Rafid writes:

Hello TWIP team,

Greetings from rural Quebec.

Thank you again for excellent podcast and for volunteering your time.  When I first listened to this case the first diagnosis that came to my mind in a man with a ring enhancing brain lesion is cerebral toxoplasmosis. However I presume that he had a negative HIV test or else a brain biopsy would not have been performed.  Also if I remember correctly,  the HIV patients that I took care of on the hospital wards in the early 90s, cerebral toxo was a late and not an initial presentation of HIV ( although the fog of 30 years may have affected my memory ). Thus it would be unusual presentation in a previously healthy person. The histology and size of the parasites does not seem to be in keeping with the  Google description of cerebral toxo as well. Therefore, although very rare, I think this patient may have cerebral granulomatous aemebic encephalitis. Balamuthia ameoba may infect healthy people and explain the histological findings of granulomatous inflammation and 50 micron organisms. Last week I attended the Canadian Society of Internal Medicine conference where a resident presented a case of a 75 year old woman with a similar lesion and no risk factors without any unusual exposure who lived in Montreal who had similar biopsy findings with 50 micron amoeba and granulomas on her brain biopsy who unfortunately succumbed to her illness. Therefore even though I am not sure what the diagnosis is I think the karma of seeing a similar case at the conference is too much of a coincidence. Therefore ameboic granulomatous encephalitis is my final answer.


Elise writes:

Dear TWiP Collective, 

I am back after another unforgivable hiatus. I hope this finds all of you well and I was so happy to write this just before your live recording at the ASTMH meeting in Chicago.

The weather in Lower Manhattan is pretty autumnal, 62 degrees F ( 17C) and primarily sunny. 

I seemed to have timed my return to a particularly worrisome case study and I also inadvertently cheated on it. While researching it, I believe I bumbled right into a paper that was written about this poor patient’s case, so it was not too much for me to guess that the gentleman is suffering from Balamuthia mandrillaris. (I am supposing that the amoeba was named because it was first identified in a mandrill that succumbed to an infection in San Diego.) This is a really devastating, and thankfully rare, amoebic infection, though the amoeba in question can be found all around the world (though it seems to somewhat prefer warmer climes).

While I can take no credit for clever deduction, I do wonder about this infection. I know that it is usually fatal and that this gentleman was rescued by an off-brand use of Nitroxoline. Were other amoebicidal drugs considered? How long did it take for the FDA to give permission for its use on the patient? Have subsequent patients dealing with this amoeba been treated the same way? 

As always, thank you thank you so much for your work and many many best wishes, 

Elise (Mac Adam, In Lower Manhattan) 

Paul writes:

Dear TWiPers ,

I’m writing you out of the lovely heat of 32 °C and 80 % humidity of The Gambia. Thank you very much for your very entertaining episodes, I’m really enjoying learning in this way. I thought I might give it a try to have a guess for your 50 year old male with a generalised seizure. We don’t have any travel history or information about sexual activity.

Neurological symptoms may be explained due to the temporal lesions identified on MRI. CSF and brain biopsy hopefully ruled out malignancy, bacterial and fungal infections and as this is TWiP we are looking for something more fancy. Glucose and protein levels in normal range make crypto and TB unlikely.

My guess would be an infection with Toxoplasma which would explain the ring enhanced lesion and can be easily transmitted from out beloved pets. Neurocysticercosis as one of the most common causes of epilepsy in adults worldwide might also be possible.

Serological testing, an HIV test and a further history of contact to pigs or pets might be helpful to find the right diagnosis.

Best regards


Byron writes:
Dear TWIP Hosts,

Good morning from Illinois, where fall is undoubtfully approaching. Weather outside is 67F and cloudy. I cannot help but kicking myself after hearing last week’s case study… such good odds to win the textbook. I shall keep trying. My research had me focused on two possible outcomes, neurotoxoplasmosis, caused by Toxoplama Gondii and Amebic Meningoencephalitis, caused by fee-living amebas. They both induce ring enhancing brain legion, but for toxoplamosis, usually in immunocompromised patients. There is no mention of such medical history in the case study, so my final guess is amebic meningoencephalitis causing by free-living amoeba. Thank you for all you do and please keep the cases coming! 


Michelle and Alexander write:

Dear TWiP-Professors,

Five unicellular parasites that invade the central nervous system come to mind when examining this case:

Nr. 1: Toxoplasma – does not typically cause granulomatous disease.

Nr. 2: Naegleria – a parasitic infection caused by naegleria fowleri, which is an ameba that leads to primary amebic meningoencephalitis (PAM), but does not cause focal granulomas. Usually, this disease leads to death long before all bacterial cultures from biopsy come back negative. Naegleria can also be detected in cerebrospinal fluid, but this is not routinely examined.

Nr. 3: Acanthamoeba – is a free-living ameba with typical, uninuclear morphology, although it typically is much smaller than 50 microns and it is more likely to be found in immunocompromised patients. Infected individuals can develop granulomatous amebic encephalitis (GAE). 

Nr. 4: Balamuthia mandrillaris – named after the animal it was first found in, this parasite causes disease in immunocompetent patients. The trophozoite ranges from 15-60 microns in size and has 1-3 nuclei, while acanthamoeba has only one. This disease can also lead to granulomatous amebic encephalitis, which is oftentimes fatal, although there are now multiple reports of patients surviving this disease. An indirect immunofluorescence assay, immunohistochemistry, and PCR may be helpful tools in diagnosing Balamuthia infection. Drugs that have shown promising effects include flucytosine, pentamidine, fluconazole, azithromycin and clarithromycin.

