Dear TWIP Professors,
Tough case! I do not know the diagnosis but that will not stop me from taking a wild guess. My gambit is Chagas disease. I know that this 60+ man with low globulins and low lymphocytes does not have a typical case of American trypanosomiasis, but some associations were intriguing:
- There is transmission in Ecuador and the parasite travels well.
- I found a report* indicating that even if you do not get megacolon, the colon can lengthen (and cause loss of haustra?).
- The Text says that Immune-compromised individuals can present with acute symptoms and diarrhea can be an acute manifestation of Chagas disease.
- The lung findings may be caused by a separate pathogen from the colon, perhaps CMV.
With all the talk on molecular testing I get reminded of a story of a talk where the scientist was studying the genetics of one phytoplankton species and had the wrong species on the powerpoint. My next question that I have is, generally how expensive is it to run a nucleic acid amplification test.
So I had a lot of fun reading on this case and I ended up getting distracted a lot. I ended up looking into Cystoisospora belli, Cryptosporidium parvum, and Dientamoeba fragilis. I think that it might be Cystoisospora belli after reading that it was identifiable in a biopsy and that it caused peripheral eosinophilia.
To jump on the weather recording bandwagon, the nearest National Ocean Service station in Westport, Wa was reading 58 F this afternoon and a water temperature of 57 F just before a high tide.
Weather in Chicago: 80 degree days and 60 degree nights.
Our 60 y/o Ecuador born man who has lived in the USA for twenty years has a chronic immunodeficiency with a superimposed year-long diarrhea resulting in disabling frailty and overall poor health. He presumably has some type of humoral immunodeficiency, most likely primary (i.e. not acquired secondarily like AIDS, CLL, myeloma etc) for which he is receiving IVIG. His intestinal workup shows involvement of the small and large bowel with a variety of histopathologic and radiologic findings.
Many of the facts in this case may be essential clues, red herrings, or just plain insignificant incidental findings. The parasitic devil is in the details.
I will confine this discussion to the topic of infectious colitis in the context of primary humoral immunodeficiency, leaving aside a proper differential diagnosis that would normally include non-pathogenic etiologies such as malignancies, inflammatory conditions, etc. Though more than 60 primary immunodeficiencies have been described, the most common is IgA deficiency (with the exception of Giardia infection, IgA deficiency is usually not associated with opportunistic infection and usually not treated with IVIG). The second most common is combined variable immunodeficiency (CVID) which is probably what this patient had, or some similar variant. Pathogens that commonly occur (though not specifically intestinal) in CVID: Strept pneumo, H flu Pneumocystis, Giardia, Cryptosporidium.
Loss of haustral folds is a classic sign of colitis and I will run down a list of potential etiologic candidates:
1: Not consistent with our case: –Shigella, Salmonella, Campylobacter, Shiga toxin-producing Escherichia coli (STEC), Clostridium diff, tuberculous colitis, histoplasmosis, actinomycosis, CMV, herpes.
2: Potential candidates for us: Various protozoans: cryptosporidium, Cystoisospora, and Cyclospora. Balantidium coli. Rarely, Pneumocystis can cause extraintestinal disease. Other bad guys: Giardia lamblia, E. histolytica, and a variety of nematodes.
Time will not permit going through the pros and cons of the many pathogens mentioned above.
Though Cryptosporidium is the most statistically likely candidate to be causing this disease, especially in view of chronic diarrhea symptoms, I would like to focus a moment on reactivation Chagas’ disease as a likely culprit or co-conspirator in this case. T. cruzi infection is endemic in Ecuador and can remain dormant in a human host for many years. Reactivation during leukemia treatment or post-organ transplant is usually myocarditis or encephalo-meningitis, but the GI tract can also be involved. Chagas’ intestinal disease is usually associated with constipation, but fast transit in a dilated small intestine in due to bacteria overgrowth can result in chronic diarrhea, malabsorption and steatorrhea.
I am going to submit a dual diagnosis of co-infection with Cryptosporidium and reactivation Chagas disease. Treatment for crypto: nitazoxanide. Treatment for Chagas: nitifurimox.
