Case guesses:

Elise writes:

Dear TWIP Trifecta, 

It is 82 degrees F (27 degrees C) in a turbulent lower Manhattan. It has been an upsetting , overwhelming week, but one in which I have really thought so much about how everything from issues of racial inequality to the global pandemic are connected and respond to each other. (Episodes 623 and 624 of TWIV have also made me think about the interconnectedness of these issues AND those of sex, gender and politics.) Thank you for giving me something for my restless mind to work on that also broadens my sympathies and engagement. 

I do have a diagnostic guess for the 69 year-old world traveler. While her husband hosted a cyclospora infection, and her symptoms were similar, that was not her parasite. Because she did test positive for B. hominis and E. nana AND because she failed to respond to a wide range of treatments that should have knocked out most of the other usual parasitic suspects (metronidazole, tinidazole,  Bactrim, etc), I think she may have been living with a Strongyloides infection. 

First, I was interested to learn that the presence of b hominis can often indicate the presence of another parasite, and this would explain why the patient continued to suffer symptoms even after having her b. hominis  dealt with. The patient’s symptoms:  gastrointestinal discomfort, mucosy stools and a general malaise are the symptoms of many parasitic infections, but when they persisted after so many treatments, I looked to see what sorts of parasites might not respond to the medications that had already been prescribed. 

Strongyloides can be found in South Africa and it is most easily contracted through water or infected soil. (Due to the water shortage, it is very possible that the patient could have gotten contaminated on her safari.) Strongyloides may not have been a diagnostic first thought because  infections can be asymptomatic for a long time and also can emerge in as skin lesions or respiratory problems, in addition to the gastrointestinal issues. Also, a single stool sample is not always sufficient to achieve a diagnosis. The preferred treatment for Strongyloides is Ivermectin, which was not  among the bundle of drugs that the patient tried. 

My hope is that a course (or two) of Ivermectin helped the patient improve and get back to feeling more like herself. 

As always, thank you all so very much for your podcast, for your work and for sharing it so generously. 

Many best wishes

Elise

Owain writes:

Dear TWiP,

I am a doctor from the UK, and I’ve been listening to TWIP for the last four years, and have FINALLY caught up! This year, I’ve been studying for a Masters degree in Medical Parasitology at the London School of Hygiene and Tropical Medicine (which the COVID-19 pandemic sadly interrupted, although that has given me an excuse to start listening to TWIV too!), which has been fantastic!

As far as my case guess goes, I found this one rather tricky. The lady’s husband had Cyclospora, and she may have initially had this or other GI infections from a similar source. However, while they might suggest contact with contaminated water/food sources, I was taught that E. nana is generally considered non-pathogenic, and so is Blastocystis hominis (although some people consider the latter able to cause symptoms). Regardless of the cause, most GI infections tend to be self-limiting, and it sounds like a significant amount of time has passed since the initial infection. The repeat OCP that this lady had was then negative, but her symptoms persisted. It sounds like she had many empirical treatments for presumptive pathogens, and regardless of what the initial cause was, it doesn’t especially surprise me that she has ongoing abdominal discomfort and loose stools given what must have happened to her gut flora! My inclination would be to undertake some watchful waiting, given we have no organism to treat, and see how her symptoms go – if they persist after discontinuing the antibiotics, we could reconsider sending stool specimens for PCR/OCP to see if anything to help guide treatment is found. In terms of non-infectious causes, she may have a post-infectious IBS-type syndrome which hopefully will settle with time. It might be prudent to consider further investigations for malignancy (e.g. endoscopy) based on her other risk factors (e.g. age) if no other cause is found, but the clear trigger of her travel history makes this less likely in my opinion. Or I’ve completely missed something obvious, in which case I’ll be very embarrassed!

I would also like to query something Dickson said in the last episode, if you don’t mind – sorry! Dickson stated last time that the Microsporidia are protozoan parasites, but we were taught on my course that while previously considered protozoa, they’re now considered fungi. I googled this and found some links which seem to corroborate that (see below).     

Having never written in before, I want to thank you very much for producing all the great podcasts you do – they definitely teach me a lot, and have been particularly useful for exams and during the pandemic! Stay safe, and I look forward to being able to guess from now on!

