CNS Amoebas| Naegleria fowleri, Acanthamoeba & Balamuthia

CNS Amoebas| Naegleria fowleri, Acanthamoeba & Balamuthia

the amoebas that I tested on USMLE step 1 this includes a microbiology pathology and pharmacology my time samson sources will be listed down below so without further ado grab some coffee get comfortable and let's get started so we are in the phylum ela zone aka circle Deena who fall here on my overall list of parasites so let's go over a typical amoeba the lifecycle which consists of two forms the assists and trophies I'd cysts are the dormant form and they're either double or triple walled and they're highly resistant to environmental stresses allowing them to exist outside their host now tofu soy is in the mobile form which allows for reproduction and feeding and they are highly adaptable to their environment now if atropos oil is presented with an environment that it cannot adapt to like changes in pH overcrowding lack of food it will undergo enca station or insist and become a dormant form it basically secretes its thick wall around itself to protect itself enabling it to survive longer likewise when environmental conditions allow and become favorable these cysts form will undergo excitation and a chav resides inside will escape through the central pore and break free allowing for mobility reproduction and feeding this is a typical structure of aromatic triples whites starting off with their sort of podía which is their means and motility it's made up of their ecto and endoplasm so the trapezoid will extend out part of its saw membrane and then for cytoplasm into it allowing for locomotion in that direction the other important structure to know is the contractile vacuole now most of these trophies oh it's existed in water that is typically hypotonic in comparison to their intracellular environment as we know if a cell is placed in a hypotonic solution water will freely diffuse intracellularly typically causing a cell to swell and ultimately lyse the contractile vacuole is the structure that allows for that not to happen so the vacuole will collect all of that water that is freely diffusing into the cell allows for ionic exchange and ensures that the intracellular environment remains stable regardless of the hypo to Nissa t of its environment and now for the names of our step 1 amoebas starting off with balamuthia mandrillaris Acanthamoeba poli figa Naegleria fowleri and to me by histolytica using the mnemonic of their first letters bein not only Bane from Batman but also they are the bane of our existence as doctors they're extremely hard to diagnose and even harder to treat for this luxury we are focusing on the purple which are our CNS amoebas now we all know the phrase in medicine we think if we hear hoofbeats think horses not zebras well guys these are your zebras because these parasites are typically not on your list of differentials when somebody presents with meningitis or encephalitis so let's go over them one by one starting off with balamuthia who is a soil-dwelling free living amoeba that much is not known about that being said there aren't really any specific risk factors there's no rhyme or reason why one person is infected in another isn't however there's a growing body of evidence showing patients who undergo whole organ transplants and subsequent immuno suppression are at risk as therewas an outbreak in 2016 I will leave that NCBI article listed down below his route of entry can be through open wounds or it through inhalation into the lower respiratory tract and water as possible remember not a lot is known about balamuthia for the epidemiology there have been 109 known cases according to NCBI in North America with Southwest us having the highest prevalence the mortality rate is greater than 98 percent there are only two or three known survivors morphologically as we've gone over for the cysts form it will insist in unfavorable conditions and they're all spherical with a central poor or osteo so when conditions allow it will exist in a trapezoid form will escape through that central osteo again this is the stage of feeding and replication and it's the true amoebic form in this case both forms are infectious and both can be found in human tissue on biopsy the pathology associated with balamuthia is granulomatous amoebic encephalitis for the pathogenesis upon exposure it will use the blood to spread to the CNS where it feeds on its favorite food which is actually the micro vascular endothelial aka the blood-brain barrier it's also able to factor some theis tissue and nerves in a competent patient the immune response will be type 4 hypersensitivity hence the name granulomatous and this is of course an attempt to wall off the invader in an immune compromised patient just a whole organ transplant undergoing immuno suppression you will view very perivascular of cuffing goes remember it's feeding on the endothelium the earliest symptoms for clinical presentation can take weeks to months to appear and will begin with a slow onset headache nausea and nuclear rigidity though typical signs of meningitis or encephalitis the patient may also present with focal paralysis or brain stem cranial nerve symptoms like Bell's palsy dysphasia or just diplopia skin lesions are possible but they will mimic bacterial lesions and your clue is that they will not go away aka not respond since antibiotics if left untreated the late stage will