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TWiP 93 letters

Sandra writes:

Daniel: I was fascinated by your answer to the case from TWIP 91 - the life cycle of the southeast Asian worm (I won't even try to spell it.) Re early symptom coughing & wheezing: if the ED did a chest X-ray out of concern about the lungs, would the X-ray give any clue as to the true cause?

Thanks,
Sandra in Dallas

Anthony writes:

If memory serves me correctly, in dogs and cats, roundworms evacuated after a dose of piperazine tend to coil in a "watch-spring" shape unlike any other worms. Is this not the case with human roundworms?
Is the watchspring shape in dog and cat roundworms an effect of piperazine? Or is the lack of this form in the human parasite images an effect of preservation?

Tangentially,the reason for the parasite jumping ship in the case study was attributed to the stress of acquiring the craft of medicine. If this wasn't meant as dry humor, should such apprenticeship be
questioned? If a parasite senses their vessel to be sinking, it would seem that these conditions could be defined as cruel and unusual punishment for a mass murderer. Is there really a need for every
doctor to have experience functioning under extremes of sleep deprivation? And should patients be exposed to a judgement impaired novice?

FWIW

Robin writes:

Human infection by Anisakis simplex (herring worm) and other nematodes, or roundworms, is caused by eating certain raw or undercooked fish. Ingestion of the worm can result in severe abdominal pain, nausea, and vomiting within hours of ingestion and has been misdiagnosed as appendicitis or other abdominal diseases. If the worms don’t get coughed up or vomited out, they can burrow into the walls of the intestines and cause a localized immune response. The worms eventually die and are removed by the immune system. In severe cases, physical removal of the worms by endoscopy or surgery is needed to reduce the pain. People who produce immunoglobulin E in response to this parasite may subsequently have an allergic reaction, including anaphylaxis, after eating fish that have been infected with Anisakis species. Albendazole may be used to treat mild cases.

Anisakis species have complex life cycles which pass through number of hosts through the course of their lives. Eggs hatch in seawater, and larvae are eaten by crustaceans, usually euphausids. The infected crustacean is subsequently eaten by a fish or squid, and the nematode burrows into the wall of the gut and encysts in a protective coat, usually on the outside of the visceral organs, but occasionally in the muscle or beneath the skin. The life cycle is completed when an infected fish is eaten by a marine mammal, such as a whale, seal, or dolphin. The nematode excysts in the intestine, feeds, grows, mates and releases eggs into the seawater in the host's feces. As the gut of a marine mammal is functionally very similar to that of a human, Anisakis species are able to infect humans who eat raw or undercooked fish.
The known diversity of the genus has increased greatly over the past 20 years, with the advent of modern genetic techniques in species identification. Each final host species was discovered to have its own biochemically and genetically identifiable "sibling species" of Anisakis, which is reproductively isolated. This finding has allowed the proportion of different sibling species in a fish to be used as an indicator of population identity in fish stocks.

"If you copy from one person it's plagiarism. If you copy from ten persons it's a topical discussion. If you copy from a hundred persons it's a subject synopsis. If you copy from a thousand persons, it's a comprehensive literature review."

Christine writes:

Dear Vincent, Dickson and Daniel,

Thank you again for a great twip. Today's case of the young woman with abdominal bloating and pain, vomiting and nausea is most likely a case of Anisakiasis (also known as herring worm disease) caused by an infection with Anisakis simplex or Pseudoterranova decipiens.

Infective larvae are found in the sea water having been deposited as eggs in the faecal material of seals. The infective larvae are taken up by crustaceans that are then consumed by fish or squid. Humans ingest the nematode larvae when they eat raw or undercooked infected fish or squid. The larvae can invade the gastrointestinal tract. Eventually when the parasite dies it produces an inflamed mass in the oesophagus, stomach or intestine.

Diagnosis is generally made by endoscopy, radiography, or surgery if the worm has embedded (worms may invade the intestine 1-2 weeks after infection). The history of raw fish consumption is helpful for diagnosis.

Signs and symptoms include abdominal pain, nausea, vomiting, abdominal distention, diarrhoea, blood and mucus in stool and a mild fever. Allergic reactions of rash and itching, or less commonly anaphylaxis can occur. The symptoms can occur within hours of eating the infected fish.

The patient therefore was most likely infected during the sushi preparation.

It is recommended that the fish, having been wild caught is gutted and processed immediately to stop the worms moving into the muscle from the fish's body cavity. If the partner who caught the fish did this quickly only very few worms may have migrated to the muscle nearest the belly which the patient may have consumed while preparing the sushi using meat from nearer the top of the fish where the meat is thicker and more colored.

The worms are white in colour and 1.8 to 3.6 cm long and < 1cm wide.

Treatment is recommended for his patient to avoid gastrointestinal invasion and further symptoms.

Successful treatment of anisakiasis with albendazole 400 mg orally twice daily for 6 to 21 days has been reported in cases with presumptive (highly suggestive history and/or serology) diagnoses. ( although it is not FDA approved for this indication and there are notes on its use in pregnant and lactating females as well as use in children.)

Today's weather in beautiful Brisbane is 20C with 53% humidity and a light, but cool breeze, ( I finally had to find my sweater).

Blue skies with 20% cloud cover, a great day for a BBQ.

Keep them coming,

Christine (from Brisbane).

Peter writes:

I would suggest ingestion of Anisakis species as the diagnosis in this case.

April writes:

Hello gentlemen,

First things first! I would have thought, given your background Dr. Despommier, that you would know what third shift is! Although, at this particular moment, I can't remember if you were an assistant in a hospital lab. My particular schedule is 10:30pm to 0630am.

Our hospital is also a reference lab for many clinicians and other hospitals in Wisconsin and Illinois. Because of this we have a robust third shift workload that handles a lot of the molecular testing (it's more cost effective to batch those tests) and all the regular microbiology testing that the hospital requires (think stat gram stains, positive blood cultures, etc.)

Anyways. You say fish and I automatically think Diphyllobothrium latum. If I am correct, then other listeners will be as well and I'm sure they'll go through the lengthy task of explaining life cycle and mode of transmission.

I will add this though-I'm wondering if the patient ingested the salmon as soon as her boyfriend brought it home, then froze it for about a week before serving it to her friends. After that one fateful undergrad parasitology course I freeze ALL meat before ingesting it!

Thank you so much for the camaraderie, you three are fabulous!

Elise writes:

Dear TWIP Trifecta,

As always, thank you so much for your challenges. It is truly summer in lower Manhattan, quite humid and warm (83 F / 28.3 C)— the kind of weather that makes the dogs exhausted and seek out cool spots to sleep.

The case in TWIP 92 is curious because the young student’s onset of symptoms is so sudden and Dr. Griffin seemed to imply strongly that they were brought on by something about her most recent sushi meal as opposed to anything consumed in prior days or weeks. With so many of the parasites discussed in other case studies, it takes some time before the parasite makes itself known through symptoms, so this one is unusual for having such a rapid onset.
My guess is that the young woman has an anisakis infestation, causing gastric anisakiasis contracted from the salmon or the tuna she ate. (Anisakis is one of the more likely parasites that can be transmitted by marine fish.) The patient’s sudden abdominal pain, particularly the tenderness in the upper left quadrant, and vomiting suggests that the anisakis larvae have penetrated her stomach wall (the stomach, spleen and some of the colon are in this quadrant of the abdomen) within a few hours of her having ingested it. 

As to why the patient is the only person from her sushi dinner party to get sick, it is likely that she was the only one to have the bad luck of eating a piece of fish that contained the larvae. (It is possible, though, for people to develop intestinal anisakiasis, the symptoms of which set in after 7 days. There is also a frightening sounding anisakis induced anaphylaxis, ) 

The literature is quite matter-of-fact about the treatment for gastric anisakiasis because the larvae can’t survive in a human host (we are called a “dead-end host” for the parasite, which needs to be passed from a fish or a squid to a marine mammal in order to complete its developmental cycle). Patients can be treated by having the larvae removed with endoscopy and patients can also be treated with albendazole.

I am not sure if I am correct with my diagnosis, but this was the most likely parasite I could find that causes such sudden symptoms. Where did the student’s boyfriend catch the salmon, by the way? I know that the tuna could also be the culprit, but I was curious.

As always many thanks.

Eric writes:

Dear TWiPpers, , I am writing with a guess for the case of the week from TWiP 92. This case seems quite a bit harder than the last two, and I don’t feel as confident that the clues lead to a clear answer. The question I wish I could have asked before I had to make my guess: how often does this patient engage in sushi making events? And especially NOT using commercially-caught “sashimi grade” fish?

I will go out on a limb and guess that this sushi-making event is not an isolated event, and that the patient has engaged in this activity many times. I will guess that the current symptoms are not from this recent event, but rather caused from an event long past, perhaps one where a fresh-water fish was consumed, perhaps caught by the patient’s brother. I will guess that this hapless young woman is suffering the effects of infection with Dioctophyme renale, a giant kidney worm. This would perhaps explain the tender abdomen, and fever, and perhaps the enlarged abdomen, although that is a stretch. I am haunted by the anemic mom factoid. How can this be relevant? Or is it a red herring (raw)?

I eagerly await the unfolding of this fishy tale.

The weather in Seattle is 29 °C, cooler than last week, but still hot for Seattle, under skies devoid of clouds, but hazy with the smoke from wildfires raging in Beautiful British Columbia™. For those interested in a sensational blog about the Pacific Northwet’s weather, climate, and related, I highly recommend following the Cliff Mass Weather Blog (http://cliffmass.blogspot.com/). It provides amazing insights into current atmospheric phenomena by University of Washington atmospheric science researcher Cliff Mass. Definitely my “listener pick”. The posts from July 8 and July 6 discuss this smoke and its effects and some great satellite images and other striking visuals.

Best wishes,
Eric

 

Jan writes:

Dear sirs,

This case is fun indeed , great anecdote to casually mention during diner with squeamish people. Earth worm lookalike, coming out both ends; Taenia sollum.

Keeping it short, my higher brain functions have melted out of my ears due to the heatwave we're suffering from. Temperature around 30 degrees C, no clouds and lots of horse flies where I'm currently working.

Greetings

SJ writes:

Greetings TWIP trio!

I was happy to get the answer to the episode 90 case study. I polled some of my coworkers and we came up with several options, (naegleri fowleri was one but the patient was not an outdoorsy type) but none of them quite fit. I missed the HIV diagnosis despite noting the candidiasis. I guess I was so focused on the single diagnosis that I forgot to consider how important it is to remember that immunocompromised individuals often develop unusual conditions that are not present in the general population.

By the way, it's 18 C at 0730 but we expect it to get very hot today, perhaps 38 C here in the Eastern Sierra.

For this week, I strongly suspect anisakiasis. The patient is an adventurous eater, the parasite comes out of both ends (a common symptom in those infected with anisakis) and the size and vermiform features also match.

The fact that he has traveled a lot may or may not be a red herring here. Anisakiasis comes from eating raw, undercooked, or preserved fish. While it is uncommon in the US due to flash freezing of sashimi grade fish, it is not unheard of. However, because he travels, he could have developed it from eating fermented cod liver, ceviche, or any number of local fish dishes all over the world. One could almost feel bad for the nematodes in question, since we humans are a dead end host.

Keep up the good work as always gentlemen. I look forward to the answer to this case study.

Mark writes:

I am neither physician, nor microbiologist, but a pharmacist who finds your show fascinating. My guess for this weeks riddle is neurocystercosis of spine complicated with neurocytercosis of the brain. Intravenous drug abusers can acquire this parasite through shared needles, and the behavioral changes, the seizures and the radiculopathy of the left arm could be the result of a cyst in the spinal cord. I don't know what to make of the white mouth, so all this is a guess. This is an interesting case. I look forward to hearing the diagnosis next twip podcast.

Dennis writes:

Doc, for twip, here's a new Leishmania vaccine.

http://stm.sciencemag.org/content/7/290/290ra90

Best,

Dennis

Eric writes:

Hey Doctors!,

Hopefully this hasn't already been plugged!, but I wanted to share a link to a case studies column on the nyt: http://well.blogs.nytimes.com/2015/06/04/think-like-a-doctor-strange-vision/

This month's case is a type of case that Dr. Griffin has promised, but has yet to deliver (I won't spoil it more than that!). While not all of the cases that the columnist, Dr. Lisa Sanders, writes up are about parasites, a fair amount are! If you're the first to guess the right cause, she'll send you a signed copy of her book. She almost always includes any pertinent physician notes and more than once I've made sense of a test or note because i had already learned about it on TWIP!

I also provided a link to another case that I thought you or the listeners might enjoy: http://well.blogs.nytimes.com/2015/03/05/think-like-a-doctor-thinner/

Thanks for all of the fun!,
eric from irvine where the sun is too bright and the temperature is too high.

Steve writes:

Hi TWiPers,

I think #90 was one of your most amusing and informative TWiPs. I was particularly impressed with the case history guesses by Daniel's daughters: very bright young women indeed!

Your bot fly case reminded me of my old friend Peter, who used to write the Belize Rough Guide. We rather thought he was taking his research for the book a bit far, sometimes, as he always seemed to come back with another parasite or disease! He was a regular visitor to the London School of Tropical Medicine and Hygiene, where they used to look forward to seeing what he came back with next!

People really do need to be careful in Belize, because Peter 'test drove', unintentionally, both malaria, and Leishmaniasis, and, on one occasion, also brought home, what he called his 'pet': which was a bot fly larva growing in his forearm. He was quite proud of it and enjoyed grossing people out by showing his pet to them! He successfully brought it to 'term', but I don't know what happened to it after that!

Peter was, actually, very careful when travelling, and researched health advice thoroughly for each of his books: he knew more about malaria than our local hospital, where they flatly wouldn't believe he could have it, when he went through a relapse episode of it while back home, and needed more medicine in a hurry. The fact that he collected several TWiPs'-worth of parasites, despite knowing the risks, and advising others on them, should serve to illustrate how vigilant one needs to be while travelling.

Sadly, despite never having smoked, Peter died, much too young, of throat cancer. I did wonder if it might have been caused by something else he 'collected' in his travels. With any luck, your triumvirate of podcasts, may help educate people to be at least a little wary, whilst enjoying their exotic holidays.

All the best,

Steve
Luton
Bedfordshire
England

Where it is rather grey, but refreshingly windy today. (Which started rather strangely, with a massed gathering of noisy Jackdaws, Crows, and Magpies, all together in the small cherry tree at the bottom of the garden! I have no idea what they were up to: there are often Red Kites overhead--they have come back very quickly, after reintroduction in the '80s--but I couldn't see them this morning.)

PS: great about the belugas. I looked for youtube reports after your show, and was interested to see the locals saying they were diving for 'bunker'--a fish that I hadn't heard of. The Wiki on it is quite interesting, and Dickson might have something to say about how the native Americans used to use it for fertiliser. I seem to recall reading advice to plant a sardine with each maize seed, before, and it is nice to find out where the idea came from.

Apparently, the fish is now overfished for oil and animal feed, which, in turn upsets the ecology of the bay, so, maybe, it is a very good sign that there seem to be enough about to attract the beluga. (Belugas? Belugae?)

Also wondered if this might clear up a mystery to me, as to where all the 'cod liver' oil on our supermarket shelves was coming from, when there is supposed to be a shortage of cod. I once asked our Food Standards Agency if they ever checked fish oils for authenticity, and was surprised to be told that they did not…

Curt writes:

I believe a head CT will reveal juvenile Taenia Solium encysting on being in the patient's brain tissue. If the CT doesn't reveal neurocysticercosis, the CT is still a good idea for new onset of seizures without prior history.

Bill writes:

Vincent, In a recent podcast you discussed the practice of using water bottles to sterilize water via sunlight.

Raw PET allows over 50% of UV to penetrate, down to about 320 nm.
Peak antibacterial activity is around 260 NM, but duration of 8 hours in the sunlight compensates for this attenuation and a very high % are killed via a day in the sun.
Spores are more resistant, but are removed to the filtration you spoke of.

This paper cover it quite well.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292282/

there are PET formulations that protect from UV light, that block almost all the UV from the product, these are usually colored.

link to the use of sunlight to sterilize water.

http://modernsurvivalblog.com/health/how-to-purify-water-with-sunlight/.

Heather writes:

Hello Doctors!

I have not had time to write to TWiP in a long time because I am back in graduate school! This is significant because my return is partially inspired by the TWiX podcasts, which were my only link to science during the years I worked "out-of-field". I am currently finishing my master's degree part-time, while working "in-field" as a laboratory manager at a small state college. I am very happy that you have added Daniel to the show, he brings a lot of energy and an interesting perspective. I have been enjoying the case studies, maybe I will have time to guess one of them soon. Would you be open to doing a fish or shellfish case study if I can find you a good one to send to you? Keep up the good work!

Heather

Dan writes:

Hello!

I just discovered your podcast and immediately became a fan. Great work!

Now to my question. I am somewhat of a parasitophobe but I love smoking cigars. Cigars happen to often come from central american countries which, I learned from your tapeworm episodes, have widespread problems with tapeworms.
Do you know if there is any risk in contagion from hand rolled cigars? If the person rolling is contaminated there could possibly be contamination of the cigar itself right? I am curious to know if I should start cleaning my cigars before smoking them. While cleaning them might cause the things to break, I'd rather have a broken cigar than a tapeworm infection...

Would to get a reply, thanks in advance/ Your new fan Dan

Brigitte writes:

Hello,
I read about an interesting theory in Carl Marx's Parasite Rex. The book did not go into great detail, but I would like to hear your thoughts. The book talked about parasites and allergies. Do you think that parasites can actually prevent allergies? People have used parasites for illnesses and infections for decades. Though, many of them did more harm than good.

Thank you,
Birgitte

Justin writes:

I thought this might be worthy of a TWiP since everyone loves pathogens that are implicated in behavior changes.

"Researchers from the University of Leeds, Queen’s University Belfast and Stellenbosch University in South Africa found a tiny parasite, Pleistophora mulleri, not only significantly increased cannibalism among the indigenous shrimp Gammarus duebeni celticus but made infected shrimp more voracious, taking much less time to consume their victims. "

http://www.leeds.ac.uk/news/article/3675/parasite_turns_shrimp_into_voracious_cannibals

Right now on the Cross Island Ferry heading to Orient Point and it's Sunny 0C and a calm windy open water day.