Yours sincerely,

Owain (Oh-wine or Owen, never Owayne!)

https://en.wikipedia.org/wiki/Microsporidia

http://www.umich.edu/~mycology/resources/Publications/Hibbett-et-al.-2007.pdf

Sophia writes:

Hello

hope you are all well.

For my guess I ‘d say that co-infection with Blastocystis Hominis and Endolimax Nana has been reported to result in Chronic Diarrhea (https://pubmed.ncbi.nlm.nih.gov/22740811/) so I would say these could be the cause of her discomfort. In the beginning I had thought of Giardia being involved as well but after all the drugs taken, this would have been wiped out as well, had it been there. What do we do? tell the patient to give it some time, after all these drugs it’s normal that it will take time before GI fauna is restored. 

As for Dickson ‘s comment on doctor’s playing with different drugs, yes, this is how they diagnose diarrhea here in Greece as well. You never know the causative organism (lab test too expensive, drug less expensive) but as long as you feel better who cares?…Worse even patients in Greece won’t even go to the doctor. Instead they go to the pharmacist, list their symptoms and try the first drug suggested (pharmacist’s advice is free of charge…why pay the doctor?) I don’t like this but it happens a lot

enjoy your summer!

Sophia

Jim writes:

Greetings digestive detectives of the troubled intestinal tract:

Several TWIPs ago, Daniel Griffin told us about two people in Africa who ate the same stuff and became woefully infected with the Cyclospora parasite.

 Dr. Griffin effectively treated them with the very same medication that he prescribed in the current case.  Still, one of them continued to suffer from frequent, super-loose propulsive stools, even  after the offending pathogen was defeated.  In that case, it turned out lactose intolerance was the culprit because it is sometimes a lingering effect of Cyclospora infections. 

If this has happened before on one TWIP, then it could happen again.  It would also explain how the current couple might get different results after they ate all the same stuff.  Of course, that means the wife in the current case must be ingesting dairy products post parasite.  If this is the issue, it will go away within a week.  Better still, she can temporarily avoid dairy for faster relief. 

Keep on rocking in the roiling ‘20s!

Take care,

Jim

Andrew writes:

Kia ora from Pongaroa,

No book won yet but I think Vincent has enough on his plate, at the moment, without having to traipse to the Post Office just to send me a book. 

Weather – raining and 11°C 

Covid-19:

New Zealand has achieved local elimination and although we currently have 14 active cases, they are all people who tested positive in quarantine having arrived from overseas. Life is back to normal although everyone is encouraged to observe the, now habituated, social distancing, hygiene, and to keep a diary of where one has been. We celebrated by attending rugby matches en masse – for those who are not familiar with rugby, it is like American football but without the PPE. The walls keeping the virus from our population are holding despite a few quickly repaired cracks that let some infected people into the general population without having been tested. Hopefully our experience will help inform policy makers in the rest of the world.

The case of the woman who went on safari:

Given that she is testing negative on a range of tests and that her intestinal tract has been carpet-bombed with a range of antibiotics, I am going to guess that she probably had c. cayetanensis, like her husband, and had cleared it or nearly cleared it by the time she was told she needed to be tested. Now she might have a helminth or another parasite that escaped the ministrations of her doctor but I think the problem is that her intestinal biome has been disrupted in the process and this has led to her current symptoms which indicate dysbiosis. As this is a “what do we do” and not a “what is causing it” problem, I would recommend that, with a normal, healthy diet, it will resolve itself. Failing that a course of probiotics and in either case she is screened again. If here condition does not improve or worsens then a course of Rifaximin might be considered. 

Ngā mihi,

Andrew

James writes:

Hm. Woman visited South Africa and has trots, runs, two step, 12/day described as watery and mucus at various times.

O and P for Blastocystis and Endolimax. True public health menaces. You WILL find a subgroup of naturopaths etc that think that these are real parasites. I did a Christian radio call-in show and found that people  out there, in Colorado where the only parasite is Giardia, are convinced they are infested. I lived in fear of the first caller being parasites/toxins, or even worse bipolar–the rest of the two hours was doomed. I’ve found these traits in my own Christian community and also in Salt Lake when I was a resident.

