Case guesses:

Kade writes:

Hiya TWiPsters,

I’m a Marine Biology grad student who rarely sees a non-medusazoan, but I think I have an idea on this one. To me, given the age range of the patient and detachment/granuloma symptoms, it seems that OLM (Toxocara cati/canis) is a good bet. It is relatively common but more usually in places where humans and pets/domesticated animals intermingle freely. Treatment would likely mean surgery, so it’s lucky that this team had a specialist to make the call on how to proceed. As for whether it could have been caught earlier, I would say that that is unlikely. Not only do a lot of things make a kid’s eye red and painful but OLM doesn’t test as accurately as VLM does. If it was diagnosed, there could have been a 3 week Albendazole treatment that could have helped but may not have.

Side note: In the S. bovis and S. haematobium paper, is it clear whether undercooked meats could cause a human to have both S. bo and S. he for hybridization?

Thank you for your fantastic podcast.

Sincerely,

K. M. Muffett

Chris writes:

Hello Professors,

its a beautiful 72 and sunny here at Stonybrook today. Its been a while, but i am finally getting some free time to catch up on the episodes! For the most recent  case I believe the parasite is Onchocerca volvulus. wish I had the time to discuss treatment and such more but i am short on time. So I will just leave it at that with my best guess.  

After your discussion about parasite global prevalence being over 50% I figure you all might be interested in discussing this meta analysis by Kamiya->https://blackboard.stonybrook.edu/bbcswebdav/pid-4729643-dt-content-rid-33958905_1/courses/1194-MAR-384-SEC01-52478/Kamiya%20et%20al%202014.pdf which is just a fantastic paper in general. Also I know Robert Poulin has several papers on the subject that could also be interesting to you in the subject of parasite diversity. here is his page ->https://www.otago.ac.nz/zoology/staff/otago008915.html#publications ( it may take a bit of  time to find the relevant papers i’m referring to as this man publishes an insane amount)

Another reason i am writing in today is because I moderate the sub reddit for parasitology, and I have recently started a  monthly journal club for us to discuss all things parasite, and I want to extend an invitation to all the listeners who are looking for more places/ people to discuss parasite papers with. We select a paper as a group ever month and then have a discussion thread on the last Sunday of every month -> https://www.reddit.com/r/Parasitology/  any thing related to parasitology is allowed, from new papers on new ant-parasitic drugs to parasite ecology.

*this can be said on air if you would like but don’t feel obligated*\

I became a donor to the podcast a few months ago at  the 5$ and I would like to receive a TWIP mug (would love it if all the members could sign it, but i understand if this isn’t possible) .

Lastly, If you have any desire to discuss bivalve parasitology/immunology my adviser Bassem Allam is an expert in the field and I think he could make a very interesting episode.  Hard clams alone make up the largest fishery on long island and make up ~100 million dollar industry on the east coast. however they are plagued by a opportunistic protozoan parasite (QPX, Quahog Parasite Unknown). and this is just one small aspect of bivalve disease. so I figures if you all wanted to talk about a different aspect of parasitology, let me know and I could get Bassem in touch with you.

All the best,

Chris

School of Marine and Atmospheric Sciences,

Stony Brook University, Stony Brook, NY

Jacquelyn writes:

Hello TWIPsters,

I suspect the 9 year old boy with a vision loss, retinal retraction, and a macular granuloma is suffering from ocular larva migrans caused by Toxicara canis. Differential diagnosis would include: ocular larva migrans due to T. Cati or retinoblastoma.

My apologies for the very brief case guess. I’m currently preparing for USMLE Step 1 and sadly, there aren’t fantastic podcasts like this one for every subject on the exam. At least I know I can handle any parasitology questions that should come up!

Cheers,

Jacquelyn DeVries

UCSD School of Medicine | Class of 2021

Wink writes:

Dear TWIP Professors,

You’ve got me again! There are a lot of causes of a red eye and many etiologies for retinal granulomas, but I do not know when one follows the other. I discounted Chagas disease and onchocerciasis because I think they are rare in Panama; toxoplasmosis and cysticercosis because they are acquired by ingestion and would not affect the anterior eye. I also considered a veterinary anterior eye pathogen: Thelazia callipaeda because it has been known to rarely infect humans, but not the retina, I believe.  I am going to go with a larva migrans syndrome possibly caused by Toxocara canis. Here’s hoping!

Wink Weinberg (Atlanta)

Kevin writes:

A Worm’s Eye View

Case of a nine year old rural Panamanian boy with a history of a red irritated eye for one to two weeks which resolved. He presented to clinic a few months later with a complaint of significant monocular vision loss. Funduscopic exam showed retinal retraction and a ‘quiet’ granuloma in the macula.

I strive for detached objectivity in my relationship with parasites. However, the malefactor in this case is displaying exceptional perversity in its choice of residence. The human liver has an estimated volume of 1500 cubic centimeters. Compare this with the volume of a typical adult eye which is six cubic centimeters. So much available territory in the human body, why settle in the eye; and even worse, why set up shop in the macula, a mere 5.5 millimeter patch of tissue, which includes the 1.5mm fovea, where all the critical visual work (such as reading), is done. The eye displays an amazing combination of vulnerability and durability— it can be punched, scratched, infected but usually keeps on working —but please do not mess with the macula. Such are the vicissitudes of human biology.

A complete recounting of ocular parasitosis would fatigue the most ardent parasitological dilettante, suffice to say that we could name at least 35 bad actors (in the parasite union) that screw up the human eye, ranging from protozoa to maggots; even the disgusting crab louse merits a mention. The list quickly dwindles however when we consider a unilateral posterior pole granuloma in a child. Our patient is unlikely to be immunosuppressed therefore toxoplasmosis is unlikely, and also is not typically associated with granuloma formation (however the case report by Massa in the endnotes describes a posterior pole granuloma due to toxoplasma.) NOTE: a granuloma can be briefly defined as a nodular aggregation of histiocytes (macrophages) and often containing multiple other of immune cells and collagen; this inflammatory mass is an attempt to ‘wall off’ a foreign body or infectious organism. A classic example of granuloma formation is seen in tuberculosis.

