Cam writes:
Hi TWiP team,
NSW, Australia, 12°C, 53°F, Partly cloudy. With the colder weather we have had here, you would think winter was still here!
To cut a long diagnosis short, my diagnosis is strongyloidiasis with adenocarcinoma of the colon, and to go further perhaps, even strongyloidiasis induced adenocarcinoma of the colon. An infection with Strongyloides stercoralis, a genus of parasitic nematodes. The rhabditid nematode can lead to cases of autoinfection. If left untreated this can result in persistent infections lasting decades, leading to the development of a hyperinfection syndrome.
Reasons:
The eggs of Strongyloides stercoralis are large and ellipsoid, 40–85 μm in length, fitting the 80 μm “Slightly ovoid” profile of the eggs observed in this case.
I ruled out other infections like Schistosoma japonicum. The eggs observed in this case, although are also around the right size for parasites such as Schistosoma japonicum, 90 µm x 70 µm, S. japonicum has a distinctly different appearance, the eggs have a distinct small lateral spine that may appear as a small hook or “knob”. What also made Schistosoma japonicum a suspect, is that it does occur in Southeast Asia and the case we are looking at is from China originally, and there are also examples of parasitically induced cancers such as a suspected case with a concomitance of S. japonicum infection and rectal carcinoid tumour in an asymptomatic patient (1.)
Overall Trematode eggs are generally much too large to fit the profile, so that tends to rule them out. (see attached egg size documentation CDC)
Another reason for deciding it was Strongyloides stercoralis instead, is that has been implicated in Colon adenocarcinoma in other past cases. (2. Parasite Infection, Carcinogenesis and Human Malignancy) [See table 1]
I eliminated Infection from parasites like Liver flukes as a possible cause, since that would tend to result in Cholangiocarcinoma and not be expected to be seen in Colon adenocarcinoma.
Egg structure and appearance would be consistent with Ascaris lumbricoides (Round Worm) but egg laying adult worms would more than likely have shown up on the CT scan and aren’t as implicated in parasitic infection-associated malignancy. The adult Strongyloides stercoralis being approximately 50 µm in diameter and between 350-600 µm in length, would not show up as well on a CT as Ascaris lumbricoides worms that are massive by comparison.
To confirm the diagnosis, serology testing via immunosorbent assay (ELISA) to test for larval antigens would be diagnostic.
Treatment could be complicated due to the surgery for the adenocarcinoma. In this case I would suggest deferring to the attending surgeon to recommend appropriate medications for the parasitic infection immediately post surgically. Neutrophilia fits the case, though may also indicate opportunistic secondary infection, which should be checked for, via signs such as fever or culture. Antibiotics as appropriate should be administered if indicated.
Plus:
Normal therapy used without regard to the surgery;
Ironically, some might say in the current climate, but the normal first line therapy would be, Ivermectin, in a single dose, 200 µg/kg orally for 1—2 days.
Additional approaches to therapy would be:
Albendazole, 400 mg orally two times a day for 7 days.
Ivermectin, 200 µg/kg per day orally until stool and/or sputum exams are negative for 2 weeks.
I think in this case we can rule out all non-egg laying organisms safely. It is not going to be a virus! I don’t know of any egg laying viruses; it would have to be a bloody big virus and I am sure Vincent would have told us about it in class (“Virology Live” 2am Thursdays Oz time). Though who knows what gems of knowledge Vincent will share with us all in “Viruses Live”, the, I am sure, most excellent, advanced virology course to come in 2022! ( I can safely predict egg laying viruses won’t be one of the gems though, LOL )
Cheers,
MrOzzyCam
Sara writes:
Dear Drs. Despommier, Naula, Racaniello, and Griffin,
I’m retruning to TWIP from a cloudy, 2 degrees Celsius (~36 F) morning in Philadelphia. I am catching up on epsides after several weeks away to prepare for Step 2. (Parasitology was sadly underrepresented among the medical licensing exam questions.) What a fascinating clinical case to return to!! And thank you, as always, for the incredible review of recent research in Leishmania…
This is a case of an older gentlemman with no significant past medical history who presents with several months of isolated, progressively worsening abdominal pain. He grew up in rural inland China and moved to large urban area in adulthood. He avidly consumes fish (cooked and raw) and leafy vegetables. We were not told he eats snails, but I’m not ruling that out. We also learn he loves to swim (including, I presume, in freshwater given the rural setting of his childhood). He lives without other people or pets. He migrated to the US 10 years prior to presentation. HIV-negative. His physical exam is unremarkable. Laboratory studies reveal a neutrophil-predominant leukocytosis (without eosinophilia), mild thrombocytopenia, and no anemia. Chemistries and hepatobiliary function studies are within normal limits. Abdominal CT reveals a colonic mass. A colonoscopy is performed. The mass is resected. Pathology reveals adenocarcinoma with…eggs! Then we learn the eggs measure 80microns in diameter, but we do not know their shape.