Anyway…

When I think of parasitic chronic diarrhea of months, I think of Cyclospora like last time, Cytoisospora, or Cryptosporidium mostly. The mucus is concerning for a more dysentery (amebiasis) presentation. I’d have to consider Giardia of course. 

How about worms?

I guess Strongyloides? Trichuris? Schisto? seem unlikely.

How about just unmasked Lactose intolerance from any of the above that succumbed to the patients like total polypharmacology?

Cryptosporidium seems like something that COULD do all this. I don’t know the sensitivity and specificity of the GI panel. It commonly gets missed as a yeast or similar on O and P and you did NOT say whether they did an acid fast this time. And I think it could have survived the antiparasitic carpet bombing the poor dear endured. I wonder if she has any normal flora left at all?

James M. Small, MD, PhD, FCAPAssociate Professor of Pathology and MicrobiologyRocky Vista University

Kevin writes:

The wife of a guy with Cyclospora diarrhea.

Relevant to our TWiP discussions during episodes 180 and 183: there have been 118 cases of Cyclospora in the midwestern USA originating in pre-bagged salad mix beginning 05/11/2020. We know now, thanks to thee three.

Our patient has participated, perhaps unwittingly, in an orgy of pharmacology; subjected to courses of at least 5 different medications (defined as polypharmacy in some classifications). A scorched earth strategy?  She remains (months after her South African idyll) with non-specific abdominal discomfort, ‘mucus’ in her stool, and ‘not feeling like her normal self’….traditional/ conventional stool studies and PCR/nucleic acid test panels have subsequently been negative. 

I recall a quotation from 1968: “We had to destroy the town in order to save it.” (Peter Arnett, quoting an officer’s description of the Viet Nam battle of Ben Tre.)

Our patient’s initial stool test on return from South Africa reported Endolimax nana and Blastocystis hominis.

Consensus opinion regards E. nana as non-pathogenic. PD7 describes Endolimax nana as a commensal whose “reporting often elicits confusion.”  Blastocystis has a more complicated story (and our patient has been treated for Blastocystis and has retested negative). Though usually described as non-pathogenic, Blastocystis will be discussed in the ENDNOTES. Subsequent multi-organism testing of our chronically symptomatic patient has all been negative. This prompts a discussion of peristent diarrhea (defined as diarrhea lasting for more than 14 days) in a returned traveler. The CDC has a concise diagnostic scheme for approaching this situation. Their 3 point scheme: 

1) ongoing infection or coinfection with a second organism. C. difficile should always be considered. In our case I would consider Strongyloides infection, though it is usually asymptomatic in the immunocompetent host. PCR should be ordered. Strongyloides is not included in the BioFire or Luminex multiplex GI panels. Eosinophilia is not always present (all discussed in the ENDNOTES.)

2) previously undiagnosed GI disease unmasked by an enteric infection. Think celiac disease, inflammatory bowel disease (IBD) and colon cancer. Standard celiac disease labs should be done.

3) a post-infectious phenomenon. Similar to TWiP 180- a transient lactase or disaccharidase deficiency. Other considerations are intestinal villous atrophy and post-infectious IBD.

After ruling out the possibilities described above, we enter the nebulous territory of ‘functional’ disorders. 

The medical term ‘functional’ has been used since at least the mid-1800s. In functional disorders, no structural, anatomical, biochemical/metabolic abnormality is detectable in spite of a demonstrable impairment in bodily function. This entire area is fraught with controversy, but conditions that are sometimes included in this area are fibromyalgia, chronic fatigue syndrome (myalgic encephalomyelitis), and relevant to our patient: irritable bowel syndrome. The difficulty with the category of functional disorders is that they may be perceived as being psychosomatic or a type of neurotic malingering, leading to premature diagnostic closure, ‘diagnostic overshadowing’ and serious lapses of medical management. 

Our patient’s  symptoms are likely due to a post-infectious irritable bowel syndrome (IBS). Note that Blastocystis has been linked with IBS for decades. Besides reassurance that she is not harboring a dangerous parasite and is in no way an infectious threat to her grandchildren, I would proceed with a trial high fiber diet or twice daily psyllium, dietary modification with a trial of avoidance of gas producing foods such as legumes, cabbage, artificial sweeteners etc. A gluten free diet may be attempted. A trial of a dairy elimination is also be recommended. In addition to the foregoing, reassurance and longitudinal follow-up with consistent primary care availability should go a long way to ameliorating this patient’s distress. 

