Sydney writes:
Hello TWiP!
The weather here in Maryland is a very humid 85 degrees today. I recently graduated with my degree in Master’s in cybersecurity. I have been listening to TWiP while filling out (many) job applications. For this week’s case study, I think the patient has microsporidiosis. Since the patient has a lesion of the back of the left eye, I read an article on ophthalmic parasitosis from Hindawi. You already ruled out toxoplasmosis and west nile virus and mentioned that a serology test came back positive. According to the article I read, microsporidiosis is diagnosed through serology testing and is present in the area where the patient lives. Hope you guys are staying safe!
Thanks,
Sydney
Anthony writes:
Greetings Day Twipers! I am writing in once again to provide my guess for case 186 – the woman with a retinal lesion.
Considering that there is no animal exposure – there really is only one other (soil borne) worm in the United States that causes retinal lesioning – the dreaded Baylisascaris procyonis!!
If this is indeed the case, not much is known about treatment but albendazole and an oral steroid are what seems to be recommended!
Hope I got this one right – Anthony S
Morgan writes:
Dear TWiP,
Here goes my guess for TWiP 186. I am a Medical Laboratory Scientist currently working in Houston, TX (where it is predictably hot and humid). I work in a histocompatiblity lab, but I have held an interest in parasitology/infectious disease since my previous work in molecular microbiology and my parasitology class at the University of Washington in Seattle. Thank you for this podcast, as it definitely challenges me!
Initially when I think of parasites + eyes, I think of Onchocerca volvulus, Loa loa, or Acanthamoeba. However, most of these don’t fit with geography (excluding Acanthamoeba) or with the diagnostic method (serology). After consulting CDC’s list of Antibody Detection Tests for parasitic diseases, I excluded everything but Toxocara canis and see that the clinical picture fits. Her unilateral visual impairment is descriptive of Ocular Visceral Migrans. Perhaps she ate some infective eggs that snuck into her garden’s edible plants.
Best,
Morgan
Wyatt writes:
Hello again TWIP troubadours,
It is Wyatt again, however this time writing from sunny California. The highs have been in the low 100s for the past week, and show no signs of letting up. I have now begun at Loma Linda, and have been learning lots, though nothing about parasites yet. I guess Anatomy and Biochemistry will have to hold me over until then. In regards to the guess for this month, the first thought that came to my mind was “larva migrans” (Ocular Larva Migrans OLM).
This condition occurs often when there is a zoonotic transmission of a parasite. Similarly to how we believe COVID arose, a zoonotic transmission comes from an animal host population to a human. The parasite attempts to find the right structure to reside in, and ends up causing accidental harm to the human, by wriggling around where they should not. Occasionally the parasite Toxicara canis can cause eye impairment in humans. This is a dog hookworm, and since the patient has been working in the dirt, she may have inadvertently picked up an egg (fecal oral route). However, Dr. Daniel said that she has not been near any pets. This does not mean that a dog never did use the facilities amongst her daffodils, but we will explore other options.
Another option would have been Toxoplasma gondii, which is again transmitted by fecal oral consumption of the oocytes, though this time from cat feces. These pesky pets and their parasitic propulsions! This however is rarely problematic unless the host is immunocompromised or pregnant, so given her normal health, I do not think it would be these.
Other parasites that cause eye issues are often found in Africa, such as the parasite that can cause river blindness.
Finally, I came across an amoeba which is my final answer, called Acanthamoeba. This amoeba can cause keratitis, when it comes in contact with the eye, and gets under the contact. Usually this only affects immunocompromised patients as well, but contact wearers can be susceptible also. This parasite often can cause granulomatous amoebic encephalitis as well. However keratitis can be picked up by unfiltered tap water, or by the soil. It would cause pain and a lesion to the affected eye. To treat, unfortunately this parasite is a tough one. The best options are topical miconazole, propamidine, and neosporin.
Hopefully this month my answer was more on target, and thanks for the interesting case,
Wyatt
Ian writes:
Greetings esteemed Doctors!
I am just a student at a small university in Mishawaka, Indiana, about to start my final semester of undergrad. I took a microbiology course my second year at college, and have since fallen in love with all things infectious! I love all of your podcasts, and want to thank you for spending your time providing such an useful and valuable resource!
I wanted to try and make a guess about the case study for TWiP 186, about the middle-aged woman with an ocular disturbance.