Firstly, I suspect his abdominal pain is due to the evolving malignancy, rather than his chronic parasitic infection.
Now for the parasite.
Even without knowing the size of the eggs found in his colonic mass, the isolated gastrointestinal location of his infection, lack of associated eosinophilia, and its chronicity without deadly sequelae rules out nematodes who squiggle into human tissues (like the terrifying rat lungworm) and all filarial worms (including Wuchereria bancrofti which I would expect from exposure to mosquitos in rural China).
Eggs that are 80 microns in diameter! Which, if I’m not totally wrong is way too big for any nematode. I remember roundworm egg size rounds out the range of average human lifespans across the globe, (that is 50 – 75yrs) and then I swap years for microns.
So, what options do we have for non-nematode intestinal-only parasites that can hang out for >10 years without causing noteworthy symptoms?
Diphyllobothrium latum transmitted through saltwater fish consumption is my favorite worm because of its incredible segmented appearance and the interdependence of its proglottids with central uteruses. It looks like an alien to me. I’m not sure how big its eggs are but I want to say big because it’s such a big worm. I think he would have noticed ribbon-like, ivory colored strings of the large, square proglottids sloughing off into his stools and I imagine this would have caused him GI symptoms.
Liver flukes: Even though he eats leafy vegetables, I’m not even giving liver flukes a second thoght because he had not biliary involvement on abdominal imaging. Liver flukes predispose to cholangiocarcinoma (not colonic adeno) because a theatrical attending taught me this on a recent rotation and his description was so mesmerizing that I have not forgotten (Thanks Dr. B)…
Dwarf tapeworm: I have no idea how large dwarf tapeworm eggs are, but this is common in southeast Asia and could be asymptomatic, though he could have also had diarrhea, weight loss and itch, especially perianal itching (or is that pinworms?). I’m keeping this one on my differential.
Anisakiasis is always what I think of when I think of undercooked oceanic fish. I received a video from a friend of a moving worm found on monkfish she was eating and I was sure it was anisakis. If she had frozen the fish completely prior to eating it, the worm would have died and she would have been safe. That or thoroughly cooking it. But these cause localized discomfort and or allergic reactions and people often feel something crawling in their esophagus. Then if you scope them, you’d see the worms wiggling around. Obviously recommended she see an MD, but i believe no need for antihelminthic treatment. Let me see if I can share the video in this email.
Now for Shistosomes. Schistosoma japonicum and Schistosoma mekongi would make geographic sense for him. Maybe he had an acute infection long ago and does not associate it with his current abdominal pain? These can hang around for a very long time!! And I know Schistosome eggs get nestled into tissue walls (I think of lungs and bladder) and are inflammation producing and therefore could absolutely cause anything from an ulcerative colitis like picture to colonic adenomas and eventual carcinogenesis. I hope to learn whether these species would be expected to avoid his lungs and liver. [Nothing was said about bloody urine or I would have thought about S. haematobium, which I remember as S. haemat(uria)bium… ]
OK, so if it is between Dwarf tapeworm, anisakis (photo attached), Schistosoma japonicum/mekongi, or some parasite I have yet to learn about…I’m going to pick the one that is most likely to give him adenocarcinoma. That’s Schistosoma japonicum or mekongi… I’m going to say japonicum because I have a 50-50 chance here and the name is closer geographically speaking.
I was recently reading a paper about malignancies associated with various bacterial species … I cannot wait for your guest expert’s appearance and to learn all about carcinogenesis from parasites!!! I also would love to know if you or your guest have come across any research that would suggest that overfishing is contributing to a higher parasitic worm-to-fish ratio in the ocean.
Thank you all so very much!! You bring me so much joy and learning!
