Christian writes:
Hello TWiP Team,
Greetings from the now cold and rainy Basel.
As this is a parasite causing voluminous diarrhea in a women with low CD4 counts the first the always comes to mind in this case would be
Cryptosporidia spp. with Cryptosporidium parvum as a common culprit
followed by
Microsporidia species
Enterocytozoon bieneusi and Encephalocytozoon intestinalis
both are more typical for CD4 counts under 200,
the next best guess would then be
Cyclospora cayetanensis
A special differential for the geographically inclined would then be
Isospora belli
which is rare in NA, but would be endemic in Haiti, where the patient is from and therefore a prime candidate in this patient.
Nowadays, these would be identified with PCR in a stool sample.
But there is also the option of microscopy, usually 3 samples.
Modified acid fast stain (pretty) and Safranin stain (very pretty) would detect
Cyclospora cayetanensis, Isospora belli, Cryptosporidia spp
Calcofluor white 2MR woudl detect Microsporia for example.
Aside from supportive therapy, the most important course of action is reconstituting the patients immune system to clear the infestations.
Best Wishes,
Christian
Marco writes:
HIV non-compliant w/ cd4 50’s
Sounds like severe Cryptosporidiosis.
Thanks!
Marco M Custodio, Pharm.D., BCIDP, BCCCP, AAHIVP
Critical Care/Infectious Diseases Pharmacist
Rafid writes:
Hello TWIP team and greetings from Maniwaki Quebec,
The differntial diagnosis in this patient is quite broad and may include tropical sprue, viral infections such as CMV, community acquired c.difficile , and although most bacterial causes of diarrhea such Enterotoxogenic E. coli ( ETEC )last 7-10 days they may become chronic in HIV with low CD4 counts as well as various Protozoa including microsporidium, cyclospora, giardia and cryptosporidium, MAC is also possible as well lymphoma.
In a patient with a CD4 count of less than a 100 and symptoms of nausea , wasting and malabsorption that suggest a small bowel pathology, the classic pathogen to explain this presentation is cryptosporidium and the treatment is to start HIV therapy and reconstitute the immune system. I would obviously get parasite PCR of the stool, c.diff stool toxin, bacterial stool cultures in this specific case, test for MAC and finally, since doing endoscopies is what I do to make a living how can I not resist the temptation to do a colonoscopy to look for pseudomembranes and take biopsies for CMV and a g-scope to check for esophageal candidiasis as well as take some small biopsies for lymphoma, tropical sprue etc..
If forced to pick one pathogen though it would be either cryptosporidium or microsporidium.
Thank you again for your wonderful podcast that really helps me review my parasitology.
Rafid
University of Central Lancashire Parasitology Club Writes:
Dear Professors,
Greetings from the University of Central Lancashire Parasitology Club in the wonderful Northwest of Britain
As a first-year microbiology student and a new member of Parasitology Club, I have been given the opportunity write this letter.
This in the case of a Haitian woman with non-resolving diarrhoea, who is HIV positive and is progressing into AIDS.
Cryptosporidium is an opportunistic protozoan parasite (Yang et al., 2021) and a leading cause of water-borne diseases in the worldwide. It contributes to the burden of diarrhoea-related deaths in low-income countries particularly affecting young children and immunocompromised people (Centers for Disease Control and Prevention, 2019, and Yang et al., 2021).
During the life cycle of Cryptosporidium, oocysts are ingested, releasing four sporozoites. The sporozoites invade the epithelial cells of the gastro-intestinal tract causing a watery diarrhoea which is persistent in AIDS patients. (Center for Disease Control and Prevention, 2019 and, Dąbrowska, Sroka and Cencek, 2023)
Cyclospora cayentanensis is an opportunistic coccidian parasite and could be another possible cause of the patient’s symptoms. During the life cycle of C. cayentanensis, sporulation happens at 22°C and 30°C for 7-14 days outside of host resulting in the division of sporont into 2 sporocysts (each containing sporozites). Cyclospora oocysts can contaminate food and water sources (Ahmed et al., 2023) which are ingested and the sporozites are released and invade epithelial cells of the small intestine (CDC, 2019, and Dubey et al., 2022).