Other common ocular parasites such as Onchocerca, cysticercosis, or Loa loa do not usually cause posterior pole granulomas and would cause the clinical presentation of our patient.

The most likely diagnosis here is ocular larval migrans due to Toxocara species, probably Toxocara canis. It frequently affects children and is typically unilateral. Disease in children is via oral ingestion of soil contaminated by infectious feces of dogs or cats. Prevalence of the disease varies widely and is common in the non-industrialized world. The disease is seen in the United States but a 20 year case series from UCSF only reported 22 cases of ocular toxocariasis. Reviews commonly state that the disease is unilateral in 90% of cases, but some reports say 40%. Diagnosis is often clinical by demonstration of typical fundus findings. Eosinophilia is not typically seen in ocular larval migrans (in contrast to visceral larval migrans.) Enzyme immunoassay is used but a negative test does not rule out infection. Treatment usually involves a combination of systemic and topical corticosteroids combined with albendazole. Unfortunately in our case, the granuloma probably represents an immune reaction to an already dead parasite with likely permanent destruction of the macula. Theoretically, if the patient was treated at the time of his initial symptoms perhaps the pathologic process could have been interrupted. I could find nothing in the literature that described very early detection and treatment of ocular larval migrans. Surgical management is used to manage late complications such as retinal detachment and vitreous opacification. I suspect that this child will have permanent visual loss in the affected eye. Prevention of this problem would involve limiting exposure to contaminated soil and treatment of infected dogs and cats.

Thanking the twippersnappers for their selfless educational mission.

ENDNOTES AND A TERMINAL CURIOSITY

¶ General references on ocular parasitosis

Update on pathology of ocular parasitic disease, Dipankar Das, Indian J Ophthalmol. 2016 Nov; 64(11): 794–802. OPEN ACCESS

Authors inexplicably use the term ‘Cystoidea’ in reference to some type of protozoan. The term should be reserved for fossil echinoderms…A servicable initial review but weak on epidemiology and emphasis on ranking diseases in order of importance/occurance.

The following is an abstract of the major points of the review:

TOXOPLASMOSIS-“The classical clinical presentation in acquired toxoplasmosis in retina is the head light in fog appearance, and pathological feature in this disease entity is a well-demarcated area of coagulative necrosis with adjacent choroiditis, vasculitis, hemorrhage, and vitritis.”

TOXOCARIASIS-“Ocular toxocariasis is usually unilateral and can have several myriad clinical presentations ranging from diffuse endophthalmitis, posterior pole granuloma, peripheral localized granuloma, peripheral or macular disciform retinal detachment to pars planitis, or papillitis…pathology shows granuloma

CYSTICERCOSIS- “Retinal involvement causes hemorrhages and edema….“Histologically, the necrotic cysticercus is surrounded by a zonal granulomatous inflammatory reaction with an abscess that contains eosinophils”

ONCOCERCIASIS- “The ocular lesions are primarily caused due to living, dying, as well as dead microfilariae. Ocular manifestations of onchocerciasis include punctate keratitis surrounding dead microfilariae, sclerosing keratitis, anterior uveitis with secondary cataract and glaucoma, chorioretinitis, and papillitis with severe constriction of the visual fields….sub-Saharan Africa and parts of South America…”

ECHINOCOCCUS- primarily affects adnexa

dIFFUSE uNILATERAL sUBACUTE nEURORETINITIS-Also called unilateral wipe out syndrome “…Earlier the causative organism was thought to be T. canis, but Baylisascaris procyonis [the raccoon roundworm] and the trematode Altaria spp. have also been suspected to be involved….classically unilateral severe vision loss….Associated features include vitritis, focal and diffuse pigment epithelial disturbance, retinal vessel narrowing, optic atrophy,”

GNATHOSTOMIASIS- rare, humans are incidental hosts, larva cause the pathology…“The most common presenting feature is anterior uveitis. Other features include lid swelling, iritis, iris atrophy, iris holes, intraocular hemorrhage, retinal scarring, retinal detachment, and rarely glaucoma.”

OPHTHALOMYIASIS- can affect both internal and external eye structures.

DIROFILARIA, ASCARIS

LOAIASIS- usually spares the posterior segment/retina, though case reports exist…

LEISHMANIA- affects the external eye

MALARIA- vascular effects in the retina…“Ocular complications in patients with malaria have been reported in 10% to 20% of patients.[85] The most common complications noted in the acute phase are conjunctival hyperemia and subconjunctival hemorrhage. Yellow pigmentation of the conjunctiva occurs due to breakdown of erythrocytes. Other ocular lesions include retinal hemorrhages, transient ocular nerve palsies, orbital edema, choroiditis, retinal embolism, papilledema…”

Intraocular Parasitic Infections, S. R. Rathinam,, Ocular Immunology & Inflammation, 19(5), 327–336, 2011

Notes from the article:

toxoplasmosis, T. canis, T. catis, O. volvulus, T. solium,

Damage mechanisms:

1.parasite alive causing mechanical damage

2.dormant organism e.g. cysticercus larva..space occupying, inflammation

3.dead parasite resulting in uveitis, inflammation, e.g. ruptured cysticercus

4.dead parasite resulting in graunuloma

RE Toxocara–“lack of good diagnostic kits….lab confirmation difficult…”…tx=steroids for anterior segemnt, albendazole is contraversial, vitrectomy (surgery) for endophthalmitis

RE: Oncocerca….disease related to microfilarial migration and inflammation due to dying MF—ophtho findings= Clinical signs include limbal edema, hyperemia, conjunctival nodules, punctate keratitis,

sclerosing keratitis, granulomatous or nongranulomatous uveitis, bilateral symmetric chronic chorioretinitis,

geographic retinal atrophy, consecutive optic atrophy, and glaucoma…NO MENTION OF RETINAL GRANULOMA. Wolbachia endosymbionts of oncocerca may intensify or even mediate corneal inflammation.

