Case guesses:
Alexander writes:
Hi all,
I’ve been working slowly through the youtube playlist you made, I was originally taught that the best way to learn it was to write it all down in a book. I’m really happy that it includes spelling, as while I was learning most of my phytoplankton taxonomy I had to guess how the names were spelled after hearing them quickly, but now I feel that I at least understand enough of it to be able to stumble my way through pronunciation and get it mostly right.
I was wondering if you had any resources to go further on the laboratory diagnostic methods.
For this case study, I focused on the lung and increased eosinophils, and found out about Loeffler of Löffler’s syndrome (gotta love a good umlaut). This gave me a few species to look at, after scanning through the book and looking at every time “lung” was mentioned (Yay for control F, gonna miss that if I ever get the book.)
I saw Ascaris lumbricoides, Strongyloides stercoralis, Ancylostoma duodenale, and Necator americanus. You said that the patient was negative for Strongyloides. From Pg. 233 of Parasitic Diseases, on hookworms “The tissue migrating larval stages do induce circulating eosinophilia one to two months after exposure”. In Parasitic Diseases, hookworms in general I guess, cause vomiting and abdominal pain though. The test for strongyloides came back negative. The man seems to have the same symptoms as A. lumbricoides moving into it’s intestinal stage.
Again as a reminder, I am not an expert in the field of parasitology, and should not be considered a replacement for a professional.
Wink writes:
Dear TWIP Professors,
Thanks for another great case! At the start of the case report I was sure he had Toxoplasmosis. Then I heard that he was on Bactrim prophylaxis and developed marked eosinophilia when the steroids were withdrawn; neither situation favors Toxo. Strongyloides then seemed very likely, but he was seronegative and had no diarrhea. So, I took out my International Health Guide and I did not look up the Dominican Republic, but I looked up Haiti, thinking that parasites found there may have been in the DR back when our patient lived there. But neither Trichuris, Ascaris, Wuchereria, Ancylostoma, nor Mansonella seemed to fit. So my guess is going back to Strongyloides stercoralis because the serology is often misleading and the intestines may stop contracting in such an ill individual. The thing I liked most about this case is that it was not my patient!
Wink Weinberg
Atlanta
Carol writes:
Greetings TWIPsters,
I am going to venture a guess for the gentleman in episode 154’s case study, but if I get it wrong I can only blame my lack of a copy of Parasitic Diseases.
I suspect the gentleman in question is suffering from schistosomiasis, possibly exacerbation of chronic schistosomaiasis due to the prolonged course of prednisone he mistakenly had. Random desperate Googling (again, I lack a copy of Parasitic Diseases) tells me that pulmonary schistosomiasis can appear as ground glass opacifications on CT and cause a cough, chronic schistosomiasis can cause confusion, and colon thickening is not unusual. S.mansoni is endemic in the DR, so the gentleman could have been infected during his visit a few months prior to presentation. I’m no doctor, but if my guess happens to be correct then praziquantel appears to be the treatment of choice. Dr Google may have misled me, but hopefully not as I would love to be entered in the draw.
Sincerely,
Carol
Chris writes:
Greetings Twippers,
It’s a relatively mild and dry 87°F in Athens, GA today but our six-legged airborne parasites are very much out for blood.
This is a challenging case with many potentially important factors at play, but the combined respiratory and intestinal signs bring to mind a few parasites. Schistosome eggs can produce the chest CT results shown, while the adults living in the vasculature surrounding the large intestine may result in its damage and subsequent thickening; schistosomiasis transmission is interrupted in the DR, however, so this seems unlikely. The pulmonary larval migration of certain GI parasites (like roundworm and hookworm) seem to be possible candidates.
I also considered Pneumocycstis arising from the extended use of prednisone, but this doesn’t explain the presence of colon thickening nor persistence in the face of antimycotics. Both TB and Strongyloides also seemed likely, but testing has ruled them out.
The symptoms seem to suggest a preexisting intestinal parasitic infection stimulated by immunosuppression. I’m very curious to see what the intestinal biopsy reveals, but until then, my guess will be one of the aforementioned geohelminth species, acquired during a visit to the DR.
