A Toddler Played With His Cat. This Is How His Brain Shut Down.
DD is a 3 year old boy, presenting to the emergency room unconscious. His mother Emily
tells the admitting nurse that he had suffered 2 seizures in the past hour.
You see, about 10 months ago DD was experiencing problems. Something seemed
to be odd one day when his told his mom that his “potty was red like an apple.”
The next day, he was playing at the mall when suddenly he
cried out in pain and found gripping his sides.
At the emergency room, he was confirmed to have hematuria. The urination of blood.
The medical team found he was suffering from hydronephrosis,
Hydro meaning water, nephro meaning kidney and -osis meaning abnormal
state. His kidneys were heavily damaged from an inappropriate abundance of water.
This was onset because DD had developed primary megaureter. Mega meaning oversized, 10 times
larger than it should have been and ureter being the tube in which the kidney drains urine into the
bladder. Primary meaning he had an anatomic abnormality at his ureterovesical junction,
where the ureter connects to the bladder. This is a problem because the enlarged diameter was
produced by an aperistaltic segment, meaning it doesn’t move along fluid to the end target,
causing that urine to back up, swell into the kidneys and rupture the nephrons. This
limits the kidney’s filtering capabilities and allows blood to spill into the urine.
DD was asymptomatic, until he was found urinating blood, but at the emergency room
it was discovered that the hydronephrosis was so severe he needed his left kidney removed.
But this wasn’t the only problem. His unilateral, one-sided, primary megaureter on his left
compressed the contralateral, or right sided ureter. So while he had megaureter on his left,
he was also obstructed on his right, causing bilateral, two-sided, hydronephrosis.
His right kidney damage was also so severe that he was in end-stage renal disease. He
had no functioning kidneys and thus had no mechanism to remove metabolic wastes
from his blood. He was put on dialysis and on a waiting list for a kidney transplant.
It’s 6 months later. The family was fortunate for a short wait
time to find a matching kidney donor and DD undergoes transplantation.
The transplant goes well and he is in good spirits post-operatively.
He is put on immunosuppressive therapy after the operation. This is because
the body can reject the organ. The kidney that DD received is
called an allograft. Allo meaning different and graft being tissue.
The immune system could identify the allograft as a foreign entity,
and mark it for removal and damage it, much like what your immune system would
do with a virus or bacterial infection— it destroys those, like it would the graft.
The boy is discharged from the hospital with some medicines to suppress his immune system,
prevent organ rejection and improve his transplant outcome,
with the end goal of sustaining his new kidney, ideally for the rest of his life.
It’s 4 months later. Things are going well for the family. They were happy together,
no more dialysis visits, and preschool was on the horizon. Everything seemed to be
well. Even at repeated pediatricians visits, they saw a child who was quickly recovering.
It was here that the family made a new addition to their family. Lola the cat,
from the local shelter.
She was playful and active.
For some reason, DD was often found playing in Lola’s litterbox. It was around this time that
he started complaining that his head hurts. It started with complaints a few days per week,
then turned into every day. He also had a non productive cough. Things got worse when
he would often be found crying at night, in a pool of his own sweat, shivering.
Finally, one day, he was worse than normal. He had a fever, wouldn’t stop coughing, and was
particularly sluggish. Emily had a pediatricians visit scheduled for later in the week.
While he plays with Lola, he suffers his first seizure. Emily calls for
an ambulance where DD is brought to the emergency room where we are now, again.
Given this past medical history, there’s a few clues as to what’s happening.
Most immediately, DD is suffering from some kind of encephalitis.
Encephal meaning brain and Itis meaning inflammation.
This is shown by his headache and seizure.
But how could this be? He underwent a kidney transplant. Physically, the brain and kidneys
are far apart, what kind of direct interaction could they really have? And he’s immunosuppressed,
so if inflammation is an immune system reaction, how is it happening in his brain?
Well, this brings us to the first clue.
Because DD is immunosuppressed, his immune system,
mainly his white blood cells have reduced activity. They still work, but the function is limited.
Of the 2 medicines he is taking to prevent organ rejection,
the first, mycophenolate produces cytostasis on T and B lymphocytes.
Cyto meaning cell, stasis meaning unchanging and lymphocyte being a
subtype of white blood cell, a main component of your immune system.
This means the drug prevents white blood cells from reproducing in large amounts. The medicine
does this by inhibiting T and B cells DNA synthesis, preventing them from replicating.
This is something you want to have as a transplant patient, because white blood
cells can and will infiltrate, replicate in mass, and destroy your new organ when unchecked.
The second medicine, tacrolimus prevents T cells from activating.
Again, this is something you want to have as a transplant patient because T cells
create signals to your immune system to notify when a foreign body is present,
and they can be cytotoxic, meaning they will kill cells of said foreign bodies.
The benefit of immunosuppression is that it prevents DD’s new kidney from being rejected.
The downside is that it puts him at risk for infection, which brings us to the second clue.
Because Lola was adopted, her past isn’t well known. Cats often eat birds and small rodents,
animals that can be infected with parasites from soil and water. The
lifecycle of some these parasites can only be completed inside cats.
Which leads us to suspect that DD is suffering from Toxoplasma Encephalitis.
As we know it today, Toxoplasma gondii is a parasite whose infective lifecycle depends on
cats. Birds and small rodents can often serve as carriers to tissue cysts of toxoplasma.
These cysts can be latent, meaning they don’t produce symptoms for animals carrying them.
But, when the cat consumes these carrier animals, the parasite begins to take on its infective form.