My first thought was toxoplasmosis, however Dr. Griffin ruled that one out for us. I did some googling about ocular eukaryotic parasites, and found this open-access article created by two medical parasitologists in India. After hunting through this article, which I found fascinating, I think that the patient had ocular toxocariasis.
Toxocariasis is caused by Toxocara canis and Toxocara cati, nematodes with dogs and cats respectively as their definitive host. Toxocariasis is acquired by the ingestion of the nematodes’ eggs, and the migration of the hatched larva outside of the digestive tract into other tissues. The above article mentions a posterior granuloma as a potential manifestation of ocular toxocariasis, and as Dr. Despommier mentioned granulomas while developing his differential diagnosis, I think that I could be on the right track (unless Dr. Despommier was also not on the right track).
Thank you all for all that you do, your podcasts are one of the few things keeping me sane during this time of physical distancing and needless politicizing of basic public health measures.
Thanks again, and stay healthy.
Ian Smith
International Health Major, Biology & Spanish Minor | Bethel University
David writes:
Dear Hosts,
Greetings from sunny North Grafton, MA. I am going to venture a guess that the patient from episode 186 is suffering from a case of ocular larva migrans caused by a wayward larva Toxocara canis. According to papers found on PubMed, Toxoplasma is the most common cause of infectious retinitis; it is possible the Toxoplasma serology tests were a false negative, but after devoting many months to learning the ins and outs of toxocariasis for my Qualifying Exam, I will stick to my guns even if I’m wrong. While Dr. Griffin mentioned there were no cat or dog exposures, it is possible she or her kids may have come into contact with infective eggs at some point (gardening or out in a park) before COVID sheltering took place, and in regards to a point that Dickson mentioned, the remnants of the cause of a parasitic lesion may have long passed since the infection began only to leave the lesion in its wake. It may be necessary to also check on the children for signs of toxocariasis, as they may have also accidentally ingested infective eggs although with increased hygienic practices due to COVID, it is possible that only their mother was unlucky enough to be infected.
Thank you once more for your entertaining and informative podcasts.
David P.
Rebecca writes:
Dear TWIP,
Hello from Baltimore where it is 29℃ and 73% humidity. I like to listen to your old episodes while cooking— that way no one knows whether I am crying from cutting onions or from Dickson’s powerful storytelling!
Sounds to me like Daniel’s patient has ocular larva migrans caused by toxocara. Maybe there are some paratenic hosts hanging out in her garden (bunnies?), or the neighborhood cats are using her mulch as a litter box! OLM can manifest unilaterally, most commonly as a whitish granuloma. Since serum ELISA alone for OLM is not reliably sensitive, (1 [thanks Dickson!]) one can attempt to compare serum antibody level with intraocular fluid antibody level for a more definitive diagnosis. (2)
Whether treatment with a antihelmintic is warranted seems to lack major consensus. Albendazole BID at varying doses to knock out the larva, taken with food or grapefruit juice to improve absorption— finally a med you should take with grapefruit juice! (3) Systemic or ophthalmic prednisone if actively inflamed… Surgical intervention for some complications… But overall it seems like vision damage is often irreversible. (4)
Here’s something interesting I came across— apparently a unique feature of OLM is that in some patients the granuloma can actually migrate (5)— I suppose because the larva itself is migrating across the eye? Incredibly fascinating for the clinician/scientist but no doubt unpleasant for the patient— as most things in medicine are!
Thanks for another great episode.
Take care,
Rebecca
1. Despommier D. Toxocariasis: clinical aspects, epidemiology, medical ecology, and molecular aspects. Clin Microbiol Rev. 2003;16(2):265-272. doi:10.1128/cmr.16.2.265-272.2003
2. de Visser L, Rothova A, de Boer JH, et al. Diagnosis of ocular toxocariasis by establishing intraocular antibody production. Am J Ophthalmol.2008;145(2):369-374. doi:10.1016/j.ajo.2007.09.020
3. Nagy J, Schipper HG, Koopmans RP, Butter JJ, Van Boxtel CJ, Kager PA. Effect of grapefruit juice or cimetidine coadministration on albendazole bioavailability. Am J Trop Med Hyg. 2002;66(3):260-263. doi:10.4269/ajtmh.2002.66.260
[CYP3A4 gets invited to all the coolest parties!]