Thanks for the fascinating and puzzling case,
Chris
Carlo writes:
Hi Twip Trio,
For the Case Study of TWiP 154 with the 79 yo man with B-cell lymphoma who received a prolonged dose of high dose steroids, the differential includes strongyloides, ascariasis, and hookworms due to a combination of findings: pneumonitis (cough, oxygen requirement, CT chest with nodules and ground-glass opacities), GI manifestations (constipation, CT with colonic thickening), and peripheral eosinophilia.
Strongyloides is the most likely cause as there can be hyperinfection and dissemination in immunocompromised individuals. In the case of our patient, he became immunosuppressed due to the high dose of steroids that he had inadvertently received. As our patient’s immune system became depressed, the nematode propagated and disseminated, leading to his state of hyperinfection. The thickening of the colon is likely due to the burrowing of the L3 larvae into the mucosa, thus propagating a cycle of autoinfection. He also likely acquired a secondary bacterial enterocolitis which lead to a paralytic ileus and his reported constipation. Transmission probably occurred during his time in the Dominican Republic (as it can be found in the Caribbean). Although, it would not necessarily have been during his last visit as Strongyloides can live for up to 5 years. He most likely became infected while he was not wearing shoes on dirt or grass, as the Strongyloides mode of transmission is via skin penetration.
Ascariasis is another potential diagnosis due to the migrate pulmonary findings and eventual signs of intestinal obstruction due to the high burden of worms in the intestinal lumen. Ascariasis larvae typically invade through the small intestine, which would not be consistent with the colonic thickening seen on CT. Additionally, there was no mention of hepatobiliary complaints – during which the worms travel up the biliary tree and feed on the liver parenchyma.
Hookworm infections could also be a possibility, but there was no mention of iron deficiency anemia, rashes (dermatitis), or abdominal pain.
To diagnose this patient, one could obtain antibodies, stool O&P, or GI biopsies. The antibodies were likely negative as per PD6th “sensitivities and specificities can vary significantly.” Additionally, if the IgG antibodies were checked instead of the IgM, then the IgG antibodies may not have been produced by the host at the time they were checked. The sensitivity of stool examination is also less than 50%. However, it would be tough to obtain a sample in our patient due to constipation. The diagnosis was likely made in this case via biopsy of the duodenal or colonic mucosa. Ivermectin would be the treatment of choice for days to weeks +/- albendazole.
Looking forward to the next podcast,
Carlo F. Palacios, MD
PGY-3, Internal Medicine & Pediatrics
University of Maryland Medical Center
Gavin writes:
Dear TWIP Team,
I get the 4th of July off, which means that I finally have time to sit down and investigate the case from TWiP 154. I found this one to be very challenging. I just wrapped up my first year of medical school, and somehow that made crafting a differential even more difficult! For example, we know our CHINA acronym for eosinophilia, so is the eosinophilia due to the H or the N? According to UptoDate “Almost any B or T cell lymphoma or leukemia can be implicated in causing eosinophilia.” In addition, some of the other non-specific symptoms could be due to the cancer or therapy.
At first, I thought that the prednisone was the key to this case, but my lab mate was looking over my shoulder at my case notes and thought that the steroids wouldn’t contribute much to the existing immunosuppression from chemo (aside from masking the eosinophilia). DLBCL is normally treated with CHOP, which is fairly aggressive and is known to have pulmonary side effects of its own:
Interstitial pneumonitis: dry cough, ground-glass on CT
Pneumocystis jirovecii: dry cough, ground-glass on CT, related to prolonged prednisone
However, we know that something was found on upper endoscopy and this is TWiV, so here is a super long parasitic differential: Ascaris, Hookworm, Toxocara, Schistosoma, Strongyloides, and tropical pulmonary eosinophilia (hypersensitivity reaction to Wuchereria bancrofti and Brugia malayi).
This email is already getting a little long, so I won’t get into the gorey details of which are present in the DR (most), which cause lung disease/ colitis, and which can be found on endoscopy. I think that this patient has hyperinfection and dissemination of Strongyloides stercoralis, and that the serology was falsely negative due to the immunosuppression. However, I would ask about other risk factors such as walking barefoot and freshwater exposure.
