The ANA Q&A: Diagnosing CNS IRIS in Sub-Saharan Africa

"The most important thing in global health work is collaborating with a team of people, often in the country that you’re working in. And that means not only the doctors there but also nurses, research staff, other people in the hospital, and the patients. And really listening to them, listening to their concerns and their needs and taking that into account in how you pursue things and how you do your research and how you work as a doctor. I think it’s extremely important to just not tackle things as an individual, but to really be part of a team where everyone is equal no matter what their background is or where they come from.  And that’s really how the best work is done." 

~Allison Navis, MD, Assistant Professor of Neurology, 2018 International Outreach Travel Scholarship Recipient 

To celebrate International Women’s Day (March 8), we’re highlighting ANA members who are doing impressive work both domestically and abroad. First up is Dr. Allison Navis.

Dr. Navis is a neurologist and an Assistant Professor in the Division of Neuro-Infectious Diseases at Icahn School of Medicine at Mount Sinai where her clinical practice focuses on neuro-infectious diseases, including HIV. She was a 2018 recipient of the ANA’s International Outreach Travel Scholarship and traveled to Zambia where her research centered on diagnostic capabilities related to central nervous system immune reconstitution inflammatory syndrome (CNS IRIS). We spoke with her to learn more about her research, how working abroad has impacted her life, and what the theme of this year’s International Women’s Day, “Each for Equal,” means to her.

You were a 2018 recipient of the International Outreach Travel Scholarship. Can you provide a high-level overview of the research you conducted in Zambia? 

My background is in neuro-HIV and my research focus is on IRIS or immune reconstitution inflammatory syndrome. You can see IRIS in many different conditions, but in HIV, you commonly see IRIS when people come in who have not been taking medication, the antiretrovirals to control their HIV, so they have a very suppressed immune system, their T cells are very low, they have AIDS, they’re very sick, they’re often coming in with other infections. And part of the treatment process is to treat those infections, but also to treat the HIV and get them on antiretrovirals. And what can happen, sort of paradoxically, is as you start treating the HIV and getting it under control, they can initially start to improve, but then they actually sometimes get a lot worse and clinically deteriorate. And often that’s due to IRIS.

So, what happens is, as the immune system starts to come back even slightly, as it starts to improve with the medications to control HIV, it starts to recognize all of these pathogens around the body, all these infections, and it creates this almost hyperinflammatory response against them, which actually makes patients sicker. And this can happen anywhere in the body, but it can also happen in the central nervous system and in the brain. And so my focus is on CNS IRIS or the central nervous system variant of this. And it’s not very common to see CNS IRIS in high-income countries, but it’s much more common in low- and middle-income countries, especially in places like sub-Saharan Africa where rates of HIV are much higher, but also the infections that occur around the brain that can trigger IRIS are much more common. And the diagnostic criteria for IRIS is sort of the same across the board no matter where it occurs in the body, but it really relies on trends in data on T-cell counts and viral loads, so you need to have previous information on that as well as other tests being done. So, for CNS IRIS, that often involves scans of the brain, whether it’s an MRI or a CT scan, lumbar puncture and testing the cerebrospinal fluid, and there’s a real question of whether resource-limited settings like sub-Saharan Africa or Zambia, which is where I did my research, have the diagnostic capability to really diagnose CNS IRIS. Oftentimes the information on T-cell counts and viral loads from previous data studies are from previous laboratories. Values are not available, oftentimes it’s challenging to get MRIs or CT scans as well as testing on the cerebrospinal fluid. And obviously if we can’t make a sort of competent or confident diagnosis of CNS IRIS, that really has a strong clinical impact because CNS IRIS can be very disabling, people can present with very severe deficits, they can look like they’ve had a bad strokes even though they haven’t and they can be deadly as well if there’s a lot of swelling in the brain.

I went to Zambia and I did a retrospective review of a bunch of patient data to see if there was enough information there to make a diagnosis of CNS IRIS and if not, to see where the major gaps lie in preventing a diagnosis that may be an area of research going forward. And so far in the review of the data we have, we’ve found that really it’s quite challenging and in most cases you can’t make a diagnosis of CNS IRIS oftentimes because we don’t have those prior T-cell counts and viral loads; that information is kept in the HIV clinic files which are usually apart from the hospital they’re admitted to. It can be challenging to get the imaging and also a lot of the diagnostic tests we do to rule out other causes in the cerebrospinal fluid and also in the blood can be challenging to get. So there are major limitations in making a diagnosis of this even though it is likely very common and very disabling and potentially deadly. So, more work needs to be done on hopefully modifying the criteria to diagnose CNS IRIS with an eye on what resources are available in places like sub-Saharan Africa to help clinicians going forward with their diagnostic capability.

