4 ms·

My father contracted cryptococcal meningitis seven years ago and, according to his doctors, was days away from dying from it (he has fully recovered since, than

My father contracted cryptococcal meningitis seven years ago and, according to his doctors, was days away from dying from it (he has fully recovered since, thankfully) The problem, though, wasn't treating it. His neurosurgeon told me they treated it with the same medication they give women for yeast infections. The problem was diagnosing it. He's not HIV positive nor has he had a transplant. Apparently, in a small percentage of the population, the fungus makes it way to a non-immunocompromised brain. It's so small that, according to his neurosurgeon, they have to treat patients like him as if they were HIV positive/transplant recipients because they don't have enough data otherwise. I'm glad to hear about this new therapy but, with my father at least, they weren't able to properly diagnose until they did a biopsy on his brain. So, it seems like improvements in diagnosis may be in order as well.

stef25 3y ago
So the fungus can cross the blood brain barrier? Or does it get there via other means?
- haldujai 3y ago
  Yes. Microbes once in the blood stream can cross/bypass the barrier by a few ways such as by crossing endothelial cells, crossing loosened or disrupted tight junctions or by entering a host cell that then traverses the barrier. Normally, intact cell-mediated immunity prevents harmless airway colonization of these types of organisms from entering the blood stream or causing clinical infection hence why they're called opportunistic infections. Rare in immunocompetent patients.
- Zelphyr 3y ago
  The surgeons never said one way or another. I got the distinct impression that they are, unfortunately, at quite a loss when it comes to people like my dad since he shouldn't have been immunocompromised. In fact, prior to the biopsy, they were convinced it was some form of cancer.
- DoreenMichele 3y ago
  One known means to enter the brain is via the sinuses. https://news.ycombinator.com/item?id=36767405 https://news.ycombinator.com/item?id=36767405
epistasis 3y ago
Thanks for sharing this. The diagnostics world is advancing quickly due to our exponential tech curve on DNA sequencing, but that's not going to solve the problem of needing a brain biopsy to diagnose... Do you know if they did testing of easier material like cerebral spinal fluid first?
- Zelphyr 3y ago
  They did but couldn't detect the fungus from that so they proceeded to the biopsy. The surgeon said that the cerebral spinal fluid can get filtered quite a bit by the time it gets to the area where they do the tap which was why they couldn't detect it using that method.
gambiting 3y ago
A lot of virus infections are unfortunately like that too. Few years ago I had a fever that wouldn't go away, night sweats, no appetite, nothing......finally got admitted to a hospital with an infectious diseases department, they ran about 40 different tests.....all negative. Did few dozen more, this time on all kinds of tropical/exotic diseases.....all negative. Few weeks of back and forth while I was still very unwell, losing a lot of weight. The doctor looking after me was suspicious it's actually HIV that's not coming up on the tests for some reason, repeated the tests like 3 times just to be super extra sure.....eventually they just said "it's some kind of virus but we don't know what, so we have no idea - go home and rest, it should improve within few weeks but in the meantime we have no solution for you". Couple weeks later several of my joints got really swollen which led to them testing me for a human Parvovirus-B6 infection, and indeed, that's what it was - but it was just a lucky guess by the doctor there, he said they don't normally test people in my age group for it because it's incredibly rare for adults to get infected or show any symptoms, but lucky me, I was in that 0.000001% group that not only got infected by also had severe symptoms. But even then it was just "ok, we know what it is but there is nothing we can do to help, it should go away, oh and btw there is a 5% chance you will continue getting symptoms for years if not forever". Well it's been 4 years and I'm still fighting it, so...........
- TheSpiceIsLife 3y ago
  May I ask some questions: Your white cell counts were indicative of viral infection? PCR was positive, indicating infection? Do you supplement zinc, C, B6, magnesium?
  - gambiting 3y ago
    For 1 and 2 I don't know, I assume so, they never showed me any stats at the hospital. And yes I do, all of those + vitamin D.
  - 1letterunixname 3y ago
    Be careful with supplementation of transition metal trace elements. Absorption of one is usually competitive to others such that it cause toxicity in one and deficiency in another. A multivitamin is a safer source but having blood levels checked regularly would allow for calibrated intake. For example, as a poor absorber of Vitamin D3 I require 12k IU / day (with all of its cofactors) to stay within the established blood range. It would be inadvisable and reckless for anyone to consume this amount of a fat soluble vitamin without monitoring blood levels. I'm also prone to iron deficiency anemia of unknown etiology (cause), but that's another problem suggesting either poor absorption (most likely), cancer, or unexplained bleeding.
pmags 3y ago