Thanks again for the awesome case! Looking forward to hearing how you reasoned through this one.
Best,
Gavin
UCSF School of Medicine
Class of 2021
Kendra writes:
Hello,
My name is Kendra. I first learned of microbe tv podcasts last summer and I enjoy listening to TWIP, TWIV, and TWIM. I recently graduated from Colorado State University with a MS in microbiology. Currently, I am working as a veterinary assistant and hope to attend veterinary school in the future. I believe the diagnosis for the most recent case study presented is Schistosomiasis – S. mansoni. Schistosomiasis is found in the Dominican Republic and may be contracted from contaminated water. A symptom of S. mansoni is nodular changes and ground glass opacifications in the lungs. It may also increase the amount of eosinophils found in the blood. The presence of a Schistomosiasis infection can be determined by using an ELISA test to measure IgG antibodies to the Schistosoma egg antigen. Praziquantel is the treatment of choice, after an initial treatment another treatment may be needed in 3-6 months. I did consider many other options.
Not Hydatidosis -echinococcus tapeworm as it usually causes coughing up blood and lung collapse. Also causes cystic lung lesions.
Not Dirofilariasis as it causes coin like lesions that may be seen on a CT scan. Symptoms also include coughing up blood and wheezing.
Not Paragonimiasis as it causes coughing up blood and pleural effusion which would be seen on the CT scan.
Best wishes,
Kendra
Kevin writes:
Chicago
Weather: zephyrs, blue skies, keening baby robins, etc
This 79 y/o patient’s immune system is behind the eight-ball in multiple ways: transformed CLL, post recent chemotherapy for B cell lymphoma, prolonged and inadvertently excessive cortisteroid therapy. He has multiple ‘lesions’ that have been uncovered by diagnostic tests or clinical history: history of treated latent tuberculosis, history of tropical residence, clinical evidence of CNS problems (cognitive slowing / altered mental status), radiographic lung and intestinal abnormalities.
With all due respect to Occam’s razor, and the fact that this man is balanced on a pathological razor’s edge, it is prudent to throw the kitchen sink at his problem. He may have multiple concurrent infections owing to the severe nature of his immune deficits. Non-infectious disease such as lymphomatous involvement of the gut, lung and meninges should also be considered as understudies in the scenario.
Prior to introducing my leading diagnosis, opportunists to keep in mind, in order of increasing taxonomic order: CMV, EBV, HSV, HBV, HCV, SC Polyoma-JC virus (progressive multifocal leukoencephalopathy), crypto, histo, blasto, candida, pneumocystis, TB, atypical TB like MAI, toxoplasma, schistosomiasis (reported from the DR)….Reactivation schistosomiasis or even T. solium reactivation in the context of organ transplant immunosuppression has been reported.
However, the intersection of several areas of the clinical history can quickly reduce the shopping list. The pulmonary /gut/CNS involvement, absence of eosinophilia followed by a rise after steroid discontinuation and history of tropical residence make disseminated strongyloides a prime consideration. Glucocorticoids greatly increase the risk of hyperinfection/dissemination (and also deceptively lower the eosinophil count). The negative stool O&P offers no consolation, as a single study has only a sensitivity of 30% (see PD6). Ground glass opacities in the lung, thickened intestinal wall, nonspecific CNS findings all raise the suspicion of nematode infection. Concurrent infections to consider however are Strep bovis or E coli bacteremia which can accompany disseminated strongyloides. Pneumocystis jirovecii is also on the list, since Bactrim prophylaxis can fail due to DHFR or dihydropterate synthase gene mutations that give rise to resistance. Regarding strongyloides infection, repeat stool O&P, intestinal aspirates, and ELISA may provide a definitive diagnosis. Due to the potentially fatal nature of the disease, early empiric therapy is essential, ivermectin being the drug of choice. Interested to know the outcome of this desperately ill patient.
Thanking the TWiP educators for your time and dedication.
