[MUSIC] A febrile toddler played with his cat. This is how his brain shut down. "DD" is a three-year-old boy, presenting to the emergency room unconscious. His mother, Emily, tells the admitting nurse that he had suffered two seizures in the past hour. You see, about ten months ago, DD was experiencing problems. Something seemed to be odd one day when he told his mother 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 was 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 - ten times larger than it should have been - and ureter, being the tube in which the kidney drains into the bladder. Primary, meaning he had an anatomic abnormality at his ureterovesicle 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 fluid along to the end target, causing urine to back up, swell into the kidneys, and rupture the nephrons. This limits the kidneys' 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 waste from his blood. He was put on dialysis, and on a waiting list for a kidney transplant. It's six 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's in good spirits post-operatively. He's 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", meaning tissue. The immune system could identify the allograft as a foreign entity, mark it for removal, and damage it, much like what 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 four months later, and 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, and even at repeated pediatrician 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, adopted from the local shelter. She was playful and active. For some reason, DD was often found playing in Lola's litter box. It was around this time that he starts to complain that his head hurts. It started with complaints a few days a week, then it turned into every day. He also had a non-productive cough, and 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 already scheduled a pediatrician's visit for later in the week. While he plays with Lola, he suffers his very first seizure. Emily calls for an ambulance, where DD is brought to the emergency room, where we are now. Again. Given his past medical history, there's a few clues as to what's happening. Most immediately, DD is suffering from some form 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, and, physically, the brain and kidneys are far apart. What kind of direct interaction could they really have? And, also, he's immunosuppressed, so, if inflammation is an immune system reaction, how is it happening to 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. Now, of the two medicines he's taking to prevent organ rejection, the first, Mycophenolate, produces cytostasis on T and B lymphocytes. "Cyto", meaning cell, and "stasis", meaning unchanging. A lymphocyte, being a subtype of white blood cell, a main component of your immune system. This means that the drug prevents white blood cells from reproducing in large amounts. The medicine does this by inhibiting T and B cell DNA synthesis, preventing them from replicating. This is something that you want to have as a transplant patient, because white blood cells can and will infiltrate, replicate en masse, and destroy your new organ when unchecked. The second medicine, Tacrolimus, prevents the activation of T-cells. 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. They can also be cytotoxic, meaning that they will kill cells of said foreign body. 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. And the life cycle of some of these parasites can only be completed inside cats, which leads us to suspect that that DD is suffering from toxoplasma encephalitis. As we know it today, toxoplasma gondii is a parasite whose infective life cycle 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 the 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 cat's 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 of 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, traversing the lining of his intestines. They then proceeded into his bloodstream, where they latched onto white blood cells that circulate the body. Because of immunosuppression, these cells were unaware that something was wrong because they hadn't received T-cells' signals. The oocysts broke down and formed tachyzoites. "Tachy", meaning fast. They're fast in reproducing and they 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 Baby's Hospital in New York. A baby girl was delivered May 23rd, 1938. She developed convulsive seizures at three days of age. Lesions were found in her eyes and brain at autopsy. Those same lesions were found on farms, in sheeps, and pigs, and this disease was found to be congenital - passed down from mother to baby. Today, we tell pregnant women not to clean the cat's litterbox, for risk of transmitting toxoplasma to the unborn baby. In Australia and New Zeland, marsupials and new world monkeys are highly susceptible to encephalitis. There wasn't a good explanation for this until the discovery of the toxoplasma life cycle in cats. Because Australia and New Zeland 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. Now, but wait. If animals and humans evolved to prevent susceptibility to toxoplasma, why did DD get it? It's because he was immunosuppressed, and most other people aren't. The same thing would've 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 twenty percent of a healthy immunocompetent human. CD4 signals to the immune system for presence of a pathogen, and its absence 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 preferentially embeds itself into muscle as well as the brain. And the heart is one of the strongest muscles 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 the cat, you may have toxoplasma living inside of you right now as an inactivated bradyzoite. It's estimated more than thirty to sixty million americans have it, and estimated worldwide projection rates make 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 chickenpox or veracella 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 a billion humans in the last two 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 that more than two billion people around the world have latent tuberculosis. For most people, it won't ever become an active infection. But it's still there. In the case of raw oysters, most people who have consumed them 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 that toxoplasma is, but it is 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. For DD, the suspicion of toxoplasmosis before confirmatory blood tests is enough to warrant antiparasitic treatment. The best way to kill off the parasite is to inhibit its mechanism for DNA and RNA production. That stops it from reproducing. A dual therapy of SulfADIAZine, pyrimethamine, inhibits the 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 form. But, if we give DD something that prevents cells from making DNA, wouldn't we stop his own cells from making DNA too? And the answer is yes. But, to get around that, he's also given leucovorin. That's folinic acid, a derivative of folic acid, which is converted to active folate without the enzyme dihydrofolate reductase, meaning that DD's cells will have folate, but not the toxoplasma. With proper antiparasitic treatment, along with persistent monitoring from the medical team, a strong social support system for the young child, and a family that was properly educated and counseled on the benefits and risks of immunosuppressive therapy, DD was able to make a full neurologic recovery, and was able to live a relatively normal childhood after very tough infant and toddler years. Thank you so much for watching. Take care of yourself, and be well. --- Primary English captioning by RWInnovation ---
TL;DW?
Why didn't anyone think at the time that maybe letting an immunosuppressed toddler play in the cat's litterbox wasn't the brightest idea?
I really want to watch this but I can't stand the way the narrator speaks
Wat.