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Felicia C. Chow, MD: Hello. I'm Dr Felicia Chow. Welcome to Medscape's InDiscussion series on meningitis. Today, we're discussing meningitis in the returning traveler with Dr Christina Coyle. Dr Coyle is a professor in the Department of Medicine (Infectious Diseases) and the Department of Pathology at Albert Einstein College of Medicine. Welcome to InDiscussion.
Christina M. Coyle, MD, MS: Felicia, thank you for having me.
Chow: I'm excited to talk with you today on this topic. Why don't we dive right in? Christina, you could start by walking us through your approach to fever and headache in a returning traveler, particularly because headache can co-occur commonly with fever and may not necessarily signal meningitis.
Coyle: That's exactly right. I think it is a common presentation for returning travelers. As a clinician, when you see somebody with these complaints, both fever and headache, you really need to get a good history of where the person's been, their itinerary, and how much time they spent in each location. You should also get the time of the headache or the illness in relation to their travel and the trajectory of the headache and other symptoms they might have. Of course, you're always getting age and immune status, but also vaccination history and whether the individual sought pre-travel advice and took any prophylactic medications. The type of traveler is very important. A student traveler would be very different than someone who's going home to visit friends and family vs a business traveler who's going in for a few days and sitting in meetings.
With migrants, we don't only ask where they come from but also their exact migration path when they present with fever and headache. We're always taking into consideration the time of year at the location that the individual was traveling in, and the activities that they did during travel and any sick contacts or medications they're taking. That's how we normally start our history with somebody who comes in with fever and a headache. As you alluded to, fever and a headache may not always signal meningitis. Actually, meningitis is rare. Bacterial meningitis is not something we see often in the returning traveler, although you always have to consider it because we need to rule this out. Certainly, both our history and our physical exam will help with that. Certain travelers may be at risk for meningococcal infection, but this is rare in returning travelers. Somebody who might be immune suppressed might be more at risk for certain bacterial infections of the central nervous system (CNS). And then we always think of things like herpes simplex virus (HSV) encephalitis, which can present as a bacterial meningitis early on.
I think it's always important to talk about sexual activity and exposures and think about HIV, HIV seroconversion, and other diseases, such as syphilis. We tend to go right toward a lot of tropical diseases and forget common illnesses. This is where the physical exam helps us in addition to the history. We're looking for rashes that can be seen with other systemic illnesses.
It's very common to present, for example, if you have dengue with a headache, which is classically described as retro-orbital. You'll be getting the epidemiology there and then looking for a rash. For example, there's Rickettsia africae, which is caused by the bite of the Amblyomma hebraeum [and Amblyomma variegatum] ticks, so patients commonly have eschars, black lesions at the site of the bite. But one has to search for them because they do tend to be painless, although you can have regional lymphadenopathy. The physical exam can be a clue. The headache may be the symptom the patient is presenting with and most concerned with, but there might be other clues that there is another systemic infection going on.
Chow: I think there were so many important points that you brought up there. Based on that approach that you've outlined and thinking about the critical history and exam findings that you're going to be looking for, if you are seeing someone and you feel like their presentation is concerning for meningitis, what are the top common pathogens that cause meningitis in a returning traveler that you're going to be thinking about? Similarly, what are the top, can't-miss, life-threatening diagnoses that you really want to be running through and thinking about in your differential diagnosis?
Coyle: We really don't see a lot of bacterial meningitis in returning travelers, but if I saw somebody and was concerned, I certainly would be concerned about meningococcal disease, especially if somebody had been traveling during an epidemic and hadn't taken vaccines. That would be very important in somebody who has been a traveler or a pilgrim to Mecca or Medina in Saudi Arabia. And then somebody with cell-mediated immunity who might be eating unpasteurized milk or cheeses and been more adventurous in their travels, I'd be worried about Listeria. In somebody who's got immune defects in cell-mediated immunity, I'd also always be concerned about Streptococcus pneumoniae the way I would be if they were here in the States. In terms of encephalitis, there are a number of viruses that can cause encephalitis. You can rule out HSV encephalitis, but you also have to think about HSV meningitis. We see this in individuals who might be sexually active, and it's their first time acquiring HSV. It's important to think about HSV meningitis, and then, of course, I'm going to throw in some viruses.
West Nile virus is actually on the rise in Europe, so we always need to keep West Nile in our minds, even though it's endemic here in the United States. We rarely see Japanese encephalitis in travelers, but it's something to always consider if somebody's been to endemic regions, especially more rural regions in Asia. Of course, you don't want to miss bacterial meningitis or HSV because they're treatable. We don't want to miss malaria. Headache can be a predominant symptom in malaria, even in uncomplicated malaria. We always want to rule out malaria basically within the minute the individual gets to the emergency room. We don't want to wait on that diagnosis because many travelers are non-immune and can get sick quite quickly. I think that's the way that I would approach that.