REFERENCES
Lancet Infect Dis. 2017 Jun;17(6):e166-e176. doi: 10.1016/S1473-3099(16)30533-3. Epub 2017 Feb 21.
Helminths in organ transplantation.
Cooper AJR1, Dholakia S2, Holland CV3, Friend PJ2.
Opportunistic Infections—Coming to the Limits of Immunosuppression? Jay A. Fishman Cold Spring Harb Perspect Med. 2013 Oct; 3(10): a015669.
Helminths in organ transplantation Andrew J R Cooper,Lancet Infect Dis 2017
Published Online February 20, 2017
Purvey S, Lu K, Mukkamalla S, et al. Conservative management of neurocysticercosis in a patient with hematopoietic stem cell transplantation: a case report and review. Transpl Infect Dis 2015; 17: 456–62.
Schwartz B, Mawhorter S. Parasitic infections in solid organ transplantation. Am J Transplant 2013; 13: 280–303.
Prophylaxis for Pneumocystis pneumonia (PCP) in non-HIV immunocompromised patients Stern, Anat et.al Oct 2014 Cochrane Database of Systematic Reviews
Strongyloides stercoralis Hyperinfection Syndrome and Disseminated Disease
Marco Kassalik, MD, PhD1Gastroenterol Hepatol (N Y). 2011 Nov; 7(11): 766–768.
Intestinal strongyloidiasis: radiological findings that support the diagnosis José Henrique Frota Júnior, Radiol Bras. 2017 Mar-Apr; 50(2): 137–138.
William writes:
Hello Twiptumvirates,
I was initially stumped by the case description from Dr. Griffin at the end of episode 154, and while I am no means certain of a diagnosis I am excited to give it a go.
Balantidium Coli seems to be a possible culprit after a close reading of parasitic diseases 6th edition and a trawl through some relevant literature. According to 6e, fever is a common symptom, and immunocompromised individuals (such as our patient following chemotherapy and extended prednisone dosage) “may develop invasive disease with organisms invading, the lungs, urinary tract, liver and heart”. This was also supported by an article I found https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570149/) that lists pneumonia-like symptoms as well as cough and weight-loss with b. coli infections. My main concern with this guess is that I did not hear any mention of diarrhea, which seems to be a fairly prevalent symptom. It is certainly possible for the patient to have picked up the parasite on his February trip to the DR as b. coli can be found almost anywhere that pigs are kept in close proximity to humans and or their water sources. If this is the case, Metronidazole seems to be the treatment of choice based on my initial research.
Acute Schistosomiasis via infection with S. mansoni (Katayama fever) matches a few of the noted symptoms, and a number of worm-diseases can present with fever and headache, but I am leaning towards my original guess due to the immunocompromised nature of the host, and the pneumonia-like illness that points towards a possible Balantidium infection.
Have a great week,
William
Eric writes:
Dear TWiP hosts,
With an immunocompromised patient, a whole slew of possibilities arise!
Initial involvement of lung sounded like Pneumocystis pneumonia (PCP), but patient was already on Bactrim prophylaxis that takes care of most PCP. Also, was the chest X-ray consistent with PCP?
I then thought about latent TB (or atypical Mycobacterium), which the patient’s travel history fits. But you said the sputum smear (if it was actually sputum) showed no TB, and eosinophilia doesn’t fit.
What about that hyperinfection by Strongyloides stercoralis which you all have mentioned a few times on recent episodes?* If so, we can explain the sustained fever, the lung opacities and dry cough, the colon responding to larval migration with edema, the ineffectiveness of antibiotics and antifungals, and the marked eosinophilia. In hindsight, strongyloidiasis can be diagnosed from endoscopy & biopsy too. Of the signs of strongyloidiasis, we are missing the rash caused by migrating larva (PD6 says a minority of patients have the rash), and a question of why we did not see larva in the sputum sample.