Thanks for keeping your GRIP, on TWiP

PS: Dr. G:  Fantastic broadcast presence on Nova! Dry clean tuxedo for Emmy’s.

REFERENCES:

General:

Cyclospora report: https://www.cdc.gov/parasites/cyclosporiasis/outbreaks/2020/index.html

Word origins: limax, neut. Latin, slug, snail nanos, masc. Greek, dwarf, Latin nanus=dwarf

Though it may be generally desirable to purge your lexicon of obscurantist Greek and Latin terminology, I don’t recommend telling your patient that she has a dwarf snail in her guts. 

CDC persistent diarrhea discussion:

https://wwwnc.cdc.gov/travel/yellowbook/2020/posttravel-evaluation/persistent-diarrhea-in-returned-travelers

Poulsen CS, Stensvold CR. Systematic review on Endolimax nana: A less well studied intestinal ameba. Trop Parasitol. 2016;6(1):8-29.

a painfully thorough review…..Some relevant outtakes from Poulsen: “Non-pathogenic commensal protozoon…Of the so-called nonpathogenic intestinal protozoa, Endolimax nana belongs to the ones least well described…. they live in the colon, eat bacteria…Dobell’s self infection lasted 17 years…(see his 1943 Parasitology article.)…Though described as ‘nonpathogenic’ the authors go on to describe ‘successful’ metronidazole treatment….Estimated global prevalence 13% “Very little research has been performed on Endolimax since the 1920s, 30s, and 40s….There are reports of diarrhea associated with E. nana infections, but the possiblity remains that E nana is just a marker/ signal of broader exposure to fecal contamination. A co-traveller if you will. 

Strongyloides References / discussion

Greaves D, Coggle S, Pollard C, Aliyu SH, Moore EM. Strongyloides stercoralis infection. BMJ. 2013;347:f4610. Published 2013 Jul 30.

Concha R, Harrington W Jr, Rogers AI. Intestinal strongyloidiasis: recognition, management, and determinants of outcome. J Clin Gastroenterol. 2005;39(3):203-211. 

over 60% cases are asx. Infection can persist decades. Stool microscopy is still the gold standard dx. Standard stool exam = 50% sensitivity, which can be improved by stool concentration techniques. Serologic tests are much more accurate….50% of chronic infections in immunocompetent patients = asymptomatic, 75% show eosinophilia… clinical: epigastric pain/tenderness, diarrhea, nausea, vomiting, weight loss….however the entire clinical picture can be very subtle

Naidu P, Yanow SK, Kowalewska-Grochowska KT. Eosinophilia: A poor predictor of Strongyloides infection in refugees. Can J Infect Dis Med Microbiol. 2013; 

n=350, seroprevalence of stronglyloides=4.6%, eosinophilia was only present in 25% of the positive patients.The present study confirms that eosinophilia is a poor predictor of Strongyloides infection (P=0.05)

Boulware DR, Stauffer WM, Hendel-Paterson BR, et al. Maltreatment of Strongyloides infection: case series and worldwide physicians-in-training survey. Am J Med. 2007;120(6):545  Prior to the correct diagnosis of strongyloidiasis, patients with previously negative stool specimens were subjected to numerous invasive procedures and labeled with an array of misdiagnoses including irritable bowel syndrome, somatization disorder, and psychogenic pruritis.

Functional Disorder:

Disease: Its Cause and Prevention, G E Richmond, London: HK Lewis, 1907

Functional Disease of the Heart, Henry Jackson; Boston Medical and Surgical Journal, CXLI, No 17, October 26, 1899 

“Further, we limit the use of the word functional to such disturbances as are dependent upon some cause as yet unknown, without known pathological lesion, and, therefore, as far as we know, capable of a complete restoration of health.”