4. Ahn SJ, Ryoo NK, Woo SJ. Ocular toxocariasis: clinical features, diagnosis, treatment, and prevention. Asia Pac Allergy. 2014;4(3):134-141. doi:10.5415/apallergy.2014.4.3.134
5. Ahn SJ, Woo SJ, Jin Y, et al. Clinical features and course of ocular toxocariasis in adults. PLoS Negl Trop Dis. 2014;8(6):e2938. Published 2014 Jun 12. doi:10.1371/journal.pntd.0002938
[yes I know the term is pathognomonic, but try saying that five times fast!]
8 Deborah writes: <=winner
You didn’t say if the patient was Jewish or not. If not, perhaps cysticercosis due to Taenia solium from undercooked pork. If the ELISA test is positive, and since treatment killing the cyst causes more inflammation, best treatment is surgery.
This was the first of your podcasts I’ve listened to. Haven’t thought of this field since I took it at UCLA from Dr. Mac, although my partner has worked on a vaccine for malaria at NIH.
Deborah
Carol writes:
Good afternoon from sunny upstate NY where it is a beautiful 27 degrees Celsius. Since listening to you for the second time, it appears that you like to hear about the weather, so I thought I would contribute. This case is somewhat of a brain teaser! I definitely had some particular parasites in mind when first hearing the symptoms of the patient. Eye infestations make me think of filarial diseases not common in the US, like those caused by Loa loa. Since the patient had not traveled any time in the relatively recent past, I ruled those typical parasites out. My thoughts are based on my knowledge of laboratory testing. Which parasites, found in the US, can serological testing be performed on….Giardia, Toxoplasma, Toxocara, Trichinella, various tapeworms? What might this patient have been exposed to either through animals or food? Since she had no known exposure to cats, and the Toxoplasma serology was negative, this pretty much rules out toxoplasmosis. Although, if she was gardening or doing yard work, it is possible that she had unknown contact with cat or dog feces making a Toxocara retinal lesion possible via migrating larvae. An ocular lesion is not the typical first symptom of giardiasis, and no foamy, malodorous stools with gas and bloating was noted in the patient. So, no diagnosis of Giardia should be made here. What’s left? Trichinella and tapeworms. Trichinella larvae usually encyst in striated muscle tissue and may find their way to the eye. The patient in this case would exhibit periorbital edema, which was not noted on examination. A clouding of vision could occur if the worm encysted in the retinal tissue. Same thing with the tapeworm Taenia solium, the larval stage can cause cysticercosis and can encyst in any tissue. This parasite tends to have a special affinity for brain tissue though, making it less likely in this case. So, I want to narrow down my choice of parasite to either Toxocara or Trichinella. Since Trichinella comes from undercooked pork, and meat production in the US has decreased the incidence of this parasite, I think this parasite is the least likely choice of the two. My final answer is going to be toxocariasis, caused by accidental ingestion of Toxocara sp. in contaminated soil since the parasite can be detected by EIA (enzyme immunoassay) methods using either serum or vitreous fluid at the CDC. According to my reference, the drug of choice would be diethylcarbamazine, which is used in the treatment of filarial infections. It tends to be widely distributed and well absorbed, reaching peak concentrations within 3 hours and would be able to reach the retinal tissue. Thanks again for keeping my brain active in laboratory diagnosis during my summer break in classes. Can’t wait for the next one!–Carol
Reference: Koneman’s Color Atlas and Textbook of Diagnostic Microbiology. Philadelphia: Lippincott Williams & Wilkins, 2006. Print.
https://www.hindawi.com/journals/ipid/2012/587402/
https://www.cdc.gov/dpdx/trichinellosis/index.html
https://parasitesandvectors.biomedcentral.com/articles/10.1186/1756-3305-4-41
Jody writes:
Hi Vincent, Daniel, and Dickson,
Greetings from sunny Seattle, where we reached 99 degrees F this week for perhaps only the tenth time in 130 years. This weekend while drinking gin at a safe distance (and enjoying the effects of climate change), some friends and I began speculating that now is probably the time to start shopping for outdoor patio heaters, as we are perhaps only a month away from the time when it’s going to suddenly be a lot less comfortable to meet up with friends in the outdoors. And at the end of September, all of the patio heaters will likely be off the shelves just like the fans all disappear the first week we hit the sweltering upper 60s around here.
