Josh writes:
Thank you for this very interesting case!
I suspect this is a case of treatment resistant strongyloidiasis as an indicator of underlying Human T-lymphotropic virus (HTLV-1) infection.
Thank you,
Josh Gray
PGY-3, Department of Medicine
Duke University Medical Center
Eyal writes:
Dear Vincent and the TWiPsters,
Greetings from Sydney, Australia! After procrastinating on last month’s case and missing the cutoff, I’ve decided to submit my guess as soon as this episode came out.
Thank you for presenting this case. It’s certainly more challenging than the previous one. While I suspect a sexually transmitted disease might be involved, I don’t believe a parasite is the culprit this time.
After diving into several rabbit holes and exploring references on parasitic infections and subsequent secondary infections, I’ve pieced together a narrative. It is probably incorrect, but it makes sense to me 🙂
I believe the middle-aged man in question was stationed in Okinawa, Japan, likely more than 10 years ago—perhaps in the late 1980s or early 1990s—where he acquired schistosomiasis (which was declared eradicated in Japan in 1996). Additionally, I suspect he contracted a chronic hepatitis B infection (HBV) through unprotected sex.
My hypothesis is that cytokines and chemokines produced in response to the schistosomiasis infection suppressed HBV replication. Once the schistosomiasis infection resolved, eosinophil levels normalized, only to rise again when HBV replication resumed.
For reference: PMC Article
Thank you, as always, for the invaluable education, knowledge, and wisdom you share with us. Since this will be my last email before the holiday season, I’d like to wish you all a Merry Christmas and a Happy Hanukkah!
Best regards,
Eyal
Håkon writes:
Greetings from muggy athens,
I wanted to thank you all for another interesting case. This one was a challenge for sure, as it made one consider interactions from not just a parasitic cause, but how it might interact with a viral agent as well. Given the lack of a specific time frame they might not even have been acquired in the same country or decade.
Considering all of this, the three most likely viral agents that came to mind given the lack of symptoms exhibited by our John Doe would seem to be Epstein Barr Virus (Mononucleosis from EBV), Human T-Lymphotropic Virus Type 1 (HTLV-1), or a Hepatitis virus (B or C). While HTLV-1 can directly cause eosinophilia by itself, perhaps EBV or Hep might cause some immune dysfunction through Th1 suppression, or exhibit a flareup in conjunction with treatment for our unknown parasites.
This brings me to our potential parasite- while we don’t have the specific dates our John Doe was serving in Okinawa, or how long he has been back for- I am going to assume it has been more than 7-10 years. Given this, certain diseases seem less likely- such as Schistosomiasis, or Filariasis as his potential for reinfection in the USA is minimal to nil and the majority of adult parasites would have likely died off by this point. However, certain papers have suggested these parasites are capable of living as many as 15 years for wuchereria or as many as 30 years in the case of schistosoma- though this is based on a case report from an individual in the 70s.
It seems more likely however, that he has maintained a constant asymptomatic infection by Strongyloides stercoralis or maybe Sarcocystis hominis/suihominis given his lack of symptoms, and the long duration of time between being in Japan and the states.
Final guess: Strongyloidiasis and HTLV-1
Thanks again,
Håkon
Jason writes:
Greetings TWiP hosts!
In TWiP Episode 247’s Case of The Asymptomatic Middle-Aged Male Marine, there were several dots to connect, such as the history with paid sex workers, the detection of eosinophilia as an incidental finding in an otherwise asymptomatic patient, serologic evidence of a prior parasitic infection, resolution of the eosinophilia with an antiparasitic drug (and the subsequent return of the eosinophilia), and serologic evidence of a prior viral infection.
Connection of these dots has led me to the following conclusion: the patient is infected with both genital herpes and toxoplasmosis.
Assuming the “paid sex worker” detail was not a red herring, this was the probable source of genital herpes, which has established a permanent though manageable viral infection in our patient. Management of genital herpes includes use of antiviral drugs such as acyclovir.
As for the parasitic infection, the absence of symptoms in the presence of eosinophilia is highly suggestive of infection with Toxoplasma gondii, as does the subsequent return of eosinophilia, as drugs such as pyrimethamine eradicate the tachyzoite stages of the parasite, but not the latent bradyzoites.
As for the connection between herpes virus and toxoplasmosis, I recalled that in TWiP episode 13 Dickson mentioned the importance of IL-12 in the inhibition of toxoplasmosis. A PubMed search for “antiviral drugs that interfere with IL-12” revealed an article (citation below) that states “two FDA-approved drugs acyclovir , and tetrahydrobiopterin were also found to prevent binding of IL-12 to IL-12 receptor.”