PD6 didn’t mention how long it takes for the Strongyloides to grow (exponentially?) from a chronic infection to a symptomatic level of infection or when the eosinophilia appears, but some searching reveals that 2 weeks is about right. This fits our patient’s timeline. Lastly, I found an article that cites a 2016 study that found strongyloidiasis in the Dominican Republic: https://doi.org/10.1016/j.actatropica.2017.03.037
I didn’t have time to be absolutely thorough, but I shall wager hyperinfection by Strongyloides stercoralis secondary to glucocorticoid therapy as my diagnosis. I hope the patient has/had a decent outcome – this particular case doesn’t sound like a pleasant experience.
Eric
Los Angeles
P.S. More questions! Are “hyperinfection” and “disseminated” strongyloidiasis the same term or does only the latter term involve tissues aside from the lung and gut? Wouldn’t chemotherapy for the patient’s lymphoma have also led to a compromised immune system?
Allan writes:
Greetings Professors TWIP,
The weather here is 33ºC/92ºF and VOGY (with a V) as our longtime volcanic eruption has moved east and grown since May and taken some 700 homes in the last 30 days. Have been working with health care for the displaced refugees on the far side and we’re working on providing housing for 20 families on our campus in west Hawaii, where much of the volcanic fog seems to like to settle.
Has been a bit too busy to get in a guess the last several episodes, but I’d still like a HB copy of PD6, so I’ll get off a guess as I’m waiting to board a flight.
The patient with 103ºF fever, headache, dry cough, weight loss and now a thickening intestinal wall….. sounds like they have ruled out TB, other helminths including strongyloides, so the thickening intestinal wall makes me think he may have an active resurgence of amoeba, (entamoeba histolytic).
Thanks for your great podcast. Miss Dickson.
Allan
Allan Robbins
University of the Nations
Global Health
Kailua-Kona, HI 96740
Lana writes:
Dear TWiP,
For case #154 of the 79 year old man with B cell lymphoma, I think he has schistosomiasis, an infection of the blood fluke, Schistosoma mansoni. Most likely, he contracted it from contaminated fresh water populated by the transmitting snail, Biomphalaria glabrata, during his visit a couple of months earlier to the Dominican Republic.
For the differential diagnosis, tuberculosis has been eliminated. Ascariasis, ancylostomiasis, strongyloidiasis, and other parasites may also cause symptoms in the lungs, but the chest CT showing ground glass opacification suggests the formation of granulomas as an inflammatory immune response to the eggs of Schistosoma.
His symptoms were likely suppressed by the two week course of prednisone he was accidentally given, becoming much worse when he went off of the steroid.
He was likely immunocompromised by his recent chemotherapy, but it seems like many of the symptoms are caused by the immune response to the invader. I’d like to learn more about how a weakened immune system might still wreak havoc with it’s inflammatory response.
Praziquantel is the drug of choice. Treatment may be delayed for about 6 weeks after symptoms in acute cases subside to avoid possible exacerbation of symptoms. This also allows the worms to mature to a stage where the drug is effective. Treatment should be repeated in 4-6 weeks to ensure that newly matured adult worms are killed.
This patient’s symptoms don’t seem to be waning, though, so this may be a chronic case. The preferred drug is still praziquantel. In chronic cases, though, the patient needs to be monitored for an acute inflammatory response to eggs in the CNS. Corticosteroids can protect against this during treatment. A followup should be done in 3-6 months to ensure that the infection is eradicated.
Thanks,
Lana in Austin, Texas
Peter writes:
Bonjour Professors TWIP,
In haste as my time is being consumed showing my daughter Isobel, just because unfortunately she broke her leg and has a full cast, she can still enjoy the summer (she might even get her name called out on TWIP!) However, I did not want let such an interesting case go without a guess. I have not had time to consult with my lab mates but I would guess Schistosomiasis based on the multifocal ground glass opacifications and this nice free review paper on parasitic infections in the lungs https://thorax.bmj.com/content/66/6/528. Given the circumstances and if I am wrong, I hope I will be given a bye and the TCD parasitology can keep their winning streak of nine!
Also an idea. Could Vincent tweet when the episode of TWIP has been recorded? Then listeners would know although it might not have been put up yet their answers will not be read and they can save their powder for the next episode. It would save people emailing answers between when it is recorded and uploaded.
Allez les bleus,
Peter
@tcdparasitology