Chow: In talking a little bit more about malaria, can you say something about how the specific travel history of a returning traveler fits into your thinking about different species of malaria and the ones that typically cause CNS disease vs those that don't?
Coyle: Yes. There are basically five species of Plasmodium that cause malaria, and all of them can present with fever and headache, although the one that causes cerebral malaria and severe malaria is Plasmodium falciparum. The fifth species is Plasmodium knowlesi, and that is really very specific to Malaysia, and so the traveler has to be from there. For the most part, the traveler has to be coming either from South America, Asia, or from Africa. The majority of individuals in the United States who have malaria are normally traveling from Africa. In Africa, the majority of individuals who are presenting to emergency departments with headache and fever have Plasmodium falciparum. If you're not treated right away, especially in somebody non-immune, you can get sick very quickly.
When we look at returning travelers, the majority of people, at least with Plasmodium falciparum, present within 2 weeks of returning from travel. But it can be up to a month after they've returned. And certainly, with the other species, it can be a little bit later. We're always keeping malaria as a cause of early and late fever and headache. It's always going to be on your differential. Most individuals do really present within the first 2 weeks of coming back, but it doesn't rule it out if it's later.
We always need to keep that in mind because if we miss it, it really can be life threatening.
Chow: Great. Another infection I wanted to hear your thoughts about is leptospirosis. We always used to say in residency that it felt like cases would come in sets of three. Recently, we've had a bit of a mini epidemic of leptospirosis in returning travelers, mostly in folks coming back from Hawaii and Central America who've actually presented with meningitis due to leptospirosis. Can you tell us more about meningitis as a presentation of leptospirosis and the different phases of the infection and when meningitis usually occurs?
Coyle: Sure. Leptospirosis is a widespread zoonosis, and it's really present in the tropical regions, although it also can be found in more temperate regions. There's actually been an increased spike here in New York recently. We not only think about it as tropical diseases but also always think about it in our returning travelers. Rodents are the most important reservoir and shed the organism in their urine. Therefore, contamination of water with animal urine can lead to exposure for us as humans. The portal of entries for us can be cuts, abraded skin, mucus membrane, and conjunctiva. It gets back to that history that we just talked about. For most individuals, it's their recreational activity. It's either kayaking, rafting, or freshwater swimming that might cause them to be exposed. For some individuals, they go home and are in rice fields, so there's increased exposure with their activities. Once you're exposed, it's a biphasic illness with an acute phase and an immune phase, with the aseptic meningitis being the immune phase. Normally, the acute disease usually begins about a week after the exposure, and it can last up to 30 days. You're going to put this into your incubation [period] at least a week to 3 to 4 weeks after they return from travel. The acute phase is normally a febrile illness that is normally associated with muscle pain and headaches. Commonly, it's described that the individual will have conjunctival effusion. Then, there's a short period of time of improvement. After that, the immune phase starts, and they can present with an aseptic meningitis, which is really just headache, neck pain, or stiffness mimicking other aseptic meningitides that we see. It's important to note that the acute phase and the immune phase can overlap, and there may not be that period of getting better. More importantly, for our neurologists listening, we know that acute phase sometimes may not be present, and the patient may just present with an aseptic meningitis. It always has to be on your differential. And the answers, or the suspicions are raised, by the activities the traveler has done, which is why it is important for us to ask about activities and recreation.
Chow: That's absolutely what we found in our little epidemic of cases. All of the returning travelers had done just what you said: They had participated in various water activities. What about the cerebrospinal fluid (CSF) in that aseptic meningitis with leptospirosis — is it usually a lymphocyte predominant?
Coyle: It's usually a lymphocytic predominance, yes.
Chow: Great. Talking about CSF, obviously the CSF evaluation is going to provide critical clues, or at least we hope it will, in helping us think about what infectious process might be at play and what type of pathogen might be responsible for a returning traveler's CNS infection. There's a really interesting differential diagnosis, of course, in a returning traveler with an eosinophilic meningitis. Christina, could you talk a little bit about the diagnoses that you think about in a returning traveler who has an eosinophilic meningitis? How do you think about travel, and which regions of the world make you suspicious for some of these different diagnoses?
