Chapter 40: Fungal & Protist Diseases in Humans

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Welcome to the Deep Dive.

We're the place that takes dense research, particularly in fields like microbiology, and boils it down to what you really need to grasp.

And today we're tackling a really interesting group,

the eukaryotic human pathogens.

So we're talking fungi and protists.

Exactly.

These aren't your simpler bacteria or viruses.

These are complex cells with some pretty sophisticated ways of causing trouble, as our sources make clear.

Yeah.

And to really get a feel for it, you have to appreciate the sheer biochemical force of fungi.

Think about that opening story our sources mentioned, Mark Tatum.

Oh, right.

The mucormycosis case.

Horrifying.

He survived, but the fungus literally digested part of his face.

It's that digestive power.

That's the core of it.

Yeah.

Fungi are masters of breaking things down.

Which connects directly to that mushrooms of death idea, right?

The infinity burial project.

Exactly.

J.

Rimmelese project.

The suit is infused with special mushroom spores meant to speed up decomposition, maybe even neutralize toxins.

It raises some questions ecologically and for sure.

It does, but the science behind it really hammers home the point.

Fungi excel at making extracellular enzymes, enzymes released outside the cell.

To digest large molecules, whether it's wood or tissue.

Precisely.

They dissolve their food externally, then absorb the nutrients.

That capability sets a pretty high bar for virulence when they infect humans.

Okay.

So our mission today, let's categorize these pathogens, look at how they're transmitted, understand how they actually cause disease and, you know, how we fight back.

Sounds good.

Let's start with a fungi.

The diseases they cause are called mycosis.

We generally group them based on, well, how deep they go.

Right.

You got the surface stuff.

Superficial, cutaneous, subcutaneous.

Those are closer to the surface.

And then the really serious ones are systemic and opportunistic infections.

And I think you mentioned something crucial about those systemic ones.

They're dimorphic.

What's that about?

Ah, yes.

The YM shift.

This is absolutely key.

Yeast mold shift.

So out in the soil, maybe at cooler temperatures, these fungi grow as a mold, you know, filamentous branching.

Like what you'd see on old bread, that kind of structure?

Sort of, yes.

But when you inhale the spores and they hit your body temperature, 37 degrees Celsius, boom, they switch to what?

To a single -celled yeast Y form.

And that transformation, that YM shift is directly tied to their ability to cause disease deep inside the body and evade our immune system.

That's a clever trick.

Adapt your form to the environment.

Okay.

Let's jump into that first big transmission route.

Airborne fungi.

These are mainly soil fungi causing systemic disease, right?

Picked up just by breathing.

Exactly.

And geography plays a big role here.

Take blastomycosis.

Blastomyces dermatitis.

It's endemic, meaning it's constantly present in the Mississippi and Ohio River basins.

Damp soil.

So you breathe it in.

You inhale the spores, infection starts in the lungs, but the trouble is it often spreads.

Disseminates.

You see these characteristic skin ulcers and abscesses as it moves through the body.

Diagnosis often relies on seeing these thick walled yeast cells and samples.

Okay.

Then there's the one that makes the news out west,

coccidioidomycosis, valley fever.

Right, coccidioids.

Thrives in those southwestern U .S.

Mexican sort of semi -arid alkaline soils.

Think Arizona, parts of California.

And how does that one work?

Same inhalation route.

Yes, you inhale these tiny infectious bits called arthrokinidia when the soil gets kicked up.

But inside the lungs, it does something different.

Instead of just turning into yeast, it forms what were they called?

Spherules.

Exactly.

Big, thick walled spherules.

And they're packed full of spores.

When these spherules rupture inside your lung tissue, they release a whole new batch of infectious particles.

Hundreds of them.

It really ramps up the

can cause a significant chunk of pneumonia cases in those endemic areas.

Often mild, but can spread widely too.

And the third big one in this group,

histoplasmosis.

Also river basins like blasto, but with a bird connection.

Yeah.

Histoplasma capsulatum.

Very common where bird or bat droppings, guano build up.

Though interestingly, the birds and bats themselves aren't infected.

The guano just acts like fertilizer for the fungus.

So how does this one cause problems?