On to the patient Daniel had seen the previous Tuesday before recording TWiP 186. She was a woman in her middle years, sheltering at home in the Long Island area, who had noticed an area of loss of vision in her left eye. From Daniel’s report, she was feeling well physically but was quite distraught due to this ophthalmic development, and likely also due to the trauma of being at least temporarily a medical mystery. West Nile and Toxoplasmosis serology tests were negative, but an eye exam revealed a lesion in the back of the left eye, and Daniel confirmed that one serology test came back positive and he subsequently recommended a retinal specialist for her to see next.
According to PD 6th Ed., Toxocariasis may be the most common helminth infection in the United States after pinworm, with Visceral Larva Migrans and Ocular Larva Migrans stated as two conditions typically caused by Toxocara canis T. cati. Ocular toxocariasis was first associated with dogs in the 1940s, and human infection was first documented by Helenor Wilder in 1950, when she discovered a larva within a retinal granuloma of a child. As you all mentioned, a granuloma is a lesion that is resolved — a structure formed by prior inflammation — but a remnant of what caused that inflammation can sometimes still be visualized upon exam.
I found a paper in PLOS Neglected Tropical Diseases about the contamination of public spaces in New York City; apparently through microscopy and QPCR, the authors found significant levels of contaminations of all five boroughs, with the Bronx having the highest contamination rate at 66.7%. The authors speculate that feral and untreated cats represent a significant source of environmental contamination. I am unsure, however, as to whether a litter box might present a hazard for the Long Island dweller as in the case of toxoplasma gondii.
The adult Toxocara live in the intestines of dogs and cats, and eggs are passed through their feces. Humans (usually the smaller ones who play in sandboxes and playgrounds and stick their filthy hands in their mouths) inadvertently ingest the eggs after they’ve embryonated in soil. Larvae hatch in the small intestine, penetrate the wall, then migrate around the body to various organs via the bloodstream, with popular destinations being the eye, the CNS, and the liver. Diagnosis can be done via Elisa or RIA, and treatment may include albendazole in conjunction with corticosteroids, as well as surgery (which would explain Daniel calling in the retinal specialist).
Another contender is Acanthamoeba, a free-living amoeba found worldwide in water and soil, that can be acquired due to contaminated contact lens solutions or lenses routinely washed in unfiltered tap water. Infection with Acanthamoeba has been on the rise due to an increase in immunocompromised patients and contact lens wearers. The authors of PD6 state that almost all humans encounter this organism at some point in their lives, but it seems very few will become sick. Acanthamoeba keratitis is an infection of the eye that occurs in healthy persons and can result in permanent visual impairment.
Acanthamoeba has only two stages in its life cycle: cysts and trophozoites, and both can enter humans in various ways: through the eye, through nasal passages, and through broken skin. The NIH states that it is quite rare for the amoeba to spread from the cornea to the retina, so my money isn’t on this critter. I’m going with Toxocariasis.
I was tickled to get my first diagnosis attempt correct last month, and my mom listened to that TWiP and called me right afterward; I swear she sounded prouder of me then than she was when I graduated from high school or college. Here’s hoping throwing my name in the hat gets me a signed book this time!
Take care, stay well, stay grumpy. Thanks for all you do.
Jody
Amanda writes:
Greetings,
I was torn between toxocariasis or Taenia solium. I’m going to go with toxocariasis (T.canis/T.catis).
Amanda
Andrew writes:
Kia ora from Pongaroa,
(by the way kia ora means ‘stay healthy’ so it is an appropriate greeting for the current times)
No book won yet. Have the movie rights been sold yet?
Covid-19:
As you will know we have gone from a handful to over 100 active cases with a new cluster.
Over the 102 days, when we had no community transmission, New Zealand achieved a fair level of herd complacency. We were not allowing ourselves to be tested, in sufficient numbers, so that when the inevitable case got past the border controls it could be easily picked up. We were not using the government-supplied app, that allowed us to keep a diary of where we went and whom we had encountered, in sufficient numbers to assist contact tracing efforts. Now the app is being downloaded apace and the testing stations are nearly overwhelmed.
The border restrictions and isolation facilities here were put together in a rather ad hoc manner — various government departments and private enterprises were cobbled together to as quickly as possible and with inadequate communication between the different parts. So when the virus took hold in a community cluster the officials and public were taken by surprise. The scientists not so much. However, the situation seems to be being bought under control with capable test and trace teams. The weaknesses in the border containment operation result from a general lack of preparedness for a non-influenza pandemic in my non-professional opinion.