Nr. 5: Sappinia species – which likewise can lead to granulomatous amebic encephalitis. But due to the fact that there is only one report of a human case in an immunocompromised patient, we doubt this is what the patient is suffering from. 

The differentiation between an infection with Acanthamoeba and Balamuthia mandrillaris is oftentimes only possible via PCR.

Thank you for this great case. All the best, 

Michelle and Alexander from the First Vienna Parasitology Passion Club

Christopher writes:

Bom dia Twip team, 

I am writing this from Brazil, where I am going to stay for a little less than a year to study HIV/AIDS in pregnancy. One of the projects I am going start in the near future is toxoplasmosis in the setting of HIV/AIDS. Some of the outbreaks of toxo that have occurred here in Brazil have interesting stories, including one that is thought to have been driven by water-borne transmission. I am currently reading the online parasitism textbook to brush up on the subject, which helped me interpret the case findings for the 50-year-old man with encephalitis. It seems like this is a slam-dunk case for Toxo, however, I do not see any glaring risk factors that could explain how the infection could proceed to encephalitis in someone who is relatively healthy. I wonder if there is something else going on, like a hematologic disorder or malignancy, that has yet to be discovered. 



Christopher Hernandez

David Geffen School of Medicine at UCLA, Medical Student 

Håkon  writes:

Hello from sunny Athens GA- currently a strong breeze on a sunny day sitting around 77 degrees. For this week’s guess based on small “round” organisms found in a human brain lesion, I gotta guess Toxoplasma or possibly hammondia given the ubiquity of the organism and the lack of distinct features in the morphological description. Treatment might include sulfadiazine, clindamycin, and/or pyrimethamine depending on the patient’s tolerance of sulfa drugs. Hope you’re all well, thanks for the episode and the fun case! 


Anthony S. writes:

Hello all again!

The symptoms and MRI are a dead giveaway for balamuthia infection but the size of cyst seems too big as balamuthia cysts are said to be only 20 microns in size and no bigger

Due to that I think I will change my reply to some sort of brainworm – perhaps pork tapeworm or raccoon roundworm? 

– Anthony S

Christian writes:

Greetings from Basel

where autumn is continuing to be uncharacteristically warm.

The history does not provide a lot of information.

Going by his travel history to East and Central Africa would make the following parasites possible

Onchocerca volvulus (river blindness)

LoaLoa (famous eyeworm)

Mansonella species (often ignored, overlooked and depending on the species hard to treat)

Tocoxara spp (less famous eyeworm)

Strongyloides stercoralis

All of them can cause a visceral larva migrans syndrome, with Onchocerca and Loaloa being on top of the list for eye involvment. All of them live long enough to be still alive in the patient.

Though without reexposure, only Strongyloides would grow in significant numbers.

They would usually go hand in hand with eosinophilia and a positive filaria serology, however, seronegativ cases have been shown to exist.

Additional symptoms included a stinging pain in different parts of his extremities, fatigue, abdominal cramps and bowel irregularities could have been caused by

the patients potential hyperventilation. Here it would be good to know what the time of onset of these symptoms was.

Also, it is not clear what the patient understands under a normal diet. Food variety in Vienna is not small, and in some of the surrounding countries meats and sausages may be a bit undercooked as good source of Trichinella.

A really left field differential could be Phthirus pubis, causing irritation of the eyelid. 

Additional questions would be:

Has he had similar symptoms before? (such as a migrating rash or lump)

Was he regularly bitten by midgets, flies or mosquitoes during his travels or walking barefoot or in sandals?

What was he doing in Central Africa and which parts? 

I am looking forward to the solution of the case.




If you are looking for parasitic cases, we do have some available from our clinic. 

James writes:

I won the book last month so take me out of the running.

It’s quite an incredible autumn in Denver, with clear blue skies, lows in the 40’s F (4-10 C) and highs near 80F (27C.) Some years by this time we’ve already had snow. My garden is still producing tomatillos for my wife’s killer green chili. I tell our medical students that “climate change” means every year in Colorado.

So on to the case. Man with no real history, shows up with a temporal lobe mass lesion, granulomatous inflammation, and “infectious forms” about 50 microns with a central dark area. A nucleus perhaps?

In Protozoa, of course I’d think about Acanthamoeba (which causes “granulomatous encephalitis” and sometimes brain abscesses.) Balamuthia can be similar.  Entamoeba abscesses have been found in the brain. Toxo is a lot smaller unless you count the “cyst” as the “infectious form.” Kind of weird for Naegleria. But the size and description of the organisms fits one of our Amebic cousins pretty well.

In Helminths, I always wonder about T. solium with cysticercosis but I don’t like the description much. Echinococcus is an interesting thought…the protoscolices/scolices might be about the right size.

I guess I still favor one of the Blobs (amebae) and would really have trouble with which one, but I guess I’ll go out of a limb and guess Acanthamoeba!

James M. Small, MD, PhD, FCAP

Professor of Pathology and Microbiology

Director of Clinical Career Advising

Rocky Vista University