It is therefore possible that the acyclovir treatment caused an inhibition of IL-12 and the subsequent resurgence of the toxoplasmosis, accompanied by eosinophilia.
Worm regards,
Jason
Seattle, Washington
Blair writes:
Dear TWiP team,
My guess for case 247 is co-infection with Strongyloides stercoralis and Human T-Lymphotrophic Virus 1 (HTLV-1).
Okinawa is endemic for both diseases and the patient has risk factors for acquisition, so there is epidemiological plausibility, and whilst Daniel was cagey about timings, I believe he was alluding to a duration sufficient to exclude many of the parasites not capable of autoinfection. From my reading the presence of HTLV-1 increases the odds of treatment failure of Strongyloidiasis up to five times, as well as making it more likely the individual acquires Strongyloides in the first place. There is also the potential for hyperinfection syndrome with coinfection, particularly if adult T-cell leukaemia/lymphoma (ATLL) develops secondary to HTLV-1.
Now moving on to a different, albeit related topic, and one that I hate to bring up…but I’m still eagerly awaiting the delivery of my copy of Parasitic Diseases from TWiP 166…
I reread my email from March 2019 where I describe my emerging interest in faecal microbiota transplantation (FMT), the gut microbiome and its role in health and disease.
I have since (almost) completed a PhD investigating FMT as a potential therapeutic to eradicate or reduce the gastrointestinal carriage of multidrug resistant Gram-negative organisms.
FMT, as I’m sure you are aware, is manufactured from donated stool and donors undergo screening for a range of potential pathogens, but the decision-making process behind what is screened for is not evidence-based to say the least!
If you could spare a few moments I would love to hear your expert opinions on which parasites you believe to be both pathogenic and capable of transfer from a healthy, asymptomatic individual into a recipient via FMT.
FMT is produced by diluting and homogenising donated stool, which is then filtered (holes approx 1mm), centrifuged (anything that would be pelleted at 500 g is discarded), before the addition of a cryopreservative (we use trehalose). It is then quarantined at -80C before being freeze dried, the resulting powder is then packed into delayed-release capsules ready for administration. Remember, there is no opportunity for embryonation at any point!
We know that blastocystis can definitely be transmitted via FMT, but there is emerging data to say that this is probably a good thing, so in my opinion donors carrying this should be screened in, rather than out.
So, in your opinions, what should we be worried about, or even hoping to find in our donors?
In all seriousness regarding the book, I have an electronic copy and I would much prefer my copy either goes to someone more in need, or any costs that would have been associated with sending it are channelled back into the podcast.
Wishing you all the best,
Blair
Michelle and Alexander from the First Vienna Parasitology Passion Club write:
Dear Eosino-pals,
This case presented some initial difficulties for us, as neither of us recognised the circumstances and symptoms as typical for any parasitic diseases. We looked through parasitic diseases 7th edition for many viruses associated with parasitic infections and found a fascinating connection between strongyloidiasis and HTLV-1 infections.
HTLV-1 is a sexually transmitted virus, which is associated with an increased risk of several types of lymphoma. Higher rates of treatment failures and severe strongyloidiasis have been reported in individuals with HTLV-1. Furthermore, it is important to know that around 5% of patients with HTLV-1 develop lymphomas and should undergo regular screening. In this case we would recommend for the patient’s wife to be educated on and screened for HTLV-1.
Thank you for this great case! All the best,
Michelle and Alexander from the First Vienna Parasitology Passion Club
Henrik writes:
Dear TWiP-hosts,
thank you for your podcast. I am not nearly up to date with all episodes but at least I am up to date in so far as I now listen to the most recent episode and the window of opportunity for a submission has not yet passed.
Regarding the case of the “middle-aged man” (that’s quite relative, isn’t it?) who had been to Okinawa as a soldier:
I first deemed the information about contact to sex workers as irrelevant (or as a hint to the previous case reg. Trichomonas), but here he probably did not contract the parasite, but the virus.
I suppose, he is therefore HTLV-1-positive as Japan is a country with high endemicity for HTLV-1, the patient is HIV-negative and the ways of transmission between the viruses are similar.
When getting an antiparasitic treatment which first leads to resolution of the eosinophilia which then comes back I had thought about filariasis. To my memory, Ivermectin impedes all stages of these nematodes, but only kills the L1-microfilariae which would be sucked up by the mosquitoes again.
It seems that lymphatic filariasis and especially Wuchereria bancrofti increases proliferation and infection with HTLV1 (https://pmc.ncbi.nlm.nih.gov/articles/PMC3153153).
Therefore I would suppose infection with W. bancrofti and HTLV1 which has been treated with ivermectin but not with macrofilaricidal medication such as DEC or Doxycycline (attacking the endosymbiont Wolbachia).
