Peter writes:

A cháirde TWIP,

I have not sent in an answer for a good few episodes. On the long and arduous journey to the land of parasitological elation some of my emails seemed to have veered off the cyber highway and not gotten to you. I also have been quite busy but still do not miss an episode. I often do solve the cases and mean to write in an answer but the next episode release beats me. I even got the recent Ascaris case confirmed by my mentor Prof. Celia Holland, tireless champion of Ascaris research (https://www.elsevier.com/books/ascaris-the-neglected-parasite/holland/978-0-12-396978-1). Part of the reason I have been busy is I have been lucky enough to be asked to be involved in the practical teaching of some parasitology to medical students at the Royal College of Surgeons in Ireland. It is great that they see the value of including someone from an ecology background. I really enjoy it and find it enriching. Great to talk to the infectious disease consultants and laboratory technicians there also, as I often wonder how Ireland, more associated with emigration, compares with Daniel’s New York, famed beacon of immigration. I of course recommend Parasitic Diseases to all the students and print out the lifecycle pages to talk through the stages of the life cycles under the slides.

Listening to the new case, it brought to mind the poem I have already sent in, “Onchocerca” by W.C. Campbell. “I don’t need your goddam eye”, I thought. Eye damage by a parasite, punctate lesions and keratopathy all sounded good. Panama did not! So I changed my mind and now am going with ocular toxoplasmosis, which I think may be more keeping with the band and certainly with Panama.

Great to hear all the female parasite heroes in recent episodes. I have not been keeping a list but just in case these have not been covered yet, the Parasitology journal has highlighted the work of Prof. Ann Bishop, Gwen Rees FRS, Letitia Obeng and Gertrude B. Elion, recently.

Finally I enjoyed the discussion on anthropozoonosis. I myself do not like this term. The world health organisation used to define zoonoses as diseases naturally transmitted from vertebrate animals to humans and viceversa”. They seem to have dropped the vice-versa, which I think may be due to the increased popularity of terms such as anthropozoonosis (which I believe originally was meant to mean diseases transmissible from living animals to humans, although many reverse this, see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958532/#R3), zooanthroponoses and reverse zoonoses. My problem with these terms is they give the impression the disease is uni-directional, often to the detriment of the wildlife host. As well as people not being aware they are an infection risk to endangered wildlife, there is also the stigmatisation of wildlife. I think this is more likely to occur in an anthropocentric world where academics are under pressure to make their results sound as impactful as possible. So although I know I am in the minority, I prefer the old WHO “zoonoses: diseases naturally transmitted from vertebrate animals to humans and viceversa”.

Slán

Peter Stuart

@tcdparasitology

Trinity College Dublin

Ben writes:

Dear Leishmaniacs,

Daniel wasn’t kidding when he said that this case was a little more difficult! I had a few initial ideas, but after digging around the literature of ocular parasitosis I couldn’t believe how many parasites had ocular manifestations. A few of the common ocular parasites immediately came to mind, like Onchocerca, Gnathostoma and Acanthamoeba but these either didn’t seem to fit the clinical picture or weren’t geographically suitable. Opthalmomyiasis, ophthalmic cysticercosis and the apparently very rare cases of ocular giardiasis seemed to fit the symptoms to some extent, although as I understand these ocular manifestations of Giardia occur along with the typical GI symptoms and these were not mentioned. I also ruled out Microsporidia, because Mother Nature would not allow a case that would eventually be featured on a parasitology podcast to be caused by a fungus J. This left me with my final diagnosis of Toxoplasma gondii. The symptoms seem to fit with ocular toxoplasmosis, except for the inflammation, although apparently secondary causes of inflammation are common. As per PD7, PCR would be the best way to confirm this diagnosis but I’m uncertain whether this PCR testing would be possible in rural Panama. Treatment would be with pyrimethamine and sulfadiazine, which is common for toxoplasmosis, but I believe corticosteroids are also common in ocular cases.  I’m not very certain of this diagnosis because the list of parasites that could cause these kinds of symptoms is so long.