Coyle: Eosinophilic meningitis is something we see, and I think you probably see it in California also. I think it's really important that you ask the lab when you have a traveler to specifically stain and look for eosinophils. Once you've established that you have eosinophilic meningitis, we can talk about the two most common, at least in the literature and even in our experience. The first is Angiostrongylus cantonensis. We always have to think about Angiostrongylus cantonensis. This is the rat lungworm, and the slug is part of the life cycle. We, as humans, get infected when we accidentally ingest slugs. Some people ingest slugs on purpose. The time from when you ingest the organism to the time that you present can be as early as 2 days and as late as a month later. What you get is the migrating larva through your brain and possibly spinal cord. It's maturing as it's migrating through. It can be a transient meningitis, or it can affect the nerve roots. Most commonly, it's an intense headache, and the patient will have neck stiffness when you examine them, and they commonly complain of paresthesias. Normally, when you do your lumbar puncture, there is a high opening pressure, and some patients require repeated lumbar punctures to relieve that pressure. It used to be considered that you would just do a lumbar puncture, and patients would feel better, but there have been more and more severe cases reported, especially out of Hawaii.
Areas I worry about include Southeast Asia, the Pacific Basin, or Hawaii. That's where we've seen most of our cases — out of patients returning from Hawaii. The other organism I would think about with eosinophilic meningitis is gnathostomiasis. We find the larvae in undercooked freshwater fish, and that's the most common way. People can ingest the paratenic host, which could be poultry, but most commonly, it's an undercooked fish. We see this in individuals that are returning from Asia. There are reports out of China, Japan, and increasing reports out of South America, for instance, Colombia, Peru, and cases in individuals returning from Ecuador where there's freshwater fish as part of ceviche, as an example. This tends to be more fulminant than Angiostrongylus. In the literature, there seems to be more radicular pain associated with it.
Again, there's an overlap with paresthesias. And this is a nematode, so it has these little hooklets, so cerebral hemorrhage or bloody CSF is associated with it. That should really make you think about it. Digging down into the way of what people were eating when they were in their travels. There are a whole host of other eosinophilic meningitides, but I think those would be the top two that I would think about. You know, Baylisascaris is here in the US, and one can get it from ingesting the stool of raccoons, and it can cause an eosinophilic meningoencephalitis. We don't see that as much in our returning travelers. And, of course, coccidioidomycosis is here in the US, and so we always have to think about it in our migrants who have walked through areas endemic for coccidioidomycosis to get where we are. A lot of times, you may not live in a coccidioidomycosis region, like New York, but I have seen coccidioidomycosis in somebody who, during their migration route, has gone through areas that are endemic. So, we always have to keep that on our differential.
Chow: Great. That is a really good point. We, of course, see a lot of coccidioidomycosis here in California where I practice. And it is true that we'll see eosinophils frequently in the CSF. One other question to follow up on that: How common is it to get a peripheral eosinophilia with Angiostrongylus and gnathostomiasis, for example?
Coyle: Angiostrongylus is reported. I have to tell you, the lack of eosinophilia, it's never as high as the CSF, so it's always going to be lower. In gnathostomiasis, it's also reported, but for both of them, lack of eosinophilia should not dissuade you from the diagnosis because it's well reported without having a peripheral eosinophilia. The eosinophils are there, but they're normally not as exuberant as the CSF. Again, lack of it shouldn't dissuade you from this diagnosis.
Chow: And would you say that that's the case in the CSF as well, that you've seen cases?
Coyle: No. In CSF, you should always see eosinophilia, but if your lab isn't staining and isn't aware of it, you may miss it. You need to just make your lab aware. I think it's a really important point for us that we always look for eosinophils and ask our lab to stain for them when we're seeing the traveler with a meningitis.
Chow: If you're looking for the eosinophils, and they're not present, then that should be pretty reassuring.
Coyle: I think there would be case reports without it that should move you away from that diagnosis.
Chow: To wrap up, Christina, I wanted to also get your thoughts on whether there were any causes of fungal meningitis that we should be thinking about in patients returning from traveling.
Coyle: I wanted to mention, too, that many years ago, patients returning from British Columbia with an aseptic meningitis were found to have Cryptococcus gattii. We always think about Cryptococcus associated with HIV, but Cryptococcus gattii can occur in immunocompetent hosts and, most classically, in those individuals returning from Australia and Papua New Guinea. We always have to think that even if somebody is HIV negative, they could have Cryptococcus gattii. There is a recent outbreak of fungal meningitis due to Fusarium. We always have to remember to ask about the cause of travel, because some people travel to get medical procedures. This outbreak has been associated with the anesthesia that was contaminated — the epidural anesthesia — and individuals have been returning back with fungal meningitis. The neurologist or the infectious disease physicians together are probably going to be seeing these patients. We always have to ask about medical procedures that individuals may have done. We always want to keep that in the back of our minds because you may be the first person to see an outbreak like the one that's currently going on in the United States.
Chow: It really gets back to the importance of the history and asking those questions in terms of where a returning traveler has gone and the activities they've been doing. We're at the end of our time. Christina, thank you again so much for joining us. Today, we've had Dr Christina Coyle discussing meningitis in the returning traveler.
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Cite this: Headache? Fever? Meningitis in the Returning Traveler - Medscape - Jul 11, 2023.