We are coming up to an election and the various political parties are presenting border policies that range from the ridiculous — self-isolation in Air-BnB apartments and the scary – confining all people arriving in the country in military compounds.
An interesting example of a case of transmission in an isolation unit most likely happened when a maintenance worker used a lift minutes after a positive tested person had traveled in it. The question is whether droplets and aerosols were concentrated in the air, on a fomite, in the elevator car in an amount to allow for infection in a shorter time frame as 15 minutes. Another possibility is that she might have shed virus in the form of aerosolized-fomites (https://www.nature.com/articles/s41467-020-17888-w ) from hair or clothes if she shook out long hair or donned a coat etc.
In any case, it emphasizes the wisdom of using masks in confined spaces alone or not. If you guys ever expand the TWempire to include This Week in Epidemiology with or without case studies — I will be your first subscriber.
The case of the woman with a loss of vision in her left eye: New York is now classified as a humid subtropical climate zone. As the climate changes so will the range of parasites.
But I don’t think we need to worry about river blindness becoming endemic in New York just yet.
Parasites that cause ocular larva migrans in the USA are, according to PD7, are mostly Toxocara canis and T. Cati, She might be reporting no contact with pets but can her children say the same? I have been caught out twice now by implicitly trusting negative test results, so I am not going to get caught out by assuming that no pets in the house does not mean that it is free from animal feces – PD7 mentions playgrounds and sandboxes and even in lock-down kids need to play and animals exercised.
So my guess is toxocariasis.
Ngā mihi,
Andrew
Cecelia writes:
Dear Doctors,
I believe your patient with vision loss is suffering from focal retinochoroiditis caused by Toxoplasma gondii. The diagnosis was made by demonstration of lesions in the eye as well as antibody tests for Toxoplasmosis.
There are many sources of infection so from the information given it’s hard to say where she acquired the parasite.
She has most likely been treated with pyrimethamine and sulfadiazine.
I was able to speak with an Infectious Disease pediatrician who treated a patient with Ocular Toxo plasmosis. He his patient was treated for a year with the above drugs and also folinic acid to prevent anemia, which is a side affect of those drugs.
Aside from the above source, I got my information from PD 7, CDC website, PubMed, and Review of Ophthamology.
Thanks very much for the great podcast, and stay well.
Sincerely,
Cecelia
Saint Petersburg, Fl
James writes:
So I thought of several things immediately from my background as a pathologist in a Bone Marrow Transplant hospital in Denver: Candida (a fungus), Toxoplasmosis, and CMV (a virus, the kind that sometimes makes you sick.) These are usually in significantly immunocompromised patients. Any of these can cause a localized retinitis/infarction.
Then I remembered my time in an Eye hospital (mostly looking at corneas and basal cells of eyelids) and thought of Acanthamoeba especially if she wears contact lenses but that’s usually the front of the eye, not the back. Lots of fungi also can infect the cornea especially with microtrauma, dust exposure.
I actually have done several three hour lectures on Eye pathology for my current medical school. There’s not much as disturbing as a bunch of “sick eyes” staring at you in a lecture!
So THEN since it’s TWIP I cast an even broader net and went to Google, found a pretty good review article on Fungal and Parasitic Eye Infections. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC88956/
That led to some interesting possibilities.
Chagas CAN do it although more commonly causes periorbital swelling (Romana sign)
Giardia of all things can cause ocular symptoms but probably by setting up some kind of autoimmune or allergic reaction, not by actually infecting the eye. Reminded me of Sympathetic Ophthalmia, a rare condition that causes the second eye to be attacked by T cells after the first eye is injured. Monsieur Braille was a victim.
Malaria can block capillaries anywhere, history is not great. I suppose if Malaria could do it then so could a nasty case of Babesia.
Dirofilaria immitis could block a retinal artery, most of the ones I saw were in lung.
Gnathostomia is on the list, what a Zebra though. Never saw/recognized it.
Cysticercus can lodge anywhere including eye (most of the cases I saw were brain biopsies and everyone was actually relieved to have something treatable.) You could certainly see it with an ophthalmoscope, don’t know about serology.
Toxocara canis and Echinococcus also are on the list.
Onchocerca and Loa loa I think are usually more anterior chamber or even cornea.