The weather here in the only city where Hamburgers are both food and its inhabitants, is sunny and 14oC

Keep up the fantastic work!

Two recent malaria paper suggestions:

https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1007761

Authors use correlative STORM-SEM microscopy to investigate the knob structures that allow P. falciparum to adhere to endothelial vasculature.

https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000264

The authors show the cyclic AMP signalling controls part of the secretion of the apical organelles during erythrocyte invasion.

Regards,

Ben

Ben Liffner

PhD Candidate – Malaria Biology Lab (Wilson Lab)

Research Centre for Infectious Diseases

School of Biological Sciences

The University of Adelaide

Kevin writes:

My father had a perplexing expression he would use to describe sub-optimal choices or outcomes: “Better than a sharp stick in the eye.” As a child I found this phrase unsettling. For some reason TWiP 170 exhumed the memory. I’ve got to say that this case really twipped me up. The minimal clinical details offered, coupled with the arcane and overlapping terminology in the ophtho literature made for choppy PubMed surfing. This whole enterprise was bit of a poke-in-the-eye.

Our patient has a chronic eye malady best categorized as a uveitis. I believe that the other observations of band keratopathy and retinal lesions are due to the primary uveal inflammation. The word uvea (collective term for the iris, choroid and ciliary body) is Greek for grape. The uvea is a frequent site of chronic inflammation which can extend beyond the uvea to involve the cornea, lens, vitreous, retina and optic nerve. Uveitis is divided into anterior, intermediate (the vitreous), posterior, and panuveitis. The terms choroiditis/chorioretinitis are often synonymous with posterior uveitis. I think that our patient has an anterior uveitis.

Our three-year-old girl is not described as blind but her problem could be the beginning of progressive visual deterioration or the development of ambylopia (lazy-eye). Corneal blindness is twenty times more common in low resource nations than in wealthier nations. Globally the most frequent cause of corneal blindness is trachoma. Other common causes of corneal disease and blindness are: bacteria, fungi, locally prepared toxic eye remedies, leprosy, measles, xerophthalmia (Vitamin A deficiency), ophthalmia neonatorium (Chlamydia or gonorrhea infection), herpes simplex infection and toxin exposure (e.g. “lime” i.e. calcium hydroxide). In previous battle zones such as Cambodia, land mine ocular trauma is a frequent cause of childhood corneal trauma and subsequent blindness or visual deterioration.

Bringing the discussion back to the parasite realm…It is unlikely that our patient has toxoplasmosis, as this is usually a ‘posterior’ eye disease. She does not have the uncommon keratitis secondary to visceral leishmaniasis (case reports), nor does she have ‘salt and pepper’ retinal lesions rarely reported in Giardia infections. Onchocerciasis is not reported from Panama, and the neighboring region has very low if any transmission. I doubt that she has cysticercosis, though this can cause uveitis. The syndrome DUSN (diffuse unilateral subacute neuroretinitis) doesn’t fit here; DUSN is a posterior disease believed to be due to a wandering nematode in the subretinal space.

I will make the reluctant guess that our patient has Acanthamoeba infection of the cornea with uveitis and anterior chorioretinitis. Disease acquisition is via exposure to contaminated water, ocular trauma and contact lens use (in higher resource/non-poverty settings). Diagnosis is most accurately achieved by PCR. Culture yields inconsistent results and requires prolonged incubation. Smears have poor sensitivity. Confocal microscopy has shown good sensitivities in diagnosis. In poor resource countries all of these modalities are limited in availability. Treatment decisions are difficult due to the lack of controlled studies. Topical miconazole, variconazole, propamide, and neosporin have been used. The opacification due to calcium deposition (band keratopathy), if it is affecting vision, can be treated with EDTA. Keratoplasty may be required in late stage infections. Prevention requires the availability of clean water for washing, drinking etc.

Thanks for your valuable and important podcast, which is helping to keep the airwaves at least partly filled with knowledge and reasonableness.

The seventh edition of Parasitic Diseases is quite fine; great new cover graphics featuring a TWip-worm. Thanks for all the education.