Treatment is in fact a real challenge. Cryptococcus isolates "in the wild" have a relatively high frequency of azole resistance alleles already (azoles are what you give someone for a typical "yeast" infection), and azole resistances arises relatively quickly in patients in both patients and animal models of disease. Coupled with this is the fact that fungi are eukaryotes, and hence share most of their core cell and molecular biology with your own cells. Hence treatments that specifically target the fungal cell with little toxicity to your own cells are hard to come by. Note that last year the WHO released a list of "fungal priority pathogens" based on criteria related to "unmet research and development needs and perceived public health importance." Cryptococcus is at the top of this list. https://www.who.int/publications/i/item/9789240060241 https://www.who.int/publications/i/item/9789240060241 General resources on fungal meningitis: https://www.cdc.gov/meningitis/fungal.html https://www.cdc.gov/meningitis/fungal.html CDC resources specific to Cryptococcus: https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/index.html https://www.cdc.gov/fungal/diseases/cryptococcosis-neoforman...
darkclouds 3y ago
> the fungus makes it way to a non-immunocompromised brain. Something I'm looking at the moment is the role zinc plays in things like membranes and blood brain barrier. When looking at how much zinc is used through out the body which combined with one of these, cysteine, histidine, aspartic acid, glutamic acid, with the first two largely involved in structural applications ranging from zinc fingers to organelle stability, cell stability and membrane health, it looks like the RDA is woefully inadequate. The problem is a blood test wont show zinc status as its so tightly controlled in serum, so if its measured and it shows a problem, its going to be an extreme problem. However if you suffer a head injury, the damaged brain cells will dump zinc straight away into the blood so that the neurons take up glutamate which then become neuro toxic leading to cell death. For example, if you take vitamin D3 supps, it needs a zinc finger, so taking VitD3 with zinc, is useful other wise you could be wasting your time taking VitD3 if there is simply not enough zinc in the body, which can explain why some people dont respond to vit D3 supps. If the zinc status is low, there are so many vitamins and minerals that are just not worth doing. But mega dosing so many vitamins and minerals can create a zinc deficiency, like mega dosing vit A or D, or even nicotinic acid (b3) to compound things. Its not been unheard of taking a few hundred mg's a day, with documented therapeutic doses at 2grams a day! There is also disputes over whether an increased zinc intake even causes copper deficiency's. Studies are mixed, so typical medical caution is order of the day with regard to high doses of zinc, but that caution can contribute to medical conditions. The digestive system has no restriction on the uptake of zinc, unlike iron which uses hepcidin, but things like fibre, phytates, tannins, found in vegetables, will all bind to zinc in the gut very easily reducing its effectiveness, and then there is calcium, iron which is known to compete, with phosphate also looking like a similar competitor of zinc. B6 is recommended for any high intakes of minerals, it can be used to reduce the incidence of sideroblastic anemia and peripheral neuropathy amongst many things. The Nicotinic Acid form of B3 works with every enzyme in the body via Nicotinamide Adenine Dinucleotide (NAD) and Adenosine triphosphate (ATP). But as there is no reliable way to measure zinc status, things like an enlarged spleen (splenomegaly), cancer, diabetes, and numerous more disease states and illness could indicate an inadequate zinc status. Put another way, Zinc deficiency is found in so many illnesses including depression. > > weren't able to properly diagnose until they did a biopsy on his brain. Did they measure the surrounding tissue around the brain and bone mineral density, to check if the blood brain barrier was intact, and immune response optimal? If its any consolation, fungi can be sniffed as a smell and end up in the sinuses where they can contribute to mental health issues, but these only show up in autopsy's, and biopsy's! When zinc acetate at 75mg was used to shorten the common cold, its typically portrayed that it shortened the cold duration by a couple of days and its not really worth taking. When looking at the studies, the common cold had a typical 8.3day duration but with a total 75mg of zinc acetate spread over a day, reduced it to a 4.5day duration. Take into account the time it takes for the immune cells to respond, with or with out supplement, and that zinc duration could be reduced to under 4 days, even fewer days if there was adequate zinc status before infection, making it much more significant and effective than its currently portrayed! So, should we be re evaluating our zinc intake to see improvements in health, to avoid situations like this?
andai 3y ago
How are brain infections of other types normally diagnosed?
- haldujai 3y ago
  It depends on what type of infection we are worried about and what structures are involved but generally an MRI and a lumbar puncture for cerebrospinal fluid analysis to start. If there's an abscess a neurosurgeon can stick a needle/drain in it. Usually a combination of clinical and MRI findings is enough for infectious diseases and neurology specialists to figure it out and start empiric treatment for something/a few somethings if the CSF doesn't give you the answer. Rarely, at least at my institution, you could do a biopsy but you don't really want to be chopping up the brain if you can avoid it.
- onemoresoop 3y ago
  And are there any particular worrying symptoms for this type of brain fungal infections?
  - Zelphyr 3y ago
    I can't speak to what's common but, with my dad it was he was increasingly confused, constantly tired and sleeping all the time, and progressive weight loss. He was down to 100lbs when they admitted him.