Non-resolving diarrhea and a CD4 count below 200 supports the diagnosis of cryptosporidiosis, which can produce symptoms of watery diarrhoea, weight loss, cramping, dehydration, nausea, vomiting, fever, and fatigue (Centers for Disease Control and Prevention, 2019). The patient may also be experiencing many other parasitic infections such as Cytoisospopora belli and Cyclospora cayentanensis.
In conclusion we suggest cryptosporidiosis caused by oocysts of Cryptosporidium spp.
Kind Regards,
Emily Lawes On behalf of Parasitology Club
University of Central Lancashire
Reference list
Ahmed, S., Rahman, M.N., Hasan, M., Hasan, A. and Mia, M. (2023). Immunogenic multi-epitope-based vaccine development to combat patients applying computational biology method. Experimental Parasitology, [online] 248(0). doi:https://doi.org/10.1016/j.exppara.2023.108497.
CDC (2019). CDC – Cyclosporiasis. [online] Centers for Disease Control and Prevention. Available at:
https://www.cdc.gov/parasites/cyclosporiasis/index.html [Accessed 14 Nov. 2023].
Centers for Disease Control and Prevention (2019). Parasites – Cryptosporidium (also known as ‘Crypto’). [online] CDC. Available at: https://www.cdc.gov/parasites/crypto/index.html [Accessed 17 Nov. 2023].
Dąbrowska, J., Sroka, J. and Cencek, T. (2023). Investigating Cryptosporidium spp. Using Genomic, Proteomic and Transcriptomic Techniques: Current Progress and Future Directions. International Journal of Molecular Sciences, [online] 24(16), p.12867. doi:https://doi.org/10.3390/ijms241612867.
Dubey, J.P., Khan, A., and Rosenthal, B.M. (2022). Life Cycle and Transmission of Cyclospora cayetanensis: Knows and Unknowns. Microorganisms, [online] 10(6), p.118. doi:https://doi.org/10.3390/microorganisms10010118.
Giangaspero, A. and Gasser, R.B. (2019). Human cyclosporiasis. The Lancet Infectious Diseases, [online] 19(7), pp. e226–e236. doi:https://doi.org/10.1016/S1473-3099(18)30789-8.
Yang, X., Guo, Y., Xiao, L. and Feng, Y. (2021). Molecular Epidemiology of Human Cryptosporidiosis in Low- and Middle-Income Countries. Clinical Microbiology Reviews, [online] 34(2). doi:https://doi.org/10.1128/CMR.00087-19.
Byron writes:
Hello Twip hosts,
Happy the week before Thanksgiving! Hope this email is not too late. One thing that stands out is the bold letters “Diarrhea is voluminous”, not sure if it is red herring or a clue??? Anyway, given the patient origin, looking for common parasitic infections in Haiti. The Yellow Book from CDC mentioned a number of candidates, Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Trichuris trichiura, and last but not least Strongyloides stercoralis. Looking through each of the agents, Strongyloides stands out as in immunocompetent individuals, it can cause a watery, mucous diarrhea. Seems to fit the bill. Heavy Ascaris infection can cause intestinal discomfort, impaired nutritional status, and obstruction. Hookworm infection and lead to anemia, particularly in children, and whipworm can cause chronic abdominal pain, blood loss, diarrhea, dysenery, and rectal prolapse. Given the patient being immunocompromised, it is hard to definitely rule out any of the above. Maybe the patient had multiple infections? For now, I am sticking with Strongyloides. Wish everyone have a great Thanksgiving and waiting for the next episode to drop. Thank you!