REFERENCES, ENDNOTES AND A TERMINAL CURIOSITY

Clinical and microbiological profile of infectious keratitis in children, Patricia Chirinos-Saldaña, BMC Ophthalmol. 2013; 13: 54. OPEN ACCESS

Case series of 41 patients. Bacteria and fungi are mentioned. Not a comprehensive review in any sense. –corneal dz=important cause of blindness worldwide. More common in low-resource nations. Concerns with pediatric corneal dz due to dev. of amblyopia and subsequent permanent visual loss. Main risks mentioned: traum and contact lenses

GOOD description of uveitis: https://nei.nih.gov/health/uveitis/uveitis

Uveitic band keratopathy: child and adult Heloisa Nascimento,J Ophthalmic Inflamm Infect. 2015; 5: 35. Published online 2015 Nov 21. doi: 10.1186/s12348-015-0062-z

DEFINITION: Calcified band keratopathy is a chronic degenerative disease characterized by the deposition of gray to white opacity in superficial layers of the cornea that typically develops over months or years. It is associated with a variety of conditions, including chronic uveitis.

Calcified band keratopathy is a chronic degenerative disease characterized by the deposition of gray to white opacity in superficial layers of the cornea, more frequently at interpalpebral zone that typically develops over months or years. Although it can occur as an idiopathic form, it is associated with a variety of conditions, including chronic uveitis. This paper is a 12 patient case series involving treatment assessment….The mechanism of calcium deposition in the cornea is unknown, but it may result from precipitation left as tears evaporate, degeneration and necrosis from inflammatory diseases, changes in the pH, and the breakdown of phosphates

Band keratopathy: often idiopathic. Other associations: Most common association=chronic inflammation. Also associated with hypercalcemia, chemical burns, intraocular silicone oil (used in vitreal-retinal surgery e.g. retinal detatchment and retinal tears), post-surgical complications. Treatment: EDTA chelation.

Deposition of calcium is usually in the interpalpebral zone. Classic presentation: chronic uveitis of juvenile rheumatoid arthritis with subsequent corneal calcification

The American Journal of Tropical Medicine and Hygiene, Volume 33, Issue 3, 1 May 1984, p. 410 – 413

Onchocerciasis is not known to occur in Panama.

Fungal and Parasitic Infections of the Eye STEPHEN A. KLOTZ, October 2000, p. 662–685 Vol. 13, No. 4 OPEN ACCESS….CLINICAL MICROBIOLOGY REVIEWS-American Society for Microbiology

All of the ASM reviews that I have seen are excellent and OPEN ACCESS.

Contains a good glossary of ophthalmological terms.

Non-viral microbial keratitis in children, Abdullah G.Al-Otaibi MD et al , Saudi Journal of Ophthalmology, Volume 26, Issue 2, April–June 2012, Pages 191-197

Only discusses bacteria and fungi as causative agents, as well as addressing predisposing factors…Corneal related blindness in tropics are 20 times higher than in higher resource nations. This paper is very brief, no significant differential dx given. No parasites mentioned at all.

Pediatric uveitis: An update Parthopratim Dutta Majumder, et al. Oman Journal of Ophthalmology, Vol. 6, No. 3, 2013 OPEN ACCESS

Resolution of childhood recurrent corneal phlyctenulosis following eradication of an intestinal parasite.

Al-Amry MA, Al-Amri A, Khan AO.J AAPOS. 2008 Feb;12(1):89-90. Epub 2007 Dec 21.

Abstract

Phlyctenular keratoconjunctivitis is a nodular foreign antigen delayed hyper-sensitivity reaction typically due to staphylococcal protein (but potentially secondary to antigen from a variety of different organisms, eg, mycobacteria and intestinal worms).(1-4) Conjunctival phlyctens are usually mild and transient, but corneal phlyctens can be severe and recurrent.(3,4) The subject of this report is a severe recurrent unilateral corneal case in a child whose stool was positive for Hymenolepsis nana. Following treatment for the intestinal parasite, the child no longer suffered from recurrent ocular surface inflammation.

