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Thursday, 01 February 2018 12:59

TWiP 146 Letters

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Published in Letters

Case guesses:

Elizabeth writes:

A parasite. I would need to see it. Amoeba or toxoplasma? That’s my guess.

 

David writes:

Dear Hosts,

I would like to take a crack at the case from episode 145, but this one was certainly tricky. The man from Thailand suffering from continuous diarrhea and abdominal pain may be suffering from a case of heavy fasciolopsiasis caused by the liver fluke Fasciolopsis buski. Acute fasciolopsiasis marked by eosinophilia, abdominal pain, and diarrhea, which may set in 1-2 months after consumption of raw infected water plants (which we know from past episodes are a common food item in Thai dishes). Assuming the man’s symptoms didn’t set in until after he arrived in America, we can also assume the elliptical objects found in his stool were the eggs of the parasite, which are typically more than 100 microns in length.

If Fasciolopsis was not the culprit, I suspect another fluke (perhaps Paragonimus or Echinostoma) or any other parasite with eggs of this size may be the causative agent. Clonorchis sinensis, another common parasite in Thailand, was ruled out of the running since the eggs of this parasite are too small to be consistent with the object found in the man’s stool; and while continuous diarrhea is a symptom that many parasitic protozoans can cause, apart from Balantidium coli they are all much smaller than the 100-micron objects found in the man’s stool (unless he has multiple infections and the eggs are showing only as a result of the diarrhea stemmed from another source).

Taking all of these into consideration, I will stick with my gut and say that Fasciolopsis buski is the culprit.

Thank you once again for the informative and educational podcasts.

Sincerely,

David P.

 

Alistair writes:

Dear Hosts,

This is my first time writing into the show. I recently introduced the podcast to my lab colleagues and we are all excited to regularly discuss these case studies.

With the information given for the case study involving the patient from Thailand, the diarrhea and abdominal pain points to an intestinal pathogen.

Since the stool cultures were negative and the patient had eosinophilia, my first “gut feeling” was that this could be some kind of helminth parasite rather than a protozoan parasite.

Indeed, the O&P or ova and parasite exam implies that parasite eggs were found in the patient’s stool.

My next step was to consult the CDC website to compare different helminth ova sizes and morphologies. (https://www.cdc.gov/dpdx/diagnosticprocedures/stool/morphcomp.html).

Since the ova were found to be larger than 100 um, this narrowed the possible candidates. Schistosome eggs can be this large but generally do not fit the elliptical shape description and Schistosomiasis as far as I know is not particularly prevalent in Thailand.

This led me to Fasciola spp. or more specifically liver flukes which use snails as an intermediate host and use many mammals including humans as the definitive host. Infection can occur by ingestion of cysts attached to vegetation such as watercress. Liver flukes can cause diarrhea and abdominal pain in cases of heavy infection. Indeed, there was recent a report of a German traveler to Thailand that became infected with F. hepatica and had all of the described symptoms including abdominal pain, persistent diarrhea and hypereosinophilia.

https://www.ncbi.nlm.nih.gov/pubmed/25902701

Another possibility would be Fasciolopsis buski which can cause similar symptoms and has a history of being endemic in Thailand. Fasciolopsis buski and F. hepatica have apparently indistinguishable ova during stool examinations.

I have to say that if I do win the book it wasn’t because of a mere fluke!

Best wishes,

Alistair from the University of Manchester.

 

Eric writes:

Dear Profs. Racaniello, Despommier, and Griffin,

Your podcast and its kin have been entertaining and inspiring me on my daily commute since I discovered them 6 months ago. Thank you very much for putting the shows together! This is my first time writing in.

My guess is Fasciolopsis buski, the giant intestinal fluke.

The chief complaint is diarrhea persisting for what sounds like a week at least. Eosinophilia, objects in the stool, and the lack I assume of other symptoms and lab tests (e.g. frankly bloody stools, pain, liver symptoms/labs, bacteria upon culture), suggests a helminth infection of the intestine specifically.

Unicellular eukaryotes are in the 10’s of microns long, and 100 microns would be on the large end of the spectrum. For example, I learned from your book that Giardia spp. and Entamoeba histolytica cysts are both around 15 microns long each.