 

TWiP 92 letters

 

David writes:

Dear Vincent, Dickson and Daniel,

I am one of the co-authors (from the London School of Hygiene & Tropical Medicine) of the PloS Pathogens paper you highlighted on the malaria parasite as part of TWiP 91 on June 20th. Thank you for dealing with the paper so well. I was wondering what to expect after some of the online interpretations and comments that arose from our work. For obvious reasons it received some media attention. Catherine Lavazec (Institut Cochin, Paris) who co-led the study (with Gordon Langsley) was understandably keen to take advantage of that possibility.

Just a brief comment to say that the use of sildenafil in our study was a proof of concept (as you pointed out). So even though sildenafil has been used in children (a question that arose on TWiP 91), the aim is not to use this drug to control malaria. In fact, sildenafil is quite a poor inhibitor of the malaria parasite phosphodiesterases (mid micromolar as you pointed out). My lab is exploring the possibility of identifying a much more potent selective inhibitor of the malaria parasite phosphodiesterases (of which there are four) with no side effects. Phosphodiesterase enzymes are expressed in multiple stages of the complex malaria parasite life cycle. So we hope that developing such an inhibitor as a drug would allow us to both treat disease (by targeting the asexually replicating blood stages) and also to block transmission (by killing the gametocytes). So in this case, the issue of altruism will not arise.

I enjoyed your TWiP podcast. Thank you.

Best wishes,

David

Professor David A. Baker

Faculty of Infectious and Tropical Diseases
London School of Hygiene & Tropical Medicine
Keppel Street
London WC1E 7HT

Jenn writes:

Hi twip team,

The "over-talking" thing is really a New York manner of speaking. You are absolutely correct when you say it's due to enthusiasm, and is not meant out of rudeness or to interrupt the other person.

This is something I try to convey to my non-NYC friends (they get irritated when I interrupt them, and I get irritated when they stop talking to " wait their turn").

http://www.pbs.org/speak/seatosea/americanvarieties/newyorkcity/

Best,

Jenn

Christine writes:

Good morning Dickson, Vincent and Daniel,

Thank you again for another enjoyable and interesting twip podcast.

I believe that our young trainee physician has an ascarid infection.

The infection with Ascaris lumbricoides may present with the emergence of a 15-30cm long whitish round worm from either mouth or anus. It usually resides in the small intestine and mild infections may be asymptomatic or rarely experiencing nausea, diarrhea and abdominal pain.

Treatment is a 3 day course of albendazole or mebendazole, repeated after 2 weeks.

Unsurprisingly the infection has a faecal/oral contamination cycle, with eggs excreted with faeces. Fertile eggs will embryonate in the soil and are infective after 18 days to several weeks depending on conditions. Larval hatching after ingestion and mucosal invasion leading to portal circulation and then systemic circulation and traveling to the lungs where the larvae further mature for 10-14 days, break through the alveoli, climb the bronchial tree to be swallowed in order to locate as adults in the small intestine.

The weather this morning in Brisbane is a brisk 11C with a beautiful sunny winters day of 21C to come, light breeze, and clear skies. Couldn't be better.

Christine
(Brisbane, Australia)

April writes:

Good morning gentlemen,

I'm a public health microbiologist in Milwaukee, WI. I work in a hospital lab currently, on third shift, and have been an avid listener for for some time now, though this is my first time writing.

Ascaris lumbricoides is my official guess. What else could be so long, besides a tapeworm! And having dissected a gravid Ascaris in a Parasitology class I can indeed say they look like earth worms to the untrained eye.

I'm taking a real guess here, with one of my only resources being the "Atlas of Human Parasitology" by Lawrence R. Ash and Thomas C. Orihel. I think Dickson gave it away though when he mentioned the case of the little girl who had visible worms coming out of her nose, because one Google image search of the parasite in question brings up that very picture!

The weather in Milwaukee is a balmy 69 degrees fahrenheit with a nice thunderstorm on the horizon.

Thank you so much for the wonderful learning opportunity, especially for this nocturnal parasitophile (is that even a thing?).

April

Robin writes:

Earthworms are annelids. Annelids are segmented. The segmented human helminths are cestodes. Cestodes are flattened with elongated segments. That might not have been the case in this instance. Annelid segments are short like a rouleaux, and also like a rouleaux, approach a circular cross section.

Nematodes also approach a circular cross section, and hence the name "roundworms"; however on closer inspection, they show no evidence of segmentation. They can vary in size from microscopic free living soil dwellers to earthworm size; most of the larger ones tend to be parasitic, including human roundworms such as Ascaris lumbricoides.

Varun writes:

Greetings

In response to the recent case challenge presented the description is matching that of Ascaris infection. Given that the patient left with the worm itself in the examination table, there isn't any additional required lab tests. Just check the morphology of worm. An additional simple stool wet mount maybe done but isn't required in this case.

Guess: Ascaris lumbricoides infection

Elise writes:

Dear TWIP Trifecta

I hope very much that this finds you all well. It is pretty balmy here in lower Manhattan 87 F/30.5 But the skies are clear and the humidity a reasonable 36%.

I do have an attempt at a diagnosis for the young resident in Salt Lake City, but I also have a bunch of questions. In looking around at what sorts of earthworm-shaped parasites could have found their way into his digestive tract, the most likely culprit seems to be a roundworm (Ascariasis lumbricoides). Certainly, the remarkable photographs one can find online match the description that the patient gave of the worms he saw and their behavior is also consistent (they emerged, alive and motile). People with intestinal ascariasis, as is the case with this patient, don’t always have elaborate symptoms beyond a range of abdominal discomforts. He felt well and has no fever, edema, discomfort, or neurological symptoms beyond the vomiting incident that first introduced the possibility that he might have a parasite (or perhaps it would be better said that the parasite introduced itself to him).

Ascaris lumbricoides is among the most common helminthic human infections, and it is most prevalent in tropical and sub-tropical climates such as the ones the patient likes to visit (he’s been to India and Southeast Asia). It is transmitted by people ingesting roundworm eggs that can be found in contaminated soil or food. The patient, an adventurous eater, could easily have been exposed on his travels.

Roundworm infestations often are asymptomatic until they have a final glaring symptom. They are typically discovered when they are either in the early stages and the worm larvae are small and migrating through the lungs causing coughing and wheezing OR in the late phase (6-8 weeks after eggs were ingested) and when they can cause abdominal pain, nausea and vomiting, and the dramatic “passage of worms” from the mouth, nose or anus. In extreme cases (usually in children) massive infestations can cause intestinal blockages.

So assuming I am right and the patient has a roundworm problem, why did the roundworms emerge both from his mouth and his rectum? Do the large worms move back and forth through the digestive tract or did one (or more) end up in the stomach and others in the large intestine? Also, was it a reaction of the worm with the beer that made the patient throw up or was it the presence of the worm in itself that did it? Finally, in the examining room, why did the worm crawl out at that time? In the cases I read, most of the times worms make dramatic appearances from orifices while their human hosts are sedated.

As always, thank you so much for your wonderful work. I look forward to hearing TWIP 92.

Best wishes

Eric writes:

Dear TWiPsters, I am writing with a guess for the case of the week from TWiP 91. I thoroughly enjoyed your tale of the emergence of the motile flesh colored worm from your young patient’s tail. I can think of only one common critter that fits the description, Ascaris lumbricoides. Perhaps there are others, but I do not know them, nor are the common I suppose. And the treatment would be the same regardless? But no guessing is needed as the patient was kind enough to supply a fresh sample right at the visit. The only mystery is: why are they emerging? I recall Dickson saying in the early Ascaris episode that fever is a common reason that Ascaris will seek to emerge, but why else? Dickson was asking here about fevers, but there were none reported. Daniel seemed to be hinting that stress in the form of sleep deprivation may be the answer? I await eagerly to hear if there is a clear reason for the Ascaris emergence. How many did he have?

Seattle is currently experiencing its first heat wave of the season. It is currently 27 °C at 8pm. We are under an “excessive heat watch”, with predicted highs of 32 for the next week, phew, very uncommon for Seattle.

Regards,
Eric

 

TWiP 91 letters

 

Heather writes:

Dear Dr.s R, D & G,

I really hate to criticize learned professors, especially my elders. I suspect I may be being overly - sensitive or perhaps it is a cultural difference. However, the "over-talking" is decreasing the quality of the TWiP podcast. I think the quality would be improved if certain hosts made a concerted effort to not speak over other hosts, but to pause and insert their wonderful insights (which I do really want to hear) only when others have finished speaking. I know it is hard to teach an old dog new tricks but the over-talking makes the discussion hard to understand at times. Please don't be offended: I love TWiX, especially the party guilty of over-talking.

Hesitantly,
Heather

Ann writes:

Dear Dickson, Vincent and Daniel,

I have wanted to write in to your show for a while now, and am finally doing so because of something mentioned in the last podcast (#90). I was in Hopland, CA busily obtaining blood samples from western fence lizards while listening to your podcast, when Dickson mentioned that reptiles get malaria. As it turns out, I was taking blood samples as part of a long-term saurian malaria research project I have been working on since 2003. I study Plasmodium mexicanum, a lizard malaria parasite that uses two species of Lutzomyia sand fly as vectors. I was so happy to hear you mention lizard malaria that I had to write in (if you ever want to chat about P. mexicanum, I am more than happy to oblige- this is a fascinating parasite!). Also, I was interested to hear Vincent’s thoughts on viruses infecting red blood cells. As a PhD student, I scanned hundreds of lizard blood smears and sometimes found small, purple-stained inclusions within the red blood cells. I was told that that these were viral particles/clusters. It appears that viruses can infect nucleated red blood cells. I attach the following article as a reference.

Thank you so much for your podcasts- it is refreshing to listen to scientists as passionate about parasites as I am. I teach Microbiology, Parasitology, Invertebrate Zoology and Ecology at Penn State York, and often refer my students to your podcasts, and utilize them as discussion tools in class. I enjoy the new additions of Daniel and the case studies. I have gotten all of the cases except the one posed in podcast #90. I cannot wait for the ‘big reveal’ in the following podcast. Thank you again for you stimulating lessons.

Sincerely,
Anne Vardo-Zalik

--------------------------------------
Dr. Anne M. Vardo-Zalik
Assistant Professor of Biology
Biology Program Coordinator
Penn State York

Steen writes:

In case you are still curious about the origin of the name of the c(ellular)-JUN protein ( ubiquitinated by FBW7, the target of the apicomplexan prolyl isomerase you discussed in TWiP 88):

"This putative cell-derived oncogene of ASV 17 is termed jun, abbreviated from Japanese ju-nana, the number 17."
http://www.pnas.org/content/84/9/2848

So the gene was in fact named after the relevant virus.

Vogt gives a perspective on the rapid identification of JUN as a transcription factor 28 years ago: " we see how convergences of seemingly unrelated research led to important insights."

http://www.nature.com/nrc/journal/v2/n6/full/nrc818.html

Perhaps June 17 should be declared 'national oncovirus day'.

Christine writes:

Dear Doctors Vincent, Dickson and Daniel,

The 28 year old patient described in today's twip with non-acute arm and hand weakness, behavioral/mental changes and a seizure, together with oral Candida albicans "infection" and high risk behaviors is suggestive to me of a multifactorial diagnosis.

The Candida in an adult suggests to me reduced immune function ( although he does report toxic habits and a cessation of smoking may help clearance of the Candida). Given his sexual history and lack of protection used I am concerned about HIV, and both he and his partner should be tested.

As a consequence of reduced immune function he would be at increase risk of Toxoplasma gondii. This may cause focal brain lesions that can explain the weakness, seizure and behavioural/mental changes. Given the seizure an MRI or CT would be my first instinct, with serology for toxo via IgG agglutination, and a stained blood smear for the presence of an active infection. If indicated in the scan and supported by blood work I may request a lumbar puncture to do PCR for toxo in the CSF.

Given that toxo is such a successful parasite and the initial infection can be asymptomatic it is likely that he has encountered this parasite possibly without knowing it. With reactivation as a consequence of immune reduction toxo can become a serious and life threatening infection.

Treatment for the toxo, Candida and if diagnosed, HIV should begin promptly for best outcomes.

The weather here in Brisbane is partly cloudy, currently 24C with a predicted max of 28C , 30% chance of any rain (0-0.2 mm), a moderate UV alert between 10.50 and 1.40, and a low-moderate fire danger.

A beautiful late autumn day, it's hard living in paradise ;-) .

Christine from Brisbane (enjoying my Sunday morning twip.)

Jan writes:

Hi sportsmen,

What better way to spend a rainy Sunday afternoon then trying to solve a puzzle using ones brain, instead of shutting it down in front of the TV watching a game ? Especially since I'm on a winning streak in my personal league. ( the pin worms were foul play ) Daniel didn't want give the results of the blood tests but I'd be surprised if the guy didn't have HIV/Aids. Do his toxic habits include needle sharing when using intravenous drugs ? Not that it matters, the unsafe sex , probably including anal, with multiple partners is dangerous enough of its own. Combining the presumed aids with the symptoms leads me to think it's toxoplasmosis. My cats agree and they're never wrong.

Greetings,

Jan

PS
Congratulations to Vincent on the pronunciation of my name, and I don't watch sports, not even the stereotypical ones.

Elise writes:

Dear TWIP Trifecta,

I hope all is well. It is soggy and stormy and suddenly chilly (56 F, 13 C) here in lower Manhattan, as I am sure it is for you all uptown.

For once I almost hope my diagnosis is not correct because if I am right, this is a sad one.

This diagnosis was tricky for me and as a result is multipart but I’ll just say first that all of the clues suggest to me that the patient has Toxoplasmic Encephalitis (or cerebral toxoplasmosis). I’ll try to explain my thinking.

The first thing I sorted out was that the patient’s symptoms seemed most like a form of encephalitis (personality/ behavior changes, left side weakness, seizure, persistent headache, low fever). I got a bit stuck trying to figure out what sort of encephalitis he might have because most of the parasites that wind up in the brain didn’t fit the profile of this patient— especially given that he has not left the United States and doesn’t have other lifestyle choices that might expose him to some of the parasites that you have discussed in other patients (tapeworms, for instance).

While I was slightly stymied by the encephalitis, I set it on the back burner and looked at some of his other symptoms. I was intrigued by the patient’s non-encephalitic symptom of having a white coating on his tongue and lacy white mucosa in his mouth. This sounds quite a bit like thrush (oral candidiasis), which can be a symptom of an HIV infection and suddenly a lot of things made sense.

The patient maintains a high risk lifestyle that could lead to him having contracted HIV. He has a lot of sexual partners of both sexes and admits to not taking any precautions to protect himself from sexually transmitted diseases. In addition he uses recreational drugs, and while you didn’t mention whether he injects himself, if he does, this is another unsafe behavior that could lead to a lot of infections, HIV among them. If the patient is HIV positive or otherwise has a diminished immune system,

Many, many healthy people have toxoplasmosis and are entirely unaware of it. (The literature tends to describe these infections as “latent and asymptomatic”). When, however, the body’s immune response is compromised, the toxoplasma gondii protozoan parasite can become “reactivated” and, if they are in the brain, cause lesions that trigger the encephalitis symptoms.

Since the patient had not been to a doctor in quite some time, it is possible that he doesn’t know about his HIV status and that all of these symptoms are a horrible surprise.

I would be very interested to hear how the toxoplasma parasite “reactivates” without a strong immune response to keep it in check. How does it remain dormant?

This was a tricky diagnosis so I’m prepared to be wrong but I am very much looking forward to hearing whatever the answer may be.

As always, tons of thanks for your wonderful work.

I await your next podcast on the edge of my seat.

Many best wishes

Shane writes:

My guess for this case is Toxoplasmic Encephalitis caused by T.Gondii infection coupled with HIV infection. The give-away was the very active unprotected sex-life with multiple partners.

Weather here in Queensland Australia is a beautiful 20 Degrees C as you entertain me on my commute home from University of Queensland.

Kind Regards,

Shane

Eric writes:

Dear Dickson, Vincent, and Daniel, I am writing with a guess for the case of the week from TWiP 90. But first, let me say as a long time listener but first time caller, errr writer, that I find your podcasts sensationally well done and informative. I started with TWiM several years ago when I finally got a smartphone with a good podcatcher. I moved to TWiV after exhausting TWiM’s back catalog around the time of the most recent Ebola outbreak, and then later discovered TWiP. I love to learn, and find it brilliant that I can turn commuting time and driving-the-kids-around time, which otherwise feels wasted, into learning time with TWiX episodes! My degree is in astrophysics, but I have since moved to the field of proteomics and have picked enough biology to follow along even when you dive deeply into the papers. Mostly.

Regarding the case of the 28 year old man with the seizures, the information is rather limited, but for the huge advantage to know that the answer must involve parasitism. I strongly suspect that this is a case of encephalitis caused by toxoplasma. Since this gentleman reports unprotected sex with multiple partners, he must be considered high risk for HIV infection, and I fear he might be immunocompromised due to early stages of AIDS. Toxoplasma in an immunocompromised individual may well cause encephalitis that can cause the symptoms described. This was the case with tennis star Arthur Ashe, who then founded the Arthur Ashe Foundation for the Defeat of AIDS. The first questions I would try to answer are: are the lymph nodes swollen? Then is he HIV positive? And then a test for toxoplasma, perhaps there is a good PCR test?

A question for you: would the signs and symptoms be any different for a new toxoplasma infection in an immunocompromised individual, and a long-latent toxoplasma infection becoming active with the onset of immunodeficiency?

I love TWiP. The new case of the week with each episode is a great idea. It turns a one-way show into a two-way experience! Brilliant! I started with episode 1 many months ago and now have finally caught up and can participate in the cases in real time.

Today’s weather in Seattle was pure “June Gloom” aka June-uary (http://en.wikipedia.org/wiki/June_Gloom), a common pattern this time of year where a low heavy cloud cover is drawn in from the ocean and hangs overhead all day. But the 10-day forecast starting tomorrow is nothing but sun. Summer in Seattle begins tomorrow!