Byron
Marissa writes:
Hello professors –
Thank you for another engaging case. I am writing from Salt Lake City, Utah, where we had a beautiful sunny autumn day with a temperature of 65F (18C). Here is my guess for the case of the ~50-year-old woman from Haiti with severe diarrhea. I read that common causes of diarrhea in patients with HIV in Haiti include Cyclospora cayetanensis, Cryptosporidium parvum, and Cytoisospera belli. All three are commonly asymptomatic in immunocompetent hosts, which explains why the rest of her multi-generational household is unaffected. When considering these three parasites in my differential, I felt I was able to exclude Cytoisospera as this woman’s eosinophils were normal. Now to decide between Cyclospora and Cryptosporidium. Both cause voluminous diarrhea in immunocompromised patients, and I have been struggling to settle on one of them. I read that Cryptosporidium can cause extraintestinal symptoms, including in the respiratory tract. As this patient has also has a cough, my best guess is Cryptosporidum. As far as treatment goes, Nitazoxanide is approved for Cryptosporidium, but unfortunately only in immunocompetent hosts. I could not find evidence to support its use in this patient. I would suggest she receive supportive care, HAART, prophylaxis for opportunistic infections, and an anti-fungal for oral/esophageal candidiasis. I hope that this woman’s condition has improved in the meantime, and I look forward to hearing the discussion of this case.
Thanks to all of you,
Marissa
References include Parasitic Diseases Sixth Edition, https://www.cdc.gov/parasites/index.html, and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806662/
[already won a book, need to ship to new address in his email]
Tom writes:
Dear Twip hosts,
Writing to you again now from London where I am completing the diploma in tropical medicine at the London School of Hygiene and Tropical Medicine. It’s a rare sunny day with a balmy temperature of 13 degrees celsius (58 F).
The differential for this week’s case in a woman from Haiti with advanced HIV disease, cough, oral/esophageal thrush and several weeks of watery diarrhea is broad, but thankfully the topic of the show narrows the differential significantly.
Sticking to parasitic diseases, some to consider:
Helminths — can cause chronic diarrhea but are unlikely to have voluminous watery features.
Amebae — Entamoeba histolytica and Giardia lamblia are both possibilities. E histolytica usually is acute/bloody diarrhea before possibly advancing to systemic disease, particularly hepatic abscess. Giardia would be more of a bloating, fatty diarrhea (classically, floating stool).
Microsporidia — I’m not sure if the TWIP hosts consider this a parasite since the classification is disputed and probably closer to a fungi.. but they are an important cause of diarrhea in people with HIV, in particular Encephalitozoon and Enterocytozoon. Both could cause chronic watery diarrhea like that seen in this patient.
Coccidian apicomplexae — most likely culprit in my opinion. The group includes: Cryptosporidium spp, Cyclospora, Cystoisospora, Sarcocystis, Balantioides coli, and Blastocystis.
Crpytosporidium will be the most common and most likely especially given the symptoms of voluminous watery diarrhea (often resembling a toxin mediated diarrhea).
Diagnosis may be made either by multiplex PCR panel if available or stool examination in particular Ziehl-Nielsen staining since cryptospordium is partially acid fast. I was struggling to connect the cough with cryptosporidium but thought Hickum’s dictum may apply.. (patients can have as many diseases as they damn well please), however, perhaps to Daniel’s chagrin, Occam’s razor may still hold. In particular, people with profoundly low CD4 counts (<50 cells/µL) can have a respiratory component including pneumonia which may explain her cough. CXR would be helpful in establishing the diagnosis of pneumonia, perhaps microbiologic examination of sputum could identify the cysts as well.
Treatment will be supportive care (especially oral rehydration and electrolyte management) and immune reconstitution with antiretroviral therapy.
No anti-parasitic therapy is very effective in treatment. Nitazoxonide and paromomycin have both been shown to have some effectiveness especially in people with HIV but immune reconstitution is the mainstay of therapy.
Thanks again for your insightful show.
Tom
James writes:
Woman with HIV, low CD4 count, “voluminous” diarrhea.
There’s an old saying in Med School, when you hear hoofbeats think of horses before zebras. AIDS patients ALSO get the common diseases like Salmonella, Shigella, Campylobacter, etc.
But it’s TWIP of course.