Larval migrans ophthalmia syndrome. A situation where humans are an accidental host–examples

Dirofilariasis –can cause subconj. cysts

gnathostomiasis–Japan, SE Asia, Latin America… lid swelling, live worm in ocular tissues, iritis,

iris atrophy, iris holes, intraocular hemorrhage, retinal scarring, retinal detachment

DUSN=diffuse unilateral subacute neuroretinitis, nematodes wandering in the subretinal space…visible moving worm is the ‘gold standard of DX’, albendazole used empirically with some success. Very difficult to speciate worm.

ocular cysticercosis Cysticercosis may get localized at the eyelids, subconjunctival tissue, extraocular muscles, orbit, anterior chamber, subretinal space (Figure 8), or in the vitreous cavity. TX: albendazole, steroids and possbily surgery.

Ocular nematode and trematode, infections in the developing world. Sabrosa NA et al Int Ophthalmol Clin. 2010 Spring;50(2):71-85.

Regarding T. canis infection: Serologic surveys in different countries reveal seropositivity rates of 39% in Brazil, 5.2% in Cuba, 10.9% in Jordan, 47.5% in Colombia, and 81% in Nepal….

TOXOCARA: Clinical presentation depends on the primary tissue or anatomic site of involvement, which may include the peripheral retina, the vitreous, the posterior pole, or the optic disc. The most common presentation involves peripheral retina and vitreous, occurring separately or together….An intraretinal or subretinal mass, or granuloma, in the posterior pole may be seen with the posterior form of the disease…Ocular toxocariasis is unilateral over 90% of the time and usually affects children, although adults may be affected as well….Initial larval invasion of the subretinal space or vitreous is followed by larval death and granuloma formation. Though VLM cases usually have leukocytosis and eosinophilia, these findings are absent in ocular larval migrans. Tx is steroids w/ or w/o antihelminthics ??The Malla and Goyal chapter say that eosinophilia is PRESENT.

ONCOCERCIASIS: Dead microfilaria in the eye and subsequent inflammation results in eye disease. Can involve the anterior (cornea, aqueous humor,iris) and posterior segment….Chorioretinal lesions typically begin in the periphery with pigmented lesions, sheathing of the retinal vessels, and visual field constriction.

CYSTICERCOSIS: Humans are incidental hosts when ingested eggs develop into larvae so called Cysticercus cellulosae (Tinea solium=the adult)

TREMATODE UVUITIS: Postulated by Rathinam,S. Culprit thought to be Philophthalmus sp, a trematode parasite of avian conjunctival sac

SUMMARY:The parasites T. canis, Onchocerca volvulus, Taenia solium, Ancylostoma caninum, Cysticercus celulosae, and Philophthalmus sps may all be responsible for blinding ocular infections, such as ocular toxocariasis, onchocerciasis, DUSN, ocular cysticercosis, and trematode infection of the anterior chamber, respectively.

Ocular parasitoses: A comprehensive review, Padhi TR et al  Surv Ophthalmol. 2017 Mar

30 page review. Of all the reviews cited in my endnotes, this article contains the best comprehensive table of diseases, infectious agents, clinical findings and geographic distributions. Numerous excellent photographs.

Parasitic infections of the external eye, Pahuja S et al, Ocul Immunol Inflamm. 2013 Aug;21(4):292-9

Parasites of importance causing external ocular disease are protozoan parasites, such as Leishmania; metazoans, such as nematodes (roundworms), cestodes (tapeworms), and trematodes (flatworms); or ectoparasites, such as Phthirus pubis and Demodex.

Ocular Parasitic Infections – An Overview, By Nancy Malla and Kapil Goyal, December 2016

BOOK CHAPTER–Book Title: Advances in Common Eye Infections.

OPEN ACCESS BOOK CHAPTER. https://www.intechopen.com/books/advances-in-common-eye-infections/ocular-parasitic-infections-an-overview

comprehensive 60 page book chapter, downloadable.

EXCELLENT DIAGRAM ON PAGE 43 (Figure 1) that combines cross-sectional eye anatomy with the infectious agents that attack each structure.

Table from Rathinam 2011

Anatomic locationClinical manifestationInfectious organism
Orbit
Conjunctiva



Anterior chamber



Iris
Vitreous


Subretinal space



Retina

Orbital Cellulitis
Subconjunctival (SC) motile wormSC cystSC granuloma

Alive motile wormHypopyonHyphemaAnterior chamber granuloma
Iris atrophy, Iris holes
Alive wormIntact mobile cystPanuveitis
Subretinal motile wormCystMultifocal chorioretinitis with new crops of retinitis
RetinochoroiditisRetinochoroidal granuloma
Dirofilaria
DirofilariaCysticercosisTrematode granuloma

GnathostorniasisRuptured cysticercosisGnathostorniasisTrematode granuloma
Gnathostomiasis
GnathostorniasisCysticercosisRuptured CC
DUSNCysticercosis
DUSN
Toxoplasma gondiiToxocara

Laundry list of ocular pests

Acanthamoeba spp

Toxoplasma

Leishmania

T cruzi

E histolytica

Hartmanella

P falciparum [rare reports]

Microsporida [rare reports] (now classified with the fungi)

Giardia [rare reports]

____________________________________

Onchocerca volvolus

Loa loa

Toxocara spp

Angiostrongylus cantonensis

Dirofilaria repens

T. spiralis

Thelazia callipaeda

Baylisascaris procyonis [raccoon roundworm]

W bancrofti

T solium

Echinococcus granulosus

Multicept multiceps

Fasciola hepatica

S. mansoni

Spirometra (sparganaosis)

________________________________

Oestrus ovis

Rhinoestrus purpureus

Dermatobia hominis

Chrysomia bezziana

Lucilia spp

Cuterebra

Hypoderma

Cochliomyia

Wohlfahrtia

Gastrophilus

_________________

Phthirus pubis

ticks

______________________

pentostmids

PUB MED list of ocular parasitosis reviews

https://www.ncbi.nlm.nih.gov/pubmed?linkname=pubmed_pubmed_reviews&from_uid=23617222

¶ Toxocara references:

Clinical Characteristics of Pediatric Patients with Ocular Toxocariasis in China. Ophthalmologica, 235(2), 97–105.  Liu, Y., et al (2016)

Case review of 46 children (33 male, 13 female), mean age 6 y/o. Follow-up duration was 3 months for all cases. Dx confirmed by ELISA (using serum or intraocular fluid). Granuloma, dx in 36 patients, was made by the Optomap 200 Tx (an alternative to conventional slit-lamp exam. Tx was with steroids in over 80% patients and 39% required surgery.