lead to hallucinations convulsions loss of consciousness and ultimately death death is typically due to brain swelling from the immune response or pressure lesions and necrosis diagnosis is typically empirical because your number-one clue is that the patient will not respond to antibiotics on MRI you can appreciate multiple ring enhancing lesions with extensive necrosis and edema this is not specific many bugs can cause me enhancing lesions if a biopsy is able to be performed we will appreciate assists or trophies awaits in the brain tissue which again is nonspecific cuz it can be any of these three amoebas though technically the gold standard if able to be performed is on culture and that culture will have to be done on mammalian or primate liver or vascular endothelial cells because balamuthia does not feed on bacteria for treatment and prognosis the prognosis is grim as I've already said the mortality rate is greater than 98% within weeks of from onset of symptoms if caught early enough the drug of choice is in Pahlavi toe aka melteth dosing which is a cytochrome C oxidase inhibitor this drug was approved by the CDC in 2013 for treatment of Leishmania Pam and this GAE the problem with this drug is that most hospitals don't carry it because it carries a hefty price tag one full course of treatment is 58 thousand US dollars next up is a Kent amoeba Paula fuga who is a freshwater free living amoeba now she has two associated pathologies and likewise their risk factors are both exposure to fresh water and contact lenses being exposed to fresh water or tap water the route of entry for GAE again is through open wounds or through the nose to the lower respiratory tract and for keratitis of course the risk factor is contact lens uses or improper usage of contact lenses Yabba D me ology for keratitis is that there's 105 known cases in North America alright this disease is found worldwide morphologically is the exact same as balamuthia with the cysts form found in unfavorable conditions and it's spherical with its central pore aka osteo when conditions allow they trophy's I will escape through that central pore and will feed and replicate and again both of these form are the infectious stages for humans and can be found in human tissue on biopsy I can't amoeba keratitis this is much more pertinent pathology for I can't amoeba the pathogenesis starts off with contact lens contamination typically with tap water because this amoeba can survive in the space between the lens and the cornea where it divides and feeds on corneal tissue and vasculature and our inflammatory response mainly contributes to the damage seen clinical presentation we'll start off with unilateral eye pain which progressively worsens rather quickly other symptoms are photosensitivity redness and extensive tearing and in the affected eye the person may also complain of a foreign body sensation so the feeling like something's in their eye and blurred vision that rapidly progresses diagnosis will be done by eye exam where you will see evidence of corneal degeneration epithelia will be intact however it will appear modeled under fluorescence unfund Aska B you may appreciate thickened corneal nerves with rugged borders that radiates outwards from the pupil and this is termed a radio video Corrado neuritis in advanced disease you may even be able to appreciate a ring infiltrate or abscess and this can be seen with the naked eye confirmation the gold standard is on corneal scraping where the gold standard is PCR you have to include differential stains like Koh and Cal go for for treatment and prognosis the prognosis is quite grim as it usually progresses to blindness in more than 98% of cases within weeks from answer docent if treatment is an option its dual therapy with topical Antonia makes like big one eyes Cora hexa diene and oral ketoconazole now this is a second Emmy but on our list that can cause granulomatous and maybe can cephalopoda and the reason I have granulomatous in quotation marks is because typically this is only seen in a compromised patient so patients with hiv/aids or those who are immunosuppressed the pathogenesis is fulminant je which will actually mimic my glare iasis which i'm going over next so the clinical presentation in a competent patient would be exact same as it would for balamuthia with the early symptoms being a salon side headache nausea and vomiting as well as focal paralysis or brain stem symptoms like Bell's palsy dysphasia and diplopia with the late stage occurring much quicker with hallucinations convulsions loss of consciousness and death diagnosis is the exact same as balamuthia with a number one clue being non-responsive to antibiotics and MRI you will see the exact same thing multiple ring enhancing lesions with extensive necrosis and edema and not biopsy you will see the exact same with tissue troffer Zoids and cysts so the confirmation would be on PCR treatment and prognosis again exact same as balamuthia with mil mm being my drug of choice and just as the last reminder this drug is not carried by most hospitals as a full course of treatment is 58 thousand US dollars pods are host to a deadly amoeba that claimed the life of a local teenager last year she just didn't know it you're looking into a deadly amoeba infection now for the true brain eating amoeba mangle area foe Larry she is a thermophilic free-living amoebas meaning she thrives in high