Does it also shift form?

It does the YM shift.

Yes.

But its other trick is different.

Histoplasma can actually grow intracellularly.

Inside our cells.

Which ones?

Inside our macrophages, the very immune cells that are supposed to engulf and destroy invaders.

It basically hides out and multiplies inside them.

Whoa.

So it uses our own defenses to travel around the body.

Pretty much.

That allows it to disseminate and it can cause lesions that look remarkably similar to tuberculosis, which can complicate diagnosis.

Incredible variations just within the soil fungi.

Okay.

Let's pivot completely now.

Moving away from airborne spores to, well, the global giants.

Protozoan diseases, often carried by insects,

arthropod vectors.

And the burden here is just immense malaria caused by plasmodium species.

Still arguably the most significant protozoan disease worldwide.

Hundreds of millions at risk, right?

Especially children in Africa.

The name itself, malaria.

Bad air.

Shows how long we misunderstood it.

Until labyrinth found the plasmodium parasite in patient blood in 1880.

And Ross linked it definitively to mosquitoes.

Female Anopheles mosquitoes, specifically.

Can you walk us through the life cycle briefly?

It's complicated, but where does the actual sickness part happen?

Okay, quickly.

Mosquito bites.

Inject sporozoites.

Stage one, they zip to the liver.

That's the exerathoracetic hiding stage.

They multiply like crazy in liver cells, forming schizons.

Then they burst out.

Right.

Releasing merozoites.

Stage two, these invade red blood cells RBCs.

This is the erythrocytic cycle.

Inside the RBCs, they multiply again.

And that's what causes the symptoms.

Yes.

The synchronized bursting of millions of infected RBCs releases parasites and toxins, causing those classic cycles of fever, chills the malarial paroxysms.

Plus, you get severe anemia from all the destroyed RBCs.

Some merozoites develop into gametocytes.

Which the mosquito picks up, starting the cycle again.

Exactly.

That's the sporegonic cycle, the sexual reproduction phase happening inside the mosquito gut.

Control has been tough.

DDT resistance, chloroquine resistance.

What's working now, besides things like bed nets?

Bed nets are crucial, as is combination drug therapy, ACTs.

But a big step forward is the RTSS vaccine.

It's a pre -erythrocytic vaccine.

Meaning it targets the parasite before it gets to the red blood cells?

Even before it gets properly established in the liver, it targets the sporozoites injected by the mosquito.

The idea is to stop the infection right at the very beginning.

Clever.

Also, isn't there that genetic link with sickle cell?

Ah, yes.

Hemoglobin as the sickle cell trait provides significant protection against severe plasmodium falciparum malaria.

A fascinating example of natural selection.

Okay, moving on.

Leishomoniasis.

Another insect vector, right?

Yes.

This one's spread by tiny female sandflies.

Reservoirs are often dogs and rodents.

The fly injects promastigotes when it bites.

Promastigotes.

Our macrophages try to eat them.

But just like histoplasma, the parasite survives inside.

It transforms into a mastigotes and multiplies within the macrophage.

And the disease, what forms does it take?

Three main forms.

Cutaneous causing skin ulcers, mucocutaneous, really destructive, damages the nose, mouth, throat,

and visceral, or kala azar, black fever.

That attacks the liver and spleen, and it's often fatal if not treated.

And then there's trypanosomiasis, two major diseases here.

Correct.

African sleeping sickness caused by trypanosoma bruchii, carried by the tsetse fly.

Starts with fever, headaches, then progresses to the neurological phase, lethargy, confusion, coma.

And the other one,

chagas.

Chagas disease caused by trypanosoma cruzi, found with the Americas.

The vector is the triatomine bug, or kissing bug.

Kissing bug.

Why that name?

Because it often bites near the mouth while people sleep.

But transmission isn't directly from the bite.

The bug defecates as it feeds.

Oh, lovely.

And the parasites are in the feces.

When the person scratches the itchy bite, they rub the feces into the wound, or maybe their eye.

And chagas causes long -term problems.

Yeah, it can become chronic, leading to severe heart damage and gastrointestinal issues year, even decades later.