Main clinical signs were ocular inflammation and unilateral granuloma

T canis: infection is via oral ingestion of L2 larva. 3 types of infection: 1) ocular larval migrans, 2) visceral larval migrans, 3) occult infection

T canis does not develop into adult worms in the human, only progresses to the development of L3 larvae in the lungs.

Population studies in Asia have estimated that 6% of children have been T canis infected (ELISA serology).

Other clinical: Larvae have an affinity for brain and eye. Leukocytosis & eosinophilia usually absent. 84% of their cases had a visual acuity of < 20/200.

Vitreous stranding seen in 63%, retinal detachment in 65% cases (this is much higher than USA and Korea case series).

Prognosis: At the 3 month follow-up visit: 74% cases had a VA <20/200. 23% cases had no light perception.

Review has good photographs of retinal granulomas

Authors end the article lamenting the poor prognosis in ocular toxocariasis patients in China.

Neglected Parasitic Infections in the United States: Toxocariasis, Dana M. Woodhall, Am J Trop Med Hyg. 2014 May 7; 90(5): 810–813. OPEN ACCESS

A very brief and comprehensive review.

Eosinophilia, hypergammaglobulinemia and elevated isohemagglutinin A and B are less likely to occur in ocular larval migrans (in contrast to visceral larval migrans). DX via enzyme immunoassay. RX: albendazole and mebendazole (not FDA approved for this indication). No controlled trial data available for optimum dose and duration of treatment. Seroprevalence data in the US show 14% of samples were positive in people > 6 years old. US soil sample studies in parks and sandboxes have ranged from 0.3% to 30% positive for Toxocara ova

Ocular toxocariasis: clinical features, diagnosis, treatment, and prevention Seong Joon Ahn et al, Asia Pac Allergy. 2014 Jul; 4(3): 134–141. OPEN ACCESS

A readable, concise 6 page review.

PREVALENCE, CLINICAL FEATURES, AND CAUSES OF VISION LOSS AMONG PATIENTS WITH OCULAR TOXOCARIASIS. STEWART, J. M., CUBILLAN, L. D. P., & CUNNINGHAM, E. T. (2005) Retina, 25(8), 1005–1013.

“Absence of antibodies does NOT rule out the infection. In the absence of confirmatory serology, typical clinical presentation and characteristic physical findings were used as a diagnostic criteria.

¶ Miscellaneous references:

Ophthalmomyiasis Interna, Rodger, D. C.et al (2016).Ophthalmology, 123(2), 247.

Case report from USC Los Angeles, patient a 52 y/o Filipino man. Interesting accompanying photograph. “fundus examination a crisscrossing pattern of depigmentation was seen tracking throughout the fundus, as seen in Figure 1 (Optos P200TX, Dunfermline, Fife, Scotland). He was diagnosed with ophthalmomyiasis interna. A clump of vitreous debris compatible with decomposing botfly

larval remnants was seen.”

Choroidoretinal granuloma in a young female patient, Massa HF1, BMJ Case Rep. 2014 Apr 17;2014. OPEN ACCESS

Case report of a posterior pole granuloma in a 16 y/o Brazilian woman. Toxoplasma was demonstrated by serology and PCR.

Diffuse unilateral subacute neuroretinitis (DUSN)

term first used 1978. Formerly known as ‘unilateral wipe out syndrome’. Despite the syndrome’s name, it can be bilateral. Postulated organisms involved: T. canis, Baylisascaris procyonis, and Ancylostoma caninum,but difficult to prove the culprit organism. Syndrome seen in SW USA, Central and South America, Caribbean, China, India, Spain….Diagnosis via visual identification of an intraocular motile worm.

TX: laser photocoagulation. Empiric antihelminthics.

Philophthalmiasis

Zoonotic trematodes in the genus Philophthalmus, also called “eye flukes”, have infected humans on very rare occasions. The three Philophthalmus species conclusively identified in humans are P. lacrymosus (also spelled P. lachrymosus and P. lacrimosus), P. gralli, and P. palpebrarum. Note that in most previously reported cases, species could not be ascertained….extremely rare…

www.cdc.gov/dpdx/philophthalmiasis/index.html

RE: Baylisascaris procyonis only 22 documented cases were reported in the United States during 1973–2010

(https://www.cdc.gov/mmwr/volumes/65/wr/mm6535a2.htm?s_cid=mm6535a2_w)

Liver volume reference:

The mean liver volume obtained with our scheme was 1504 cc, whereas the mean gold standard manual volume was 1457 cc, [Med Phys. 2010 May; 37(5): 2159–2166. Kenji Suzuki et al. ]

note: 1 cubic centimeter=1 milliliter

¶ A TERMINAL CURIOSITY

As a child I was always mystified by the image of someone putting a raw steak on a black-eye (sugillation, ecchymosis, hematoma…). Of course I never saw a real person doing this, it was a trope from television, in sit-coms and cartoons. It made absolutely no sense to me. Years later in a color atlas of parasitology I saw a picture of someone using a frog in a similar manner. This brings me to the bizzare tale of ocular sparganosis, a condition rarely due to the application of frog or snake raw-meat poultices. Or… perhaps the practice is not so bizarre: see Dr Despommier’s book “People, Parasites, and Plowshares” where he discusses the theoretical benefits of the frog poultice due to antimicrobial frog-skin compounds [named ‘magainins’ by M. Zasloff], as well as describing the depredations of Spirometra mansonoides. I will leave the reader to explore this topic independently and exit with advice to generally avoid the application of raw meats to the face.