Of the nematodes, cestodes, and trematodes, I only found the trematodes to have sufficiently large eggs. The most common and largest* intestinal nematode, Ascaris, for example, has eggs around 50-70 microns in length only.

Of the trematodes, Schistosoma spp. and Fasciola spp. have large eggs, but the patient’s clinical picture lacks important symptoms (e.g. liver involvement) that we’d expect for those infections.

Fasciolopsis buski matches my expectations. It produces large eggs, around 130-150 microns in size, that travel in the stool. It is indeed endemic in Thailand and is a common infection worldwide**. Transmission by eating metacercariae on aquatic plants is plausible for our patient. The worm attaches to the small intestine epithelium and causes diarrhea. In heavy infections the diarrhea can be continuous, with nausea and vomiting, among other complications.

There are other species of intestinal flukes (e.g. Echinostoma spp.) in humans which produce >100-micron eggs, many reported from Eastern and Southeastern Asia, but none as common as Fasciolopsis**.

Treatment is praziquantel, at least 15 mg/kg (Bunnag et al. 1983). WHO recommends one dose of 25 mg/kg for all intestinal flukes (UpToDate -> http://apps.who.int/medicinedocs/es/d/Jh2922e/3.8.1.html).

Sincerely,

Eric

Los Angeles, CA

*I wonder how well the size of the adult worm corresponds to the size of the eggs. Can I argue that the largest worm of a clade has the largest eggs as well? Such a rule seems to work often for vertebrates. Fasciolopsis is the largest intestinal fluke in man.

**A study 35 years ago found 10% prevalence in a school in central Thailand (Bunnag et al. 1983) A library book mentioned Norman R. Stoll’s 1947 estimate of 10 million cases worldwide, but Stoll didn’t cite a source. It was hard to find a more recent estimate for these neglected tropical diseases; see Fürst et al. 2012 for two estimates.

Bunnag D, Radomyos P, Harinasuta C. Field trial on the treatment of fasciolopsiasis with praziquantel. Southeast Asian J Trop Med Public Health 1983;14: 216-219.

Stoll, NR. “This Wormy World”. The Journal of Parasitology. Vol. 33, No. 1 (Feb., 1947), pp. 1-18.

Fürst T, Keiser J, Utzinger J. Global burden of human food-borne trematodiasis: a systematic review and meta-analysis. The Lancet Infectious Diseases. 2012;12(3):210-221. doi:10.1016/S1473-3099(11)70294-8

—————————

(not part of the case answer)

P.S. I think there’s a typo in the table of contents of the book I downloaded from parasiteswithoutborders.com: on page viii, “Mansonella ozzardi” is spelled “Manzonella …” Not a big deal, but just pointing it out for any future editions.

 

Carl writes:

Dear Twipniks,

In trying to solve this case, I looked through the egg pictures in Appendix C of Parasitic Diseases sixth edition.  I figured that most parasite eggs are smaller than 100 microns, so that was a good place to start.  I found several species with appropriate eggs, which I used to build an elaborate spreadsheet indexing organisms against symptoms (if I were a real parasitologist I could do this in my head).   I was then able to eliminate all but one species. Here’s how I did eliminate them.

  • Schistosoma is not found in Thailand, except Schistosoma Mekongi, whose eggs are too small.  
  • Paragonimus Westermani doesn’t cause swelling, and causes epigastric pain rather than abdominal pain (I’m assuming the case report makes this distinction– but maybe epigastric pain is a kind of abdominal pain?)  Also, Paragonimus would be expect to show some lung symptoms in its acute phase.  
  • Fasciola Hepatica doesn’t cause diarrhea.
  • Fasciolopsis Buski doesn’t cause swelling.

The sole species left standing is Echinostoma, which is actually a genus that nobody seems to distinguish among.  Different species have different size eggs, but some are the right size, and they all cause violent watery diarrhea, eosinophilia, abdominal pain, and edema (hence swelling).  And they’re endemic in Thailand.  So my guess is that the unfortunate traveler has echinostomiasis, I hope he got better and I hope I win a book!