A DNA dot hybridization model for molecular diagnosis of parasitic keratitis. ,Huang FC, et al, Mol Vis. 2017 Aug 24;23:614-623. eCollection 2017.  basically an Acanthamoeba paper

Onchocerca volvulus infection and serological prevalence, ocular onchocerciasis and parasite transmission in northern and central Togo after decades of Simulium damnosum s.l. vector control and mass drug administration of ivermectin,Komlan, Kossi et al, PLOS, Published: March 1, 2018

The main ocular pathologies in the examined village populations, reported for the right eye, were papillitis (19.5%), cataract (17.6%), chorioretinitis (9.8%), conjunctivitis (7.8%), tropical limbo-cojunctivitis (LCET) (6.3%), iridocyclitis (4.6%), sclerosing keratitis (3.9%) and blindness of either eye (7.4%)

Corneal blindness: a global perspective., J. P. Whitcher, M. Srinivasan, and M. P. Upadhyay Bull World Health Organ. 2001; 79(3):  214–221. Published online 2003 Jul 7. PMCID: PMC2566379 PMID: 11285665 OPEN ACCESS

Corneal blindness is the second largest cause of global blindness after cataract. Largest cause of corneal blindness is trachoma. Epidemiology of corneal disease is complex and is due to multiple inflammatory, nutritional and infectious causes…(other causes: land mine injuries outranked trachoma as a cause of corneal blindness in Cambodia. Usual causes of corneal blindness overall: trachoma, onchocerciasis, leprosy, ophthalmia neonatorum and xerophthalmia (caused by vitamin A deficiency. With the diminishment of leprosy and onchocerciasis, other etiologies are becoming more important: trauma, corneal ulceration, complications due to traditional eye medications. Trachoma is the leading cause of preventable blindness (in 2001) HSV, vernal keratoconjunctivitis, chemical keratitis (e.g. lime) leprosy causes blindness due to chronic uveitis and associated cataract formation. Facial nerve involvement can cause lagophthalmos (eyelid dysfunction) with subsequent exposure keratitis, corneal ulceration, scarring, neovascularization and opacification/blindness. M leprae can also cause interstitial keratitis.

Ocular Parasitic Infections, SMJ Journals 2017, Puca, Edmond (Infectious disease MD in Albania). et al. OPEN ACCESS

Risk factors- contact lenses, trauma, exposure to contaminated water, poverty, use of ophth. folk remedies. Poor description of pathogenesis. No mention of retinal involvement. Dx mentions conventional culture and newer methods: PCR, MALDI-TOF and H-NMR

VITAMIN A AND MEASLES BIG CAUSES…..

Causes of severe visual impairment and blindness in children in schools for the blind in Ethiopia., Kello AB1, Gilbert C., Br J Ophthalmol. 2003 May;87(5):526-30. OPEN ACCESS

RESULTS: Among 360 pupils examined, 312 (96.7%) were aged <16 years. Of these children, 295 (94.5%) were blind or severely visually impaired. The major anatomical site of visual loss was cornea/phthisis (62.4%), followed by optic nerve lesions (9.8%), cataract/aphakia (9.2%), and lesions of the uvea (8.8%). The major aetiology was childhood factors (49.8%). The aetiology was unknown in 45.1% of cases. 68% of cases were considered to be potentially avoidable.

CONCLUSIONS: Vitamin A deficiency and measles were the major causes of severe visual impairment/blindness in children in schools for the blind in Ethiopia. The majority of causes acquired during childhood could be avoided through provision of basic primary healthcare services.

Corneal calcific band keratopathy, Vishal Jhanji, Current Opinion in Ophthalmology 2011, 22:283–289

Conditions associated with the occurrence of band keratopathy are as follows:

(1) ocular diseases

(a) chronic uveitis;

(b) phthisis bulbi;

(c) long-standing glaucoma;

(d) interstitial keratitis;

(e) dry eye and corneal exposure syndromes;

(f) spheroidal keratopathy;

(g) keratoprosthesis;

(2) hypercalcemia

(a) hyperparathyroidism;

(b) excessive vitamin D (e.g., oral intake, sarcoidosis, and osteoporosis);