RED HERRING DISPOSAL:
The finding of leukocytosis following ivermectin empiric treatment is concerning for the possible development of DRESS syndrome, a drug reaction (see Ref). The CMV viral load of 4000 is intermediate and not really a smoking gun for disease (the threshold in one study was 10,000 copies for renal transplant patients). As for the rhinovirus positivity: Like the fighter pilot who faces an instrument panel with every light blinking and alarming: shut the whole thing off and use your mind.
Thanking entire TWiP staff for chronic mental stimulation.
The immunology of parasite infections in immunocompromised hosts T. Evering 1,2 and L. M. Weiss1,3Parasite Immunol. 2006 Nov; 28(11): 549–565. doi: 10.1111/j.1365-3024.2006.00886.x
Immunosuppression and Chagas Disease: A Management Challenge María-Jesús Pinazo, 1
PLoS Negl Trop Dis. 2013 Jan; 7(1): e1965.
In this article we describe our experience with three immunosuppressive conditions (HIV infection, neoplastic disease, and systemic autoimmune disease) in patients with T. cruzi infection…Immunosuppressive doses of corticosteroids have not been associated with higher rates of reactivation of Chagas disease.
Diagnosis and Treatment of Gastrointestinal Disorders in Patients With Primary Immunodeficiency
SHRADHA AGARWAL* and LLOYD MAYER‡ Clin Gastroenterol Hepatol. 2013 Sep; 11(9): 1050–1063.
Published online 2013 Mar 13. doi: 10.1016/j.cgh.2013.02.024 [Big section on Giardia. ]
Parasitic Colitis Elizabeth M. Hechenbleikner, MD1 and Jennifer A. McQuade, MD, FACS, FASCRS2 Clin Colon Rectal Surg. 2015 Jun; 28(2): 79–86. [nice free review article]
Coccidian protozoa usually parasitize small intestine epithelial cells but have also been found in the appendix, colon, and rectum, particularly in the setting of cryptosporidiosis. Characteristic histopathologic changes include an intense inflammatory response as well as blunting and atrophy of villi. Nonspecific mucosal abnormalities may be noted at the time of colonoscopy.
Diagnosis, management and treatment of chronic Chagas’ gastrointestinal disease in areas where Trypanosoma cruzi infection is not endemic. Mar´ıa Jes´us Pinazo et al Gastroenterol Hepatol. 2010;33(3):191–200 [free article]
Radiological Diagnosis of Chagas’ Disease, Luiz FeIippe Mattoso, MDSeminars in Roentgenology, Vol XXXIII, No 1 (January), 1998 [more than you need to know about plain radiography of this disease; exhaustive]
Incidence of Parasitic Diarrhea in Patients with Common Variable Immune Deficiency.
Uysal S1 Turkiye Parazitol Derg. 2016 Jun;40(2):67-71. [free article]
The most common parasites detected in this study were Cryptosporidium spp. (n=9; 69.2%), Giardia spp. (n=7; 53.8%), and Blastocystis spp. (n=3; 23.1%).
Ivermectin-induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome
Ines Kerneuzet,JAAD Case Rep. 2018 Jul; 4(6): 524–527.
Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome, also known as drug-induced hypersensitivity syndrome, is a rare, potentially life-threatening adverse drug reaction with an estimated mortality rate up to 10%.1 We report a case of DRESS syndrome caused by ivermectin, which, to our knowledge, has not been reported previously.
PNEUMOCYSTIS CARINII INFECTION OF THE SMALL INTESTINE Kraig Kinchen, MD,J Natl Med Assoc. 1998 Oct; 90(10): 625–627.
The Chronic Gastrointestinal Manifestations of Chagas Disease
Nilce Mitiko Matsuda Clinics (Sao Paulo). 2009 Dec; 64(12): 1219–1224.
Interpreting Quantitative Cytomegalovirus DNA Testing: Understanding the Laboratory Perspective
Kraft, C et.al. Clin Infect Dis. 2012 Jun 15; 54(12): 1793–1797.
Transplant Proc. 2015 May;47(4):1136-9.2014.11.066.
Which CMV viral load threshold should be defined as CMV infection in kidney transplant patients?
Dear TWiP hosts,
I’m usually reluctant to guess when I don’t think I’ll get it right, but I figure it’s good to challenge (and embarrass) myself once in a while and let other clueless listeners know that they’re not alone.
