40: Febrile Digest - Toxo + Transplant

I also do some research focusing on noninvasive diagnostics for different types of infectious diseases in immunocompromised patients. Um, and so I'm very excited to be here. Additionally, I serve as co-chair for the American Society of Transplantation, um, our Infectious Diseases Community of Practice Education workgroup. And so I wanted to give a little bit of a plug for one of the initiatives that we're doing through the education work group.

We have a survey that we've created for our ID trainees, both adult and pediatric, including both our current trainees and recent graduates in the last five years. And what we're really trying to do is better understand and improve upon the Transplant ID training curriculum. So we want to characterize what are the educational experiences and needs that our ID trainees are having, especially for those who want to further careers in Transplant ID.

And so these data will add significantly to the existing knowledge that we have about Transplant ID training and help us to, kind of, identify gaps in training that are present and update our recommended, uh, curriculum, and really try to improve that and make it more cohesive for our trainees. So we hope to have this survey live within the month and it'll be open for about four weeks. You may see various methods of potential distribution.

We're sending out emails through the program directors, through my IDSA say listserv, um, the AST ID COP, our online hub, and you'll see some social media blasts for it as well. But if you do see that present and you're a recent or current trainee, then, please feel free to engage. It'll really help us out and help future trainees as well to improve upon their curriculum. So thank you.

We have some amazing international colleagues that have been joining for that series. And the most recent episode, number 39 called Seal of Approval, talks through the approach and challenges in a case with congenital toxoplasmosis. But one of the most awesome and fun parts about ID is that we get to learn about infections in a variety of hosts.

And so I thought today we could talk a little bit about toxo in a different setting and transplant recipients, which I think people probably could guess by our introduction. So as a quick refresher, toxoplasma is a protozoal infection and transmission can be foodborne, zoonotic or congenital, but there's also human to human transmission on rare occasions through blood transfusion and organ transplant.

And it's been estimated that anywhere up to probably half or so of the world's population has probably been exposed, although it's always kind of hard to get those figures. Um, so Julie, can you talk a little bit about screening for toxoplasmosis before transplant and the things that we are worried about in that setting?

The seronegative recipients of toxoplasma IgG positive donors have the highest risk of infection. So those are, you know, so donor positive recipient, negative mismatch. And the highest concern is for those who are heart transplant recipients because of the propensity of the Toxoplasma to want to encyst in that cardiac muscle. And they can have up to a 75% risk of early post-transplant infection unless they received the appropriate antimicrobial prophylaxis.

And so this is particularly important in the first, you know, three months or so after transplant, when they have the highest levels of immunosuppression, so highest concern for potential transmission of infection.

Although the risk of transmission is highest or most concerning in our heart transplant recipients, we have to also consider it in our other non-cardiac transplant patients as well, particularly if they still have that donor positive recipient negative mismatch, and so increased recognition of this donor derived infection in non-cardiac transplant patients has led to a, more of a mandated toxoplasma IgG donor screening for all organs.

I was even part of like a multicenter study, where we looked at a couple of centers in the Southeast USA and the toxoplasma rates in our transplant patients. And we found that, yes, we did have it in our cardiac transplant patients, but you actually also had it in the majority were actually in our non-cardiac transplant patients as well, and more frequently in the setting of rejection and then patients who did not receive appropriate antimicrobial prophylaxis at that time.

So I think some of that stems from the fact that as people become more aware of toxoplasma, they get appropriate prophylaxis maybe at the time of transplant, and that helps prevent in that acute setting. But then down the road, people tend to maybe forget about their toxoplasma status. And then they get augmented immunosuppression in the setting of allograft rejection and they don't get appropriate toxoplasma prophylaxis, and then that leads to downstream potential infections.

So those would probably be like the two biggest times to consider it would be like immediately after transplant, and then also when you're treating for rejection.