I suppose I have to favor Toxoplasmosis in a Yankee and wonder if she might have some underlying condition that is suppressing her like a Hodgkin or other lymphoma or maybe even a sneaky HIV.
| James M. Small, MD, PhD, FCAPAssociate Professor of Pathology and MicrobiologyClinical Career AdviserRocky Vista University |
Elise writes:
Dear TWiP Trifecta,
I hope this finds all of you well and comfortable. It is currently 90 Degrees F (32.2 decrees C) and super sticky here in lower Manhattan, and the wind seems to be picking up a bit.
Again, I really appreciate that you continue to do TWiP in spite of the near constant barrage of fascinating virology based information, news, scandal (!!?!), stories and intrigue that appears on even my non-scientist-centric news radar daily.
My diagnostic guess for the patient Dr. Griffin described in TWiP 186 is that she has managed to find herself with a ocular toxocariasis.
I admit that some of my diagnosis comes from a process of elimination since her location on Long Island, combined with her sheltering-in and not receiving guests from afar, rules out many of the more far flung parasites that can take up residence in the eye. Also, I saw from the description that she was tested for toxoplasmosis and that test result was negative. (It was very kind to rule out one local parasite from the outset.)
In this case, the woman’s symptoms and the discovery of the granuloma on her retina pointed toward ocular toxocariasis. While she doesn’t have a dog or a cat that is a typical source for exposure, she has been outside, doing a bit of gardening in Long Island where there are roaming foxes, and that (or a wayward “outdoor cat”) could have been the source of the infection. Everything I have read suggests that ocular toxocariasis is usually an infection to which children and people with pet cats and dogs are most susceptible, but I wonder if she perhaps was just unlucky and failed to wash her hands super thoroughly after gardening.
I am guessing that the secret serology test that was done that confirmed the diagnosis was the ELISA test.
How did you treat the patient? Did the patient need to have the lesion physically removed? Will her vision be permanently impacted?
As always, I can’t tell you how grateful I am to all of you for everything you do, and for your creation of this community. It means a lot when so many other things are suspended.
Best, best wishes
Elise
Owain writes:
Dear TWIP,
I hope my case guess this month is not too late – I’ve been very remiss!
Having initially jumped to Toxoplasma, I was very sad when Daniel said the serology was negative.
However, an ocular lesion with a confirmatory serological test made me think of two differentials – either ocular larva migrans (OLM) due to Toxocara canis or cati, or ocular cysticercosis due to larval stages of Taenia solium. The lack of cat or dog exposure makes the former less likely, but given the lack of other lesions on brain imaging I’m going to plump for it anyway – she’d have to be very unlucky to have cysticerci only end up in the eye and nowhere else, although I suppose anything is possible!
I look forward to hearing the correct answer, and thanks as ever for all you do!
Owain
Kevin writes:
Granny’s granuloma or Gettin’ down to the nitty gritty.
The entire topic of granuloma begets a lot of confusion. It stems from the Latin granulum: “little grain.” It doesn’t help that there are many similar medical terms such as granulation tissue, pyogenic granuloma and granuloma inguinale. I would like to digress earlier than normal and advertise my aversion to the trendy term granular, which is trying to displace the humble word ‘detailed.’ I lament the disuse of the old 70s locution the nitty gritty which is much punchier than ‘granular’.
The term granuloma was first used by Virchow in the 1860s. The 1888 New Sydenham Lexicon defines granuloma as: “… certain neoplasms which generally do not advance in structure beyond the stage of granulation tissue, and which usually proceed to ulceration. Under this head he included syphilitic gummata, lupus, elephantiasis Graecorum, farcy, and glanders, to which others have added tubercle, yaws,and actinomycosis. ” (elephantiasis Graecorum is a Roman term for leprosy- not to be confused with elephantiasis arabum…) As you can see, Virchow’s original definition has no relevance for our case.
For our purposes, the pathology definition of granuloma refers to an organized collection of macrophages seen in histological preparations under the microscope. Bad to have in the retina. You want rods and cones, not immune cells back there.