Sara (MS4)
—
Sara Rendell, PhD
MD candidate
Pronouns: She/Her/Hers
Perelman School of Medicine
and Department of Anthropology
University of Pennsylvania
Susan writes:
Hello Twippers,
Greetings from Seattle, where the weather is rainy, in the mid-forties Fahrenheit. My oasis of sanity over the past couple years has been microbe.tv shows. I especially like the audience participation format in TWiP, but have been reluctant to submit an answer myself. Until now. The small number of submissions this week has propelled me into action. (Shout out to Wikipedia)
The elderly man who presented with abdominal pain has, I suggest, been infected with the fluke, Fasciolopsis Buski, which is endemic in rural China, where he grew up and where he has continued to visit. Humans acquire this parasite by ingesting metacercariae on aquatic plants and in infected water. Since this gentleman has a diet that includes many vegetables and fish, both cooked and raw, and visits an area where the parasite is endemic, it is reasonable to speculate that he could have ingested the organism. Abdominal pain fits possible symptoms of fasciolopsiasis.
Diagnosis of the disease is by microscopic identification of the eggs. The ovoid 80 Micron eggs observed in the pathology sample are consistent with this parasite.
(This next paragraph is pure speculation. If I’m right, Perhaps I may be lucky enough to beat Dickson to the pun line.) The fact that you will have a special guest connected with this case on your next TWiP suggests to me that this gentleman himself might be joining you. If that is true, it was a “fluke” that the adenocarcinoma was detected and treated early.
Thank you for all you do. The far-reaching effects of your efforts are immeasurable.
Susan
Lorne writes:
After watching a few Twip episodes, I decided to give the “Name that parasite” challenge a go.
I’m going to name the Parasite “Xi” Since the WHO avoided the name. A family name less common than “Mu” in China.
All joking aside, I found this sleuthing to be quite challenging and educational.
Clonorchis sinensis (My guess for this challenge) came up early in my search but I originally dismissed it as the issues it causes are listed as hepatic and biliary.
After going down a few rabbit holes and over a dozen research papers, I emerged with a better understanding and appreciation for parasites. They are both fascinating and creepy.
Eventually, after a few re-watches of Daniel’s case description and searching Wikipedia for Adenocarcinoma, I was able to piece together that Adenocarcinoma, Cholangiocarcinoma, Bile duct cancer and Colorectal cancer could all be synonymous.
Call it a “Fluke” but I had my answer… and a bad Trematode pun. At least, that’s what “Xi” said.
Thanks Daniel. It was an educational challenge.
Janine writes:
Hi,
My guess for this case is Schistosoma japonicum. This patient likely acquired the parasite in China. The pair of adult worms live for 20 years and clinical disease in humans is caused by a host inflammatory reaction to the many eggs produced by the worms.
Haematobium eggs which collect in the bladder are well recognised to cause bladder cancer. It seemed plausible to me that inflammation in the bowel wall caused by egg deposits from the species whose eggs are excreted via the GI route could eventually progress to cancer.
Google kindly provided some papers suggesting this is the case and interestingly, it seems there is a stronger association with japonicum, the species present in China, compared with mansoni.
The size of the egg and ovoid shape I think is in keeping (japonicum is more rounded than mansoni and haematobium).
I did my DTMH (diploma in tropical medicine and hygeine) in Liverpool in 2011 and it seems I am out of date, as google shows eggs of 5 Schisto species whereas I recall only learning of 3. If I win a book, I’m sure it will help me to update up my knowledge!
Take care,
Janine Carter, specialist registrar in infectious diseases, Leeds, UK
Kevin writes:
Dear TWiP Tetrad,
Searching through PD7, I saw that Fasciola hepatica and Fasciolopsis buski produce ovoid eggs 80 microns in width but over 130 microns in length. The exposure risks (some fresh freshwater veggies in China) and abdominal pain line up, and PD7 notes that Fasciola hepatica is sometimes found outside of its usual liver lounge as a tumor mass. Fasciolopsis buski is normally in the small intestine, though a heavier infection may have pushed it into the colon. However, both of these trematodes generally result in an eosinophil-dominated blood count.
Echinostomid flukes have similarly plausible eggs, but similarly results in eosinophilia.
Clonorchis sinensis fits the geographic range and fish-eating habits, and is noted for inducing carcinogenesis, though mostly notably bile duct cancer. Eosinophilia expected again, drat.
Anisakids can be associated with colon cancer and raw fish consumption. However, the abdominal pain would be rapid onset, and the eggs and eosinophils don’t line up.
Overall, I’m unsure but I’ll submit Fasciolopsis buski as my final answer.