The first bug that comes to mind is Cryptosporidium and that would have to be my odds-on guess.But others might include Giardia, Entamoeba, Neobalantidium coli (yes, new name), Cytoisospora belli (yes, renamed), Sarcocystis, Cyclospora. Microsporidia have been reassigned to Fungi based on genetics!
I’ve won my book although it hasn’t come yet!
James M. Small, MD, PhD, FCAP
Professor of Pathology and Microbiology
Director of Clinical Career Advising
Rocky Vista University
Christopher writes:
Hi twip team,
I am writing in on a warm sunny 74*F day in Porto Alegre, Brazil. For the patient described in Twip case 222, I believe our patient has the dreaded cryptosporidium parvum infection, an AIDS-defining illness that typically is self-resolving in immunocompetent hosts but can cause chronic, incurable, and deadly diarrhea that leads to wasting and dehydration among those with AIDS. Of course, the differential is massive, and we should consider other parasitic pathogens that can cause chronic diarrhea among people living with AIDS, including Entamoeba histolytica, isospora belli, and strongyloides stercoralis. A stool ova and parasite test with modified acid-fast stain will help us make the diagnosis. We should start this patient on IV fluids. Before we start her on ART for HIV infection, we should ensure that her concomitant cough is not caused by a pathogen that can also localize to enclosed internal spaces, like within the pericardium or central nervous system, as an immune reconstitution syndrome in this setting can be deadly.
In the last episode, I stated that the patient had a slam-dunk case of toxoplasmosis. I learned two things, 1) be far more humble and 2) that ChatGPT is not the best resource to double-check my work. A glimmer of hope for us prospective ID physicians who are terrified of going into a field that is often cited as one of the most threatened by AI.
—
Christopher Hernandez
David Geffen School of Medicine at UCLA, Medical Student
MPH, Infectious Diseases and Vaccinology
University of California, Berkeley
Ben writes:
Dear TWIP team,
My guess is Cryptosporidiosis.
Ben in Liverpool
Agnese writes:
Good evening,
I am a really enthusiastic resident in Infectious Diseases and I am at the very beginning of my journey in the world of Parasitology. I have recently discovered your podcast and I love it! Thank you all (speakers and audience) for sharing your interesting cases and even more interesting differentials.
Regarding the last case presented, I would like to know more about the feces appearance, including volume, texture and colour, if there is blood and the frequency of evacuation. Having excluded Cholera for the topic of the podcast and the apparent absence of an outbreak/sick contacts, I have immediately thought about the protozoa associated with AIDS.
First, Cryptosporidium spp, in particular C. parvum has been proven to be a great burden in immunocompromised patients with diarrhea in the tropics. It can cause fulminant diarrhea, acute, persistent (as in this case) or chronic diarrhea. I think it matches the patient’s presentation, being reported associated with voluminous stool passage, weight loss, prostration.
Cystoisospora belli would be my second guess. Both are commonly asymptomatic in immunocompetent individuals, and this would explain why the patient denies any close contact with the same presentation. Also, they are associated with poor sanitation and overcrowded settings.
Microsporidia would also be an option, but I think is more uncommon. Anyway, never say never.
Giardia duodenalis could also explain the symptoms, but has not been associated with HIV or AIDS.
If blood in stool was reported, I would also consider Entamoeba histolytica and Balantidium coli, as possible causative agents. E. histolytica is more common in the tropics and immunocompromised individuals are at high risk for symptomatic presentation. However, no mention of disenteria was made.
Regarding helminths, I tend to associate severe Strongyloides stercoralis to AIDS. However, the constitutional symptoms of the patients seem attributable more to the uncontrolled HIV infection, than to a disseminated presentation of strongyloidiasis.
I would stick to Cryptosporidium parvum, but luckily I would have asked three serial stool examinations for microscopic search of oocyst, ova and parasites for any of these guesses.
I am sure there a lot of possible differentials that I missed, including pathogens that I don’t even know exist, but thank you for this opportunity to rack my brain.
I hope the woman from the case recovered and was able to start antiretroviral treatment, and of course I think one day things in Haiti will be better for all Haitians.
Thank you for this inspiring podcast and thank you in advance if I will win the book!
Agnese