(c) renal failure (e.g., Fanconi’s syndrome);

(d) hypophosphatasia;

(e) sarcoidosis;

(f) multiple myeloma;

(g) milk-alkali syndrome;

(h) metastatic carcinoma to bone;

(i) idiopathic;

(j) Paget’s disease;

(3) systemic diseases

(a) discoid lupus;

(b) gout;

(c) tuberous sclerosis;

(d) Norrie’s disease;

(e) congenital band keratopathy;

(4) chemicals

(a) mercury fumes;

(b) phosphate-containing drops;

(c) intraocular silicone oil;

(d) viscoelastics;

(e) thiazides.

Misc fact: (from somewhere)

Band keratopathy often does not decrease vision and requires no treatment or only treatment of the underlying condition. As it is typically seen in eyes with chronic uveitis and in blind eyes after multiple ocular surgeries, the majority of these patients have no complaints especially in the early stages.

Acanthamoeba Keratitis: A 12-Year Experience Covering a Wide Spectrum of Presentations, Diagnoses, and Outcomes ,Michael A. Page et al, Journal of Ophthalmology Volume 2013

TERMINAL CURIOSITIES

¶  In conversation, if I mention that I have contributed a letter to “This Week in Parasitology,” the listener invariably thinks that I’m interested in telekinesis and spoon bending. I find this strange since I associate the word parapsychology with the 1970s and never hear it in speech anymore. If you look at the quantitative word usage curve for parapsychology in the Ngram viewer (https://books.google.com/ngrams) you will see that it peaked in 1976. TWiPlets please continue your TWiP work; the public MUST STOP mixing-up parapsychology and parasitology!

¶ Addendum to my list of zoological medical metaphors in medicine (see TWiP 165 notes) : Leopard skin — dermatologic depigmentation finding in chronic onchocerciasis (mentioned in PD7 p 556).

¶ Annals of obsolete medical terminology.

I recently learned of an archaic term for blindness: Gutta serena. “An old term for amaurosis.” Who says amaurosis anymore?

Definitions [from https://www.medilexicon.com/dictionary/38795] —

1. former term for blindness of unknown etiology; the “serena” suggested that the anterior segment of the eye was clear and tranquil, that there was no visible cause for the blindness, no corneal scar, no inflammation, no cataract. Thus, gutta serena became the code word for blindness due to some unfathomable posterior cause, some damage to retina, optic nerve, or brain. This was the name given to John Milton’s blindness. With the opthalmoscope, in 1851, the diagnosis of gutta serena suddenly became old-fashioned and inadequate. [https://www.medilexicon.com/dictionary/38795]

The Study of Medicine, Volume 3, John Mason Good, Wells and Lilly, 1823 – Medicine – 494 pages

From John Mason Good’s 1823 text:

Drop serene: dimness or abolition of sight with an unalterable pupil, usually black and dilated; but without any other apparent defect. “This is the gutta serena of the Arabic writers, whence the term “drop serene,” of our own tongue….Milton is well know to allude to this affection in his beautiful address to light, as he does also to the cataract by hum called suffusion, as the Latins call it suffusio: but it is singular that, in the course of this allusion, he seems boubtful as to which of the two diseases he ought to ascribe his own blindness:

Thee I revisit safe

And feel thy sovereign, vital lamp: but thou

Revisit’st not these eyes, that roll in vain

To find thy piercing ray, and find no dawn.

So think a drop serene has quench’d their orbs,

or dim suffusion veil’d.

(Paradise Lost, 111:21)

¶ Other terms which I will not define but have a nice ring to them:

seclusio pupillae

iris bombe

synechiae

¶ gutta opaca= cataract.