Enzootic Sparganosis in Guangdong, People’s Republic of China, Ming-Wei Li et al, Emerg Infect Dis. 2009 Aug; 15(8): 1317–1318. OPEN ACCESS

The plerocercoid larva of the cestode Spirometra. Larval invasion can affect many tissues including the eye. Authors state that in China approximately 1000 cases were reported in the 80 year interval between 1927 and 2007. Transmission is due to eating frog meat and the application of raw frog meat poultices to open wounds and lesions. Authors sampled 544 frogs, 25% of which were infected. Frogs are the second intermediate hosts of Spirometra spp.; pigs, mice, and humans become infected as paratenic hosts by ingesting Spirometra larvae in cyclops or frogs

A review of human sparganosis in Thailand, Viroj Wiwanitkit, International Journal of Infectious Diseases (2005) 9, 312—316

Case series, n=34 collected from reports dated 1943 to 2002. The infections were ocular (17 cases), subcutaneous (ten cases), central nervous system (five cases), auricular (one case), pulmonary (one case), intraosseous (one case) and intra-peritoneal (one case). Most cases presented with superficial ocular mass lesions. Only 2 cases had a history of using poultices made from frog or snake meat. The most common method of transmission in Thailand is the consumption of contaminated water containing infected copepods. Reports from Korea identify consumption of raw snake or frog as the most common means of sparganosis transmission in humans.

Ben writes:

Dear biological and technical TWiPlicates,

My case guess for this week is ocular larva migrans, caused by either Toxocara canis or cati. According to Parasitic Diseases 6th edition, the child is around the right age and the symptoms seem to fit well. I’m not sure whether or not seeing the child when they first developed the eye inflammation and treating would have had much benefit, from PD6 it seems as if there isn’t enough information on drug treatment of OLM to know.

I did have two other questions regarding OLM that hopefully the TWiP team can answer. Toxocara canis and cati are regularly spoken about together when it comes to OLM, do we know what proportion of OLM are caused by each species and does the pathology differ? Also, considering OLM can present like retinoblastoma, would it be feasible in a resource limited setting to exclude retinoblastoma in the child? Particularly if you didn’t have an ophthalmologist around.

Just because it fits the theme of the case (I hope), I’ve attached an SEM image I took of Toxocara canis at a fantastic parasitology course run by the Australian Society for Parasitology.

I’ve temporarily vacated sunny Adelaide and moved significantly northward as part of a collaborative research grant and so, the weather here in Hamburg, Germany is currently 13oC and raining.

Regards,

Ben

Ben Liffner

PhD Candidate – Malaria Biology Lab (Wilson Lab)

Research Centre for Infectious Diseases

School of Biological Sciences

The University of Adelaide

Nathan writes:

I’m very excited that we’ll be discussing eye parasites for the next few case studies. They are my favorite dinner table stories to tell!

There are four organisms that come to mind immediately when eye parasites are mentioned: Acanthamoeba spp, Onchocerca volvulus, Toxocara canis, and of course – Loa loa.

This was the case of a 9 y/o boy visited a mobile clinic in Bocas del Toro in the Caribbean.

He Developed redness in the eye followed by significant vision complications. The boy has some recognition of movement, but is unable to see anything clearly. Retinal retraction and granuloma were noted over the macula of the infected eye.

Question 1: What do you think this is?

This sounds like a classic case of Toxocara canis. The two biggest complications of this parasite in humans is visceral larva migrans and ocular larva migrans.

People can become infected when they ingest embyonated eggs. This is common in low-income communities with lots of stray dogs.

According to the 6th edition of PD (Page 314), Toxocara canis commonly causes ocular larva migrans in kids ages 5-10 years old. The most serious complication is invasion of the retina and a granuloma that can drag the retina which can lead to a detachment of the macula. This can present as a unilateral vision impairment.

The boy was likely infected through contact with dog feces. This parasite is common in dogs, particularly in the developing world. Sometimes kids can ingest the feces when playing in the dirt, the dreaded sandbox or directly interacting with a stray dog.

This organism is unable to complete its life cycle in humans, so the damage is caused by the migrating larva.

The treatment for this organism is albendazole 2x per day for five days. I would also recommend that the boy stop playing with stray animals!

Question 2: What might we have done when the boy was first seen at the mobile clinic?

If the redness of the eye was investigated further during the first visit, I suppose a CBC with differential would lead the docs to suspect some type of parasitic infection due to an elevated eosinophil percent. There are immunological tests available for Toxocara canis, so perhaps one would be ordered based upon the eye redness and eosinophilia.

Eye am looking forward to the next few cases,

Nathan

Carrie writes:

Dear Hosts,

An eye condition with pain and vision loss, in a parasitic context, immediately brings Onchocerca vovulus to mind. But on second glance this doesn’t fit really any of the case details: we have no report of itching or skin nodules, the findings from the eye exam aren’t consistent with river blindness, and although O. vovulus is found in the Americas, there aren’t many areas where it’s still common.

A better fit would be one of the intestinal nematodes that normally infect animals, but in humans, being unable to complete their lifecycle, crawl off into other parts of the body and wreak various kinds of havoc – cutaneous, visceral, or in this case ocular larva migrans.

There are a pair of handy look-up tables in PD6e. A few of the organisms that infect skin affect the conjunctivae, but we’re seeing something in the eye itself here. However on the VLM table, Toxocara spp. stand out as uniquely affecting the eye (as well as the viscera.)

Usually, toxocariasis results in either VLM or OLM, not both, and children over five are more likely to have ocular infection. In ocular toxocariasis the larva – sometimes only one – invades the retina and may cause the formation of a granuloma, which can distort or detach the retina and naturally causes visual impairment (potentially blindness.) Infection is typically unilateral, and redness and inflammation of the eye are also symptoms. In short, it fits our clinical picture exactly.