There are not many parasites that cause retinal granulomas (or do you say granulomata…Latin and Greek plurals are so last season.) I think that our patient is afflicted with the same disease as the child discussed TWiP 170 (May 08, 2019): A Worm’s Eye View. Though Toxocara is usually a pediatric problem, there are numerous case series of affected adults. S J Ahn’s 2014 case series of 101 South Korean adults with Toxocariasis. The diagnosis was made by Toxocara antibody detection (ELISA) combined with serum IgE levels. Note that Ahn’s first reference is to a review by Dr Despommier. Childhood ocular larval migrans is usually acquired by ingestion of embryonated eggs (geophagy), but presumably the adult is infected through ingestion of undercooked or raw meat. I am assuming that larva are ingested in these cases but the literature glosses over the exact biology of transmission in adult ocular larval migrans. Treatment is usually with a combination of albendazole and prednisone, though I am not aware of any large clinical trials that clearly support the customary treatment regimens. Differential diagnosis is fairly wide and is outlined in the endnotes. In Ahn’s case series 38% of cases improved or resolved with treatment, so there is hope for our patient.
I remain amazed that your coronavirus transmission schedule has not tapped you all dry, and that you have some remaining vital sap to broadcast the TWiP. Thanks for that.
ENDNOTES:
Etymologies & Definitions: an extremely succinct treatment of the term granuloma: https://librepathology.org/wiki/Granuloma
The origin of the term granuloma: Klippe HJ, Kirsten D, Andrée C. Rudolf Virchow (1821-1902) und der Ursprung des Begriffes “Granulom” [Rudolf Virchow (1821-1902) and the origin of the term “granuloma”]. Pneumologie. 2004;58(6):449-454. doi:10.1055/s-2004-818459
More on the granuloma structure: Immunopathology of mycobacterial diseases, Stefan H. E. Kaufmann, Seminars in Immunopathology volume 38,135–138(2016)
Today, we know that granulomas are primarily composed of cells of the hematopoietic lineage, notably, mononuclear phagocytes and lymphocytes. A more careful analysis reveals dendritic cells and neutrophils, and both T and B lymphocytes. Current dogma holds that T lymphocytes and mononuclear phagocytes are the central collaboration partners in the lesion. Granulomas are induced whenever material cannot be degraded and eliminated in due time, be it infectious as in TB or noninfectious, as for example, in sarcoidosis.
For an instructive table of parasites and the ocular regions affected: see my references for TWiP 170, A Worm’s Eye View (May 8, 2019)
Differential diagnosis of ocular granuloma:
lymphoma (masquerade syndrome) usually a uveitis-like picture
autoimmune disease
fungus: e.g. Sporothrix
vasculitis
toxoplasmosis
TB
syphilis
Lyme dz
bartonella infection
Stewart, J.M., Cubillan, L.D. & Cunningham, E.T., Jr. Prevalence, clinical features, and causes of vision loss among patients with ocular toxocariasis. Retina 25, 1005-1013 (2005).
Ahn, S.J., et al. Clinical features and course of ocular toxocariasis in adults. PLoS Negl Trop Dis 8, e2938 (2014). Study from Korea. A 101 patient retrospective cohort study. Identified risk factor: consumption of raw cow liver. Despommier is ref #1. T. canis and T. catis…the most ubiquitous GI helminth in dogs & cats.Treatment w/ albendazole & steroids…69% of cases had elevated IgE…they ruled out ocular toxoplasmosis and sarcoidosis & TB. In their series 50% of granulomas were in the posterior pole, 44% peripheral retina, and 5.4% combined. Uveitis was also present in 58% of patients. All granulomata were unilateral. 38% of patients had partial or complete resolution of the granuloma with treatment.
Ahn SJ, Ryoo NK, Woo SJ. Ocular toxocariasis: clinical features, diagnosis, treatment, and prevention. Asia Pac Allergy. 2014;4(3):134-141. doi:10.5415/apallergy.2014.4.3.134 A succinct review with good retinal photographs
Characterization of the parasite-induced lesions in the posterior segment of the eye Article in Indian Journal of Ophthalmology · December 2015 Nagwa Mostafa El-Sayed et al Exhaustive review of parasitic ocular involvement. Lavishly illustrated. Discussions of such arcana as malarial retinal involvement and ocular giardiasis.
Acta Ophthalmologica Volume92, Issues253 Cystoid macular edema and ocular toxocariasis in adult patients R DESPREAUX et al 20 August 2014
Karaca I, Menteş J, Nalçacı S. Toxocara Neuroretinitis Associated with Raw Meat Consumption. Turk J Ophthalmol. 2018;48(5):258-261. doi:10.4274/tjo.27085 Case report from Turkey. 36 y/o man. A rare case of optic nerve involvement with Toxocara. He was treated with glucocorticoids and albendazole. Dx was confirmed by Western Blot and suggested by elevated IgE.