stef25 3y ago

So the fungus can cross the blood brain barrier? Or does it get there via other means?

haldujai 3y ago
Yes. Microbes once in the blood stream can cross/bypass the barrier by a few ways such as by crossing endothelial cells, crossing loosened or disrupted tight junctions or by entering a host cell that then traverses the barrier. Normally, intact cell-mediated immunity prevents harmless airway colonization of these types of organisms from entering the blood stream or causing clinical infection hence why they're called opportunistic infections. Rare in immunocompetent patients.
Zelphyr 3y ago
The surgeons never said one way or another. I got the distinct impression that they are, unfortunately, at quite a loss when it comes to people like my dad since he shouldn't have been immunocompromised. In fact, prior to the biopsy, they were convinced it was some form of cancer.
DoreenMichele 3y ago
One known means to enter the brain is via the sinuses. https://news.ycombinator.com/item?id=36767405 https://news.ycombinator.com/item?id=36767405

epistasis 3y ago

Thanks for sharing this. The diagnostics world is advancing quickly due to our exponential tech curve on DNA sequencing, but that's not going to solve the problem of needing a brain biopsy to diagnose... Do you know if they did testing of easier material like cerebral spinal fluid first?

Zelphyr 3y ago
They did but couldn't detect the fungus from that so they proceeded to the biopsy. The surgeon said that the cerebral spinal fluid can get filtered quite a bit by the time it gets to the area where they do the tap which was why they couldn't detect it using that method.

gambiting 3y ago

A lot of virus infections are unfortunately like that too. Few years ago I had a fever that wouldn't go away, night sweats, no appetite, nothing......finally got admitted to a hospital with an infectious diseases department, they ran about 40 different tests.....all negative. Did few dozen more, this time on all kinds of tropical/exotic diseases.....all negative. Few weeks of back and forth while I was still very unwell, losing a lot of weight. The doctor looking after me was suspicious it's actually HIV that's not coming up on the tests for some reason, repeated the tests like 3 times just to be super extra sure.....eventually they just said "it's some kind of virus but we don't know what, so we have no idea - go home and rest, it should improve within few weeks but in the meantime we have no solution for you". Couple weeks later several of my joints got really swollen which led to them testing me for a human Parvovirus-B6 infection, and indeed, that's what it was - but it was just a lucky guess by the doctor there, he said they don't normally test people in my age group for it because it's incredibly rare for adults to get infected or show any symptoms, but lucky me, I was in that 0.000001% group that not only got infected by also had severe symptoms. But even then it was just "ok, we know what it is but there is nothing we can do to help, it should go away, oh and btw there is a 5% chance you will continue getting symptoms for years if not forever". Well it's been 4 years and I'm still fighting it, so...........

TheSpiceIsLife 3y ago
May I ask some questions: Your white cell counts were indicative of viral infection? PCR was positive, indicating infection? Do you supplement zinc, C, B6, magnesium?
- gambiting 3y ago
  For 1 and 2 I don't know, I assume so, they never showed me any stats at the hospital. And yes I do, all of those + vitamin D.
- 1letterunixname 3y ago
  Be careful with supplementation of transition metal trace elements. Absorption of one is usually competitive to others such that it cause toxicity in one and deficiency in another. A multivitamin is a safer source but having blood levels checked regularly would allow for calibrated intake. For example, as a poor absorber of Vitamin D3 I require 12k IU / day (with all of its cofactors) to stay within the established blood range. It would be inadvisable and reckless for anyone to consume this amount of a fat soluble vitamin without monitoring blood levels. I'm also prone to iron deficiency anemia of unknown etiology (cause), but that's another problem suggesting either poor absorption (most likely), cancer, or unexplained bleeding.