Unsure of where to start, I tried googling (and searching your textbook for) the gut-related keywords in the case description. This didn’t give me the quick answer I was hoping for, but it did point me toward two possibilities: Entamoeba histolytica and Cryptosporidium. Crypto can cause crypt hyperplasia in the small intestine, chronic diarrhoea, and weight loss, but I’m not sure about the other described symptoms. E. histolytica can also cause diarrhoea and weight loss, but from what I’ve been reading, it colonises the colon rather than the small intestine. It could, however, be responsible for the granular appearance to cecal mucosa.
According to Parasitic Diseases 6th Edition, Cystoisospora belli can also cause protracted diarrhoea and weight loss in immunocompromised patients, but I don’t know if it can cause the described gut pathology.
The closest match that I can find through Googling is actually to ulcerative colitis: that would explain the ulceration, loss of haustral folds, and granular mucosa. Since this is TWiP, I’d be surprised if there wasn’t a parasite involved somehow, but could it be that this patient has more than one thing going on?
I expect I’m barking up the wrong tree here, but it’s been fun, and I look forward to hearing what it actually was!
I am Toni from Spain.
Now, the weather report: today in Zaragoza, Spain, we are expected to be between 35 and 20 ºC, mostly sunny day. But we are in the middle of a hot wave!.
With respect to the case study for TWIP 155, this is my guess:
Some findings strongly suggest amoebiasis caused by Entamoeba histolytica, a very highly prevalent parasite in developing countries, including Ecuador. The ulcers are consistent with Entamoeba histolytica, but these tend to be localized in the large intestine rather than in the small intestine. Also, eosinophilia is not common in protozoan infections in general and in amebiasis in particular. Eosinophilia should suggest some worm infection. Since this patient is immunocompromised, the WBC must be interpreted with caution. Assuming this is a “real eosinophilia”, we must consider a possible worm infection. Schistosomiasis by Schistosoma mansoni and, AGAIN, Strongyloides stercoralis can be two possibilities. Schistosoma mansoni typically affects the large intestine and ulcers,granulomes and pseudopolyps are visible with image techniques. Eggs are easily seen in faecal concentration samples. In the case of Strongyloides, the small intestine is its prefered niche, and ulcers can also be visualized in endoscopy procedures.
In both cases, Amebiasis and Strongyloidiasis, diagnosis can be very difficult and several additional samples may be necessary. I once read and article, where 12 consecutive faecal samples were necessary to detect S. stercoralis larvae!.
Serology may be helpful in the case of amebiasis, but in this very case, where the patient was on chronic Ig therapy, the interpretation may be difficult. I think the Negative Predictive Value is much more valuable in our case than that of the Positive Predictive Value. Trophozoites and cysts can be visible in faecal samples, but the chronic condition surely guarantees that the concentration of both forms must be very low. So, in this case, a colonic biopsy can be helpful to detect the metabolically active forms, trophozoites, inside the colonic wall. If confirmed, I would look for additional cryptic undetected infections within the close contacts.
So, finally, my guess is: our patient has a chronic infection by Entamoeba histolytica and, may be, a coinfection with Strongyloides stercoralis or, less likely, Schistosoma mansoni.
P.S.: I listened with great interest the last episode about Dracunculiasis in otters. That reminded me the case of Dracunculus medinensis in Africa where, recently, dogs have been implicated as reservoirs for this nematode. I have some doubts I wanted to share with you.
- Some researchers suggest that this is not a recent phenomenon and that spillover must have occurred long ago. Only when we are in the verge of elimination of this condition, this situation has been detected and, some argue, this is because of a high level of surveillance. So, do you think is a recent phenomenon?
- Is the life cycle similar to that of humans? Do the dogs develop itching/painful blisters that force them to search for water sources to alleviate their symptoms?
- How do we manage this infections in dogs? We must keep them tied to ropes in order to prevent them going to water points?
- How this new reservoir threat the goal of eradication campaigns?
As always, thank you very much and best regards.