Best regards,
Eric from Seattle

Varun writes:

Greetings Profz,

In relation to the paper discussed, I want to cite an earlier work Patrick Duffy and colleagues identifying the importance of CD55 and CD59 in malaria. The study found also that the CD55 and CD59 levels dropped with age of RBC. Maybe by using the CD55, falciparum is trying to get into those RBC that are much younger which makes a lot of sense.

http://www.malariajournal.com/content/pdf/1475-2875-10-386.pdf

In the podcast there was a discussion on is there a possibility of virus replicating inside RBC. As Vincent explains, for obvious reasons such as lack of cell machinery this doesn't seem to be possible nor I could find any published examples. This has fueled some scientists to look into use of RBC as viral traps. This has been tried with little success for HIV too.

The second question that came up was why does human RBC lose their nucleus during development. The answer is that RBC is mostly a bag of hemoglobin and nucleus is expelled through a specific mechanism so as to accommodate more hemoglobin. Additionally, loss of nucleus makes the cell extremely flexible allowing the RBC to move easily inside very small capillaries. The flexibility of RBC is also attributed to a protein called Spectrin, problems with which lead to spherocytosis leading to anemia. This automatically brings into question why does some animals have nucleated RBC. Straight answer is I don't know. Perhaps somebody can chime in.

With respect to case described, I want to ask is the patient HIV and HBV status. Bisexual Men are known to acquire parasitic infections related to GIT (such as Giardia and Entameoba). The only parasitic STD I know of is Trichomonas. But I'm not sure if this is even a case of STD.

I'm not able to correlate the case to any organisms to explain the symptoms described. Sorry, but no guess this time.

Rebekah writes:

Dear TWiP doctors,

My guess for the case study is Toxoplasmosis. It is easily Transmitted is by eating raw meat or ingesting the fecal Oocysts (which can be anywhere). Most healthy individuals do not become ill, however I have suspicions that our patient is not entirely healthy. The white film on the patients tongue suggests an infection with Candida spp. which can occur in patients with an immunocompromising disease. With this patient's risky sexual behaviors he very easily could have picked up an infection such as HIV/AIDS. Toxoplasmosis can cause flu like symptoms and encephalitis in immunocompromised people. Historically Toxoplasmosis has been a problem for the HIV/AIDS population. I am a bit nervous that I have read too much into this patient's case, but it was the only thing that made sense logically to me.

Thanks again for this truly enjoyable podcast!

Rebekah
Microbiology Section Head
Hastings MI

Bjorn writes:

Dear Twippers ;)

Case of the week, twip 90

So on this one I’ll guess encephalitis caused by toxoplasmosis caused by an infection of the parasite Toxoplasma Gondii. The short reason why I think this is a reasonable guess is that the patient has a history of high frequency unprotected sex with both men an women and recreational drug use. This means that this guy has multiple risk factors for acquiring a HIV infection. Since this patient does not seem to visit a doctor very frequently, he may also not have had a HIV test, so may in fact be HIV positive without knowing it. Assuming that he has HIV, he may be immunocompromised and on his way to developing AIDS. The clinical signs and symptoms are consistent with too:

dull, constant headache
intermittent fever
seizures
Symptoms may also include focal neurological deficits, such as:
weakness, or even paralysis, of one side of the body;
speech disorder, especially slurred words;
weakness or loss of sensation in any limb;
loss of an area of vision.

The actual infection he can have gotten from many places e.g. from direct contact with feline feces or through eating raw or undercooked meat. Toxoplasmosis Gondii is one of the most common parasites on the planet, it’s very easy to get in contact with it. It’s not easy to get sick from it unless one is immunosuppressed. Foetuses may be infected in the womb and this infection may cause abortion or serious disease in infant children (congenital toxoplasmosis), but I don’t this is a relevant aspect of the disease for this guy.

He presented with seizure and weakness on one side of the body. The “not being himself” could be consistent with the above list, but it is of course hard to tell. To firm up this diagnosis there are a number of tests that can be done:

T cell count (CD4). Less than 200 cells / mm^3 would be consistent with 3 AIDS.
HIV antibodies or virus would pretty much determine if he has or hasn’t got a HIV infection.
Wikipedia says that diagnosis of toxoplasmosis can be done through "biological, serological, histological, or molecular methods, or by some combination of the above.” so I guess that would be a good idea to do. It also says that it can be tricky and another way of diagnosing would be to start medicating and see how well the patient responds.

Another thing that can be done is to MRI/CRT to look for signs (http://radiopaedia.org/articles/neurotoxoplasmosis)

Guess that’s it.

Love twip. I don’t think I’ll stop trying to work on the case studies, even if I don’t find the right diagnosis every time, which I don’t :-)

Best wishes

Bjørn

Alberto writes:

Dear TWiP Triforce,

I'm a long time fan of the TWiX universe and always wanted to write in expressing my admiration and gratitude for your efforts to disseminate science on the internet, and now with Daniel's case mysteries I finally do it.

I'm a PhD student in Immunology in Berlin, but I'm originally from Rio de Janeiro, Brazil, where I did my Bachelor's degree in Pharmacy and Laboratory Medicine. Even though parasites are not present in my daily work (my thesis' subject is tumor immunology and T-cell biology) I find them absolutely fascinating and think there's much to learn about human immunology by studying them. Vincent, have you ever considered starting a TWiI (This Week in Immunology)?!? Even though I like to think that by combining TWiV, TWiM and TWiP the end result is already a big TWiI, since in almost every single episode there is mention of a function or cell type of our immune system!

But I should get to the case! My guess is that the patient is suffering from complications of Toxoplasmosis due to a weakened immune system caused by HIV. When not properly controlled by the immune system Toxoplasma gondii can cause neurologic symptoms, which would explain the seizure and the pain in the left arm and hand. The white coating on the tongue can be caused by Candida. If the patient really has AIDS a low leukocyte count would be visible in the complete blood count. CD4+ T-cell count and serology for HIV would help the diagnosis. I would also ask for IgG and IgM serology for T. gondii.

Thank you all for doing this extraordinary, informative and fun podcast! The case studies are really a good idea to engage in conversation and thought about infections and biology! Keep it up!

All the best,
Alberto

Robin writes:

Left upper monoparesis. Subacute mental status change. White coating mouth and tougue, candidiasis? Seizure with post-ictal state. Low grade fever.

Toxoplasmosis is the most common cause of space-occupying brain lesions in AIDS. Neuroimaging usually reveals multiple nodular or ring-enhancing lesions with edema and mass effect.

Usually, the patient with CNS toxoplasmosis will present with focal neurologic symptoms and signs often superimposed on a global encephalopathy. Mild hemiparesis is the most common focal finding. Headache, confusion, lethargy, brain stem and cerebellar disorders, and seizures are also observed

Evaluation and management of intracranial mass lesions in AIDS
Report of the Quality Standards Subcommittee of the American Academy of Neurology
http://www.neurology.org/content/50/1/21.full.pdf

~~~~~~~~~~~~~~~~~~~~~~~~~
I left Africa 50,000 years ago.

How Homo sapiens populated the Earth:
PBS: The Journey of Man
http://www.youtube.com/playlist?list=PL895E779F2D722DAF
~~~~~~~~~~~~~~~~~~~~~~~~
Coleoptera, diptera, hymenoptera etc. are insect orders, rather than genera.

https://www.google.com/#q=insect+orders
http://en.m.wikipedia.org/wiki/Category:Insect_orders
~~~~~~~~~~~~~~~~~~~~~~~~~
Entomology started long before Cornell.
A group of primordial arachnids passed through a bottleneck, with only a hexapod four-winged form emerging. From it in 300 million years has radiated today's diverstiy of Insecta.

~~~~~~~~~~~~~~~~~~~~~~
Tissue stains to antimcrobials... shoulders of giants.

It was the great Rudolf Virchow who mused on the possibility of differentially staining tissues with dyes so that some dyes might be specifically toxic to microbes.