Cheers,
Kevin
Martha writes:
Dear TWiPers,
I hope this finds you all well. I very much enjoy these cases. No rush sending out the book, I have more than enough reading with the Principles of Virology.
The case presented in episode 201 is of an elderly man, originally from rural inland China, who later moved to a city and finally came to the USA. This history would give him ample opportunity to acquire a variety of parasites. Fortunately, Dr. Griffin narrows the field of candidates by disclosing that the patient has a biopsy of a colonic lesion which is cancer associated with 80μm eggs.
I did not know that parasites could do this. And I’m rather horrified.
So the search is on for the creature.
Strongyloides stercoralis apparently can be associated with malignancy in the duodenum and jejunum and the eggs are bordering on the right size at 40-85μm. I’m thinking it’s not this one since the lesion was in the colon and the biopsy was obtained by colonoscopy.
Schistosoma mansoni has been found associated with colon cancer, but the eggs are described as 115-180μm. So the eggs are not the right size.
Finally, Schistosoma japonicum which has also been found in association with colon cancer. This can be acquired by swimming in infested water. He might have come in contact with the parasite in his youth in rural China. The eggs are reportedly 70-100μm. So this is my guess.
Was it possible to resect the tumor by colonoscopy or did he require a partial colectomy?
It seems I was late to respond to the last case, so I’m trying to be a bit quicker this time.
Best wishes to you all
Martha
Mark writes:
Parasitology was my favorite lecture and laboratory. My guess for the type of eggs AND potential cause for the adenocarcinoma is Schistosoma japonicum. Schistosomiasis has been implicated as a cause for several cancers including this type. I chose this species of Schistosome due to the egg size and the endemicity coinciding with patient residences and travel.
Thank you for these case studies!
Mark
Alderson, WV
Christine writes:
Dear Professors Racaniello, Despommier, and Griffin,
My name is Christine; I am currently a fourth-year veterinary student at UC Davis, and I will be starting my pathology residency and Ph.D. next year at Washington State University. The pathology portion of this case is what caught my interest, and I’m very excited to be writing in for the very first time. I suspect that the 65+ year-old man with abdominal pain and a colonic adenocarcinoma with parasite eggs measuring 80 microns present in biopsied tissue has Schistosomiasis, more specifically Schistosoma japonicum. S. japonicum is a zoonotic trematode that is endemic in mainland China and that has been associated with liver and colorectal cancer. These intravascular flukes are acquired by skin invasion by swimming or wading in contaminated freshwater, where the infective cercariae (larval flukes) are released from the snail intermediate host. I thought that this fits well with the history of the patient swimming in the river while growing up in China. Humans are the main reservoir of infection, but dogs, cats, rodents, pigs, horses, and goats all serve as reservoirs for S. japonicum. Chronic inflammation plays a pivotal role in carcinogenesis, as the eggs that are deposited in the large intestinal mucosa and submucosa result in a severe focal inflammatory reaction. Over time, this chronic inflammation causes fibrosis, mucosal hyperplasia, the formation of polyps and ultimately, cancerous transformation. In addition to chronic inflammation, immunomodulation, the mutagenic effect of schistosomal toxins, and bacterial coinfection particularly with Salmonella species may also play important roles in the carcinogenic process.
Thank you so much for your excellent work on this phenomenal podcast!
All the best,
Christine
Christine Haake
Radiology Club | President
UC Davis School of Veterinary Medicine, 2022 | DVM Candidate
Hamid, Hytham KS. “Schistosoma japonicum–associated colorectal cancer: A review.” The American journal of tropical medicine and hygiene 100.3 (2019): 501.
Qiu, D-C., et al. “A matched, case–control study of the association between Schistosoma japonicum and liver and colon cancers, in rural China.” Annals of Tropical Medicine & Parasitology 99.1 (2005): 47-52.
Van Tong, Hoang, et al. “Parasite infection, carcinogenesis and human malignancy.” EBioMedicine 15 (2017): 12-23.
Andrew writes:
Kia ora from Pongaroa,
My guess is Schistosomiasis and most likely with S.japonicum. The geography works and the size of the eggs (big enough to poach) works as well. However, I don’t think the carcinoma is a result of the infection but rather the ova got trapped in the tumour which had another cause.