Inside the cat, tissue cysts of toxoplasma burst and spill out bradyzoites. Brady meaning slow and
zoite meaning common organism. In the cats intestines, several generations of parasite
are created and sporulated until they become infective. They reproduce with one another
to form millions of oocysts, which are secreted into the lumen of the intestines and ejected out
the cat in its feces, depositing in the litterbox where DD played. It’s here where he was exposed,
likely from touching cat poop, then touching his mouth sometime afterwards.
The oocysts traveled down DD’s GI tract from his mouth, traversed the lining of his intestines,
proceeded into the blood stream where they latched
onto white blood cells that circulate the body. Because of immunosuppression,
these cells were unaware something was wrong because they hadn’t received T-cell signals.
The oocysts brokedown and formed tachyzoites. Tachy meaning fast.
They’re fast in reproducing and traveled inside the body where they gained access to the brain,
reproduced and caused lesions. As they infest neurologic tissue, they produce deficits,
causing DD’s headache and seizures. If untreated, the parasite can spread into
other neurologic tissue, including the eyes, causing him to go blind.
All of this is newly discovered by humans. The first case of toxoplasmosis was documented at
the Babies Hospital In New York. A baby girl was delivered May 23,
1938. She developed convulsive seizures at 3 days of age, lesions were found in her eyes
and brain at autopsy. Those same lesions were found on farms in sheep and pigs and this disease was
found to be congenital— passed down from mother to baby. Today, we tell pregnant women
to not clean the cat’s litterbox for risk of transmitting toxoplasma to the unborn baby.
In Australia and New Zealand, marsupials and New World Monkeys were highly susceptible to
encephalitis. There wasn’t a good explanation for this until the discovery of the toxoplasma
lifecycle in cats. Because Australia and New Zealand didn’t have feline presence until the
arrival of European settlers, animals there never evolved to be exposed to cat feces,
preventing their resistance to the parasite. This is contrast to
marsupials and monkeys in America and Europe, who did evolve alongside cats and toxoplasma.
But wait, if animals and humans “evolved”
to prevent susceptibility to toxoplasma, why did DD get it?
It’s because he is immunosuppressed, and most other people aren’t. The same thing
would have happened in DD if he had AIDS instead of a kidney transplant. In AIDS,
T-cells containing the protein CD4 are depleted and counts are less than 20% of
a healthy immunocompetent human. CD4 creates signals to the immune system for presence of
a pathogen. In its absence like in AIDS, or in T-cell inactivation like in DD’s case,
means the opportunity for infection through toxoplasmosis is much greater.
Had DD received a heart transplant instead of a kidney transplant, he would be at a greater
risk for toxoplasmosis as the parasite also preferentially embeds itself into muscle,
of which the heart is one of the strongest in your body.
If you own, or have owned a cat, or have eaten undercooked meat from a farm animal who may have
come in contact with a cat, you might have toxoplasma living inside of you right now,
as an inactivated bradyzoite. It’s estimated more than 30 - 60 million Americans have it,
and estimated worldwide projection rates makes it
one of the most common latent infections in human beings.
In general, this isn’t something to worry about. It’s another latent infection that has become a
central part of the human experience for the last couple thousand years.
Many people here have had chicken pox, or varicella,
when they were younger. It’s a form of herpes. After the initial infection,
the virus stays dormant in your nerves and can reactivate later in life as shingles.
Tuberculosis is a bacteria that has killed more than 1 Billion humans in the last 2 centuries. It
was documented by Hippocrates in Ancient Greece, and Ancient Egyptian Mummies from 2400 BC show
evidence of tubercular decay in their spines. Today, it’s estimated 2 Billion people around
the world have latent TB. For most people, it won’t become an active infection, but it’s there.
In the case of raw oysters, most people who have consumed it have hepatitis A.
Raw shellfish typically live in water that has been contaminated with stool that has
hep A. Without cooking, the virus is passed to the person eating it, causing a self-limited,
typically mild disease that confers immunity once symptoms have passed.
Hep A may not be a latent infection in the same way as toxoplasmosis, but it is yet another part
of the human experience of living in a world where we coexist with microorganisms, and our survival
after infection could be passed to humans several generations in the future, just like it was shown
in the Egyptian mummies, and how it will be shown in the kangaroos and monkeys of Australia.
For DD, the suspicion of toxoplasmosis, before confirmatory blood test for antibodies, is
enough to warrant antiparasitic treatment. The best way to kill off the parasites is
to inhibit its mechanism for DNA and RNA production. That stops it from reproducing.
A dual therapy of sulfadiazine and pyrimethamine inhibits utilization of folate, or vitamin B9,
which is vital to producing parasitic DNA. Most importantly, Pyrimethamine inhibits an enzyme
named dihydrofolate reductase, which reduces the molecule into biologically active forms.
Ok, but if we give DD something that prevents cells from making DNA,
wouldn’t we stop his own cells from making DNA too?
Yes. So to get around that, he is also given leucovorin. That is folinic acid,
a derivative of folic acid, which is converted to active folate without the
enzyme dihydrofolate reductase, meaning DD’s cells will have folate, but not toxoplasma.
With proper anti-parasitic treatment, along with persistent monitoring from the medical team,
a strong social support system for the young child, and a family that was properly counseled
and educated on the benefits of risk of immunosuppressive therapy, DD was able
to make a full neurologic recovery, and was able to live a relatively normal childhood after tough infant and toddler years.
Thank you so much for watching. Take care of yourself and be well.