That led to experimenting with aniline dyes, leading to Prontosil rubrum, then Prontosil album, sulfanilamide, and the rest of the sulphonamides.

~~~~~~~~~~~~~~~~~~~~~~~~~~~
Blood group antigens presented on the surface of red cells are handles: for what hands, present or past, is yet mostly unknovn.

We've prabably had malaria since our shrewlike ancestors or even our reptilian ancestors, the disease co-evolving with us.

Erythrocytes have the glycolytic (pentose phosphate) pathway. Without the nucleus the cell size is smaller (hence lower viscosity), and there might be some greater flexibility.

IRIS immune reconstitution inflammatory syndrome https://en.wikipedia.org/wiki/Immune_reconstitution_inflammatory_syndrome

 

TWiP 90 letters

 

Christine writes:

Dear Vincent, Dickson and Daniel,

I think the latest case describes cutaneous furuncular myiasis.

The lesion on the young man's buttock is suggestive of a botfly infection with the larvae most likely of the species Dermatobia hominis. The eggs deposited onto a smaller vector-fly or mosquito which lands on the person. The eggs are deposited onto the skin of the person (or other mammal) and the body heat causes the egg to hatch the the larvae penetrate the skin, often through the mosquito bite or along a hair follicle. Six to twelve weeks later the larvae leave, exiting through their original hole, and fall to the ground to pupate.

It is this exiting that I expect lead to diagnosis on that fateful Sunday.

Infections are most commonly located on exposed skin where flies and mosquitoes most often land, usually the limbs, but have also occurred on the scalp, neck, back, breast, scrotum, tongue and eye.

The condition is self limiting but most patients prefer its removal prior to its own exit. This is done through killing the larvae followed by surgical removal.

The weather here in brisbane is delightful, a mostly sunny autumn day with blue skies, a smattering of clouds temps from 16 to 23 degrees C. A 60% chance of any precipitation between 1 and 3mm.

Christine from Brisbane, Australia.

Robin writes:

Local treatment of human botfly myiasis in Belize.

http://biological-diversity.info/Downloads/botfly.pdf

The human botfly (Dermatobia hominis) is found from Mexico to northern Chile and Argentina. The larva of this forest-dwelling fly develops in the skin of birds and mammals, including man. The female botfly captures and lays her eggs on the legs of a dipteran, usually a mosquito, although at least 48 species of dipterans and one tick are confirmed vectors. Upon contact with the host, eggs immediately hatch and larvae penetrate the skin. Pre- existing lesions are not required for entry into the host. The developing maggots form furuncular lesions with a central respiratory orifice. A pair of spiracles located on the caudal extremity re- main in this orifice allowing the maggot to breathe. Transverse rows of epidermal spines anchor the maggot within the muscle. Maggots do not wander and development to pupal stage requires about six weeks, although infections up to three months have been reported. At maturity maggots measure up to 25 mm long and 7 mm in diameter. Pupae exit the host and pupation is completed in the soil.

Cutaneous Myiasis: Diagnosis, Treatment, and Prevention:

http://www.researchgate.net/profile/Marjolaine_Giroux/publication/5572533_Cutaneous_myiasis_diagnosis_treatment_and_prevention/links/00b4953baf6e941375000000.pdf

Cutaneous Myiasis Merck Manual

http://www.merckmanuals.com/professional/dermatologic-disorders/parasitic-skin-infections/cutaneous-myiasis

http://en.m.wikipedia.org/wiki/Myiasis

Peter writes:

Greetings DayTWiPers

Here are my thoughts on the TWiP 89 mystery infectious disease case.

Daniel's description of this as a 'fun case' leads me to think that it is an interesting but not a serious or life threatening condition.

Based on the information given in the programme I would say that the patient has furuncular myiasis caused by Dermatobia hominis, the human botfly, this parasite is common in Central America.

The location of the infection in this case is unusual as botfly larvae are usually carried by mosquito vectors and the head and neck are more common sites of infection, the buttocks are not normally that accessible to mosquitoes.

Having done further reading on botflys, I see that they also utilise some tick species as vectors, so I think it probable that the EIS trainee received a bite from a tick that was carrying a botfly larvae which then parasitised him.

http://entnemdept.ufl.edu/creatures/misc/flies/human_bot_fly.htm

Regards

Rebekah writes:

Hello TWiPers three,

My guess for the case study is the Myiasis caused by a screwworm. The CDC page that discusses myiasis states that the flies may lay eggs on drying clothes that are hung outside. Which may have been how this person caught this infection by hanging his swimsuit out to dry.

Thanks as always for providing me with hours of edutainment as I sift through the piles of culture plates on my otherwise lonely weekends at the lab.

Rebekah
Microbiology Section Head

SJ writes:

Hello proffessors,

First email, thanks for the TwiX series of podcasts, I've been enjoying them since the start of the ebola outbreak, when someone suggested TwiV to me on Facebook. It's 21 C, windy, with possible thunder showers forming out here in the Eastern Sierra of California.

I'm a lab assistant at our local hospital, looking to go back to school to become a lab tech sometime in the near future. Unfortunately we send out our parasitology testing with the exception of a rapid giardia/cryotosporidium test so I haven't gotten to see any eukaryotic parasites in person.

Anyhow, is it Dermatobia Hominsis? There are bot flies in Belize, the symptoms match, the only thing that doesn't quite work is the larvae should have waited about 3 more weeks before dropping out, but perhaps the patient noticed other signs that the larvae was present? That's all I could come up with. Not super happy with the location of the bite, given the fact that he stayed in a screened room.

Anyhow, keep up the good work! Looking forward to hearing the answer to this puzzle.

Elise writes:

Dear TWIP Collective

I hope this finds you all well. It is very warm and sticky here in lower Manhattan, about 25 degrees C but humidity is 65%, having the effect of making everyone cranky, except me because I am working on your new puzzle.

I’m going again to hazard a guess diagnosis, this time for your Superbowl watching Belize-traveler and I hope my guess can also satisfy the answer the question: what happened as he was watching the Big Game?

It sounds as if the EIS trainee patient has Dermatobia hominis cutaneous myiasis. I believe he may be hosting botfly larvae.

The botfly (Dermatobia hominis) is found in Central and South America (generally— Belize specifically). Its eggs usually get transmitted to non-human mammals, which is why the symptoms of this infestation are often misinterpreted or misunderstood as being something like an infected cyst or boil, leishmaniasis or cellulitis.

Typically, mosquitoes inadvertently deposit the botfly on a mammalian host when feeding. (This is fascinating because the mosquito is carrying around eggs that only hatch when they sense the warmth of the mammalian body.) This transmission can also happen by the mosquito (also inadvertently) leaving eggs on clothing that has been hung out to dry, as the patient’s likely non-Speedo-type bathing suit was. (For this reason, an account I found in the UK Daily Mail publication advised that travelers iron the clothing they have left out to dry. This seems like well meaning but pretty impractical advice at best given the circumstances under which most people are traveling in these locales.)

The patient’s symptom, a bump that gradually grew and developed a small central hole or impression, that seemed almost like a boil or a pimple are consistent with what happens when one is hosting botfly larvae. The indentation in the center of the bump is the spot where the larvae’s spiracles are enabling it to breathe. There is not usually excessive pain for the host, but I did find accounts of itching and occasional sharp pains when the larvae moves around. The patient didn’t describe either of these symptoms, but perhaps that is because of where he was hosting the botfly larvae. Some of the accounts I read involved the eggs taking up residence on the scalp or beside patients’ ears or even in their eyes, so those may be much more sensitive areas.

The other thing that leads me to suspect cutaneous myiasis is your collective secretiveness about WHAT HAPPENED to the patient during the Super Bowl after he had been incubating the larvae for 5-6 weeks. Did he “give birth” to a 3rd stage botfly larvae? According to accounts I have read, if the larvae isn’t removed, after 4-10 weeks, the larvae needs to fall away from its mammalian host and finish developing underground.

If this event wasn’t so dramatic, perhaps the patient just felt the larvae moving, which is probably pretty freaky, and went to an ER or a clinic. It is interesting that so many of the sources I found recommend home remedies for removing the botfly larvae, by covering the bump (especially the spiracles) with vaseline or nail polish or anything else that would prevent the larvae from breathing, and then extracting it as it moves to the surface in an effort to breathe. Removing that larvae is the cure for the infestation and there are no accounts of lasting side-effects. Would it be wise for the patient to take some sort of antibiotic after getting rid of the larvae?

Often I want to discuss my amateur parasite sleuthing with the people around me, but I must say that in this case I have restrained myself because it is a little too gross for my audience. But not for me.

As always, thank you so much for your wonderful podcast. It it great fun.

Best

James writes:

Dear TWIP Team,

I think that I finally have a reasonable guess. It's for TWiP 89! I am a graduate student in analytical chemistry, so I don't know much about parasites (though I'm slowly learning!). Though out of my field, I find the TWiV, TWiM, TWiP, & UrbanAg enriching listening while I perform experiments in lab. Keep up the good work.

Now onto the guess...

I think that what was ailing the young EIS trainee was botfly. When I was a junior in high school, we took a class trip to Belize and heard all about the botfly. I even got to see an active case of it. One of the guides on the trip had a large bump on the back of his neck, he convinced a second guide to cut open his large red bump with a "sterilized" (read: rinsed with vodka) pocket knife. The second guide then took a can of Raid Roach Killer and sprayed it onto the wound. The whole procedure looked quite painful, but the two acted in a way that made me think this wasn't the first time they'd done it.

Hopefully, this guess isn't too off the mark, but the botfly ordeal makes for a good story even if I am wildly incorrect.

Oh, almost forgot, the weather here in central Illinois is rain with a high of 51 F (10.5 C). It's quite chilly for springtime, but it will be warming up this weekend.

Thanks,

James

Carol writes:

Greetings Team TWIP,

My guess for this episode's case study is cutaneous larval migrans, or creeping eruption. Whether I'm correct or not, it sounds unpleasant! The more parasites I learn about, the less I want to leave my house... At least treatment for many parasites is relatively easy, in case reasonable precautions fail.

Looking forward to the next episode,

Carol

Heather writes:

I finally have time to make a guess on the case study: the young man has a butt fly....I mean a bot fly, otherwise known as a "warble".

Joseph writes:

dematobia hominis

Grace writes:

Dear Day Twippers,

Grace and Caylee here again. We write to you from the parking lot of the closest pizza parlor with free wifi after getting rained-out from a day of squirrel trapping.

We guess that the young man who traveled to Belize and returned with a red bump on his rear was bitten by a mosquito or other biting insect carrying the eggs of the human botfly (Dermatobia hominis).

If we are right, then we extend our sympathy for the poor man's right buttock. We occasionally run across chipmunks and deer mice harboring botfly larvae and don't envy them the experience. I hope your case subject's team won the Superbowl, however, a larval botfly emergence probably made for an exciting halftime show regardless.

Wishing you sunshine and squirrels,
Grace and Caylee

Allan writes:

Aloha Doctors,

The weather in Kona today is a pleasant 77ºF/25ºC, partially cloudy with VOG (volcanic fog) so thick I cannot see the horizon, although its there somewhere.

I like your new podcast format but as you’re now turning podcasts out weekly, by the time I finish listening to an episode in the car and am ready to take a stab at the case study a new episode arrives… but don’t slow down!

Fun case study this week:

I got to spend two full years between the 1984 and 1990 living and working in Belize and Guatemala, helping start community health training programs, volunteering in the out-patient clinic at the national hospital in Belmopan and working in the refugee camps that were scattered at that time around the capital.

On hearing this week’s case, I immediately suspected the patient has a simple botfly larva myiasis (most likely from Dermatobia hominid), although I have seen a few non-typical myiasis over the years in Belize and Guatemala as well, where the larva would develop in a tight spiral just under the skin, which is not typical of my experiences with the human botfly larva. My guess is that these were probably from other dermatobia species, but I never followed up. (perhaps I can dig up an old photo for you to identify).

My guess is that on SuperBowl Sunday the small larval breathing hole opened up on your patient’s lesion, or perhaps the larva actually emerged at that point.

We always used to treat by covering the breathing hole with vaseline and if the larva was small enough, it would emerge on its own far enough to grab with forceps and remove. Larger botfly larva needed to have a small incision made to fully remove intact. In Guatemala or Belize, this could be done in 20 minutes by a minimally trained community-based health care worker. Take a botfly larva back to the states and the treatment can becomes a circus with consultations from four medical specialties.

While a botfly myiasis fits the symptoms described, I would want to rule out a Primary Stage Onchocerciasis nodule, however Onchocerciasis in Central America is just in the Sierra Madres, where there is highly oxygenated falling water. In Belize you would only see it in refugees, but back in the day the thought was you could control River Blindness by popping out the subcutaneous Primary Stage nodules before they matured (we didn’t realize how many hid out in the deep tissue.)

I don’t know if botfly larva would find albendazole or ivermectin disagreeable, as I never needed to treat it systemically.

In reviewing the “modern” botfly literature today, I learned for the first time of the Botfly’s use of transitional vectors, such as houseflies and mosquitoes to deliver botfly larvae to their hosts like guided missiles. (This might help explain the nodule’s location on a less accessible area.) Nor had I realized the Inuit people apparently consider the larva quite tasty….perhaps an acquired taste. (wait of the groan)

I always enjoy your perspectives and interaction.

Regarding your discussion on water purification.
I have a little experience teaching and using solar disinfection (about 30 years). The first research I ever saw on Solar Disinfection came out in 1979 from the American University in Beirut, later confirmed repeatedly by WHO-Geneva, Ireland’s Royal College, Texas A&M and many others, because no ones believes it. Solar Disinfection has its place for some situations, (in refugee situations after the media/money intense spotlight disappears and the donated reverse osmosis filter breaks down), but before real health-security/development conditions are re-established. Solar Disinfection, on non-turbid water in 2L PET containers left in intense sunlight for some 5 hours, seems to really kill the diarrheal disease causing bacterial and viral organisms. While solar heating of the water from 30-50ºC makes this process more efficient (3X more at 50º), the heating is not the essential element, highly oxygenating the water by shaking for 20 seconds probably helps as much. I’ve used it with our teams for up to 3 months and while it works, it is inconvenient. If I can afford $18 Sawyer 0.1micron micro-tubular filter with no moving parts to break, and a 1 million gallon warranty, I now typically use that… or their $80 0.01 micron viral filter, both using basically kidney dialysis tubules. We were apart of the wide scale testing of this filter in 70K families after the 2010 earthquake in Haiti, and its now what most thru-hikers on the AT or PCT trails carry.

Always value your thoughts and experience.
Vince are you aware if Solar Disinfection has been tested against poliovirus?
Dickson, whether or not the glacial ice is contaminated, I’m with you in guessing that as ice cubes in a glass of Scotch, the organisms don’t stand much of a chance.

Best regards and keep up the great work

Allan

Jan writes:

Hi guy's

Since you started calling me a friend, I suppose I can be a bit more informal. I didn't have the time ( changed jobs) to look up the most likely species, but my guess would be an insect which deposited an egg in the poor man's posterior. Why did he find out during watching a game ? Must have been the bouncing on the couch and the agitating moving sports fans exhibit when watching something completely inconsequential.

Greetings

Jan

PS the weather in Rotterdam is 15 C with light overcast

Eloise writes:

Dear TWiPers,
I totally deserve an award. I am a twelve year old girl who wants to be a writer, and I listen to TWiP. Of course I must admit, I did not start of my own volition. My father a “humble scientist”, wrote a letter and appeared on the show and did not mention me. This letter is a reminder, Father, that you better start mentioning me. Anyway, in your last episode I found the case very interesting, and I am dying to know what happened on Super Bowl Sunday! My guess for the case is Pilonidal Cyst, but it’s probably not because that’s not a parasitism. My sister, Daisy, swears (ohh, sorry, she’s yelling at me that she “ thinks” that, not swears it.) that it bot fly larva, and my friend, Cricket, (who I forced to listen to the show), says she thinks it a leech bite. I have never been right on a case before, but I thought you might want to hear from a “Fangirl” of TWiP.
With all due respect and ANNOYANCE AT MY SISTER,
ELOISE CLEMENTS GRIFFIN the first

Daisy writes:

I think that the guy in the last episode had a botfly larva buried in his skin. This insect lays its eggs on a mosquito, tick, or fly and the eggs hatch when the vector feeds on a host. The lesion seems like the bump that would be made by a botfly larva, which would be raised, painful, and have redness around it, usually mistaken for a mosquito bite. This will swell as the larva grows, which would be why the bump got bigger. The central part of the lesion could be the hole in the skin the maggot creates so that it can breathe. If left untreated, the larva will mature and emerge in about 5-10 weeks, which is consistent with the time between his trip to Belize and Super Bowl Sunday. The human botfly is also found in Central and South America, which is also consistent with this case. Getting a botfly on a visit to those areas is rare, but cases are increasing as tourism increases to those areas. If the man had discovered what his bump was before Super Bowl Sunday, he could have done something to cut off the larva’s air supply and kill it.

Bill writes:

Vincent, Dickson,

I recall that humans have one aspect that resembles camels. In certain tropical areas they both store fat against leaner times. In women this is called Steatopygy aka steatopygia

http://en.wikipedia.org/wiki/Steatopygia

It seems to have become part of the beauty ratings of African women, as manifest in booty-worship - a certain KK being renowned in that respect.

Logically, a beauty aspect is a proxy for a survival attribute - women with stored fat will live on while their fashion model sisters = seen as more beautiful, will starves in droves.... I wonder if some camels are also seen to be more attractive for similar reasons?

As for the hapless student in Belize, I wonder if his growing red nodule has a breathing hole, which might indicate a possible Dermatobia hominis infestation carried to him by some intermediate host?

http://en.wikipedia.org/wiki/Dermatobia_hominis

 

TWiP 89 letters

Robin writes:

Cerebral cysticercosis
.....

(trichinosis?)

Left shift:
This is from the days when dinosaurs roamed the earth:
Manual counters for the differential count had the buttons left to right for neutrophils, bands, eosinophils, basophils, lymphocytes, and monocytes. More of the one hundred button presses on the left buttons constituted a left shift.

differential counterFive key differential counter

 

image2

When this one is needed, the patient has a problem.

Christine writes:

The case described sound like neurocysticercosis caused by brain infiltration of larvae of the pork tapeworm Taenia solium and the immune systems response to it. Although she claims to not currently eat meat other than chicken (for economic reasons) this does not exclude consumption at celebrations or on rare occasions in the more distant past.

This diagnosis is supported by the lack of eosinophilia and the neutrophilia without left shift is most likely due to demargination.

As a side note Dickson's explanation of left shift is right on the money as I was taught.

The weather here in Brisbane is changeable after a devastating east coast low that brought flooding, intense rains on Friday, to a delightful, sunny autumn day with 26 C temps for Saturday, we have clouded over with light showers again today (Sunday) but still a delightful 26 degrees and a light breeze.

Christine from Brisbane.

Jan writes:

Gentleman,

Is it Cystiscerosis ? That would fit the complaints, it's common in that part of the world and the fact that you can acquire this parasite from fecal contamination of foodstuffs by infected animals without eating meat makes me lean that way.

greetings

Jan

PS

the weather is 15 c, occasional drizzle and the cherries are blooming.

Wink writes:

With the information provided, you must expect neurocysticercosis. If it's a zebra, my wild and crazy guess would be an errant Echinococcus vogeli.
Wink

Bjorn writes:

I’m making a wild guess on this one. Wild in the sense that it’s atypical, but not entirely
impossible: I’m guessing tht this was a case of latent malaria breaking out, possibly
in the form of cerebral malaria. The reasoning is this:

o The patient is from central america, where she lived for many years.
She might very well have picked up Malaria there. The shaking chills she presents
is a typical symptom that may well be caused by malaria.

o The seizure she had is consistent with cerebral malaria, so this is consistent.

o If the form of Malaria she picked up was Plasmodium Vivax or p. Ovale or p. Malariae,
since these particular species have an abiity to hibernate in the liver for many
years or even decades in the form of clinically “invisible” hypnozoites.

o She might not even have had any malaria apparent infection previously, so this could
be the first time she experiences malaria symptoms. It is also possible that she
has had malaria previously, but has ignored it. The family only took her to the
ER after she had multiple seizures, so a little bit of shaking chills might not have been
enough to make medical attention seem necessary.

To confirm or reject this diagnosis use a quick diagnostic test for all the known malaria forms,
and if any of them are positive start medication immediately. Blood smearr (thick + thin) would
also be nice to confirm/reject malaria and also identify the species.

The internet tells me that he weather is nice outside, but since I’m in a train, in a tunnel on my way to work
I really couldn’t tell.

Elise writes:

Dear TWIP Trifecta,

I hope this finds you all well and frolicking in this gorgeous moment of New York springtime. It’ll only be here for a few moments before summer swamps in, so frolic while you can.

I think I have a diagnosis for the patient featured in TWIP 88. I suspect strongly that the patient has Neurocysticercosis, caused by tapeworm larvae (taenia solium). (There are two types of neurocysticercosis — the parenchymal and extraparenchymal — and I don’t know if both can cause the seizures the patient has so I can’t be more specific, diagnostically.) I know the patient was emphatic about how she doesn’t eat any meat, but it is much more likely to become infected with tapeworm larvae through fecal-oral contamination than from eating undercooked meat (which would lead to intestinal tapeworms, anyway). Fecal-oral contamination also makes it possible for the larvae to make their way to the brain, eventually creating cysts that can lead to seizures of the sort that brought the patient to the emergency room.

There are a lot of possibilities as to how the patient got infected. She came to the United States from El Salvador ten years ago. Cysticercosis and neurocysticercosis are both quite common infections in developing countries, and the incubation period can be extremely long. In addition, she could have contracted the parasite from someone who visited who was infected. In general, most cases of cysticercosis and neurocysticercosis in the United States do occur in immigrants from Latin American countries, but they can also show up in people who travel to countries where tapeworm infections are common or patients who have contact with carriers. Cases in the United States are on the rise. The CDC was very clear about how widespread this sort of infection is and has put it on its list of “Neglected Parasitic Infections” (which is a great name) that need public health attention.

I was interested to read that neurocysticercosis is a leading cause of adult onset epilepsy in developing countries. I didn’t realize that the diagnosis of “epilepsy” could refer to this sort of seizure disorder.

What would be the best thing to do for this patient? Her seizures are not the sort that would necessarily regulate with epilepsy medications. Most of the sources I found noted that antiparasitic medications would cause more brain swelling and pressure. (And also, unless I misunderstand, it seems as if the seizure activity occurs as the larvae are dying, so does it stop once the larvae are dead? Will this eventually resolve?)

As always, thank you so much for your work and for your wonderful podcasts. I truly look forward to them.

Best

AJ writes:

Hello parasailing parasitologists!

Another interesting case! I’m shooting from the hip here, but sounds like neurocysticercosis. Not eating pork keeps her from acquiring the adults, in her intestines, like the worm wants. But if one of her meat eating friends had adult worms, got eggs on their fingers, and then made everyone a salad… well then she could very well have dead or dying larvae in her brain. Then no one wins! Taenia solium is still very common in many South American countries, and while it seems unusual that she could be experiencing symptoms from a ten year old exposure, the adults could easily live that long in a friend or family member’s intestines. Or, maybe a friend visited San Salvador and picked up some worms more recently.

Looking forward to hearing the answer!
AJ

PS. The weather in San Diego: still dry.

Grace writes:

Dear Twippees,

This is another joint effort by me, Grace, and my science girlfriend, Caylee. We think the culprit in the case of the seizure-ing woman from El Salvador is Taenia solium, the pork tapeworm.

This lovely parasite may have taken up residence in the patient years ago through contaminated pork before she ever moved to the U.S. and found purchasing meat too costly.

We write to you from mile-marker-18, Idaho, the closest place to our field residence that gets cell service. The small mammals of Idaho send their greetings.

Best wishes,
Grace and Caylee

Carol writes:

Greeting, TWIPpers,

I missed writing in last episode, but I was pleased to hear that what I had guessed was correct. This time I'm managing to write before the next episode is up.

My guess for the case study this episode is neurocysticercosis; just because she reports not eating meat due to the expense now doesn't mean she didn't eat it during the 23 years before she immigrated. I don't eat meat now, partly for ethical and partly for economic reasons (finding meat that has been raised in a manner I can accept is possible, but it's out of my price range), but my entire extended family does and I did while growing up.

The weather here in Victoria is, again, sunny and mild, with a nice ocean breeze. Vincent will be happy to hear that there are no longer any cherry blossoms messying up the trees, though he might be disappointed that the lilacs are in full bloom.

Looking forward to the next TWIx podcasts eagerly, as they provide a nice break from studying for summer courses without making me feel guilty for not learning things,

Carol

Dona writes:

Heard your recent podcasts and am writing re the case study this week. First though, feel obliged to update you on the weather in Oxford, UK today - warmish (up to 18 degrees) and cloudy but no rain.

Is the case study cysticercosis caused by Taenia solium? If it is, would you treat the family, especially the infant?

Found this paper from 10 years ago, suggesting cases were going up in US http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1176337/ - is this true today?

thanks

Varun writes:

Greetings Professors,

In response to TWiP# 88 case..

There is a series of parasite to be considered when it comes to parasites related to seizures. Ref: http://www.epilepsycurrents.org/doi/pdf/10.5698/1535-7511-14.s2.29.
From the given list of symptoms is probably pointing towards Neurocysticercosis. Though classically it is a meat derived condition, there are sufficient conditions described by transmission through unwashed vegetables, with fecal contamination. Am also considering that it also can sometimes have a unusually long incubation periods.

I would like to know if there was any significant findings from brain imaging, what was the differential count, an IgG ELISA for cysticercosis and Toxoplasma.

My guess- NCC (Neurocysticercosis), casued by cystic larvae of Taenia solium

Anne writes:

Dear TWIP team,

My thoughts for the woman from El Salvador are that the case description best fits that of cerebral cysticercosis (neurocysticercosis.) It is acquired through ingestion of tape worm eggs in the feces of an infected human carrying the intestinal tapeworm Taenia solium. This represents an aberrant form of the life cycle. Typically, the lifecycle would be completed by a pig ingesting material contaminated with human feces containing the eggs and humans would then in turn acquire the tapeworms through ingestion of undercooked pork containing the larval stage. It is an important cause of acquired epilepsy in areas where Taenia solium infection is common and sanitation is poor.

Turns out it occurs in my home state too :
O'Neal S, Noh J, Wilkins P, Keene W, Lambert W, Anderson J, Compton Luman J,Townes J. Taenia solium Tapeworm Infection, Oregon, 2006-2009. Emerg Infect Dis. 2011 Jun;17(6):1030-6. PubMed PMID: 21749764;PubMed Central PMCID: PMC3320238.

I am mildly disappointed with Dickson’s dismissive comments this week about current veterinary education. Certainly the scope of knowledge required to become a board certified veterinary pathologist is extensive. I will point out that we don’t have the luxury of studying only one species.

I adore the show and look forward to the podcasts as they come out. Thanks as always.

Anne
Beaverton, OR

Adam writes:

Hello my good sirs,

In response to TWIP 88's case, unless the little 10-year bit is a total red herring, I believe this may be Chagas disease, or Trypanosoma cruzi!

A quick story about why this comes to mind: A few years ago, I was in rural Nicaragua working on a water sanitation project. We had a Peace Corps volunteer accompany us who woke everyone up in the middle of the night because she found one of the "kissing bugs" that we learned were vectors of T cruzi. She explained that if we were to see one in the stable where we were staying (yes, we were sleeping in a converted stable), to trap it and find her so she could capture it and give it to the government health organization, presumably for epidemiological purposes. This raised lots of questions and she had to explain that these bugs can give people a parasite that can cause sudden death 10 or 20 years after being bitten. Needless to say, this freaked a whole bunch of people out and kept them up all night. I, for one, thought it was fascinating and it made me seek out more information about parasites when I got back home!

On this same trip, I went swimming barefoot in a lake with some locals (spectacular idea, I know...). I thought this was really great and all until I came out of the water and noticed that grass leading into the lake was littered with cow pies! Within 24 hours, I had some nasty diarrhea that passed within a day. Luckily I had some Lomotil to keep me "stopped up" for the bus ride home. Wish I could figure out the pathogen that made me sick!

Anyway, sorry for the lengthy reply and story. Thanks for all you do to promote scientific literacy! I am a middle school science teacher in Chicago who is applying to medical school this year. The podcast trifecta give me lots of great lesson ideas for my kids, and keep me intellectually stimulated after long, monotonous days. Keep up the incredible work.

Cheers,
Adam

PS - Is it weird that I hope I picked up some parasite in Central America? I went to school in Eugene, Oregon, which happens to be just about the grass pollen capital of the world around this time of year, and developed some severe allergies while there. It would be cool to see if they persist after my trip - my own little "hygiene hypothesis" experiment!

I emailed a heme/onc doc I have been shadowing who guesses that "she has neurocysticercosis - a form of T. solium, the pig tapeworm. The fact that she doesn't eat meat doesn't mean anything, It can be transmitted fecal-oral, so if no hand washing she can get it."

After researching this a little bit more and learning that T. solium is the leading cause of adult onset epilepsy worldwide, it seems like neurocysticercosis is a much better guess than Chagas disease!

Cheers,
Adam

Someone wrote:
This is a review but is gamma interferon the intrinsic factor described by Dixon versus leishmania?
https://drive.google.com/file/d/0B8dwAT4VdQdjdGJVV0FlMXFLNVBfVE9PZXQyQ2V6azI5eXA0/view?usp=sharing

AJ writes:

Hello fellow parisamaniacs,

This week's case study seems to me to be a case of Leishmaniasis. The ulcer sounds much like leishmaniasis, especially as it is painless, and the subject knows he's been bitten by some sort of dipteran or another. Italy isn't an unreasonable place to pick the disease up, although it isn't terribly common.

I'm not sure if the hep C would tie into that. Also, Dick kept asking about fish and beaches, which made me consider vibrio and mycobacteria briefly, but those are outside the scope of twip. I'm not sure if phlebotamous would bread near beaches specifically, and they only feed at night, so I'm not sure it's relevant.

Keep up the great work! I love the clinical cases, although this is the first time I've had any clue as to what the diagnosis might be.
Thanks always,
AJ

Grace writes:

Dear TWIP Team,

This attempt at cracking the case study is a joint effort. It comes to you from a duo of small mammal biologists searching for enzootic plague out in west central Idaho. With no good radio stations, downloading episodes of TWIP and TWIV for our long commute to the field each day helps keep us sane.

Apologies if the format of this letter is wrong, and if our answer is totally off the mark. We researched what we thought were the pertinent clues in a sunny cafe in Boise, and our most educated guess is Cutaneous Leishmaniasis caused by Leishmania infantum. The patient could have been bitten by a sandfly during one of his trips to southern Italy. Sandflies are at their lowest levels during the time of his trip (winter), but the incubation for L. infantum can be long, lasting up to years.

Thanks for the great podcast! It's lots of fun for those of us in the uncertain purgatory that is the time between undergrad and grad school to have a reason to use our brains again.

Best wishes,

Buboes from Idaho

George writes:

Hi Vinny. Nice discussion brought to my attention by Monica. Of course, I had to explain the story to everyone in the lab

TWiP 88 letters

 

Robin writes:

Cutaneous leishmaniasis.
CL has been endemic in Italy at a relatively constant level since the 1970s, in the same areas that are endemic for VL. CL is largely underreported to the MoH. Only cases that are diagnosed and treated in hospitals are reported, but those diagnosed in private clinics are not. It was estimated that 450–500 cases occurred both in 2004 and 2005.

http://www.who.int/leishmaniasis/resources/ITALY.pdf

Christine writes:

Dear Doctors Vincent,Dickson and Daniel,

Having listened to your latest podcast I am less disappointed that I was stumped over twip 86. I had excluded most things I could think of due to a lack of fever or diarrhea.

This week however sounds like a case of cutaneous Leishmaniasis. This would have been transmitted by the bite of a sandfly. Would be worth sampling the edge of the lesion to id.

The weather here in brisbane has been beautiful blue skies, fresh westerly winds and a high of 25C.

Chris

Wink writes:

If this is leishmaniasis, my question for Dixon is where do sand flies live -- beach, desert, grass?
Wink-Atlanta

Bjorn writes:

Hi

My guess would be is cutaneous leishmaniasis. It’s not that common in Italy, but it’s certainly not unheard of.

He could have been bitten by a sandfly vector while on the beach. A definitive diagnosis can be made by demonstration of the organism in the tissue surrounding the lesion. If the organism spreads beyond the skin, it can establish a visceral leishmaniasis. Here are some signs one can look for to confirm a diagnosis for that condition:

* There may be hypergammaglobulinemia and hypoalbuminemia
• Liver enzymes commonly elevated
• Pancytopenia very common
• Diagnosis by demonstration of the organism
• Commonly done through splenic puncture, liver or bone marrow biopsy, lymph node aspiration, or staining of peripheral blood buffy coat.

Assuming that this is cutaneous leishmaniasis, the treatment may be just to let the thing heal itself. However, do observe for signs of visceral leishmaniasis since that will require treatment. Most commonly utilized medication is pentavalent antimonial compound
stibogluconate. Alternative options can include liposomal amphotericin B, pentamidine, azoles and miltefosine.

All of this is fresh off my notes from the wonderful Coursera course in “Tropical Parasitology: Protozoa, Worms, Vectors and Human Diseases". As a software engineer I don’t know much about parasites, but what little I do know comes from "this week in parasitism" and that single coursera course. Parasites are fascinating :-)

Keep it up doctors, you are an inspiration.

Elise writes:

Dear TWIP Gang,

How are you? Many thanks again for your case studies. I love working on these and was not event remotely mortified by not getting the answer to TWIP 86 correct. I never would have guessed pinworms would be the culprit. (And that is a sentence I am glad I have never had an opportunity to compose prior to today.)

For TWIP 87, I have done some research and it looks very much like cutaneous leishmaniasis. All of the symptoms the patient exhibits pretty much line up. The lesion he presents is consistent with cutaneous leishmaniasis: large, painless, unhealing sore (beginning as a small painless bump), with a fibrous scabby covering, with the infection limited to the lesion, and not spreading beyond.

The patient was in Southern Italy and spent time on the beach, where he very well may have offered up an appealing meal for the sand flies that spread the infection through bites. The CDC and other sites report that cutaneous leishmaniasis is widespread (present in large parts of: Asia, the Middle East, Africa, southern Europe, Mexico, Central America, and South America), and the incubation period is about right. I suspect the patient’s elevated blood pressure is unrelated to the lesion.

(I should also add that the glee with which all of you introduced the description of the symptoms and the patient profile made me think that this would probably be a less subtle problem than the one in TWIP 86, which is why I am offering a not-uncommon diagnosis.)

Finally, I read in a number of places that these lesions cause permanent scarring. Would it be possible to minimize the scarring if the diagnosis is made sooner or is the damage inevitable?

Thank you so much again. It is 68 degrees F (20 degrees C) in lower Manhattan and the skies are blue, and it is hard to believe that it is going to pour in a couple of hours.

Cheers and best to all of you

Scott writes:

Gentlemen,

As a longtime listener, I have enjoyed your case presentations, and though I have no competence as a diagnostician, have enjoyed speculating about possible diagnoses.

The case presented in the current TWIP struck a chord with me. Living here in Costa Rica, where myiasis caused by Dermatobia hominis is fairly common (there are some really gruesome photos to be found on the web), the presentation sounded actually quite familiar. I can't speculate as to the species involved, as I am not that familiar with the species of parasitic flies that are found where the patient had been traveling, but myiasis would be my guess at a diagnosis.

Somewhere I heard a story about a biologist who was infested here, and decided to let nature take its course once he got back home, so he could document the development of the larvae to its emergent stage. As I recall, it got just too painful to tolerate and he had to remove it prior to the emergence, but even so, doing such a thing strikes me as being truly heroic dedication to science. I was infested with one once, and removed it as soon as I discovered it - I can testify that it was painful even when still quite small.

Regards,
Scott
Cartago, Costa Rica

 

TWiP 87 letters

 

Jan writes:

Hello doctors,

This was indeed not easy to Google; one of my attempts even had a dr oz page as one of search results. Clearly a dead end. However with some persistence I came up with Entamoeba Histolytica.
As for clean water; I use the boiling method when hiking and camping, and if you take a thermos flask along you can boil extra water while making your morning coffee and have tea or other hot beverages during the day. If you want cold water, just boil it in the evening when preparing dinner and let it cool overnight.

Greetings and thanks,

Jan

Robin writes:

Seems like Katayama's syndrome if a diagnosis is clinched in the parasitology lab.

Stool exam for cysts in amebic liver abscess is unhelpful, and trophozoites would not be expected in the absence of dysentery.

Murphy's sign as classically understood, is an inspiratory catch at the right costal margin at the midclavicular line, and not, as is now commonly described, as just right upper quadrant tenderness. The classic Murphy's sign is also well localised, and is a reliable indicator of a problem gall bladder.

Wink writes:

No, I’m the chump!!

You got me this time. I considered trypanosomiasis: the incubation would be OK but the presentation is wrong. Anisakiasis is not common there. He shouldn't have been walking around barefoot or wading in fresh water. I think the incubation for ascariasis is longer and a tourist would most likely be asymptomatic, but -- common things being common -- I'm making a wild bet on A. lumbricoides.
Wink Weinberg (Atlanta)

Richard writes:

I think that this gentleman has some sort of intestinal helminth infection, my vote is ascaris because it is soil-transmitted and the patient lacks high risk food exposures.

Further wikapedia-ing indicates that one still has to ingest ascaris eggs, but they are hard to kill so I think even the "westernized" food chain at a big hotel may be the culprit.

Else writes:

Dear TWIP Collective,

How are you? It seems that spring has finally settled in here in New York, so in spite of the high winds here in lower Manhattan (where it was in the lowest of 60’sF — 15-ish C) it has felt great.

I am again, trying my hand at a diagnosis. I know you were going for a trickier case study this time, and without a medical or science background I may be out of my depth, but here is my attempt.

I think that the young man who has recently returned from a trip to Kenya may be experiencing amebiasis brought on by entamoeba histolytica.

It was a bit tricky to think about what was going on with the patient because his symptoms were not particularly dramatic (which is great for him, but hard for this highly amateur detective), and the primary symptoms: stomach pain and decreased appetite, occur in many instances (or even without the help of a parasite, when exposed to too much family, at holiday time).

Amebiasis is apparently a common parasitic infection in many parts of the world but for the purposes of this case study, parts of Africa including Kenya and it expresses itself in many ways. 90% of people who are infected are asymptomatic. In people who are symptomatic, the symptoms can show up in 2-4 weeks, so given the duration of the patient’s visit and the fact that he has been home for a week, the time frame makes sense.

For people who are symptomatic, the range of symptoms includes abdominal pain as a primary symptom. (The patient does not have fever or other GI symptoms, but infected people don’t always exhibit these.)

As for how he could have contracted this parasite in spite of such care he took, staying at a hotel that caters to Western visitors and avoiding the water, I think it is possible that he slipped a little. It was mentioned that he ate salad at the hotel, which is raw and if it had been washed in local water, some parasites could have found their way to the patient. Also, he did drink soda, but if he had any ice cubes, again, this could have been a point of contact with the parasite. They are common, hard to avoid and it sounds like people can be colonized and have no idea.

As for the diagnosis, it is recommended that multiple stool samples get tested because the parasite can be hard to find.

I fear I have missed something critical, but this is the best I could come up with.

What was the vaccine that the patient should have gotten before he left that he did not get?

Many many best wishes. I am very grateful for your fascinating and brain-stretching (for me) podcast and challenges.

 

 

TWiP 86 letters

Jan writes:

Dear Doctors

This one is a bit more tricky; both Giardia and Cryptosporidium are possible. The symptoms are more those of Cryptosporidium, so that would be my semi-educated guess. Most of that education comes through you, with some help of some CDC webpages in this case.

Thanks for the podcast.

Jan

weather report Rotterdam:

The sky is 50 shades of grey, need I say more ?

Michael writes:

I'm guessing Giardia lamblia (beaver fever---GO OSU) even though Daniel made it sound like it wouldn't be the obvious answer. Really like this part of the show that engages the listener.

Mike in Oregon

Robin writes:

If the three stools had tests for Cryptosporidium requested and performed, then a string test might be considered.

Empiric treatment with metronidazole is not quite kosher, but might be cheaper.

Giardiasis
http://emedicine.medscape.com/article/176718-overview

Cryptosporidiosis

http://emedicine.medscape.com/article/215490-overview