Good morning to my 3 favorite Parasitologists, and yes Vincent after 148 episodes I think you can consider yourself a parasitologist. Here in Central Jersey it is a sunny but cold day at 37 degrees without a cloud in the sky. I am emailing you today for a multitude of reasons, the first one being that I really enjoyed the discussion of the paper I sent you a few weeks ago on raccoon roundworm, so I have come back to suggest another ecological parasitological paper. I think This paper would be cool for the Podcast because it is a cool cross between basic parasitology, applied science, and anthropocentric environmental impacts. Also is wants to use parasites as a tool which I know Dickson is a fan of. The Paper is a little old but still very relevant, and I think its cool to discuss some of the older influential papers.
Secondly I have just been accepted to grad school at Stony Brook University in long Island where I will be studying the Parasites of Alaskan fish! So if I catch Giardia while sampling in Alaska I know which Infectious doc i’m going to visit! Additionally, I want to thank you and all the members of your other Podcasts for helping me stay involved in science and the countless advice you have given to me and the others in my position.
So a question I have been wondering for a while is, because there are so many infectious diseases caused by using human feces as fertilizer, has there been a foundation devoted to just making fertilizer? I feel like instead of investing millions in researching complicated prevention methods the money could be spent to make large composting/ fertilizer facilities in countries that use feces as fertilizer and then distribute this fertilizer to farmers. The initial costs might be a bit but once it is set up it would just involve collecting leaves, grass clipping, food waste etc. then composting it and distributing it. Am I over simplifying the problem with this approach? After listening to your podcast it seems like there are so many diseases that wouldn’t exist if people could just avoid feces, and by removing the benefits of feces people would probably be fine with not using human feces as I can’t imagine people enjoying using it as fertilizer in the first place. I would love to hear your take on this idea.
Lastly, I am currently catching up on TWIV and I was listening to episode 72 and Alan’s pick of the week (NOAH Iphone App) reminded me of something I think you and your listeners would enjoy. New Jersey has an Invasive species strike team which is a group that is devoted to monitoring and removing invasive species in the state. The reason the NOAH app reminded me of this is because the Invasive Species Strike team has a very similar app that allows people to document, and report invasive species found in the state. This app allows the team to effectively control and monitor invasives with the help of citizen science. Furthermore the app has really detailed descriptions, picture and control plans for each invasive species. I thought this would be a cool pick for your listeners due to the fact that you all commonly talk about invasive species, ecology, and its educational. here is a link to the website and the app :
app tutorial :http://njisst.org/documents/Map%20Them%20and%20Zap%20Them%20-%20Using%20NJ%20Invasives.pdf
Paper link: https://pdfs.semanticscholar.org/1e05/1125148dc2906e7af7275a41e64053ef8952.pdf
Sorry for sending such a long email again.
No sooner do I hear of a barnacle parasite speeding crabs to a gruesome death, on TWiP, than this, or another barnacle parasite, turns up on Jordan Klepper’s comedy show, sterilising male crabs!
Thought you might like.
2 days of summer heat straight from wintery cold, and now we’re into the first thunderstorm of the year…
Dear TWiP Crew,
I must begin by saying that I’m not a parasitologist – I’m a poet. I found your podcast several months ago and have been hooked ever since. TWiP is so accessible and I’ve had a great time exploring your archives.
For the past several years, I’ve been writing parasite poetry. My debut poetry collection, Red Mother (NYQ Books, 2018), is a love story told from the perspective of a parasite. This series of short poems explores the intimacy, desire and devotion we all experience by following the sometimes tender, often distressing relationship that emerges between a parasite and its host. Far from romanticizing either role, Red Mother takes readers on a tour of their own innards, exposing the hooks and claws of all involved.
You should know that Red Mother is not about any one parasite. Instead, the book is an explores the intimacy of parasitism by utilizing characteristics from multiple parasites. Following the parasite’s life cycle, the book blurs the line between science and poetic license to create a fantastical romp not for the squeamish.
If you’d like, I’d be very happy to send you a complimentary copy of my book, along with a few others for you to give your weekly winners. Just let me know where to send them. Red Mother is also available on Amazon, Barnes & Noble, Ingram and other online booksellers. Visit https://books.nyq.org/title/red_mother for details.
Thank you for providing such an interesting podcast. While I’m not from a science background, TWiP has let me experience a community that I’m very grateful for.