How has the experience of traveling to Zambia to conduct your research affected your life both personally and professionally? 

This was my third time going to Zambia, but this was the first time doing my own research. And as a whole, working in Zambia has impacted me professionally and personally and has really been the focus of my career development and what I want to do down the road. You learn so much by being on the ground and in the field in these other countries and especially for what I do in the field of neuro-HIV, it’s places like sub-Saharan Africa that are still really hardest hit and that are still really experiencing a lot of complications from AIDS. And so going there you really see what the needs are that you might not be aware of otherwise if you’re not on the ground in these countries. And you see what patients are presenting with on a daily basis and what the diagnostic challenges are and how you need to rely more on your exam skills and maybe less so on other tests. And professionally it’s an amazing learning opportunity. You work with the providers in the local country and you learn so much from them because they’re the ones that have been there dealing with this. And so I am educated about their thoughts on the field of neuro-HIV and how they go about diagnosing and treating these conditions. Professionally it’s a wonderful growth experience.

Personally, it can be very challenging. I think we hear all the time about what healthcare is like in other countries and we might have ideas of what it’s like, but you really don’t know until you go there and being in Zambia, it can be challenging. Patients are presenting very sick, you can’t always help them as much as you would like, but you do what you can and I think any little bit really helps. And I think going there really reminds me of what made me become a doctor to begin with. I think everyone becomes a doctor because they want to help people. But when you’re there and you’re working with the providers with the patients and really trying to help improve their diagnostic capabilities and help provide treatment and you really see the changes in these patients and how you can benefit them, again with working with the providers there, it’s a very meaningful experience and I think it really reinvigorates me and pushes me forward in wanting to pursue global health work. And then I come back to New York and I’m inspired. It can be challenging but I really love being there and it’s been something that has driven everything that I’m doing and is really the focus of my career at this point.

What advice do you have for neurology residents considering applying for the International Outreach Travel Scholarship? 

My number one piece of advice would be if they’re applying to go to a country that they’ve never been to before or they’ve never worked in, to really spend a lot of time beforehand either on the phone or over email getting to know the doctors, the providers, whoever they would be working with there and really trying to get a good sense of what the healthcare system is like there, what the infrastructure is, what are the things that people commonly see there, what are the things that they think need to be addressed and how they think it would be best addressed. Because I think it’s very easy to come in with a Western perspective on things and to have an idea of a question you want answered and how you’re going to go about doing it, and very rarely does that sort of Western question and thought process work or directly apply in a global health context. So it’s extremely important to develop a collaborative process and to work closely with the providers in the country you’re going to in order to better understand what the needs are and to focus your application around that and to work closely with everyone because the research you’re doing on the ground it’s a teamwork approach, you can’t do it by yourself and especially the healthcare you’re providing it’s a team approach and so looking at the application from that angle and not just a personal application of what you want to do.

How has the ANA supported your career? 

The ANA has been extremely supportive. I think in general over the past few years you’ve really seen the ANA try to spotlight global health research much more especially at the annual meeting and try to put the research findings out there and that has been very helpful in learning about what other people are doing and meeting other people in the field. But I think the biggest support has definitely been receiving this International Outreach Scholarship. Doing global health research, oftentimes the biggest challenge is just getting started. You need to get funding to go to these countries to work there, but oftentimes to get the K-level awards you need to have some pile of data, you have to have already been there and done some work. So, it’s sort of this catch-22 of how do you get there for the first time if in order to apply for those initial grants you need to have already been there. So that first step is often the limiting step. The International Outreach Scholarship allowed me to go and really start developing my own personal research focus in Zambia and with the data I have received this past year, it really highlighted those clinical gaps and areas that need to be further researched in terms of CNS IRIS. And it’s helping me develop grant applications that I wouldn’t have been able to otherwise. So, it really kind of got me in the door, which is often the most challenging thing.

The theme for this year’s International Women’s Day is “Each for Equal.” What does this mean to you and how does this concept apply to your career? 

“Each for Equal” means to me in a very basic sense that everyone is equal and we really need to do more to elevate the voices and perspectives of people who historically or currently are not elevated and are not always part of the conversation in terms of healthcare and research. How this applies to my career I think really goes back to the aspect of collaboration. The most important thing in global health work is collaborating with a team of people, often in the country that you’re working in. And that means not only the doctors there but also nurses, research staff, other people in the hospital, and the patients. And really listening to them, listening to their concerns and their needs and taking that into account in how you pursue things and how you do your research and how you work as a doctor. I think it’s extremely important to just not tackle things as an individual, but to really be part of a team where everyone is equal no matter what their background is or where they come from.  And that’s really how the best work is done.