~~~~~~~~~~~~~~~~~~~~~~~
Heterodont dentition has to accommodate to a changing jaw size. Hence two sets of teeth in diphyodonts.

Homodont polyphyodonts have no such problem, such as in sharks and crocs. Heterodont polyphyodonts tend to have lifespans sufficiently long to wear out the first set of "permanent" teeth, and go through life with more sets of teeth, as in the case of the elephant.

The natural life expectancy of hunter-gatherer humans is somewhere into the mid twenties and early thirties, enough for one set of "permanent" teeth. Agriculture has been around for 10,000 years, too brief in the relevant evolutionary time scales to have significant selection pressure towards polyphyodonty. And with modern dentistry and prosthodontics, selection pressures for polyphyodonty have been effectively evaded.


Elise writes:

Dear TWIP Collective,

Thank you so much, as always for your wonderful podcast. Again, I was very pleased to have had a successful diagnosis with TWIP 84. I’m not sure if I can continue my streak but here is what I suspect.

I think this young mother probably has Giardiasis, but I will hedge my bet, slightly and also say she could have Cryptosporidiosis.

Both diseases have extremely similar symptoms and are both caused by protozoa. Both commonly infect people in Colorado in the summer and early fall. Both have similar incubation periods. Both are found in all kinds of streams and lakes in Colorado.

In an effort to try to distinguish between the infections, I tried to see if either Giardia or Cryptosporidium are more easily detected in a stool O&P, but as it turns out they can both be hard to spot, even on multiple tests. (There has been much complaining online about how there is a huge and growing shortage of good lab technicians who can spot these things.) I did find a couple of sources that indicated that Giardia, due to “intermittent or low levels of shedding” might be somewhat harder to find on the O&P, which could account for why 3 tests came up negative on the patient.

Another reason I am inclined to suspect Giardia is that it seems to be somewhat more common in Colorado, that is, there are more reported cases of it. Also, it has the nickname “beaver fever” and Dr. Griffin did mention that the family saw quite a number of beaver while camping, so it seemed to be a good clue… unless of course it was a red herring, which is why I am not committing 100% to Giardia and also mentioning Cryptosporidiosis.

I was interested to see that both of these infections can resolve on their own in people who are not immunocompromised. I was also surprised to see that even though there are many many many official web sites cautioning people to bring their own water while camping or at least to filter water and treat it, there are still wilderness types who seem to think such precautions are silly and which recommend trying to drink water from fast running streams and creeks. This seems to be Asking For It.

But of course I am now dying to know what sort of infection this woman had, so I’ll be checking in regularly to see what’s what.

As always thank you so much.

Lots of rain today in lower Manhattan but they say the weather will be swell for the half-marathon (which I am not running) that is happening tomorrow.

All best

Christine writes:

Dear Dickson, Vincent and Daniel,

Another fascinating twip, from the description of the case I think the patient is suffering from cryptosporidiosis. Although the beaver reference suggested giardiasis, the symptomology didn't match as well as crypto. The onp didn't show parasites are they are often tricky to pick up and a zn stain may help locate them in stool rather than a straight wet mount, the incubation period is a little longer than I'd like if it was picked up on the camping trip but everyone is different. No treatment other than good hand hygiene ( to avoid contaminating others) and sufficient hydration is required and it should resolve within a couple of weeks. Treatment is generally for immune suppressed individuals.

Chris from brisbane where the weather is 32 degrees C, blue skies and a light breeze. (heaven).

Rebekah writes:

Hello TWiP doctors,

I have finally caught up to the most recent episodes and was planning on responding to episode 84 today, when I saw a new one was posted. For me, the crawfish was not the telling sign this was a case of paragonimiasis. It was Daniel's description of the symptoms, particularly the rust colored blood tinged sputum. I teach Clinical Microbiology for Medical Laboratory Technicians at a community college, so I am familiar with the classic presentation for some of these parasites and Paragonimus is a favorite Board of Certification question. I shall, again, be recommending this podcast to my students especially the new format should help cement the knowledge into their heads by getting them to think about real patients.

As for the case in the current episode I believe this is Cyclosporiasis. The main reason I pick this organism over Cryptosporidium or Giardia is because the x3 ova and parasite exams came up with negative results and because the other members of the house hold were not sick. Person to person transmission is unlikely with Cyclospora since the oocysts take days to sporulate and become infective. The O&P exams were likely negative because there are not many if any recognizable oocysts in the feces. Laboratories do not typically screen for Cyclospora unless there is a specific request ( since testing requires the use of acid-fast staining or PCR-based methods), therefore a routine O&P would not yield positive results. If this woman had consumed raspberries instead of drinking contaminated water it would have been another classic Boards question. :-)

This disease is typically self-limiting as long as the patient is in good health. If not she could use Trimethoprim/sulfamethoxazole, unless of course she has a sulfa allergy in which case I don't know.

Love the Podcast and thank you for all your hard work.

Rebekah MLS (ASCP)

Ruben writes:

Dear Majestic Trio,

My training was in physics and math and I will be succinct:

Google diarrhea and beaver to get the answer: Giardia (aka beaver fever).

Additional tests: order a Giardia, Cryptosporidium, or Entamoeba histolytica antigen test since the actual parasite or ova was not detected in the stool.

Treatment : albendazole or the like (see the reference below saying that it is less toxic and more effective than metronidazole).

** A suggestion for future case presentations in case my answer is right: I think the case should not not be 'googlable' from keywords or, at the very least, not lead to a single possible answer. Furthermore, the case may be sprinkled with irrelevant information and red herrings as it happens with real cases. Non-Google-singlet rule should be strictly enforced.

Daniel mentioned 'beavers' two times and, even with an apparent attempt to water it down with elks and cow feces, it was a google-give-away.

Must haves: the weather in San Diego is always the same, not much to talk about.

With deep respect and appreciation,

Ruben

Reference.
PLoS Negl Trop Dis. 2010 May 11;4(5)
A meta-analysis of the effectiveness of albendazole compared with metronidazole as treatments for infections with Giardia duodenalis.