pmags 3y ago

Treatment is in fact a real challenge. Cryptococcus isolates "in the wild" have a relatively high frequency of azole resistance alleles already (azoles are what you give someone for a typical "yeast" infection), and azole resistances arises relatively quickly in patients in both patients and animal models of disease. Coupled with this is the fact that fungi are eukaryotes, and hence share most of their core cell and molecular biology with your own cells. Hence treatments that specifically target the fungal cell with little toxicity to your own cells are hard to come by. Note that last year the WHO released a list of "fungal priority pathogens" based on criteria related to "unmet research and development needs and perceived public health importance." Cryptococcus is at the top of this list. https://www.who.int/publications/i/item/9789240060241 https://www.who.int/publications/i/item/9789240060241 General resources on fungal meningitis: https://www.cdc.gov/meningitis/fungal.html https://www.cdc.gov/meningitis/fungal.html CDC resources specific to Cryptococcus: https://www.cdc.gov/fungal/diseases/cryptococcosis-neoformans/index.html https://www.cdc.gov/fungal/diseases/cryptococcosis-neoforman...

darkclouds 3y ago

> the fungus makes it way to a non-immunocompromised brain. Something I'm looking at the moment is the role zinc plays in things like membranes and blood brain barrier. When looking at how much zinc is used through out the body which combined with one of these, cysteine, histidine, aspartic acid, glutamic acid, with the first two largely involved in structural applications ranging from zinc fingers to organelle stability, cell stability and membrane health, it looks like the RDA is woefully inadequate. The problem is a blood test wont show zinc status as its so tightly controlled in serum, so if its measured and it shows a problem, its going to be an extreme problem. However if you suffer a head injury, the damaged brain cells will dump zinc straight away into the blood so that the neurons take up glutamate which then become neuro toxic leading to cell death. For example, if you take vitamin D3 supps, it needs a zinc finger, so taking VitD3 with zinc, is useful other wise you could be wasting your time taking VitD3 if there is simply not enough zinc in the body, which can explain why some people dont respond to vit D3 supps. If the zinc status is low, there are so many vitamins and minerals that are just not worth doing. But mega dosing so many vitamins and minerals can create a zinc deficiency, like mega dosing vit A or D, or even nicotinic acid (b3) to compound things. Its not been unheard of taking a few hundred mg's a day, with documented therapeutic doses at 2grams a day! There is also disputes over whether an increased zinc intake even causes copper deficiency's. Studies are mixed, so typical medical caution is order of the day with regard to high doses of zinc, but that caution can contribute to medical conditions. The digestive system has no restriction on the uptake of zinc, unlike iron which uses hepcidin, but things like fibre, phytates, tannins, found in vegetables, will all bind to zinc in the gut very easily reducing its effectiveness, and then there is calcium, iron which is known to compete, with phosphate also looking like a similar competitor of zinc. B6 is recommended for any high intakes of minerals, it can be used to reduce the incidence of sideroblastic anemia and peripheral neuropathy amongst many things. The Nicotinic Acid form of B3 works with every enzyme in the body via Nicotinamide Adenine Dinucleotide (NAD) and Adenosine triphosphate (ATP). But as there is no reliable way to measure zinc status, things like an enlarged spleen (splenomegaly), cancer, diabetes, and numerous more disease states and illness could indicate an inadequate zinc status. Put another way, Zinc deficiency is found in so many illnesses including depression. > > weren't able to properly diagnose until they did a biopsy on his brain. Did they measure the surrounding tissue around the brain and bone mineral density, to check if the blood brain barrier was intact, and immune response optimal? If its any consolation, fungi can be sniffed as a smell and end up in the sinuses where they can contribute to mental health issues, but these only show up in autopsy's, and biopsy's! When zinc acetate at 75mg was used to shorten the common cold, its typically portrayed that it shortened the cold duration by a couple of days and its not really worth taking. When looking at the studies, the common cold had a typical 8.3day duration but with a total 75mg of zinc acetate spread over a day, reduced it to a 4.5day duration. Take into account the time it takes for the immune cells to respond, with or with out supplement, and that zinc duration could be reduced to under 4 days, even fewer days if there was adequate zinc status before infection, making it much more significant and effective than its currently portrayed! So, should we be re evaluating our zinc intake to see improvements in health, to avoid situations like this?

andai 3y ago

How are brain infections of other types normally diagnosed?

haldujai 3y ago
It depends on what type of infection we are worried about and what structures are involved but generally an MRI and a lumbar puncture for cerebrospinal fluid analysis to start. If there's an abscess a neurosurgeon can stick a needle/drain in it. Usually a combination of clinical and MRI findings is enough for infectious diseases and neurology specialists to figure it out and start empiric treatment for something/a few somethings if the CSF doesn't give you the answer. Rarely, at least at my institution, you could do a biopsy but you don't really want to be chopping up the brain if you can avoid it.
onemoresoop 3y ago
And are there any particular worrying symptoms for this type of brain fungal infections?
- Zelphyr 3y ago
  I can't speak to what's common but, with my dad it was he was increasingly confused, constantly tired and sleeping all the time, and progressive weight loss. He was down to 100lbs when they admitted him.