Blastocystis:

Blastocystis is a genus of single-celled heterokont parasites belonging to a group of organisms that are known as the Stramenopiles (also called Heterokonts) that includes algae, diatoms, and water molds. (wiki)

Boorom KF, Smith H, Nimri L, et al. Oh my aching gut: irritable bowel syndrome, Blastocystis, and asymptomatic infection. Parasit Vectors. 2008;1(1):40. Published 2008 Oct 21.  Who is Blastocystis? Traditionally classified as a protozoan, rRNA analysis suggests that Blastocystis is a Stramenophile: the phylum that contains diatoms, brown algae, slime nets and water molds….Boorum extensively discusses taxonomic classification difficulties within the genus Blastocystis and casts doubt on the validity of the species name hominis. Boorom quotes Zierdt 1992: “Diarrhea is not standard, and constipation is common. The symptoms gleaned from the literature include abdominal pain, discomfort, anorexia, bloating, cramps, diarrhea, constipation,… vomiting, dehydration, sleeplessness, nausea, weight loss, inability to work, lassitude, dizziness, flatus, pruritis, and tenesmus. Blood in the stool as well as excessive mucus and leukocytes have been reported.”……..Boorom states that protozoans have been identified in the stool of 46% of patients diagnosed with the ‘functional’ gastrointestinal disorder IBS (irritable bowel syndrome). The association of Blastocystis and IBS has been widely discussed in the literature but clear evidence of causation is lacking.

Kurt Ö, Doğruman Al F, Tanyüksel M. Eradication of Blastocystis in humans: Really necessary for all?. Parasitol Int. 2016;65(6 Pt B):797-801. doi:10.1016/j.parint.2016.01.010

A commercial PCR diagnostic test for Blastocystis is manufactured in Spain. It does not seem to be FDA approved.https://www.certest.es/products/multiplex-blastocystis-hominis-dientamoeba-fragilis/

Evaluation of Multiplex Tandem Real-Time PCR for Detection of Cryptosporidium spp., Dientamoeba fragilis, Entamoeba histolytica, and Giardia intestinalis in Clinical Stool Samples D. Stark,et al Journal of Clinical Microbiology Dec 2010, 49 (1) 257-262;——–>Blastocystis is the most commonly detected protozoan in stool samples.

Shah M, Tan CB, Rajan D, et al. Blastocystis hominis and Endolimax nana Co-Infection Resulting in Chronic Diarrhea in an Immunocompetent Male. Case Rep Gastroenterol. 2012;6(2):358-364   many case reports of diarrhea due to coinfection (an African study of schoolchildren showed high coinfection rates with associated diarrhea….) Nevertheless the authors conclude that the significance of the co-infection is unclear in immunocompetent patients. 

A TERMINAL CURIOSITY(S)

  • Annals of Filthy Lucre: (see also my entry in TWiP 168) Endolimax nana has been found on banknotes (Moreno, “Bol Malariol Salud Ambient”)
  • TERM:   “A spurious passage”:  This is not a literary or biblical term in this context. It refers to the presence of a non-infectious worm or ova found in a patient’s stool. Example: a free-living soil nematode found in stool. Georgis’ Parasitology for Veterinarians, Dwight D. Bowman 2009   Non-Human Primates in Biomedical Research, B Bennett, 1998, Academic Press
  • Strange article documenting protozoans discovered in peritoneal dialysis fluid.  Simões-Silva L, Correia I, Barbosa J, et al. Asymptomatic Effluent Protozoa Colonization in Peritoneal Dialysis Patients. Perit Dial Int. 2016;36(5):566-569. Protozoa were found in PD effluent of 10.2% of evaluated PD patients, namely Blastocystis hominis, in 2 patients, and Entamoeba sp., Giardia sp., and Endolimax nana in the other 3 patients, respectively….Our results demonstrate that PD effluent may be susceptible to asymptomatic protozoa colonization. SOME rather unconvincing photographs. No nucleic acid amplification diagnosis performed…
  • What is the OFFICIAL definition of ‘fresh stool’?? American Association of Clinical Chemistry: A fresh stool sample transported to the laboratory within 2 hours or one that has been placed in a transport medium. https://labtestsonline.org/tests/stool-culture. I was unable to easily find unequivocal definitions of ‘fresh’ except for the AACC reference above. 
  • Quote of the week: Stool is not just a simple waste material. (Kasırga E. The importance of stool tests in diagnosis and follow-up of gastrointestinal disorders in children. Turk Pediatri Ars. 2019;54(3):141-148.)
  • Latrinalia.   I have recently reviewed some literature on ‘latrinalia’, the category of grafitti that is found in public toilets. Relevant to our pursuits are some verses regarding crab lice. Special mention to Dr Despommier, who may still be partial to the toilet seat theory of crab transmission (see TWiP 153). Though dubious, the ‘toilet seat defense’ may have saved many a relationship. Poetry below:                                                                                                       