Dickson said that “axenic” was Greek for “known life”.  But he’s thinking of “Gnotobiotic”, from “gnotos”, known, and “bios”, life.  “Axenic” is “without strangers”, from “a-“, without, and “xenos”, strange.

In reading about Paragonimus Westermani I noticed that it is usually triploid, but also sometimes diploid.  And I found a paper describing relatively rare tetraploid forms.  How the heck does meiosis work in a triploid species? Is this something that’s stable on an evolutionary timescale, or is it just a weird phase that’s happening for a few generations before the species settles back to normal even-numbered ploidy? And how did it get started in the first place?  I’m a mere electrical engineer, so I can’t work out what’s going on from the papers I can google.  I’m hoping you can explain it for me.   

Thanks,

–Carl

 

Chris writes:

Good morning to the three wise TWIPers,

My name is Chris and now that I have finally caught up on every TWIP episode (now working on TWIV and TWIM) I can finally contribute and send in my case study answers! Due to the fact that the man from Thailand had eosinophilia and visible eggs in the stool I instantly thought helminth parasite so my first guess was Clonorchis sinensis due to the location of the patient and the fact that he has eosinophilia and diarrhea which are possible symptoms of this parasite, but upon looking up the size of the eggs of this parasite it cannot be. Clonorchis sinensis has fairly small eggs which was one of the main  clues Dan provided. After looking through Parasitic Diseases I found Fasciolopsis buski. I believe the man from the case study has Fasciolopsis buski because this parasite can cause continuous diarrhea, can cause eosinophilia even in light infections as this parasite likes to feed on columnar epithelial cells, and it commonly causes abdominal pain. the last key that helped me reach this conclusion was that I found a nice picture of one of Fasciolopsis buski eggs which is both elliptical and is measured at 140 µm x 80 µm in Parasitic Diseases 6th edition. I’m feeling pretty good for my first write in answer for a clinical case so I am very much looking forward to the next episode!

In addition to listening to TWIP today I read this cool paper in The Journal of Parasitology this morning and I think It would be cool to hear you all talk about it. I think I talks about some cool life cycle stuff and some good fundamental parasitology. Additionally it talks about a parasite that was once a case study answer  The raccoon roundworm Baylisascaris procyonis! Once again thanks for all your work and I am hoping to win the textbook!

Warm Regards,

Chris

P.S I just finished People Parasites and Plowshares, and it was a fantastic read! I highly encourage every TWIP listener to go out and get their own copy, YOU WON’T REGRET IT!

The paper: https://www.ncbi.nlm.nih.gov/pubmed/28732456

 

email

John writes:

TWIP Trio,

Greetings from a chilly and snowy Creighton University in Omaha. I’m writing to reply to Sara’s excellent request to hear about a parasitology heroine. I commend Marietta Voge, a former president of the American Society of Parasitologists. Below is the 1988 In Memoriam from the University of California

Marietta Voge, Microbiology and Immunology: Los Angeles

In July of 1984 the UCLA School of Medicine lost a great scholar, teacher and friend with the passing of Dr. Marietta Voge. She had spent almost her entire academic career on the faculty of the medical school, first in the Department of Infectious Diseases and then the Department of Microbiology and Immunology. During her tenure, she and her colleagues developed one of the most innovative and comprehensive curricula in medical parasitology for students of medicine. The textbook that she wrote with her friend and colleague, Edward Markell, is presently in its sixth edition and is considered among the very best texts for students of medicine.

Voge served as the major professor for many graduate students and postdoctoral fellows from all points of the globe. She precepted medical students who would eventually apply their knowledge in laboratory parasitology to clinical practice, public and world health. She spent much of her own vacation time working in developing countries, refugee camps in Central America and isolated mission clinics.

Above all, Marietta Voge was a great teacher. She was a creative educator who taught by example. She had scientific honesty, high standards of behavior toward colleagues and students, and she never put her name on a piece of work unless she had participated actively in the project.