Mark writes:

Dear TWiP 2.0 Team,

I've been an intermittent TWiP listener since episode #1. Intermittent only because of the variable recording and release schedule. The show is great!
This year's reboot and addition of "Doctor Doctor" (MD, PhD) Daniel Griffin to the podcast has catalyzed an exciting TWiP renaissance.

I listened to TWiP #85 today while driving home to San Jose, CA from a weekend getaway to California's Central Coast to celebrate my birthday. Over the weekend cities there, Paso Robles and San Luis Obispo, hit record high temperatures in the mid-80's. California's drought is very real.

The case in this episode is subtle and delightfully thought provoking. There are competing candidates for the parasite causing the infection AND exposure to both of them is possible. The candidates are Giardia and Cryptosporidium.

Giardia is consistent with symptoms of diarrhea. Other causal clues were the woman was camping with her family in areas where beavers, an intermediate host, were present. Tantilizingly, it was reported that the patient and family drank from streams and used iodine to treat the water. D.D. later commented that iodine had effectiveness against bacteria - so its possible Giardia cysts would be unaffected. D.D. asked about the presence of fat in the stool to which D.G. replied no fat test was done. D.D. then prompted with the word "steatorrhea" which elicited no response. Given that steatorrhea is characterized by
especially foul odors and that the patient commented about mucus in her diarrhea without commenting on smells or odors, and the negative response to D.D.'s probing it seems unlikely that the patient was suffering from Giardiasis. Finally, the patient had a temperature which is not a symptom associated with Giardiasis -- see: http://www.cdc.gov/parasites/giardia/disease.html

So, what about Cryptosporidium?

Many forms of Cryptosporidium exist, targeting different mamalian hosts. Cryptosporidium symptoms include diarrhea and fever. Crypto is very prevalent
and can be spread via cows. Here is a webpage at the Colorado State University School of Veterinary and Biomedical Sciences about crypto:
https://www.cvmbs.colostate.edu/ilm/proinfo/cdn/98articles/CryptosporidiosisNov98.pdf

The patient's case history indicate she and her family were camping and hiking in an area where there were a lot of cows, so many cows that she commented about how it diminished their enjoyment. Exposure to Crypto oocysts while walking is one source of infection. Another source is the incident described wherein the patient had contact with her child after who fell in cow feces.

Based on the patient's symptoms more completely matching those for Crypto, and the direct contact with cow feces I conclude the patient is suffering
cryptosporidiosis. As per the CDC - http://www.cdc.gov/parasites/crypto/treatment.html - treatment focuses on
managing the symptoms of diarrhea, ensuring replacment of fluids. In some cases Nitazoxanide may be prescribed.

All the best.

Keith writes:

Dear All,

Love the TWIP Reboot, Dr. Griffin blends wonderfully with the milieu. We have not heard a story from Dr. Despommier in a while, he is a fantastic story teller. Also from Dr. Racaniello, I miss his explanations. For example, when he briefly describe the micro inhibition test and hemagglutinin test. The cases are just fantastic, it really heightens my attention when I'm listening and makes me read and think after listening to the episodes.

Having lived and hiked in backcountry of the Rocky Mountains of Colorado the first two things that instantly jumped my mind were Giardia and Cryptosporidium. In the 90s when I lived in Colorado I was convinced that my dog had Giardia. She would have explosive extremely foul smelling diarrhea with mucus intermittently. As long as she had access to the outside all was okay but one year we did have an awful Christmas trees Incident. Let's just say I had to remove many of the branches from one side of the tree.

After reviewing the various disinfection methods in their effectiveness my guess would be cryptosporidium. Cryptosporidium is easily filtered a very resistant to chemical disinfection. Since their sole method of disinfection was iodine the most likely culprit would be cryptosporidia. Giardia is moderatly susceptible to chemical disinfection and therefore a less likely candidate.

Please keep up these case Studies.

Anne writes:

Dear TWIP team-

So enjoying the new format.
RE: TWIP 85 Patient from Colorado

Excluding bacterial and viral causes of diarrhea that would need to be considered in this patient (if we weren’t being presented the case on TWIP), Cryptosporidiosis and Giardiasis seemed the most likely based on the consumption of unfiltered water potentially contaminated with animal feces.
Cryptosporidiosis appears to be more often associated with low grade fever and watery diarrhea than Giardiasis. Also Cryptosporidium is quite a small parasite and could potentially be missed on the O and P. Diagnosis is enhanced by the use of acid fast stains and molecular diagnostics. However, the typical incubation period is 2 to 10 days after ingestion, which is much shorter than the patient reported. Does this case represent an unusually long incubation period, another source or a different pathogen altogether?

Giardiasis is less often associated with fever and the stool is described as floating and greasy. I briefly considered amebic dysentery due to Entamoeba histolytica and Strongyloides stercoralis infection, but they seemed less likely water contaminants for Colorado.

Cryptosporidiosis is a common opportunistic infection in SIV-infected macaques and often sets up infection outside the intestinal tract: gallbladder, common bile duct, pancreatic ducts, trachea, and bronchi. We’ve even seen it in the salivary gland ducts. I include photomicrographs.

Unrelated, I was delighted to see the February 2015 case of the month on the CDC website featuring a hunter with abdominal pain and difficulty breathing after consuming bear meat. http://www.cdc.gov/dpdx/monthlyCaseStudies/2015/case389.html

I would like to make a plug for inclusion of fungal and microsporidian diseases. They are way too interesting to exclude from the clinical case presentations.

Is Dickson phylist (adjective 1. having or showing the belief that a particular phylum is superior to another)?

Best wishes
Anne


Markedly enlarged salivary gland duct with thickened mucosa and inflammatory infiltrate.

image001


Salivary gland mucosa is proliferative and has undergone squamous metaplasia. Variably sized Cryptosporidia are evident on the surface.

image002


Anne Lewis, DVM, PhD
Beaverton, OR

Nancy writes:

Twippers:

"Beaver Fever"/Giardiasis. My grandmother picked this up when my parents lived in Fort Collins. She never remembered drinking anything not treated whilst visiting Estes Park, but was diagnosed after returning home to Reno. A lifetime western resident, she was savvy to the symptoms and felt vindicated when her doctor's lab tests confirmed her self-diagnosis. She believed she must have picked it up via washing her hands in the creek down the block from the home in Fort Collins. All this must have been 20 or more years ago.

"Sure", Dan, Fort Collins is a city. Of sorts, but quite livable, being a college town with a high percentage of college graduates.

Well, if I'm wrong it's because I'm a happy unit clerk at our local hospital's outpatient surgery unit, as my retirement job. My sole diagnostic qualifications are curiosity and long life experience.

I do enjoy all the Twixes, Twip the most, due to fewer dictionary and pubmed lookups necessary. Podcast on! and thank you for your generously donated work and time!

Richard writes:

I guess cryptosporidium Bovis. Arguing against giardia are: watery stools (not steatorrhea) and the negative studies. But giardia was definitely my first guess up till the end.

As a question for the panel: which Water-borne organisms/viruses are not killed with iodine treatment? Do filters miss anything? Boiling? Thanks guys keep em coming.

Jeff writes:

Dear TWIP hosts,

Love the new format! After weeks of speculating in my daily commute on the various cases, I am going to take a stab at the case of the week as Giardia lamblia. The focus on the beavers gave a hint as it is sometimes referred to as “Beaver fever” even though there is not typically a fever with Giardiasis (could never figure out that disconnect). The negative O&P threw me off for a bit until I did some digging and found that this is only diagnostic in ~70% of cases (J Clin Microbiol. 1989 Sep; 27(9): 1997–2002.) and the cysts are not shed in the stool on a consistent basis. Also considered Cryptosporidium as that is pretty common in that area of Colorado.

You should try not to drink the water from any streams around Durango as past mining activity left the streams with a pretty high mineral and metal content and other runoff from those activities.

Jeff

Jeff Fairman, Ph.D.
Vice President, Research
SutroVax, Inc.

Carol writes:

Greetings TWiP Team,

I'm writing with a guess for the case study, and to ask how I could get a copy of Dickson's book. I currently work as a veterinary technician, but have recently returned to university in order to pursue a degree in microbiology and pathogenesis. I love your podcasts, which I discovered 3 weeks ago, and am working my way determinedly through the back episodes. Luckily between school and work I spend a lot of time commuting.

Coming from an animal health background, I immediately thought the case study was giardiasis, particularly with the repeated mentions of beavers, but that doesn't usually cause a fever. I then amended my guess (I hesitate to use the word diagnosis, since it is entirely a guess) to cryptosporidiosis. Am I close?

Enjoying the sunshine and spring flowers in Victoria, BC, Canada while listening to old podcasts,

Carol

Varun CN writes:

Greetings Professors,

TWiP 85 presented a very interesting case. I would like to do a string test (Entero-test). The stress on presence of beaver and iodine treated water makes me think of Giardiasis (Beaver fever). Am not sure how do I explain, negativity for Stool O&P examination. Am really stabbing in dark.

My guess: Giardia lamblia.

I have happened to cross this article regarding cerebral malaria. The paper suggests that the change in brain volume leading to raised intracranial pressure may play a role in fatality of cerebral malaria. I wonder if this topic is TWiPable .
http://www.nejm.org/doi/full/10.1056/NEJMoa1400116

Looking forward to the next case challenge..

Thumbs up to the team.

TWiX fan,

Varun C N
NIMHANS, Bangalore

 

Tim writes:

Dear TWIP trio,

First of all I'd like to say that adding a third member to TWIP was a great idea. I love the case studies although I can't say I have enough expertise to make much more a wild guess based off my listening to early episodes of TWIP and google searches.

I found this paper this morning and can't remember this parasite ever being discussed on the show so I though I'd forward it on. I don't have access beyond the abstract so I apologize if it's not an interesting paper.

Have a great week. I'm off to the farm to haul manure on the fields while they're still solid in the early morning cold before they turn back into their spring muddy state by mid morning.

Clinical Microbiology Reviews 2015 Apr; 28 (2) : 295-311.
Human Infections with Sarcocystis Species.
Ronald Fayer, Douglas H Esposito, Jitender P Dubey
PMID: 25715644

Anne writes:

Dear TWIP team

Wonderful case this week of the patient from Missouri. I love the shift to sharing less info about the cases (although Dickson can’t bear not to ask the question that nails the diagnosis. Go Dickson!) Wouldn’t have gotten it without the crayfish question. Paragonomiasis is the diagnosis. If it is the same species that occurs in cats and other fish eating carnivores then the infection is Paragonimus kellicotti. I have seen this in a cat many years ago. Not sure of the cat’s ‘travel history’.

Many thanks for enriching my commutes.

http://www.foodsafetynews.com/2010/12/raw-crayfish-cause-rare-parasitic-disease/#.VP4LfPl6B8E

Anne

Anne Lewis, DVM, PhD
Diplomate, American College of Veterinary Pathologists
Beaverton, OR

Kenneth writes:

Paragonimus kellicotti?
Treat with Praziquante?

Best guess of a long-time listener, full-time layman; and someone who watched the first season of Monsters Inside Me. (Which I heard about through this podcast -- Don't actually own a television, so I downloaded the show to my computer. Thought it a tad sensationalist though.)

Hopefully I didn't miss something obvious, but I tend to listen to the podcast at work. All the TWIXs have been great company through many an overnight shift of dementia/hospice care-giving. (All my coworkers think me a weirdo.)

Loving the new format and increased frequency.
Danke, danke,
Kenneth S

Jennifer writes:

Hi TWIPers,

I'm a grad student and one of your undocumented listeners (I use the stitcher app) and I really like the show, especially the new cases! My guess for the current case is Paragonimus (due to the under-cooked crayfish).

A few weeks ago - I think it was on #83, a listener mention Bob Lane's work that shows the western fence lizards have a bactericidal agent in their blood that cleanses lyme-infected ticks. This is cool, but I was surprised that the malaria parasite, Plasmodium mexicanum, which commonly infects these lizards was not mentioned, especially with all the musings about malaria infected dinosaurs.

Actually, In the vein of looking at parasitic infections of wild animals, the malaria infection of the western fence lizard may be one of the longest running studies out there. Dr. Joseph Schall, who was my parasitology professor while I was in undergrad at the University of Vermont, has 30+ years of blood smears from infected lizards from a Hopland, CA field station and has done many studies on the impact, ecology, and clonal diversity of infection in these lizards. Perhaps you'd like to read one of his current articles or have him call into the show for comment? I wonder if lizard telomeres are shortened by malaria infection too??

Also, right now in grad school I work with the organism in which telomerase was discovered (Tetrahymena thermophila), and enjoyed the shout-outs to the Nobel winners for this. Tetrahymena is really way more interesting than many give it credit for, so I thought this episode was just all-around fantastic!

Thanks,
Jennifer Fricke Pinello

Allan writes:

My guess would be Paragonimiasis (P. kellicotti). Confirm with an ELISA if readily available, but that’s what it is.

Give him some of that wonder stuff that my parasitology professor back at Tulane, Barney Cline, helped bring over from the Vet’s for human treatment, Praziquantel, which sure beat what was used before it.

We have our own cousins of this on the Big Island of Hawaii, sort of our own local LongIsland/Nantucket Babesiosis. I won’t give it away so if you want, some time I’ll send you a case workup as a weekly mystery.

Keep up the good work. Best podcast on the web.

Allan

Allan
Kailua-Kona, HI

Bjorn writes:

Hi

Don't know if this is too late, but here goes (I havent listened to any later twip or read any notes, so I don't know if it's to late but I also haven't cheated :-):

The lesions and the description of the skin surrounding the lesion sounded a lot like a description of cutaneous leichmaniasis, and since the patient had been in Guyana, using the 'what does the sound of a hoof imply' rule that Dixon refered to, tells us that he may have an infection of Leichmania Guyanensis, so that's my guess. I understood why Vincent asked about the genital area, since this lesion may in fact have a been a shanker caused by syphilis, and finding one on the genital area would clearly strengthen that hypothesis. To make a diagnosis of leichmaniasis one would have to find signs of the organism by finding the organism in and around the lesion, but I don't know exactly how to do that. Treatment would probably be by stibogluconate, but this thing may in fact also heal itself given a year or so.

If this happens to be right, then I'm happy :-) I started listening to twi{m,p,v} about a year and a half ago when I was following Vincents virology course on itunes. I later took the part 2 course (how viruses cause disease) on Coursera. Now I'm taking a Coursera course on "Tropical Parasitology: Protozoans, Worms, Vectors and Human Diseases" and just finished the module on leichmaniasis :-) So if what I wrote above is correct then I've learned something from the course, and if not then I guess I haven't learned enough yet.

Anyway. I love twip, and although I certainly don't love parasites, I do find them fascinating.

Best wishes

Bjørn

AJ writes:

Hello DDV,

I have been a long time fan of TWiX, with TWiP being my favorite. I want to start by thanking you for all the time that you put into the TWiX series, it strikes an amazing balance between scientifically relevant, yet fun and accessible.

I’ve been interested in starting a career in parasitology and pathology for about two years, but have been rather baffled in where to start. Let me explain my background without delving into self pity. I am a 26 year old who graduated with an Bachelor degree in Ecology, Behavior, and Evolution. Before going to college at UCSD I wanted to be a marine biologist so I could swim with sharks all day and get rich (because scientists probably make tons of money, right???), but once in school I eventually drifted into focusing on entomology. I graduated with a GPA of 2.5, due primarily to a lack of attendance. I now find myself in a high paying position with a local government doing inspections (started in Agriculture inspections, due to my entomology experience, but now I do scale and meter inspections).

While my job is decent in every way, I really feel I am in the wrong place for me. I like the idea of being a doctor because I am (now) hard working, scientific minded, and like the idea of making peoples’ lives better in such a direct way. Parasitology especially calls to me in all the ways that entomology did (really, I just like learning about lifecycles that are so vastly different from ours). I am also still interested in research, as I have been for my whole life.

Here’s the actual questions…

What sort of degree program is right for me? I’ve looked a lot about getting a MD, or MSTP, or Clinical laboratory Scientist Certificate… I’m living in San Diego, so I’ve been looking at UCSD Extension programs, but I’m willing to relocate pretty much anywhere.

How do I get into such programs? With a low GPA, I know I need to retake classes, get some lab experience, and probably pass the MCAT (I have a near perfect GRE score), but without having any connections to the academic world, particularly the medical world, it’s been difficult even to find an unpaid internship. And impossible to know what effect different classes at different schools will help with getting into different schools.

What should my focus be? I know I’m interested in a huge variety of subjects, and I’m sure I will be able to blend them together, but what are the new hot topics? What are the essentials? For example, I’ve gathered that immunology has a growing importance whether you’re interested in viruses or parasites or even cancer, are there other subjects like that?

I understand these are personal questions that you can’t actually answer for me, but if you want to shoot me a short email, or even do an episode about how to get into the field I would be extremely grateful! I know you’ve done a lot of talking about how things are for those who are just starting to make a career in TWiX topics, but what about us who don’t know where to start?!

Sorry for the long windedness of this email,
Thank you for your time!

AJ

In San Diego, where it is 80 degrees, arid, with a gentle breeze.

 

 

TWiP 85 letters

 

Jan writes:

Dear Sirs

This is fun, and although I'm sure someone will gripe about Dicksons enthusiastic response to the crayfish, it made my life easier. I think it's Paragonimus kellicoti. As for eating raw crayfish; how drunk would you have to be ?

Greetings

Jan

PS

I'm not an expert in Dutch elm disease, I'm a treeworker. Inspecting trees for potential dangers is part of the job. So I have a working knowledge of the most common problems. Dutch Elm disease is caused by a fungus Ophiostoma and spread by beetles

PPS

The weather forecast for today in Rotterdam; heavy showers, 7 centigrade and winds up to 6 bft

Robin writes:

Thanks to Larry Page, Sergei Brin et al. and to Steve Jobs, Steve Wozniak et al.:

Like shooting fish in a barrel.

http://news.wustl.edu/news/Pages/20808.aspx
http://en.wikipedia.org/wiki/Paragonimus

Chris writes:

Just as I was about to send you my answer of lymphatic filariasis the new twip arrived in my inbox and I was thwarted by your rapid turnaround.