A granuloma typically forms when the larva dies, so since they cannot reproduce in humans, the infection has probably already run its course. Anti-helminthic drugs probably won’t be of any use, and in the event that there are more larvae present killing them all at once could make matters worse rather than better. Unfortunately, the damage to his eye is permanent and he probably won’t recover vision. There are surgical techniques which can repair or ameliorate the damage, however I harbour doubts as to what surgical options would be available to this patient, given the circumstances.

Had the patient been able to access treatment when symptoms first appeared, he should have been treated with corticosteroids, which may have helped reduce the damage to his sight. Surgery – if available – may still have been required.

As far as exposure goes, Toxocara is found worldwide. Eggs from the faeces of an infected cat, dog, or fox embryonate in soil and are then ingested. Infection is most likely in children who eat sand or dirt, which would tend to be younger children, but can also occur through e.g. inadequate hand washing, which seems likely in the circumstances. It is unlikely that dogs and cats that in this impoverished, remote community are regularly de-wormed.

Diagnosis would normally be based on the clinical presentation, since the immunological tests aren’t particularly reliable for ocular toxocariasis. It is thought that with a lower parasitic load the larvae are likely to quietly migrate to the eye, while a higher load produces a larger immune response, resulting in both visceral disease and positive tests. This is also why younger children, who are more likely to infect themselves with many larvae by playing with and sometimes eating dirt or sand, are most likely to present with VLM.

An ELISA test, if it didn’t come back with a false negative, could distinguish between T. canis and T. cati, but the distinction is probably not important for the patient.

One other condition that should be particularly carefully ruled out is retinoblastoma. Granulomas from ocular toxocariasis are often mistaken for this type of cancer, and while that’s an undesirable mistake to make (potentially resulting in the unnecessary removal of an eye,) the reverse would be worse.

Best regards,

Carrie, of Newcastle upon Tyne, England – solo, on this occasion. Caitlin sends her regards but could not assist as she was bitten by a radioactive spider in the course of her day job, and is currently busy with her new secret identity.

If I win the book, please leave it at a major railway station with a label tied to it saying “please look after this book.”

Regular email

Anthony writes:

https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0007001

This was mentioned on Puscast.

Perhaps an arbovector is relevant to Leprosy in NYC:

https://academic.oup.com/cid/article/46/6/899/349479

Danae writes:

Hello Vincent and Dick,

First off I want to say thank you for your effort and also for sharing your knowledge with others. I’m hooked on your show!

I’m a Veterinary Technology student in Houston, Texas looking to get my license in Veterinary Technology and later specialize in lab work. I have a vast interest in parasitism. In my program we typically focus on parasites that affect all kinds of animals and wildlife as well as zoonotics as a public safety concern.

I would love to hear your views and ideas on parasitism from a veterinary standpoint and also, would your ever consider doing an few episodes specifically on canines, felines, farm animals,  and zoonotics?

Thanks again,

Danae d.

Kevin writes:

The lair of the white worm

Mis en scene:

A peaceful nursery school, morning light filtering into a well ordered classroom- suffused with cleanliness and safety. At a stroke all is upended: birthed from an unspeakable portal is a half-foot long etiolated worm; utterly incomprehensible in this world of innocence.

We live in a state of ever-expanding security services complete with gallon dispensers of hand-sanitizer wherever we turn…into the context of such illusory order plops a sluggish six inch worm. Is this an exorcism? The teachers are divided: do we call a priest or a doctor? They decide to phone the host’s mother.

For the past year the stricken child has lived with his parents in a low-resource, non-industrialized nation. He was treated with single-dose albendazole before return to the US and has been home for 3 months. Of course the single pill was perceived as 100% effective. Would you expect less in this era of ‘personalized medicine’ and pharmacologic triumphalism?

This case, in spite of its superficial resemblance to a straightforward clinical parasitology problem, is actually burdened with a potent psychic and emotional overlay. Here we have a worm that is more than a worm, in spite of Freud’s apocryphal quote that “Sometimes a cigar is just a cigar.” More to the point, Dinah Washington’s 1954 hit, “Big Long Slidin’ Thing”, clearly refers to a musical instrument but may leave room for broader interpretation (song written by Kirkland and Thomas). Which brings us back around to that worm writhing on the nursery school floor. Is it more than just a humble Ascaris lumbricoides, completely innocent and incapable of disease transmission? I will argue that our worm is a stand-in for primitive fears of contagion, pollution, bodily penetration and defilement.

The most likely reaction that this case elicits in the uninitiated is disgust. This is a complex feeling or set of behaviors (disgust’s status as an ’emotion’ is still debated) that is triggered by components of our own bodies and a plethora of environmental cues. Valerie Curtis from the London School of Hygiene and Tropical Medicine specializes in the study of disgust and argues that it is an adaptive response protecting humans from infection. She also harnesses the disgust response in public health strategies (see refs).

University of Michigan law professor William Miller’s 1997 book, The Anatomy of Disgust, is encyclopedic in his examination of disgust; his following quotation is of relevance for us, “But when our inside is understood as vile jelly, viscous ooze, or a storage area for excrement the orifices become dangerous as points of emission of polluting matter, dangerous both to us and to others.” The nursery school staff in our case have been exposed to a swirl of disgust: excretion, anality and a foul mucus covered invertebrate. We might as well throw ophidiophobia into the mix too. Pace Dr Curtis, there is really no significant threat of infection here. It takes 2-4 weeks of soil incubation for ascaris eggs to become infectious. There is the possibility that the toddler harbors other parasites such as enterobius or strongyloides, but simple handwashing and common-sense cleanup of the discharged worm should suffice. Though this nursery school ’emergency’ is more aesthetic than medical, it doubtlessly inspired a janitorial scorched earth policy. Of course there is no reason to remove the child from school, something that probably exacerbated the stigmatization surrounding the mishap. The difficulty of complete sanitization is suggested in PD6 where the expression ‘filthy lucre’ is embodied by the fact that ascaris eggs have been recovered from currency. (Mommy is vindicated in her oft repeated injunctions about putting money in your mouth.)