Off topic: Vincent mentioned in an Q&A with A&V short TikTok type videos and it reminds me that Dicksen is already a TikTok Star. Well, not quite but @questella has a video of him reading pandemic poetry and it can be found on https://vm.tiktok.com/ZSeaufWTJ/
Should you ever consider expanding Microbe.tv to TikTok then short selected questions and answers from Q&As could work well in short 1 to 3 minute formats they allow. That is a not so subtle hint for a TWiP Q&A 🙂
I am looking forward to 2022 with lots of intriguing parasites.
Nā,
Andrew
Elise writes:
Dear TWiP Quartet,
Happy new year and many best wishes.
While it was a super humid 56 degrees F yesterday (13 C), the temperature now is a rather bleak 28 degrees F (-2.2 C) with grey skies and a pretty sharp wind. While yesterday felt weird, it now feels definitively January-esque.
I am writing quickly with a guess diagnosis (quickly because if I don’t, something or someone will get in my way and I’ll miss yet another month of guessing, which is unacceptable).
I suspect strongly that the patient’s abdominal issues were caused by the cancerous mass in his colon, which in turn was caused by Schistosomiasis. (My further guess is that this is a Schistosoma japonicum infection.)
Even though Schistosomiasis is not found in New York (or really the United States), the patient grew up in rural China, where it is endemic. I suspect he became infected with the parasite in China and has lived with it for quite a long time, long enough for the infection and irritation to create the cancerous mass. The eggs discovered in the mass are also consistent in shape and size with Schistosoma japonicum.
I do have questions about the patient. How long would he have had to harbor the infection before a cancerous mass developed? How does the cancer develop? Is it really the product of relentless irritation from the infection? I did find quite a number of articles about people whose Schistosoma infections did develop into colon masses, (thus my diagnostic guess) but how long does this take? Also, once the mass is removed, was the patient also treated for the Schistosoma infection or was the mass removal sufficient?
Thank you so very much , as always, for your amazing work. It is always such a happy distraction for me to get to hear (or watch) your podcasts and attempt my amateur detective work.
Best best wishes
Elise (in Lower Manhattan)
Owain writes:
Dear TWIP,
Your plea last time for more guesses made me feel very guilty! I haven’t guessed in a while, in part due to moving flat, and in part due to finishing the dissertation component of an MSc in Medical Parasitology, which your podcast definitely helped inspire me to pursue – so thank you! Hopefully that’s not too bad an excuse..
My guess for this case is that Paragonimus eggs were found in the biopsy samples. They’re the right size and shape, and most of the other raw fish/vegetable-acquired helminths I could think of don’t have eggs the right size. I did consider Schistosoma japonicum, but think it’s less likely, as it’s been a while since he lived in rural parts of China where he could have picked it up.
Hopefully the reduced guess numbers improve my odds of a book!
All the best, and Happy New Year,
Owain
P.S. As a fellow Stargate fan, I enjoyed Daniel discussing symbionts at length in episode 200, given how heavily they feature in the show!
The Parasitology club at University of Central Lancashire writes:<=winner
Dear TWIP professors,
Happy New Year and greetings from the Parasitology club at University of Central Lancashire located in the currently wet and cold Northwest of England.
This was appearing to be a tricky case until Daniel revealed that slightly oval 80um ova had been found in tissues of the colon and linking this with a childhood in rural China we immediately thought of Schistosomiasis.
Referring the parasite ova identification chart in PD7 and reviewing the geographical distribution of Schistosoma species we think that this Chinese gentleman may have been living for many years with an historic infection with Schistosoma japonicum.
Wang et al (2020) described infection with Schistosoma japonicum as a critical risk factor in development of colorectal cancer from a study of over 220,000 Shanghai county residents aged over 45.
It is exam season so we will keep our response rather brief, but we are constantly grateful for the challenging and fascinating case studies to help us learn more.
David
On behalf of the University of Central Lancashire Parasitology Club
References
Despommier, D.D., Griffin, D.O., Gwadz, R.W. and Hotez, P. Parasitic Diseases. New York: Parasites Without Borders, Inc.
Wang, Jing and Zhu, Meiying and Zou, Ansheng and Du, Qinghu and Yu, Baohua and Liu, Zhenguo and Wang, Lei, Schistosoma Japonicum Infection is a Critical Risk Factor for Presence and Pathologic Subtypes Redistribution of Colorectal Cancer in Rural China (3/22/2020). Available at SSRN: https://ssrn.com/abstract=3559546 or http://dx.doi.org/10.2139/ssrn.3559546
Dr David Wareing
Senior Lecturer in Medical Microbiology
Course Leader for B.Sc. Microbiology
University of Central Lancashire
Preston