I am loving twip 2.0 and I have been trying to infect others with it. I have been listening since twip started and it encouraged me to go back to uni and become a medical laboratory scientist as a mature age student. Since graduation I have ended up in cytogenetics but still look forward to each episode of the twi triumvirate.
The weather today in Brisbane, Australia is 30 degrees C with about 60 percent humidity and little wind, so a lovely autumn day.

Today's case did intrigue me somewhat, particularly with the intermittent fevers and lack of travel. The key however is the consumption of raw crustaceans.

Paragonimus sp. (most likely kellicotti in the US) metacercariae encysted within the crustacean excyst in the duodenum, penetrate the intestinal wall into the peritoneal cavity, then through the abdominal wall and diaphragm into the lungs, where they become encapsulated and develop into adults. The worms can reach other organs and tissues including the brain and striated muscle.

The patient has presented during the chronic phase during which pulmonary manifestations include cough, expectoration of discolored sputum, hemoptysis, and chest radiographic abnormalities. Extrapulmonary locations of the adult worms result in more severe manifestations, especially when the brain is involved (these are indicated with the visual disturbances).

Diagnosis at this stage can be by the presence of eggs in the stool or sputum. Concentration may be required, immunoassays are matched to Paragonimus westermani and may not pick up Paragonimus kellicotti (more likely in the us.) The three month delay in seeking treatment gives sufficient time for the eggs to become present for diagnosis.

Treatment with praziquantel is indicated with corticosteroids to reduce the inflammatory response caused by the dying worms (particularly important in cerebral cases).

Elise writes:

Dear TWIP Collective,

I was so excited to have heard my letter read on TWIP and to have gotten the diagnosis right that I had to plunge in again (and I suppose that is an apt enough metaphor, given the case study of the week) with another diagnosis. I am delighted to be able to play along.

I believe the 32 year-old gentleman from Missouri is suffering from Paragonimiasis— an infestation of lung flukes.

Since Dr. Griffin mentioned that this guy ate a huge raw crayfish plucked from the river (no doubt lured to its death with a bit of bologna or hot dog, which the “Floater” web sites suggest are good bait for crawfish, and which it bears mentioning, could be eaten instead of the crayfish and the consumer could avoid considerable unpleasantness), a quick Google search revealed that there was an uptick of Paragonimiasis cases in the United States starting in mid-2010. One side-effect of this small but significant rise in cases is that there were a lot of articles about Paragonimiasis in a lot of places beyond medical journals and the CDC web site. Even the “Float Missouri” web site has a page warning “floaters” (people who float recreationally, not corpses found in water) not to eat live, raw or even dead, raw crawfish.

The symptoms of Paragonimiasis are consistent with those of the patient: fever, exhaustion, cough (somewhat productive, often containing a bit of blood, which might account for the brownish sputum he has— the sputum of people with this parasite can be used in diagnosis since it contains microscopic Paragonimus eggs). His chest x-ray also had fluid around his lungs, which is consistent. Many patients have central nervous system symptoms as well, which would account for the gentleman’s headaches and reported visual symptoms (blind spots, floaty things).

According to a couple of sources, the recommended medication to get rid of the flukes is Praziquantel, taken for three days. This seems like a pretty efficient drug for something that has been making someone so sick for three months.

I do have a question about this patient’s fevers which had come and gone for 3 months, which is what causes the pattern in the fever? Is it linked to the fluke eggs being released into the lungs, their hatching, or some other part of their life cycle?

Another question I have is about why these cases started coming up more in 2010. Most of the sources I found (not just the “Float Missouri” folks) point out that lung flukes are quite common in Asia, but have been relatively infrequent here. How did this parasite arrive in large enough quantities to be noticeable? I fear the question is about the arrival of the flukes, since there is zero chance that eating raw crawfish while drunk on the river is a brand new diversion.

I hope I am right. These exercises are an absolute pleasure. Many thanks for all of your work.

Lower Manhattan is getting showered with little ice pellets now after a day of snow. I am hoping that the promise of a 40 degree F (4.4 degree C) day tomorrow is not just the weather service stringing us all along with false hope.

Many best wishes,

Dr. wink writes:

As an ID physician, I am used to being nonplussed and non-judgmental by my patients' histories. However, as a vegetarian, I was repulsed by your most recent TWIP case presentation! My guess is paragonamiasis.

The TWIP duo was always great; The TWIP trio is fantastic! Thanks.

Human Paragonimiasis After Eating Raw or Undercooked Crayfish --- Missouri, July 2006−September 2010
Weekly. December 10, 2010 / 59(48);1573-1576

Dan writes:

Hello,

The case under discussion dealing w/ the 32 year old male with peripheral eosinophilia, fever and symptoms of lung infection is likely the result of the ingestion of raw crayfish as mentioned in the workup. In the US this disease would be from a parasitic infection caused by the lung fluke, Paragonimus kellicoti. So, that is my diagnosis...paragonimiasis.

My diagnosis is based entirely on a peek at the literature and specifically from a paper published in Clinical Micro Reviews (see attached pdf).

Id like to mention another point that I’ve been meaning to address since it was incorrectly stated in the podcast by Dixon.

Hibernating bears do not have circulating AFP's (antifreeze proteins). We find these in teleost fish sera in arctic waters of the No. Atlantic and elsewhere; and other organisms but not in hibernating mammals.

I studied these proteins in the 1990's. I ended up synthesizing a type I AFP from a deduced amino acid sequence published in the fish literature. This was made into a transcriptional/translational fusion to a phytohaemogluttinin coding region to subcellularly locate the fusion AFP to the extracellular space in potato plants to confer a form of frost tolerance as monitored by electrolyte leakage. You can find all of this old news in Plant Mol Biol. 1997 Oct;35(3):323-30.
Expression of a synthetic antifreeze protein in potato reduces electrolyte release at freezing temperatures.
Wallis JG1, Wang H, Guerra DJ.
Author information
Abstract
A synthetic antifreeze protein gene was expressed in plants and reduced electrolyte leakage from the leaves at freezing temperatures. The synthetic AFP was expressed as a fusion to a signal peptide, directing it to the extracytoplasmic space where ice crystallization first occurs. The gene was introduced to Solanum tuberosum L. cv. Russet Burbank by Agrobacterium-mediated transformation. Transformants were identified by PCR screening and expression of the introduced protein was verified by immunoblot. Electrolyte-release analysis of transgenic plant leaves established a correlation between the level of transgenic protein expression and degree of tolerance to freezing. This is the first identification of a phenotype associated with antifreeze protein expression in plant tissue.

Sorry I dont have a pdf and the paper reprints are long gone.

I used to be a plant lipid biochemist but shifted to human lipid metabolism in the 2000's.
Anyway, AFP I's function to alter the hydrogen bonding patterns of water such that the isodiametric nucleation of the ice crystal is thwarted by the alpha helical secondary structure of the AFP that is both ALA rich and sequentially patterned with repeating THR residues which do the hydrogen bonding.
Other AFP's are glycoproteins and their is a solid literature on them even in the surigical field where they have been used to allow the lowering of the incision temperature during the procedure.Something about decreasing ROS production I think but again, this is from memory and is decades old.

Bears do not need to thermoregulate like fish in 4 degree waters. Rather they live in dens that are well above freezing and indeed their body temp never drops more than a few degrees below normal physiological if at all.

I could explain the lipid metabolic pathways by which hibernating bears convert depot fat to NADH, FADH2 and acetyl CoA but that is just beta -oxidation. Ultimately they burn the acetate in the TCA cycle in their muscles and this helps prevent muscle wasting proteolysis.

They do not carry out the glyoxylate cycle wherein this TCA bypass allows the conversion of fatty acyl carbon to glucose...no mammals do this. Plants do because they express two key enzymes...isocitrate lyase and malate synthase...look this up if you are interested...microbes do this too.

OK so the final question you might have would be the following...why dont bears in hibernation suffer from ketoacidosis...I can explain this but it takes too much space on the email. If you want to know, let me know or try to tease it out of the literature.

So, NO ...bears dont have AFP's in their muscle. That is rubbish.

Also they are not enriched in other forms of paradigmatic frost tolerance mechanisms such as super high elevations of circulating carbohydrates or sugar alcohols...you do see this in 13 line squirrels and maybe frogs but I havent looked at this literature in close to 20 years. There was a husband-wife team..the Storeys... who did a lot of work in terrestrial animal frost avoidance but you can look that up.

I should make another comment that is always in my mind when I listen to podcasts and increasingly when I read biomed literature. [My current job involves teaching physiological biochemistry to grad and undergrad students and writing exam questions in biochemistry for 1st year medical students].The other point is...biochemistry is being increasingly avoided or diluted in the medical sciences. There are fewer and fewer investigators who know their biochemistry and classical molecular genetics. Because of this, I repeatedly encounter mistakes in reasoning and accuracy when biochemistry is brought to the front. This is radically obvious when people stumble over lipid metabolism. Too bad since we have an obesity epidemic. Oh well.

Finally, the rounding out of the host lineup with Daniel is a welcome event. Keep him on board if you can.

Ciao,
Dan

Varun CN writes:

Greetings Professors,

In response to the case made in TWiP 84, I would like to have a BAL (bronchoalveolar lavage) done for parasitic eggs. High eosniophil count rules out bacterial and viral etiologies.

My guess- Paragonimus westermani. I'm not sure if I also need to consider P kellicotti
Treat with 75 mg praziquantel per kilogram of body weight in 3 divided doses for 2--3 days.

The TWiP reboot keeps getting better and better. Thank you for the time spent in educating.

Varun CN
Bangalore, India.

Trudy writes:

Thank you so much for the "reboot". Love the case of the week and the mental stimulation it provides!

The unfortunate crawfish cruncher had Paragonimus or lung fluke.

I am a former public health nurse epidemiologist. I suspected a fluke almost right away. In public health epidemiologists "case classify" and don't diagnose unless a qualifying medical license is held. I used an ASM Journal via the SearchMedica app as well as a search via the Medscape app which resulted in a link to this article:

Paragonimus kellicotti Flukes in Missouri, USA
Michael A. Lane, MD, MSc; Luis A. Marcos, MD; Nur F. Onen, MBChB, MRCP; Lee M. Demertzis, MD; Erika V. Hayes, MD; Samuel Z. Davila, MD; Diana R. Nurutdinova, MD; Thomas C. Bailey, MD; Gary J. Weil, MD

I copied the recommended Tx from the CDC website:

"Treatment
Praziquantel is the drug of choice: adult or pediatric dosage, 25 mg/kg given orally three times per day for 2 consecutive days.
Alternative: Triclabendazole, adult or pediatric dosage, 10 mg/kg orally once or twice. For cerebral disease, a short course of corticosteroids may be given with the praziquantel to help reduce the inflammatory response around dying flukes.

Triclabendazole is not commercially available in the United States, it is not approved by the Food and Drug Administration. However, it is available through CDC, under an investigational protocol."

The biggest hint to me was the ingestion of raw shellfish!
Thanks again for your super podcast!

All the best,

Trudy
Naples, FL

John writes:

TWIP Tri-(per)-fecta,
I love the new TWIP format -- both the case studies and the more frequent episodes. Keep them coming!

I particularly enjoyed the Big Foot episode (#84). Your discussion of the tsetse fly paper had me laughing out loud. Fortunately, it's Spring break here at Creighton University and no one was around to hear me.

I also enjoyed your discussion of the case study, which included several engaging factoids and anecdotes. I'm currently teaching Zoology and we recently covered Wuchereria. Next time I teach it, I'll be sure to include some of these stories. Students remember the material better when it's accompanied by interesting narratives. The great thing about parasitology is that it's more than biology. It touches on so many different subjects and disciplines. To paraphrase your Car Talk counterparts, parasitology is historical, folklorical, economical, pharmacological, socio-political and pathological.

Finally, I'd like to take a stab at the case study. I believe this man is infected with Paragonimus kellicotti, which is a common lung fluke in the midwest. The symptoms (fever, low energy, aches and brownish sputum) are consistent with paragonimiasis. Diagnosis can be confirmed by ID'ing eggs in the stool or sputum. The man can be treated with praziquantel. He also needs a good dope slap for eating raw crayfish!

peace

Ken writes:

Hi Vincent, Dickson and Daniel,

Episode 85 (Bigfoot) was yet another good episode. I am looking forward to the case studies each week. It is a great way to learn about parasitic diseases. My guess for this week is Paragonimus trematodes. Dickson's leading questioning of Daniel and focusing on crayfish pointed me to it. I found this highly relevant article from a 2010 issue of Food Safety News. http://www.foodsafetynews.com/2010/12/raw-crayfish-cause-rare-parasitic-disease/
Testing of stool and sputum samples should be able to reveal eggs. A more expensive approach would be a CT scan of the lungs to look for the flukes. If flukes or eggs are found and Paragonimus is confirmed then Praziquantel would be the prescribed treatment.

Here's hoping that I might be able to win a TWiP mug :-)

Best wishes from Ken

Keith writes:

Paragonimiasis kellicotti, commonly known as lung flukes. Would explain the fevers and lung involvement and eosinophilia. Could look for eggs in sputum or bronchoalveolar lavage fluid, pulmonary biopsy, serum for antibodies by ELISA. Parasites could travel throughout the body, to the brain causing nerve symptoms, under the skin causing moving nodules, to the heart, pericardial effusion. Treat with 75 mg praziquantel per kilogram of body weight in 3 divided doses for 2--3 days.

Sorry very short. I love the cases I love TWIP. The addition of cases every week is fantastic. Please keep TWIP and the case of the week coming. Although this email a short at least you know people are listening learning and enjoying.

Keith

Andrew writes:

Hello TWiP, my name is Andrew. I'm a 23 year old programer who works for a tiny company named Menards. Actually, we're third largest home improvement company in the US..but that's not important. I was writing today to mention that I listen to TWiP and TWiV as often as I can. I greatly appreciate that you three take your time to supply everyone with so much in depth information. I'm also a huge fan of the the new reboot to the TWiP show. Daniel is a great part of the team and really meshes with you two. The case of the week is by far my favorite thing at the moment. I know nothing about the medical aspects, but I thought I knew this weeks answer. Dracunculiasis (guinea worm disease) was/is my guess. This was until Daniel started to explain that the gentleman wasn't feeling any pain. I look forward to hearing more information about this case, and many more in the future. Oh yeah, it's currently -11 degrees celsius and when I went into work today it was -22 degrees celsius.

Mike writes:

Dear Drs. Racaniello, Despommier, and Griffin,

First let me express my great appreciation for the effort you put into these excellent podcasts. I discovered TWIP, TWIM, and TWIV a month ago and they quickly become my daily routine while driving to lab. With so many episodes I am like a kid with a giant ice cream sunday too large for me to eat. Fortunately you seem less likely to melt. As I am immunology graduate student focusing on the immune response to H. capsulatum, I feel the only thing lacking is a TWIF podcast (this week in fungi)!

I would like to make a guess for the recent TWIP case study: filariasis, caused by Wuchereria bancrofti worms clogging up the patient's lymphatics. The dramatic, chronic, non-pitting, painless swelling of the lower leg is very typical. The open lesion is not so typical, but could be caused by a secondary infection. Blood smear should be diagnostic and cheap.

Connecting this guess to the earlier TWIP podcast describing M.bovis in cape buffalo, I would recommend the recent paper "Filarial Infection Modulates the Immune Response to Mycobacterium tuberculosis through Expansion of CD4+ IL-4 Memory T Cells" by Chatterjee et al in JI. Patients with filariasis had an increased percentage of CD4 T-cells producing the cytokine IL-4 in response Mtb antigen. Il-4 is a TH2 cytokine and maladaptive in tuberculosis.

Finally, I'd like to recommend that your podcast delve a bit more into the shifting labyrinth of CD4 T-cell polarization. The generalization that TH1 cells induce cell-mediated immunity while TH2 cell are immune regulatory and/or induce antibody-mediated immunity is somewhat outdated. TH1 cytokines are important for controlling intracellular pathogens and promoting IgG2a; TH2 cytokines are important for clearing helminths and promoting IgE. However, the role of Tregs for immune regulation and TFH for antibody production are needed for the full picture. [Perhaps you could convince an expert labyrinth navigator to join you for an episode. John O'Shea would be great if you can get him.]

All the best,

Mike
University of Cincinnati MSTP
UC/CCHMC Immunology Training Program

Varun CN writes:

Greetings Professors,

In following up with the case presented in TWiP 83, the case description looks similar to elephantiasis. The lab tests that I would ask for is his Blood counts and especially Absolute Eosinophil count and Giemsa or Leishman stained blood smear for sheathed microfilaria. I would also look for wet blood smear, to look for any slashing motile microfilaria. Wish I could see the patients leg photo.

My guess of pathogen- Wuchereria bancrofti

Thanks for all the shows and I simply love "TWiP reboot". You guys are simply awesome.

Thank you

Varun CN

Adam writes:

TWiP team,

Is elephantiasis too simple of a diagnosis for the case presented in TWiP 83? The fact that the scrotum did not swell makes me skeptical, but maybe the worms didn't impede lymphatic flow enough proximal to that area to cause swelling? (Which raises an interesting question: Is gravity - in opposition to lymphatic flow - ultimately the reason why elephantiasis usually occurs in the lower limbs?)

My mom was a clinical microbiologist at UC Irvine and I will never forget flipping through one of her books when I was no more than 10 years old. I came across an image of a man with a gigantic leg and was transfixed. Later, she had to explain that this was what was called elephantiasis. With my youthful imagination, I promptly decided that this condition was caused by a disease spread by elephants! I suppose knowing the actual science behind it - parasitic life cycle, pathophysiology, etc. - is equally fascinating.

Short aside: I teach middle school science in Chicago and your podcast trifecta keeps me intellectually stimulated, makes my commutes go by quickly, and gives me lots of cool things to share with the kids every single week. It's snowing here now, but you probably could have guessed that!

Cheers,
Adam

Suzanne writes:

I'm sure someone else has written in, but I believe the character Klinger was supposed to be Lebanese. I do remember he was from Toledo and a fan of the Mud Hens. He was one of my favorites as a kid. Actually I might have counted the whole cast as favorites. I loved that show and learned a lot from it from what kimchi is to being more tolerant of others. Along with a good respect for the science of medicine and surgery. It was a great show to grow up with.