A TERMINAL CURIOSITY:
While researching this case I came across a medical term unfamiliar to me: ocular masquerade, also called masquerade syndrome or uveitis masquerade syndrome. The term was coined in 1967 and is used to refer to disorders that are misdiagnosed as idiopathic chronic uveitis. This term is often associated with intraocular malignancies such as lymphoma. The term has a mysterious, poetic ring to it.
“Primary intraocular lymphoma often poses a diagnostic dilemma with presentation like vitritis, intermediate uveitis or subretinal plaque-like lesions. Diagnosis is often challenging in such cases, and this is why it is often one of the diseases referred to as a masquerade syndrome.” https://eyewiki.aao.org/Intraocular_Lymphoma
An ongoing column in EID discussing medical etymology. This enjoyable entry contains the term ‘elephantiasis graecorum’ : Etymologia: Leprosy. Emerg Infect Dis. 2015;21(12):2134. doi:10.3201/eid2112.ET2112
University of Central Lancashire Parasitology Club writes:
Dear TWIP Professors,
Hello again from the Parasitology Club at the University of Central Lancashire in the beautiful North West of England.
After a short break for exams our club is meeting remotely during the summer recess.
We have been considering the likely culprit for Daniel’s case of the middle-aged lady, sheltering at home presumably to avoid COVID-19 and distressed when noticing area of loss of vision in left eye. She was otherwise asymptomatic.
It is unclear for how long she has had this loss of vision but there appears to have been no acute infectious symptoms so she may have been living with this for some time.
Our binocular view of parasitic suspects for ocular involvement includes:
Acanthamoeba sp.
Echinococcus granulosus
Giardia lamblia
Gnathostoma spinigerum
Leishmaniasis
Malaria
Onchocerca volvulus
Toxocara sp
Toxoplasma gondii
Taenia sp
Although Daniel said that he was being kind by giving some leading clues and excluding Toxoplasma, we found this quite tricky.
We excluded Gnathostoma, Leishmania, Onchocerca and malaria based on geographical distribution of the disease and the assumption of no recent travel history. Giardia was excluded based on the rarity of eye involvement and no other prior symptoms. Acanthamoeba may be acquired from the environment and is more commonly associated with keratitis of the cornea and likely to be a more aggressive and acute infection and this lady appears to be symptom free.
This leaves us to focus on a handful of zoonotic worms that are associated with ingestion through contaminated meat or unwashed vegetables or contaminated water resulting in larval migration and complications in the eye.
Daniel was specific to mention no cat or dog exposure so we were tempted to exclude Echinococcus and Toxocara and there was discussion on consumption of raw meat which was also excluded so this should likely exclude Taenia spp. leaving us with no suspects in plain sight.
Searching through PD7 with key words to find more clues we find that exposure to Toxocara spp does not directly need to involve cat and dog exposure but ingestion of embryonated eggs that need at least 2 weeks to mature in soil. The parasite is distributed worldwide and approximately 5% of the US population has evidence of exposure to Toxocara and infection is usually acquired in childhood through playing in sandboxes and soil contaminated with Toxocara ova.
On the balance of probability, we think this lady has a granulomatous lesion in one eye due to ocular larva migrans with Toxocara spp. The diagnostic test that Daniel mentions could be an ELISA test for antibody to Toxocara larval antigens.
Thank you as always for your wonderful podcasts and stimulating case studies.
We are keeping our fingers crossed for a signed copy of your wonderful book to make the long voyage across the Atlantic to Lancashire.
David
On behalf of the University of Central Lancashire Parasitology Club
References
CDC Parasites. Available at: https://www.cdc.gov/parasites/ (Accessed: 25/08/20).
Despommier, D.D., Griffin, D.O., Gwadz, R.W. and Hotez, P. Parasitic Diseases. New York: Parasites Without Borders, Inc.
El-Sayed NM, Safar EH. Characterization of the parasite-induced lesions in the posterior segment of the eye. Indian J Ophthalmol. 2015;63(12):881-887. doi:10.4103/0301-4738.176028.Jin Y, Shen C, Huh S, Sohn WM, Choi MH, Hong ST. Serodiagnosis of toxocariasis by ELISA using crude antigen of Toxocara canis larvae. Korean J Parasitol. 2013;51(4):433-439. doi:10.3347/kjp.2013.51.4.433