temperatures specifically in warm fresh waters risk factors would be lakes and hot springs as well as activities that would expose you to send bodies of water like windsurfing or just straight-up swimming route of entry is via the nose so Nigel area goes through your nose G&B is the olfactory epithelium and follows it through the cribriform plate up to the frontal lobe for the epidemiology since 1960 there have been 138 known cases in North America with greater than 95 percent mortality only four people have survived this for the morphology pay close attention we of course have these cysts form because the Tropos will insist in cold temperatures in this case less than 50 degrees Fahrenheit she can survive in the environment for months her trophies or warm whisky through that central pour when the environment allows aka and greater than 50 degrees Fahrenheit this of course is her true amoebic form over logically described as a large nucleus with a surrounding halo now unlike the first to Nigeria has a flagellated form yet another evolutionary adaptation allowing her to survive the flagellated form exists when she's exposed to high potency so this is typically the form you will find in freshwater this form can be inhaled while swimming and she will then transform into the trophy's away form and this transformation only takes hours you will not see the flagellated form in human tissue but you will see it on a CSF sample primary amoebic meningitis uh Politis AKA night glare iasis starting off with the pathogenesis upon exposure to freshwater and nasal epithelium she will transform to more trophies away form if necessary remember this is a stage of feeding and replication so she's able to phagocytize tissues and nerves but she follows the olfactory nerve through the cribriform plate to the frontal lobe where she feeds on our astrocytes clinical presentation for this is very different than the first two that we've spoken about the number one most important thing is the patient's past medical history which will be contact with warm fresh water within the last seven days if you don't know this fax you will not think of neglect the patient will complain of a new onset frontal headache with or without a NAS Neha's member she's eating up our olfactory nerve and this headache can come on as quickly as one day after exposure to water those symptoms will quickly progress into the meningitis triad being nuchal rigidity photophobia and fever quote-unquote late-stage which is really only a few days after onset of symptoms most commonly reported symptom is hallucinations convulsions ultimately loss of consciousness and ultimately death for diagnosis an MRI can be pretty telling if you know what to look for as you will see extensive edema and necrosis localized to the frontal lobes on spinal tap you can see the flagellate or trophy's waveform and it will be a turbid draw meaning it will be cloudy however it will obviously be culture-negative because it's not bacterial so that being said a culture is typically not done because there's just not enough time if you suspect it and want to confirm it it will be done on a non nutrient agar coated with e.coli which will then be cleared into linear lines because my Gloria does feed on bacteria and the technical gold standard test is the flagellation test where you would add a drop of distilled water at 42 degrees to the culture plate and observe flagellation because remember her flagellated form exists in hypo Tennessee for treatment and prognosis as I've said it's very grim the mortality rate is more than 95% within 7 to 12 days from onset of symptoms and there are only as of 2018 for known survivors since step 1 is sort of behind the times technically the drug of choice is amphotericin B even though there's been a little success with it and it's actually an antifungal they lengthly side-effect profile and high toxicity risk if you haven't seen my antifungals video I will link it up in the eye right now in reality so when your actual clinical practice has been success in one case with therapeutic induced hypothermia and finally as I've stated melteth dosing is currently the actual German choice as in 2013 it was a provided CDC for treatment of primary amebic meningoencephalitis so for all three of these pathogens but specifically for night Glary I'm just going to stress the importance of taking a proper past medical history from your patient as you've seen above it presents just like meningitis which we would typically associate as bacterial all of your cultures are gonna come back negative and your patient is not going to respond the antibiotic therapy so in that situation you guys remember your zebras especially Nigeria ask the patient if they've come into contact with fresh water especially if you're in the southern or western parts of the United States where it's always warm night Larry can infect anyone the prognosis 100% depends on a speedy diagnosis and by speedy I mean one to two days after onset of symptoms before she's able to eat her way so far and she causes permanent brain defects or paralysis hoofbeats are not always horses sometimes is zebras if you keep this in mind you can save this patient's life okay doctor I know that was pretty morbid but you made a bunch of NCBI articles listed down below in the description for those of you interested in learning more especially about research being done to improve Diagnostics.