No need to stand on the toilet seat                                                                                                                             For the crabs in this place jump forty feet.                                                                                                                      It REF: HERE I SIT–A STUDY OF AMERICAN LATRINALIA, 1965 Alan Dundes ,University of California, Berkeley

  • Stoners

Cecelia writes:

Dear Doctors, 

   I’m very happy to hear the news about the lower cases of COVID in your area. Unfortunately, in Florida we are not so lucky! 

  My first guess about the patient in case study 184 has to do with her gut flora. It’s possible that since she has diarrhea with no apparent cause that her intestinal flora is not normal for her since she has received several different treatments that may have affected her normal flora.

   My second guess has to do with her co-infection with B. hominis and E. nana. Although their pathogenicity is disputed, they have been associated with gastrointestinal symptoms in immunocompetent and immunocompromised patients.

  According to “Case Reports in Gastroenterology “, if a patient is previously infected with a parasite causing inflammation to the intestines, other parasitic organisms can infiltrate the gastrointestinal tract causing infection with more than one organism. This article also describes an immunocompetent patient with diarrhea lasting six weeks with a co-infection of B. hominis and E. nana.

  Since the patient may also have been infected with C. cayetanensis before, followed by her co-infection with B. hominis and E. nana, her intestines may still be healing. I remember you mentioning lactose intolerance in patients with previous infections of C. cayetenensis. Since she has no documentation in her medical record to prove that, it’s just a guess. Also, her latest labs were all negative, so that is why I have more than one guess. I’m very curious what your diagnosis was!

  Sincerely,

Cecelia 

St. Petersburg

Luke writes:

Hi Twip. 

I was lucky enough to return to South Africa over the southern summer for a placement as a medical student. I grew up there,but now live in Canberra, Australia. It’s bloody cold cold here today, it was -3C when my son woke at 6.30. 

It sounds like Dickson was at Mala Mala Game reserve, next door to Kruger. A school friend was a ranger there in the late 90’s. I managed to get to a Imfolozi game reserve on my trip and had an excellent time. I thankfully didn’t contract Cyclospora cayetanensis, like I presume your unfortunate 70 y/o did in case 183. 

Thanks for the show. I love the conversational style, and it’s always really interesting.  

Luke. 

Christine writes:

Hey guys! I haven’t written since I won my book last September, quit my job and opened a pub. I still listen every month and my staff think I am really weird and maybe they’re right haha! 

Covid was a nasty hit for us, we were 5 months into owning this business when we got shut down. Thankfully, unlike so many other places, we had the most amazing support from our customers, friends, family and most important, our landlord and we pulled through and opened the doors on May 15th when the lockdown started to loosen up. We are grateful our city got very minimal cases and aside from buying TP and yeast, it wasn’t really that crazy here. 

So I attach a picture for you, I was cutting up chicken for a batch of chicken fingers. And one of the breasts I pulled out didn’t look like the others. It had a dead worm hanging out of it. I gave it a little tug and it popped right out. I am pretty sure it’s a round worm but I’m not positive. I can say I have never actually seen this before. I like eating the food at my place and that breast did get tossed. As cool as it was to pull out and play with, I would never eat or serve that to anyone. I look forward to knowing whether I was right or wrong and if I’m wrong what type of parasite it was. 

I hope you are all doing well and can’t wait for the next episode! Maybe I’ll even have the time to throw in a diagnosis! 

PS: weather was 22 degrees Celsius today, we were supposed to get thunderstorms but all we got was some cloud, a couple claps of thunder and then the sun came out and it was a beautiful not too hot day 🙂 

Love, peace and chicken grease!

Christine