The old saw that ‘there’s no such thing as a clean bill of health’ applies to our case. Though our returning family ‘felt good’ about their albendazole treatment, there was no discussion about cure rates or egg reduction rates in the region of their missionary work. The benzimidazoles, discovered in the 1960s (albendazole and mebendazole) are a significant improvement over earlier more toxic vermifuges (e.g. oil of chenopodium). However, widespread veterinary use of benzimidazoles has led to significant resistance in livestock. Resistance is less frequent in humans but is well documented. Though cure rates and effective egg reduction ratios are in the upper 90% range for ascaris, treatment failures are not rare. Multiple studies outlining efficacy and treatment failures are in the end notes. Some treatment failures have been ascribed to locally produced benzimidazoles which may be improperly synthesized, adulterated, or incorrectly compounded. Also, as stated in PD6, children have much higher worm burdens than adults; a consideration in single dose treatment failure. In the era of mass administration of benzimidazoles used in attempts to mitigate or eradicate soil transmitted helminth transmission, resistant human nematodes are expected to increase in frequency. Our patient (and probably the family) needs re-treatment with a benzimidazole and it would be prudent to examine his stool post-treatment to demonstrate absence of ascaris eggs and document absence of other soil-transmitted helminths. The school staff needs reassurance and a primer on helminth biology and the negligible risk of contagion in this case.

Gratitude to the TWiPlets, who have an admirably high disgust threshold.

END NOTES AND A TERMINAL CURIOSITY

i) Parasitology references on treatment efficacy etc:

Reduced efficacy of albendazole against Ascaris lumbricoides in Rwandan schoolchildren, Krücken J, et al. Int J Parasitol:Drugs Drug Resist. 2017 Dec;7(3):262-271

It is estimated that 800 million people are infected with Ascaris worldwide. Global progress in soil transmitted helminth reduction exemplified in the 70% decrease in disease burden between 1990-2010. Nematode resistance to benzimadazoles is common in veterinary settings.

BZ mechanism of action: drug binding to tubulin, which prevents the production of microtubules, eventually killing the worm. SNPs in the tubulin gene has been demonstrated in drug resistant worms…problems…A suum and A lumbricoides: are they even a separate species? Problem: inaccuracy of the measure “complete cure”. Problem: methodological problems in the estimate of FECR

3.1.1. Pre- and post-treatment prevalence of Ascaris sp. Out of 1182 recruited children, paired stool samples (pre- and post-treatment) of 850 and 709 individuals were analysed by wet mount microscopy and mini-FLOTAC, respectively. Overall prevalence was 33%. post-treatment Ascaris prevalence was 13% (using wet mount method) vs 13% (using mini-FLOTAC method). Overall cure rate=70% (by mini-FLOTAC)…

Assessment of the anthelmintic efficacy of albendazole in school children in seven countries where soil-transmitted helminths are endemic. Vercruysse J1PLoS Negl Trop Dis. 2011 Mar 29;5(3):e948. doi: OPEN ACCESS

The paper attempts to address a neglected area, that of the efficacy of antihelminthic treatment. The question the authors try to answer is: what is the efficacy of a single dose of albendazole on Ascaris lumbricoides, Trichuris trichura, and the two major hookworm species. Study was conducted in the following 7 countries: Brazil, Cameroon, Cambodia, Ethiopia, India,Tanzania and Vietnam. Cure rates were above 95% for Ascaris but only 50% for trichuris.

Assay to determine efficacy: FECR=fecal egg count reduction and CR=cure rate

An identified problem in STH (soil transmitted helminth) control has been the lack of studies documenting the efficacy of the standard anthelminthic regimens. It is very important to know the cure rates so that the value of intervention programs can be assessed and to monitor the development of drug resistance.

method: the McMaster egg counting technique.

Efficacy of anthelminthic drugs and drug combinations against soil-transmitted helminths: a systematic review and network meta-analysis, Naomi E. Clarke, Clin Infect Dis. 2019 Jan 1;68(1):96-105

Included 114 studies. A recent meta-analysis shows that single-dose albendazole and mebendazole are highly efficacious against A. lumbricoides, with pooled cure rates of 95.7% and 96.2% respectively and egg reduction rates of 98.5% and 98% respectively…this study only mentions ascarisis twice…..

Efficacy of mebendazole and albendazole for Ascaris lumbricoides and hookworm infections in an area with long time exposure for antihelminthes, Northwest Ethiopia, Adugna S,et al, Ethiop Med J. 2007 Jul;45(3):301-6.

RESULTS:

Mebendazole exhibited cure rates of 90.6% and 83.5%; egg reduction rates of 96.7% and 94.2% against Ascaris lumbricoides and hookworm infections respectively. Albendazole showed a cure rate of 83.9% and egg reduction rate of 96.3% against Ascaris lumbricoides and a cure rate of 84.2% and egg reduction rate of 95% against hookworm infection. Albendazole appeared to be more effective against hookworm infection (egg reduction rate of 95% versus 94.2%, p = 0.04).

CONCLUSIONS:

Mebendazole and albendazole showed reduced efficacy against Ascaris lumbricoides and hookworm infections at the recommended doses. This may be a sign for emergence of drug resistance in this region. Care in routine use of the anthelminthes and continuous drug efficacy surveillance is recommended.

A comparative study on the efficacy of albendazole and mebendazole in the treatment of ascariasis, hookworm infection and trichuriasis. Jongsuksuntigul P, Southeast Asian J Trop Med Public Health. 1993 Dec;24(4):724-9.

