the infections to worry about with some of the medications. So what I'd like to do now for the sort of second half of our interview here is to go through some of the more common medications used for MS, and if we have time, for NMO, and just sort of go kind of rapid fire here, and for each medication, if you can tell us the kind of top infectious concerns and whether when to consider them or what screening needs to take place before or during administration of the medication, and then any vaccine considerations we should be aware of. Some of these will obviously be quite short depending on the medicine. So, going back to the two medications I alluded to earlier that were the only ones in play when you and I last saw each other on the wards when I was a medical student, beta interferon, glatiramer acetate, any infections or vaccine considerations with these medications?
Dr Nath: No, I think they're probably your safest medications now as far as immunomodulatory therapies are concerned. These two, and IVIG, if you ever use them, are probably the safest, do not require any vaccine considerations, per se.
Dr Berkowitz: Perfect. Okay. So, moving on to fingolimod and others in the sphingosine-one phosphate receptor modulator family, what are the infectious considerations? Any prescreening or vaccination considerations?
Dr Nath: I think all your patients should be prescreened for antibodies to JC virus, because there is a risk for PML, and those who are positive should be closely monitored. So, it's not an absolute contraindication for using these medications, but they just require closer monitoring. With this class of drugs, PML is of consideration. Also, these varicella-zoster virus infection, yeah, with that you can develop zoster encephalitis or myelitis. It can present with motor symptoms as well, which can be atypical. You don't usually see them otherwise in immune-competent individuals. So, varicella-zoster, sometimes you can develop encephalitis, also vasculitis with varicella-zoster, so one has to be careful. So, getting the shingles vaccine can be actually very helpful to prevent these things. And then some patients can even develop herpes simplex encephalitis also, and that can be extremely atypical. So, they don't- they can involve the basal ganglia, can involve the brain stem and cerebellum. So again, your index of suspicion should be very high. Interestingly, although HSV encephalitis has been associated with NMDA receptor encephalitis, those reports of NMDA receptor encephalitis have not been published yet with NMS patients. Not sure why, maybe they just have been missed. But that doesn't seem to be a major concern. And then there are a whole host of other infections that can occur with this class of drugs, and that can include toxo; fungal infections, particularly crypto. There's a case report of histoplasmosis; hepatitis virus, particularly hepatitis C; and then the poxvirus is a good example. You can get molluscum contagiosum; warts with papillomavirus; you can get atypical mycobacteria; and even Kaposi sarcoma, which is HHV8. So, there's a huge variety of infections with the sphingosine one phosphate receptor modulators.
Dr Berkowitz: And any- aside from screening for JC virus before initiating these, any- and then continuing to monitor for JC antibody index, any other considerations as far as labs to send, monitoring before or on the drug or vaccine considerations for patients on fingolimod and the others in this category, siponimod, etcetera?
Dr Nath: Yeah, there are a lot of things to consider. All the details are really available in the chapter if you look at them. But briefly, all the things that one could potentially vaccinate patients for, all these infections I mentioned, one should do so. The timing is critical so that if you can do it before treatment, I think, before starting treatment, that is absolutely important. And you got to give them at least, you know, two to three weeks for these vaccines to take effect before starting your medication. If your patient already arrives on a medication, then you got to play this game of you know, before the next dose, give them again two to three weeks before the next dose and start vaccinating them and get all the vaccines in. Broadly, about the things to worry about the vaccines are you have live vaccines, and you've got the inactivated vaccines or the subunit vaccines. You have to be careful with live vaccines, because if your patient is immunocompromised, that virus can sometimes itself cause harm. For example, you know, yellow fever is one, and there you can develop encephalitis from it. Measles, mumps, rubella, these are all live vaccines. Now, the good thing is that a lot of us have been immunized very early in childhood, but that may not be the case any longer. And so, these things, one has to be very careful with when you're giving live vaccines, that we want to avoid them as much as possible, and individuals are gonna be immune-compromised. But all the others, meningococcus, for example, you should- the HPV vaccines, the varicella zoster vaccines, all these things, you've got to pre-vaccinate and make sure that they have an antibody response to them before starting immunocompromising therapy.
Dr Berkowitz: Perfect. Oka