Tim writes:

First - Thank you for the TWIx podcasts. I enjoy them all.

Second - it is great to see the TWIP crew expanded with the addition of Daniel. I also very much like the new case-of-the-week segment. Alas, this week’s mystery parasite has me stymied, but I find it intriguing as much for learning more about the diagnostic art as for the specific parasite.

Third – Yes, in a past TWIP Dickson did explain at length why the “P” in TWIP should be “parasitism” instead of “parasitology”. It seemed to make good sense at the time, although I cannot recall the specific episode.

Fourth – In this last TWIP (#83), as has happened at one time or another on all the TWIx podcasts, there were once again some questions raised which took the form of “why” questions, and in response there was the admonition that (to paraphrase) “we don’t ask why questions”. I find this apparent proscription of “why” questions across the TWIx realm (and presumably therefore in biology in general) troubling.

To ask “why?” is to elicit a response “because…”. In science it seems to me that “why X?” is the fundamental question to ask, for its intent is to elicit the causal entailment structures underlying X. Without the causal structures, we have merely lists of data and phenomena, but no organizing principles or explanatory power. It is only with hypothesizing and elucidating the causal structures that we have organizing principles and explanatory power – that we have science.

Imagine asking a physicist “why does the cannonball arc as it travels through the air rather than travel in a straight line?” and the physicist responding “we don’t ask why questions in physics”. Or asking a geologist “why is the top of that hill rounded in that manner?” and the geologist responding “we don’t ask why questions in geology”.

Of course those would be absurd conversations, because those are perfectly valid questions and there are perfectly valid answers that involve the causal structures involved on those scenarios.

There can of course be unscientific answers to “why” questions. For example, “the hill wanted to be less angular so it became more rounded”. But such mistakes surely do not, and cannot, lead us to eviscerate “why” from the scientific enterprise.

It seems that perhaps in the struggle to shed itself of an inherited legacy of vitalistic, anthropomorphic, teleological and religious of answers to “why” questions, biology has chosen a linguistic strategy to avoid such categories of answers by simply prohibiting questions of the form which may lead to such answers.

It is perfectly valid to ask “why did organ X evolve in species Z?” To deny this is to deny the role of causal entailments in biological nature; in effect, denial of these kinds of questions as being scientific leaves a void to be filled with NOTHING BUT vitalistic, anthropomorphic, teleological and religious answers. Whether or not we currently have in science sufficient data or robust answers to such questions is quite beside the point that the question is valid.

If need be for palatability, such questions can be temporarily reformulated as “what” questions. “Why does the cannonball arc as it travels through the air rather than travel in a straight line?” can be rewritten as “what are the causal entailments structures that underly the phenomenon of the cannonball arcing as it travels through the air rather than traveling in a straight line?”

Similarly, “why did organ X evolve in species Z?” can be rewritten as “what are the causal entailment structures underlying the phenomenon of the evolution of organ X in species Z?” Surely no TWIxster can deny the scientific validity of this question. (Again, the tractability of this particular question is beside the point.)

Such “what” reformulations leave us with an answer in the form of an enumerated list of causal entailment structures. This is by itself not enough. In this sense, “what” is more passive than “why”: ultimately, we want to return to answering the “why” by taking those enumerated causal entailment structures and employing them in logico-mathematical models and leveraging the explanatory powers they can provide. Thus it is that science is ultimately concerned with “why” questions and the answers they generate. Evading unscientific answers to questions about physical phenomena, such as organisms, by evading “why” questions would be, I think, quite destructive to science.

Once again, thank you for the great podcasts that are so helpful, entertaining and informative!

Regards,
Tim

Robin writes:

Can ‘extinct’ be used as a verb?
http://forum.thefreedictionary.com/postst14084_Can--extinct--be-used-as-a-verb--Nowadays-is-it--wrong--to-use-it-as-a-verb-.aspx

http://www.verbix.com/webverbix/English/extinct.html

Mary writes:

Dear TWIP,

1) Part way through episode #84-Bigfoot, I cannot help but wonder this. If the substance secreted by the filariae that "inhibits division endothelial cells of the lymphatics," mentioned by Dick, were isolated, identified, and its mechanisms determined, would we be looking at a possible applications for cancer treatment?

2) My career goal is to become a Registered Diagnostic Medical Sonographer. I will be on the look out for parasitic worms from heretofore.

3) This is my first TwiP episode, and I usually listen to TwiV during weekends at work. As a receptionist, I'm chained to a phone in a mini plexiglass fortress. Your podcasts are a delight while attending to bureaucratic paperwork.

4) Can you suggest a social platform (twitter, etc) to broadcast questions like item #1? I have no problem exposing my scientific naïveté in a public forum. It seems like a waste to have my curiosities disappear completely. Given a financial situation* that prevents the education needed for a career with serious bench work, I want to throw my ideas to the wind and have the professionals sort it out.

*Though during retirement, I fully intend to take advantage of free community college classes offered to seniors.

-MJ

Keep up the great podcasts. You wonderful folks connect science to the public and that is a noble service indeed.

 

TWiP 84 letters

 

Jesse writes:

Doctors TWiP,

I liked the discussion of the interaction of bacteria and Leishmania in sandfly guts; it was very interesting! Here is another suggestion if you need a topic to discuss:

Delivery of a functional anti-trypanosome Nanobody in different tsetse fly tissues via a bacterial symbiont, Sodalis glossinidius
http://www.microbialcellfactories.com/content/13/1/156/abstract

Cheers,
Jesse

 

TWiP 82 case:

Allan writes:

My guess is: Malaria (most likely P vivax or P oval).

On another note, I listen to TWIP while driving home on the Sticher phone app, which much like a radio, lets me listen to a list of my favorite, frequently updated podcasts (news & health-related in my case), and alerts me when there is an updated episode. The audio podcasts are small enough that I stay under my allotted cell minutes and don’t have to download or delete episodes. I actually discovered TWIP via the Sticher app about three years ago, and while I have no financial connection to the app, had never heard you mention it as a conduit for TWIP.

Keep up the good work.
Allan
Kailua-Kona, Hawaii

Richard writes:

My guess is P. vivax malaria. The patient has fever every other day (tertian fever) with shaking chills, general malaise and headache, and the labs are all consistent with malaria. This could be either a recurrence (with the symptoms of the primary infection masked by mefloquine treatment) or a long incubation period (maybe due to the thalassemia minor). Either way a 6 month asymptomatic interval is, I think, not unusual with vivax. Add primaquine!
-Richie
Columbus, OH

Richie writes:

Hey guys, I am loving TWIP 2.0! I am a medical student considering a career in infectious disease and tropical medicine in particular; TWIP was always great but the added clinical component has improved it. I also love the commitment to more frequent episodes.

Regarding the case presentations: I like the structure in #82 with Daniel supplying the basics and Dickson and Vincent asking follow-up questions, but is there any way you guys could limit the "guessing" at that point? I personally think it would be more fun to just present the history and selected other findings, and then save the differential diagnosis for the following episode. For example, the discussion of the first and second cases included the correct diagnoses. I don't yet know the answer to the third case but I was pretty sure it was vivax even before Dickson began talking about why that was probably it. I think it would be more satisfying to form a diagnosis from the presentation alone. If I'm wrong and it is not vivax, well, that undermines my point entirely and please disregard this email.

Richie
Columbus, OH
9F, -13C

TWiP 83 case:

Jan writes:

Dear doctors,

Thanks to google, I think it's lymphatic filariasis, transmitted by the culex mosquito. Love the (twix) show(s) where I learn a lot outside my normal field which is trees. We still are in the dark ages there. Our treatment options after diagnosis are rather limited; improve the soil, let's wait and see, amputation or euthanasia. Sadly it's mostly the latter due to economic reasons.

Greetings
Jan
ps The weather here in Rotterdam, the Netherlands is 7 degrees centigrade and showery, wind is not too bad for a change.

Elise writes:

Dear TWIP Trifecta,

I am a longtime fan of yours and think you’re terrific both as a duo and a trio. Thank you so much for your work. I am not a scientist at all, but I love listening to you and do my best to follow both TWIP and TWIV out of pure interest.

Of course I have been following along with your recent case studies and have taken notes and done my own, non-scientific, non-academic, searches to try to diagnose these patients. I was privately pleased that I figured out the Babesiosis diagnosis in the gentleman on Long Island by myself but did not write in due to embarrassment.

With this new case, I am feeling reckless, having gotten one right. I think the gentleman from Guyana may have Lymphatic Filariasis. Here’s why:

The nematode worms that cause the disease are common in Guyana and this gentleman didn’t drink filtered water or take other precautions.

An infection can take years to manifest while the worms multiply and many infected people are asymptomatic, so he wouldn’t have had cause to complain about much, which he hasn’t done (and in what is behavior somewhat typical of many men I know, he still didn’t feel he wanted to do much about it even with significant swelling and an open wound).

Dr. Griffin did say that the man’s genitals were normal, and while it is apparently common for the genitals to also become swollen, perhaps this man is fortunate (since not all people who are infected have this symptom), or the disease had not progressed.

The edema described in patients with later stage Lymphatic Filariasis matches the sort that Dr. Griffin described, non-pitting and “brawny,” with skin color and texture changes.

In reading about Lymphatic Filariasis, I was a bit confused because there is not always a mention of a chronic abscess or wound, but apparently a single abscess can be caused by collections of dead worms on the lymphatic tract, so that symptom fits.

I was interested to see that, for diagnosis, blood collection should be done at night because that is the time when the microfilariae are circulating. Does this mean that diagnoses are often missed because blood is most often drawn during the day or is there so much suspicion about what is causing this constellation of symptoms that medical practitioners know to draw blood for this diagnosis in the evening hours?

Thank you very much for your webcast. If I get this wrong, I hope very much that my having written is not something embarrassing (to me), and if I get it right, or close to right, or wrong in an interesting way, perhaps it is due to the way you explain everything so well and are such good teachers that even someone with no training could play at-home detective.

It is very cold here in Lower Manhattan where I am right now, -5C, 23F.

Best wishes,

Elise

Ken writes:

Hi Vincent, Dickson and Daniel,

I have been listening to the TWiX series for a long time, and even got to experience the TWiV bump by appearing in an episode of TWiV when Vincent visited MedImmune last year.

Having done postdoc work in a trypanosome lab at the Univ of Buffalo, I particularly enjoy TWiP and am really enjoying the recently revamped format. During episode 83, you were talking about primaquine and a MASH episode in which it was discussed. The character was Klinger, who was a Lebanese American. According to what I found on Wikipedia (not always a reliable source, but I think in this case it is) hemolysis is an adverse effect of primaquine in Africans or Caucasians of Mediterranean descent.

Also, I wanted to take a stab at the case study in episode 83. My diagnosis is lymphatic filariasis due to Wuchereria bancrofti. I would recommend doing blood collection at night since the filaria circulate at night in the blood and then doing a smear for identification.

Looking forward to more excellent episodes of TWiP!

Best wishes
Ken

Wikipedia entry for primaquine

http://en.m.wikipedia.org/wiki/Primaquine

Curt writes:

Hello all,

Didn't write in last week because the time course threw me off of malaria, which was my only suspect. The epidemiology, time course, and some of the syndrome is right for elephantiasis secondary lymphatic filariasis. However, while lymphatic filariasis may produce numerous bacterial infections, I would anticipate these to either be short-lived or ultimately proceed to sepsis. As such, I anticipate that the persistent, unhealing, painless wound would demonstrate leishmania amastigotes under tissue sample light microscopy.

At this stage in the disease, it's clear that at least some of the worms have died, which complicates testing, but he may show some microfilarea in a thick blood smear if the sample is taken at night and some worms persist. Check for splenomegaly and preform an Ig assay to rule out visceral leishmania, refer the patient to a lymphatic specialist for possible elephantiasis therapies, active filariasis has been known to respond to doxicycline (since we're on the cheap), and treat the leishmania with miltefosine.

Wink writes:

At 1:11 I'm saying Wucheratia bancfofti.
Wink from Atlanta
(P.S.: The vivax was at 9 months)

Bill writes:

TWIP Trifecta,

I love the new format with the case studies.

I came across the TWIX trio a few years back, and they give my mind a welcome diversion during my commute to and from work where I spend my days managing a team of talented engineers in the auto industry.

I was disappointed to see just one response to last weeks case, so I thought I would give it a shot.

This weeks case sounds like lymphatic filariasis - a.k.a. elephantiasis. It is recognizable by Lymphedema - commonly called big foot. The decreased lymph system function causes the build up of fluid, and makes infection more likely. The open sore seems to be a secondary bacterial infection.

Regarding tests to schedule, I would like to see a thick blood smear with a H&E stain collected as late as possible - this should help to confirm the presence of microscopic nematodes.

There are currently three known vectors – Aedes aegypti, Culex and Anopheles – in Guyana that can transmit the disease. Vincent's question on the swollen genitals would suggest ruling out Wuchereria bancrofti, but in my literature search, it was not clear if Brugia malayi and Brugia timori are prevalent in Guyana, so perhaps it could still be W. bancrofti.

On to treatment, Diethylcarbamazine (DEC) looks to be the drug of choice. An alternative could be ivermectin to kill the microfilariae with doxycycline to take care of the adult worms.

For the open wound - antibiotic to clear the infection.

Many Thanks,
Bill
Buffalo, New York.

Weather - Very cold, lots of snow but no risk of mosquito bites.

Jesse writes:

I really enjoy TWIP, both the entertaining banter and the science. I particularly enjoy Dick's expositions on the myriad parasitic ecologies. Daniel's clinical expertise is a welcome compliment to Vincent and Dick's tributes to Abbott and Costello. Thanks Vincent, for supplying Dick with a new microphone and coaching his microphone technique. As a turnabout, a video of Dick teaching Vincent how to cast with a fly rod, while unrelated to parasitism, would make for bemused viewing.

Here's my take at episode 83's listener quiz. From perusing my wife's medical references I'll venture that the Guyanan gentlemen with the discrete travel plans is suffering from lymphatic filariasis. He has probably been infected for many years as the swollen leg's skin has "brawny" characteristics.. According to my reference text the lack of genital involvement, swelling limited to the lower leg, and an ulcer along his inner shin point to an infection by Brugia malayi. I don't recall Daniel's physical exam mentioning enlarged popliteal lymph nodes but I imagine they were present.

I look forward to listening to your next episode to learn if my guess is on the mark. Thanks again for a great podcast.

Robin writes:

My four episodes of malaria were in childhood before my teens, in East Pakistan (now Bangladesh) and West Pakistan (now Pakistan). That's the closest we come to cohabiting with a photosynthetic organism: the malarial parasite is descended from a lineage of photosynthetic Dinoflagellates and still carries in its genome a few vestiges from its ancestral photosythetic machinery.

A far cry from corals and free-living non-photosynthetic microbes which associate with photosynthesisers that act as symbionts, endosymbionts and even become acquired organelles.

Some New Guinea tribes had a 95% prevalence of asymptomatic malarial parasitemia in adults. The prevalence among adults in Gambia was 70+%. If in deep time past the parasite could have found a way to ride along through the vertebrate germ cell line, they might have found a way to earn their keep, and become an endosymbiont.

Old wives' tales: these are best spread by GYN specialists.

Swollen leg: The patient usually does not worry if the condition is painless.

Night time thick and thin blood smears from a finger stick, Giemsa stained, could be examined.

First thing to treat elephantiasis is a course of penicillin or other related drugs if the patient is not allergic to them. Prompt attention with treatment for episodes of local cellulitis and special attention to local hygiene and cleanliness to prevent cellulitic episodes can be very helpful.

Albendazole with ivermectin should deal with the microfilariae. Doxycycline against Wolbachia should permanently eliminate microfilariae and halt progression of elephantiasis.

If the ulcer looks like leishmaniasis and shows no improvement with PCN, a PCR is in order, but since it is not reportable, neither the CDC nor the state health department would be persuaded to pick up the tab. The physician may bill TWIP (Take What Insurance Pays) but the laboratory service is another matter.

Meanwhile fluconazole may be an option until laboratory results. Miltefosine may be a consideration then.

Oscar writes:

That was a sneaky way to get someone to listen to the back episodes! Well played Dr. Griffin, well played.

Also, keep up the experimentation! You all have good instincts, follow them. The world needs a new cartalk (weekly, enlightening mysteries). You could do it. At least three different mysteries presented and solved per episode. There are some back episodes where Dixon and Vincent trade off questioning each other through the whole presentation and it really works. Instead of the car talk guys questioning the listener you question each other and it steps the listener through the paper.

Here are some free ideas--instead of 'case' or 'paper' or 'presentation' I'm going to use the term 'mystery'.

1. All three of you should laugh at least three times per episode.
2. Instead of listeners call in, have a 'smarter person than us' call out (perhaps to enlighten a mystery or present a mystery or share news or report on location), that parasitalogist from Mayo--Bobbi Pritt, that you had on a couple months back would make great regular--not too often and not too long--like when some professor from MIT would call in to yell at Tom and Ray.
3. Figure out what kind of mysteries the bit you're doing is--figure out some sort of taxonomic classification. Get a few solid kinds so you and the listeners can start to catch a rhythm.
4. Know how much of the mysteries you want to give away going in.
5. Have at least one mystery that goes on for more than a week, maybe an easy and a hard one. Perhaps the 'smarter person than us' could give all three of you a mystery that is outside your expertise and even outside the scope of parasitology. The Car Talk hosts weren't afraid to blindly grasp for an automotive engineers solution to a relationship problem that had nothing to do with cars--you shouldn't either--it keeps you extra human.
6. Here's a mystery presentation idea: 'One Question'. Give a really short background and have people email (or perhaps fill out a form) where they get to ask a question and take a guess. If they get it the first week on the first question they get lauded. If they ask a question and guess wrong it goes to the next week with a new person where the short presentation (one or two sentences) and then a summary of all questions and the new person gets to ask a question and guess. The longer it goes the better the prize? If all three of you took turns coming up with the mystery you could compete with each other as well as to who could stump the listeners the longest.... oooh... I like 'stump'. Maybe you could call it 'Chump-The-Stumps!' for a shameless-but-not-copyright-infringing homage to Cartalk.
7. Have fun!

Eagerly listening,
Oscar

 

 

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