¶ Another entity previously unknown to me–White Dot Syndrome. Article with some very arresting retinal photography:

Observation and Clinical Pattern in Patients with White Dot Syndromes: The Role of Color Photography in Monitoring Ocular Changes in Long-Term Observation, Joanna Brydak-Godowska, Med Sci Monit. 2017; 23: 1106–1115. OPEN ACCESS

The following paragraph from the above ref contains some sublime terms with associated contorted acronyms:

In this cohort of 62 patients, the following WDS entities were identified: multifocal choroiditis with panuveitis (MFCPU), multifocal choroiditis (MFC), punctate inner choroidopathy (PIC), birdshot, acute posterior multifocal placoid pigment epitheliopathy (APMPPE), subretinal fibrosis and uveitis, multiple evanescent white dot syndrome (MEWDS), serpiginous choroiditis, and single cases of acute annular outer retinopathy (AAOR)….The etiology of WDS is unknown and the hypothesized causes include viral infection, parasitic infestation, and autoimmune or genetic predisposition.

The Boston Globe, Stop saying that! A 2009 expression to forget By Jan Freeman January 3, 2010

“Now, it’s true that some images of hurting oneself are time-honored phrases. ”Cutting off your nose to spite your face” has been around since the 16th century. ”It’s better than a sharp stick in the eye” has been faint praise at least since the 1870s. Children have sworn ”cross my heart, hope to die” for more than a century, and for many of them, the next line is ”stick a needle in my eye.” Eventually, such familiar phrases lose some of their shock value.”

http://archive.boston.com/bostonglobe/ideas/articles/2010/01/03/stop_saying_that/

Shawzy writes:

Aloha,

I am a survivor of Rat Lungworm Disease. This podcast hosts were very rude and disrespectful when they started laughing about Sam Ballard’s case of eating a slug on a dare in episode 149, Stranger in a strange land. If you jerks are going to report on such a horrific disease you should be grown up enough, have some intelligence and respectful for your listeners and Rat Lungworm Disease victims that have died or are in the process of dying. You are not helping anyone by behaving that way.

Now go eat a Salad and think about Rat Lungworm Disease with every bite!

Mahalo

Shawzy

Rachel writes:

Hi,

  I may have missed your mention of this, but wanted to be

sure you were aware of it just in case: https://www.foldscope.com

Erica writes: (case 165)

Good afternoon,

I am no doctor and I am starting nursing school in the fall so I am not sure I am even close but I believe it could be one of these options.

Hydrocele

Hernia

Idiopathic scrotal edema

Have a great evening.

Anthony writes:

Hearing the folk “wisdom” of evicting a worm by trickery brought back memories.  I heard such a suggestion here in Jersey City probably well over 50 years ago. The suggested protocol (originally European?) was based on the “fact” that worms like sweets.  One was to make up a cup of coffee with lots of sugar and then stand in front of a mirror, breathing deeply through an open mouth. The worm would be enticed by the prospect of a delicious meal and abandon all caution.  When the worm was seen in the mirror (Dropping the coffee? With the free hand?), one was to grab the worm and pull it out.

# # #

On a more serious note, as a child, I heard linseed oil or garlic added to a dog’s food to rid it of worms.  Does either provide any relief? Might national diets that regularly include certain ingredients or spices help in the prevention, elimination or control of worms?  Might the mystical / religious practice of fasting eliminate tapeworms?

FWIW

Ben writes:

Dear hosts,

Sorry for the double email, but I couldn’t help myself! Ran across a TWiP, TWiV crossover pre-print, where they’ve potentially discovered the first virus of Plasmodium and appropriately named it after Russian Matryoshka dolls (a virus within a parasite within a host cell). If I remember correctly, I think Daniel said he worked with one of the authors, Nick Anstey, at some point!

https://www.biorxiv.org/content/early/2019/05/01/624403.full.pdf

Regards,

Ben

Ben Liffner

PhD Candidate – Malaria Biology Lab (Wilson Lab)

Research Centre for Infectious Diseases

School of Biological Sciences

The University of Adelaide

Steve writes:

The TWiPsters should be pleased to read this guest blog for the UK MRC on recent moves to really get to grips with Leishmaniasis and Chagas‎. I expect that there will be some familiar faces to the team in the pictures.

All the best,

Steve Hawkins

Luton

Beds.

UK

https://mrc.ukri.org/news/blog/the-gene-editing-workshops-tackling-invisible-diseases/?utm_medium=email&utm_source=govdelivery