I hope, my first attempt is not completely out of scope and am glad to be hearing more from you!
Greetings from drizzly Tübingen in Germany
Henrik
Chris writes:
Dear Esteemed TWIP team,
Greetings from sunny Baltimore.
I am commenting on the patient with eosinophilia and prior residence in Okinawa where he engaged in activities associated with transmission of a variety of viral infections including HTLV-1.
The differential for eosinophilia and persistent or recurrent eosinophilia is broad. However, given the clinical characteristics, at the top of my differential is that this man acquired HTLV-1 infection while in Okinawa (where it is endemic) and sometime thereafter was infected by Strongyloides stercoralis. Strongyloides infection is associated with the eosinophilia the was identified on routine blood testing. The presence of HTLV-1 increases the risk for the dreaded Strongyloides hyperinfection syndrome and increases the chance of treatment failure with standard treatment of strongyloidiasis. Because of the tight knit relationship between this viral and this parasite, when one is diagnosed it is often recommended to check for the other as well. Longer duration and higher dose ivermectin may achieve cure of the Strongyloidiasis for this patient.
Warm regards,
Chris
Ben writes:
Hello all,
My guess is Giardiasis caused by Giardia lamblia. Shelton (2004) states that this protozoan is often transmitted by fecal-oral contact during sex. Unlike Amebiasis, it commonly causes eosinophilia.
For the virus, I guess a herpes virus, because they can cause eosinophilia.
As an entomologist, I feel foolish I didn’t listen to episode 244 in time. Always appreciate the insect stories!
Thank you,
Ben in Liverpool (ineligible returning champion)
Shelton AA. Sexually transmitted parasitic diseases. Clin Colon Rectal Surg. 2004 Nov;17(4):231-4. doi: 10.1055/s-2004-836943. PMID: 20011264; PMCID: PMC2780057.
Rafid writes:
Hello TWIP team,
My guess for the man with eosinophilia from Okinawa is Strongyloides with co-infection with HTLV virus. This is very well described in your wonderful Parasitology text that I have the privilege to own as you gifted me one.
Greetings this time from Glasgow and not from rural Quebec. Last episode Cristina talked about the wonders of Scottish smur and I told myself that I have to experience this. So I cancelled some clinics, switched call with a Colleague and booked myself a last minute to the UK. Seriously though my daughter was accepted into masters programs at the universities of Glasgow and Stirling and we are here visiting to decide which one to choose. I have just arrived and the weather has been rather wimpy compared to back home Pretty balmy actually. I have not taken my wool socks or long underwear from out of my backpack yet. Hope to get some smur soon as I am only here for a long weekend.
Writing from beautiful Glasgow.
Rafid
Jay writes:
Dear TWiP Team,
This seemingly healthy, middle-aged male, without physical complaints, was found on routine blood work to have high eosinophils. He lives in the NY area now, but he served in the marines in Okinawa at some point in the past. It seems reasonable to guess that his time in Okinawa was 20 or 30 years ago, so if he still harbors a parasite that he acquired there, it’s one that can persist for decades.
There is a known association between strongyloidiasis and HTLV-1. The prevalence of HTLV-1 in Okinawa is quite high, up to 10%, and this virus can be sexually transmitted.
Both strongyloides infection and HTLV-1 can cause eosinophilia. Treating his strongyloides infection may have led to the initial decrease in his eosinophilia. But his eosinophils later rebounded, likely because his HTLV-1 remained. From what I read, there’s a complex interplay between HTLV-1 and various other infectious diseases. HTLV-1 can shift the Th-1 and Th-2 response one way or another. But in writing even this much, I’m getting way over my immunological head. I’m hoping you or some of the other contributors might shed some light on this.
This case also prompted me to look a bit deeper into the controversy-filled history of the discovery of the HTLV group of retroviruses. I may be wrong in my guess, of course. The answer here may not be HTLV-1, so I fully understand if you want to skip my digression that follows.
Dr. Robert Gallo identified HTLV-1 in 1980 and the less pathogenic HLTV-II in 1982. No controversy so far. But In 1984, from a tissue sample sent to him from Dr. Françoise Barré-Sinoussi and Dr. Luc Montagnier’s lab in Paris, he isolated a new virus. He called this new virus HTLV-III, and he proposed it was the cause of AIDS. The problem is, Drs. Barré-Sinoussi and Montagnier had also identified a new virus from that same tissue sample in 1983, a year before Dr. Gallo, and they published their findings that year in the journal Science. The French and the Americans called their discoveries by different names at the time, but it was the same virus. We now call that virus HIV.
Controversy over the discovery went on for several years and the governments of France and the US got involved, each side wanting to claim credit. In the end, Drs. Barré-Sinoussi and Montagnier were recognized for the discovery. They were awarded the Nobel Prize in Medicine for it in 2008.