And that can include, you know, three times a week regimen as well as their daily regimens as well. Lower dose regiments are probably less likely to be effective. Some centers though may potentially can use lower dose regimens for other center-specific reasons, or even consider adding things like pyrimethamine to it in particularly high risk combinations, if they were to have that medication available.

There's a little bit less data for other alternative regimens for toxoplasma prevention, like dapsone or atovaquone. Um, there is some concern that there have been some breakthrough infections on atovaquone and so concerns for failure there. Potentially some breakthrough infections on dapsone if you're using lower doses to make sure you're dosing that appropriately. And other Pneumocystis regimens like pentamidine are not going to be effective against toxoplasma.

So something to take into consideration, you know, a lot of our patients get trimethoprim sulfa right after the time of transplant for their pneumocystis prophylaxis, but then they get switched off of it for various other reasons, you know, kidney injury or myelosuppression or other things. And so you just have to keep in mind that if you're doing that and you're transitioning them to a different pneumocystis regimen, you potentially could be sacrificing their toxoplasma coverage as well.

So just something to consider. The other thing that's a bit debatable as well is the duration of prophylaxis for these type of patients. And again, that can be center dependent, depending on how endemic the infection is in your area. What particular organ groups you're working on. You can do between three to six months versus a year. Sometimes they'll do a lifetime prophylaxis if you've got really high risk or cardiac transplant patients. Um, and again, that can be a bit variable.

So I think that covers the first part of your question there that you're talking about, you know, pro uh, antimicrobial prophylaxis for these patients, but certainly there are other things you can do to counsel your patients on lifestyle interventions that can help prevent against like acquisition of new infection. So we tell our patients about ways to try to avoid this, um, infection.

So trying to avoid eating raw or like under cooked meats and avoiding contact with surfaces that may have been contaminated by these undercooked meats, um, unless they've been thoroughly cleaned afterwards. Untreated drinking water as well is something you want to avoid. You know, given the concern for cats for transmission, we tell transplant patients to avoid, you know, contact with stray cats or kittens. You know, if you don't know what their toxoplasma status is.

Um, telling our patients as best they can to avoid changing their cat litter boxes, or if they are going to change it, that they'd try to take appropriate precautions, including gloves and washing hands and considering, you know, wearing masks and things like that.

And they should still be changing the litter box daily or somebody in their house should be changing the litter box daily because it can take at least 24 hours for the parasite to become infectious after it shed in the cat feces, but in addition to, you know, undercooked meats and cats as potential methods of transmission, you also want to keep in mind that gardening can also be a potential risks.

Telling our patients that if they're going to be in contact with soil or sand, for things like gardening, that they take appropriate precautions again. Uh, wearing gloves with appropriate hand washing after removal. So we don't want transplant patients to change their entire lifestyles, but we just want them to be able to take in, you know, appropriate precautions to make sure that they can do those activities safely for them and for, uh, the rest of their family.

Um, a couple of things that you really want to think about and some of the main organs that are involved would be, one of the primary ones that I think about is pulmonary infection. So patients will present with your typical respiratory symptoms, including fever, dyspnea, cough. And typically when you look on their imaging, they'll see bilateral, oftentimes diffuse kind of infiltrates. And so keeping that in mind.

Uh, CNS or central nervous system infection is another big one that I think about, especially once I've identified toxoplasma in other organ systems and they can present with, you know, a variety of different types of neurologic symptoms. So if they're having an unexplained headache or encephalitis or seizures or other focal neurologic deficits.

You want to think about it and on their imaging, you'll typically see, you know, the buzzword is the multiple ring enhancing lesions, um, that you'll notice on their imaging. And those are typically localized near the, to the basal ganglia area. And so if you see that on imaging, that definitely raises high concern for toxoplasma CNS infection. Um, of course, as I said, you know, the predilection for muscle, it can infect the hearts.

And so myocarditis you know, and congestive heart failure can be a presentation of that. Although sometimes that can be difficult to distinguish, um, from like rejection or other things if you're looking at heart transplant patients, and so sometimes you'll need to look at biopsy in order to be able to do that. Um, and then visual changes is another big one too, for the patients that have chorioretinitis. Um, because then they might have, you know, again, vision changes, photophobia things.