Cure rates for Ascaris were 100%

Reducing Intestinal Nematode Infection: Efficacy of Albendazole and Mebendazole, A. Bennett and H. Guyat, Parasitology Today, vol. 16, no. 2, 2000

DEFINITIONS–

+Cure rate (CR): percentage of infected population who are negative for parasite eggs after drug treatment

patients

+Egg Reduction Rate (ERR)- pre vs post treatment difference in ‘egg intensity’ expressed in reduction in eggs per gram of feces

Note: a link to a discussion of ancient feces and parasites

https://www.cam.ac.uk/research/news/ancient-faeces-reveal-parasites-described-in-earliest-greek-medical-texts

The Encyclopedia of Life, E O Wilson, Trends in Ecology and Evolution Vol.18 No.2 February 2003

“Of the nematode worms, making up to four of every five animals on Earth (and, it is said, so abundant that if all solid matter on the surface of the planet were to disappear, its ghostly outline could still be seen in nematodes), 15 000 species are known but millions more might await discovery.”

NOTE: there is another self-experimentation reference in PD6: the Koino brothers helminth self-infection. See my end-notes for TWiP 168 where I entreat the TWiPlets to do a snippet on noble self-experimenters.

ii) PSEUDO-LITERARY FILLER

• This case put me in mind of the myth of the infant Hercules wrestling snakes:

Wiki: The child was originally given the name Alcides by his parents; it was only later that he became known as Heracles. He was renamed Heracles in an unsuccessful attempt to mollify Hera. He and his twin were just eight months old when Hera sent two giant snakes into the children’s chamber. Iphicles cried from fear, but his brother grabbed a snake in each hand and strangled them. He was found by his nurse playing with them on his cot as if they were toys. Astonished, Amphitryon sent for the seer Tiresias, who prophesied an unusual future for the boy, saying he would vanquish numerous monsters.

• The Lair of the White Worm…Bram Stoker’s (author of the much more well known novel Dracula) 1911 novel, which is fraught with multiple fin de siecle fears including misogyny, racism, anti-semitism and generalized moral panic. (Also a 1988 Ken Russell film.)

• In the interest in being tedious, according to Max Braun’s 1908 Die Tiereschen Parasiten des Menschen, the ‘ascarides’ mentioned in the Aphorisms of Hippocrates actually refers to our oxyuris. The Greeks used the words helmins strongyle to describe Ascaris lumbricoides. Pliny refers to it as Tinea rotunda.

iii) NOTES AND REFERENCES ON DISGUST

•Question: What’s worse than biting into an apple and finding a worm?

Answer: Biting into an apple and finding half a worm.

•Why disgust matters, Valerie Curtis, Phil. Trans. R. Soc. B (2011) 366, 3478–3490

“The new synthesis about disgust is that it is a system that evolved to motivate infectious disease avoidance….disgust is a source of much human suffering… It arose in our animal ancestors to facilitate the recognition of objects and situations associated with risk of infection and to drive hygienic behaviour, thus reducing micro- and macro-parasite contact…Those with lower disgust sensitivity are known to suffer from more infectious disease… Our group is devoting efforts to finding ways of making sanitation sexy, setting-up events such as the ‘Golden Poo Awards’ for example. Artistic exploration of the disgusting such as the Wellcome Trust’s season on ‘Dirt’ and the ‘Grossology’ exhibitions that tour the world, help to attract interest and expose disgust to the light of day. Such efforts are beginning to pay off in terms of increased research funding.

This 13 page review proposes to examine the evolutionary significance of the phenomenon of ‘disgust’. The author discusses the positive and negative consequences of this often poorly understood human feeling (the status of disgust as a bona fide emotion is still being debated). Curtis even argues that the phenomenon of disgust suffers from its own ‘disgustingness’ or unattractiveness in the research arena, where other topics such as anger and fear generate much greater quantities of research. She suggests that a massive killer like diarrhea, perhaps as a consequence of the disgust it (subliminally) generates, results in other illnesses such as HIV or malaria receiving disproportionate attention by researchers and funders.

Val Curtis (LSHTM) studies disgust.”Don’t Look, Don’t Touch, Don’t Eat” (Chicago University Press, 2013

supports a theory holding that disgust functions to reduce contact with pathogens and parasites.

https://www.seeker.com/culture/disgust-helps-humans-avoid-infectious-diseases-but-the-emotion-isnt-perfect

• Miller, William Ian, The Anatomy of Disgust, 1997, Harvard University Press

Miller weighs in on the anus:

“Yet more than any other orifice, it is the gate that protects the inviolability, the autonomy, of males and indirectly of females too. Only feces and gas are to pass through. This fact makes it indelibly the lowest-status place on the body, rendered disgusting by feces and buffoonish and comical by gas.”

“The allure of disgust (film, entertainment and news) banks on it…”

“Disgust shocks, entertains by shocking, and sears itself into memory.”

•Paul Rozin, psychologist at U Penn who specializes in disgust: Disgust is not merely an extension of distaste, but rather “an entirely new category of ideationally based, contamination-sensitive revulsion or withdrawal.”

Rozin and colleagues state: “the most threatening aspect of humans’ animalness is their mortality, and that disgust serves as a defense against pondering mortality.”

George Orwell on disgust….ages between 7 and 18, where “one seems always to be walking the tightrope over a cesspool”

A TERMINAL CURIOSITY

•The philosopher Edmund Burke used the word ascaride as a metaphor for the Nabob of Arcot’s indebtedness to politically influential members of the British East India Company:

“That debt forms the foul putrid mucus, in which are engendered the whole brood of creeping ascarides, all the endless involutions, the eternal knot, added to the knot of those inexpungable tape-worms which devour the nutriment, and eat up the bowels of India.” speech made in 1785.

footnote to accompany Burke quotation–The Nabob (Nawab of Arcot) formally Muhammad Ali Khan Wallajah †1795, ruled Carnatic region of southern India. The Nawab was heavily in debt to officials of the East India Company. Some things never change: the corruptions of globalism avant la lettre: “Elections in the UK could be, and were, influenced by nabob money, with the result that a group of about a dozen Members of Parliament formed a discernible “Arcot interest”, as it was called.” -Wikipedia