It’s a complex and colorful tale. And to continue the confusion, the name HTLV-III was later recycled to describe a completely different retrovirus, unrelated to HIV.
Thank you for these challenging cases, your entertaining banter, and the limitless learning. I love the work you do.
Jay
Jay Gladstein, M.D. | Chief Medical Officer
APLA Health & Wellness
Olympic Medical Clinic | 5901 W. Olympic Blvd, Suite 310 | Los Angeles, CA 90036
Nathan writes:
Dear TWI(su)Per Heroes,
I am writing to you from freezing Montréal, Canada.
In an era filled with misinformation, I deeply appreciate the work you do at MicrobeTV—serving as heroes in the fight against falsehoods and promoting scientific understanding. Please keep up the incredible work!
Regarding this week’s case, as someone relatively new to the world of eukaryotic parasites, I turned to the literature for guidance. Based on my research, I suspect that the patient is coinfected with Strongyloides stercoralis (threadworm) and Human T-cell Lymphotropic Virus Type 1 (HTLV-1), as both pathogens are endemic to Okinawa. Given the patient’s prior sexual encounters, it is plausible that HTLV-1 was sexually acquired. This viral coinfection may have contributed to the failure of the antiparasitic treatment previously administered.
If left untreated, this coinfection could lead to severe or even fatal complications. Fortunately, this patient was not receiving corticosteroids, which, as seen in TWIP 112 (the case of the woman from the Dominican Republic with Strongyloides and E. coli bacteremia while on corticosteroids for temporal arthritis), can exacerbate such infections.
Looking ahead, according to the 2016 Committee to Advise on Tropical Medicine and Travel (CATMAT) guidelines (co-authored by former TWIP guest Dr. Michael Libman), if the clinical syndrome is asymptomatic with or without eosinophilia, treatment with ivermectin 200 µg/kg/day orally for two consecutive days or in two doses 14 days apart is recommended. I hope my interpretation of the guidelines aligns with the current best practices.
Thank you very much for your dedication and for inspiring a new generation of learners like myself.
Best regards,
Nathan
Pharmacy student and ID-aficionado
(also friend of Angela’s 🙂 )
06.12.2024
Sources consulted:
Mukaigawara, M., Narita, M., Shiiki, S., Takayama, Y., Takakura, S., & Kishaba, T. (2020). Clinical Characteristics of Disseminated Strongyloidiasis, Japan, 1975–2017. Emerging Infectious Diseases, 26(3), 401-408. https://doi.org/10.3201/eid2603.190571.
Ye L, Taylor GP, Rosadas C. Human T-Cell Lymphotropic Virus Type 1 and Strongyloides stercoralis Co-infection: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2022 Feb 14;9:832430. doi: 10.3389/fmed.2022.832430. PMID: 35237633; PMCID: PMC8882768.
Boggild AK, Libman M, Greenaway C, McCarthy AE, on behalf of the Committee to Advise on Tropical Medicine and Travel (CATMAT). CATMAT statement on disseminated strongyloidiasis: Prevention, assessment and management guidelines. Can Comm Dis Rep 2016;42:12-19. https://doi.org/10.14745/ ccdr.v42i01a03
Kimona writes:
Dear TWiP Team,
My best guess is that this man contracted a co-infection with HTLV-1 and the helminth, Strongyloides stercorales, (likely during romantic interludes after barefoot beach strolls while stationed in Japan..). There is an interesting dynamic between these two infections, with each one influencing the course of the other. Japan is endemic to both and particularly high rates of HTLV-1.
HTLV-1, a retrovirus, infects CD4+ T Cells (but also others) and can ultimately transform these, causing adult T-cell leukemia/lymphoma (ATLL). Co-infection with Strongyloides seems to potentiate the course of this infection. HTLV-1 also effects multiple cytokines and regulatory cells and can shift the normal ‘anti-parasitic’ Th2 response to a Th1 response and thus hamper the body’s defense against a Strongyloides infection. Ivermectin is often the initial treatment but may require a longer duration or combination with albendazole in co-infections – presumably why this man’s eosinophilia returned after treatment. A cure for HTLV-1 infection doesn’t seem to exist, but he may be lucky and remain asymptomatic. It would be advised that he inform his wife of the HTLV-1, as she is at risk of contracting.
In my on-line browsing, I found the below review article helpful.
In eager anticipation of the reveal.
Kimona
https://pmc.ncbi.nlm.nih.gov/articles/PMC7692131
Pathogens. 2020 Oct 29;9(11):904. doi: 10.3390/pathogens9110904Human T-cell Leukemia Virus Type 1 and Strongyloides stercoralis: Partners in Pathogenesis