In her presidential address to the American Society of Parasitologists she wrote, “It is the teacher that sparks and stimulates the minds of students to produce new ideas. It is the teacher who gives the impetus to students to become the most important propellant to our society and civilization–the innovator, because without innovation and originality, society becomes stagnant and decadent. A superior teacher is the interpreter and keeper of our past, the critic of our present, the dreamer of things to come.” Dr. Marietta Voge was all of these and much more.

Larry Simpson Jerrold Turner James Seidel

From: http://texts.cdlib.org/view?docId=hb967nb5k3&doc.view=frames&chunk.id=div00057&toc.depth=1&toc.id=&brand=calisphere?

 

Neeraj writes:

Dear Educators,

I hope you all are having a wondering 2018 so far and I look forward to listening many more hours of incredibly educational podcasting from your esteemed team. At my end, I would like to personally thank you for your insatiable desire to learn and educate the broader audience. Personally, I feel incredibly fortunate to have been introduced to the TwiX series (especially TWiP) since the last 2 years, and have greatly benefited from listening to it.

Professionally, I work for a vaccine development company namely SutroVax, Inc. where we use cell free protein synthesis (CFPS) to express and purify “hard-to-make” vaccine targets (primarily by overcoming the issue of cellular toxicity associated with the antigens under investigation). Incidentally, after joining the company in 2015, I started working on a malarial protein namely Pfs25, which is a cell surface antigen expressed on malaria during the course of its lifecycle in the mosquito and not in the human host. In addition to this protein antigen alone, the malarial GPI (glycophosphatidylinositol) linker has also been shown to be strong activator of host immune response. Thus using our proprietary CFPS technology, not only were we able to robustly express copious amounts of Pfs25 (historically it’s been quite difficult to make copious amounts of this antigen in a scalable expression system), but we could also design a non-natural amino acid site at the C-terminus to conjugate it to a synthetic version of the glycan core of Malaria GPI using click chemistry. Finally and most importantly, using this conjugate vaccine target we immunized mice and showed that the anti-sera thus generated, was broadly neutralizing and conferred protection against development of malarial oocysts in the mosquito’s gut. This to us was quite intriguing and I am happy to update that only recently this work was accepted for publication.

On a different note, I am sure at this point you all must be wondering, well that’s interesting but what’s the rationale for inundating us with these details J. Well the point of that detailed outline was to update you with the referenced research work and thank you for your podcast (especially some of the earlier episodes on Malaria) since it was greatly beneficial for me when I was getting started on the project. Your educational podcasts helped me put things into context and see the merit of the research we were undertaking. Thus even though you all weren’t directly a part of the actual research (in spirit you were), none of this work would have been possible without the help of the incredible TWiP team, and in particular the amazing story teller that is “Dr Despommier”. At the time we initiated this investigation, I  had no prior research background in Malaria and was desperately looking for resources to help educate and familiarize with this enormous field of investigation. In this regard, several TWiPs came to my rescue and helped me get abreast with why it’s so tricky to treat malaria and what are the several major initiatives than have been undertaken but have unfortunately not yielded in development of viable treatment option before the infection hits. Artemisinin based combination therapies are still the primary mode of treatment, but post infection. Furthermore, even the proposed use of bed nets along with vaccination using the GSK developed RTS,S vaccine has largely been unsuccessful in a field setting to provide significant and sustained immunity. Thus even with all the years of toil and desperate effort, we are far from controlling, let along curing, this enormous global health epidemic. So to think of ways to help produce meaningful vaccine candidates,  we utilized our in house proprietary platform for generating a synthetic conjugate vaccine that combined a malarial protein and carbohydrate into one entity. And I am happy to report that the relevant work was only recently accepted for publication in Biochemistry. Thus as a token of deep gratitude and immense appreciation for your scientific generosity, I am attaching a copy of the same for your kind consideration. I hope you enjoy reading it as much as I have enjoyed working on this very exciting project (and please feel free to send any queries my way in case there is anything I can help with).