And when you look at their retinal exam, you'll often see these like yellow to yellow, white lesions on their retina as well. And those are kind of, that's kind of a red flag of toxoplasma infection. So those would be some of the main manifestations that would kind of raise a little bit of a flag in my head. And you should keep a vigilant eye out for toxo.

Um, especially, you know, I do agree that sometimes it does sort of fall a little bit to the back of the differential, but if you're, if you see any of these kinds of clinical syndromes and your other diagnostic workups, thus far as becoming unrevealing, then, you know, taking into consideration that patients and, you know, donor and recipient toxoplasma status, it should definitely be something that should be.

Really if you can you really want to try to get a PCR, polymerase chain reaction testing, in these patients because that can really expedite diagnosis in these folks. And what's nice is that you can do it from different bodily fluids, depending on what organ system you're concerned for infection. So if you're concerned about CNS infection, you can get it off the CSF. You can get it off of the blood, if you're concerned for disseminated infection.

If you're worried about the lungs, you can get it from the BAL fluid, you can get it from the vitreal fluid. And so if you, depending on, if even if they just have a localized to an organ system, you can still get, try to get a PCR from that bodily fluid, if possible, and that can really help you make a diagnosis.

The nice thing about PCR testing is you can also quantitatively follow that as well, in addition to their clinical progress to determine how they're responding to treatment because their parasite loads, you know, theoretically be declining and, you know, while you're treating them with their appropriate therapy. I think the PCR of the bodily fluids or blood would be your first choice and probably the least invasive.

Um, additionally of course, you know, one other gold standard would be, you know, if you had a biopsy and you were able to get that. And then if you see, you know, the tachyzoites on a, you know, on a cardiac biopsy, when you're concerned for that, then that would also determine the presence of acute infection. But obviously that's much more of an invasive procedure and not necessarily always as easy to be able to get in real time.

Um, of course there can be alternative regimens if you, if the patients either can't tolerate sulfas or if they can't get access to the drugs, you know, there can be other things. Various kind of mix and match regimens. Clindamycin and pyrimethamine or, you know, trimethroprin sulfa monotherapy, or potentially atovaquone monotherapy, kind of combinations of depending on that.

But, but those would not, those would kind of be second line, if for some reason, either they had an, a drug intolerance or they couldn't get access to the drugs that were available.

And so I always refer to these and in fact, many of the Febrile transplant based episodes, we've tried to structure in a way that reflects those guidelines. And so these are really great to get caught up on topics yourself, but I also think they're a really good resource to give to learners on your team if they're starting on a transplant rotation or aren't as familiar.

Um, so for example, I'll put a link to the tissue and blood protozoa one that has toxoplasmosis in the Consult Notes, but I'm also put the link to the collection that has the other ones. In addition to this, there is an AST, it's kinda like a Zotero library, and so, you can go to the website, transplantid.net as well as on Twitter they're at @transplantIDnet.

And this is an awesome, I guess I use the word crowdsource, but basically they see ID Community of Practice members have built this and maintained it and they have it sort of grouped into various clinical questions or topics that are related to transplant. And so it's a really great reference to find key resources, if you're in a, in a bind or maybe you're really busy, it's a fast way to find, find resources.

And I don't know if you have any other thoughts on this Julie or other things you wanted to mention

And, um, I'm also of course, going to give one more plug for our little survey that's going to be coming out, um, that, you know, we really, you know, again, in the spirit of improving, you know, education and training for our transplant ID trainees. Please when you see that come out, um, feel free to engage and let us know. We can get a better idea of where the gaps are in your transplant ID training. So that way we can further develop a more comprehensive curriculum in the future.

So, uh, so thanks for that. And thanks so much, Sara, for, for allowing me to be on here. I really enjoyed myself.