Historically, the premise of vaccine development against malaria has been to use antigens that are expressed in the human host. However unfortunately, none of those endeavors have yielded a potent vaccine candidate that has conferred significant protection against acquiring this infection. Thus to circumvent this, we have tried to attack the problem through design and generation of Transmission blocking vaccine (which blocks the development of malaria in the definitive host rather than block the progression of infection in human host). In support of this hypothesis, the published results have given us confidence that this line of reasoning can probably help but then again, these are all results generated in a lab setting and whether these will pan out in a field setting is a question we would like to further investigate.

Thus overall (and I apologize if my email has sounded too convoluted and information dense), I would just like to personally thank and commend each one of you for your tireless effort in putting out these podcasts for the general audience. And I hope my small token of appreciation will help consolidate and reinforce  the belief that at times you might not hear back from everyone that listens and feel that we are not benefitting from these podcasts, but rest assured, WE ARE J. If anything, my only grimace is that I wish I had found this series earlier but nonetheless, I am eternally thankful to my boss Dr Jeff Fairman (who has been a longtime dedicated listener of the TWiX series as well) for introducing me to this amazing world of insights into the parasitic world. Thus please continue to march on and educate us as you have done for several years now. I know I have singled out Dr Despommmier as the most important cog in the wheel but I am sure he will agree that without the diligent effort and expertise of Dr Griffin and Dr Racaniello, this journey would probably not have been as rewarding and memorable as it has been. And if you kind folks ever visit the bay area, I would love to have an opportunity to meet and engage with you personally (as a starter, you are always welcome to our company wide happy hour on Friday afternoons where “spirited” (pun intended) discussions happen J).

A listener in constant debt of your teaching,

Best,

Neeraj

Neeraj Kapoor, Ph.D.

Scientist II

SutroVax, Inc.

 

Andrea writes:

Greeting Twipitos!

Have you seen this one?

https://www.rawstory.com/2018/01/california-sushi-lover-pulls-5-foot-tapeworm-out-of-his-own-body/

First the patient extracting the guinea worm from his own body and now this

Still rainy in Seattle…..

 

John writes:

TWIP Trio,

Greetings from a snowy Omaha, NE! Creighton University’s snow day gave me some time to listen to your latest episode.

Oddly, this made the news right after you posted TWIP #145 and the Case Study featuring Diphyllobothrium:

https://www.npr.org/sections/thetwo-way/2018/01/19/579130873/man-pulls-5-1-2-foot-long-tapeworm-out-of-his-body-blames-sushi-habit

The man with the tapeworm complained of bloody diarrhea, but most sources I’ve consulted, including the 6th edition of Parasitic Diseases state, “infection with the fish tapeworm results in no obvious symptoms. Infections with multiple worms may cause nonspecific symptoms such as watery diarrhea, fatigue, and rarely mechanical obstruction of the small bowel.” (p 359)

Question: Did the man’s tapeworm infection result in the bloody diarrhea or does he have something else to worry about?

peace

John Shea, SJ, Ph.D.

Jesuit Community Creighton University

2500 California Plaza

Omaha, NE

“He sighed from the depths of his spirit”  (Mk 8: 12)

 

Anthony writes:

This is from 2010.  I’m sending it because I have two questions.  Could the roundworms directly infect the eye by fecal contamination?  Even if that is so, could the infection/infestation progress to such an extent in less than 24 hours?

AO

On the mend, toddler in dog mess scare

https://www.manchestereveningnews.co.uk/news/greater-manchester-news/on-the-mend-toddler-in-dog-mess-scare-898639

Vincent Racaniello

Vincent Racaniello, Ph.D. is Professor of Microbiology at Columbia University Medical Center. As principal investigator of his laboratory, he oversees the research that is carried out by Ph.D. students and postdoctoral fellows. He also teaches virology to graduate students, as well as medical, dental, and nursing students.

Vincent entered the world of social media in 2004 with virology blog, followed by This Week in Virology. Videocasts of lectures from his undergraduate virology course are on iTunes University and virology blog. You can find him on WikipediaTwitter, Facebook, and Instagram. His goal is to be Earth’s virology professor. In recognition of his contribution to microbiology education, he was awarded the Peter Wildy Prize for Microbiology Education by the Society for General Microbiology. His Wildy Lecture provides an overview of how he uses social media for science communication.

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