Now, you mentioned these protozoa are really good at dodging our immune system.

Why is making a vaccine, say, for African sleeping sickness so difficult?

It comes down to something called antigenic variation.

These trypanosomes can change their coats, essentially.

Change their surface proteins.

Constantly.

They have a huge repertoire of genes for surface glycoproteins.

They express one type.

Our immune system starts making antibodies against it.

And then the parasite population switches to expressing a completely different surface protein.

So they're always one step ahead.

Our antibodies become useless almost as soon as they're made.

Pretty much.

Yeah.

It's a major challenge for vaccine development.

Makes sense.

Okay, let's shift gears again.

Route three.

Direct contact and food or waterborne diseases.

Starting with the fungi we get from touch or surfaces.

Right, the mycosis of the surface.

Superficial mycosis are really minor, like peadress little nodules on your hair shafts.

But more common are the cutaneous mycosis.

Ringworm and athlete's foot territory.

Exactly.

Caused by fungi called dermatophytes.

We call the infections tinius.

Tinius capitis is scalp ringworm, common in kids.

Tinius corpus is ringworm on the body.

Kekipetus is athlete's foot.

What's the key thing to know about these?

They're persistence.

They live on keratin, the protein in our skin, hair, nails.

And the fungi can stay alive for a long, long time and shed skin cells, what we call discomated cells.

So cleaning the environment, showers, locker rooms, towels is just as important as treating the person.

Absolutely crucial.

Otherwise, reinfection is almost guaranteed.

And if these fungi get under the skin?

That's subcutaneous mycosis.

A good example is spartricosis, often called Rose Gardener's disease.

Why that?

Because you typically get it from a puncture wound, a thorn prick, a splinter that's contaminated with the fungus, sporothric skinky.

It implants the fungus deep into the subcutaneous tissue.

So it's an occupational hazard for gardeners, florists, people working with soil implants.

Now, direct contact protozoa.

You mentioned trichomoniasis.

Yes, trichomonas vaginalis, a sexually transmitted infection caused by a flagellated process.

How does it present?

It's often quite different in men and women.

Women frequently get a really noticeable,

profuse, often foul smelling vaginal discharge.

Sometimes doctors see what's called a strawberry cervix because of tiny hemorrhages.

Men are frequently asymptomatic, partially because prostatic secretions actually have some natural activity against the organism.

So they can carry it and transmit it without knowing.

Right.

Okay.

Moving to the things we ingest, food and waterborne protozoa.

Let's start with amoebiasis.

Intamoeba histolytica.

Right.

You get it by ingesting infectious cysts, usually from contaminated water or food.

And what happens then?

In the gut, the cysts release the active form, the trophozoites.

These guys invade the wall of a large intestine and they have this potent weapon, a protease.

An enzyme that digests protein.

Exactly.

It degrades the extracellular matrix, holding our intestinal cells together, basically chews through the tissue.

This can cause severe bloody diarrhea, amoebic dysentery, or if they escape the gut, they can travel to the liver and form abscesses.

Nasty stuff.

But you also mentioned some waterborne amoebae that aren't ingested, causing even scarier diseases.

Yeah.

These are the real nightmare fuel ones.

Naegleria falleri.

The brain eating amoeba.

That's the one.

It causes PM primary amoebic meningoencephalitis.

You don't swallow it.

You get water forced up your nose, swimming in warm lakes, diving, even using contaminated water in a neti pot.

Wait, neti pots?

If you don't use sterile water, yes.

The amoeba travels along the olfactory nerves, through the bone, directly into the brain.

It's incredibly rare, but almost always fatal.

Terrifying.

And the other one, acanthamoeba.

Acanthamoeba is more associated with eye infections specifically, amoebic keratitis,

severe inflammation of the cornea.

How do you get that?

Often linked to improper contact lens hygiene, using tap water to rinse lenses or homemade saline solutions.

The amoeba gets trapped between the lens and the eye.

Okay, a good reminder to follow contact lens instructions carefully.

Now, two other big waterborne protozoa, cryptosporidium and giardia.

Right.

Cryptosporidium is a major public health concern.

Its infectious stage, the uticist, is tiny, hard to filter out of water supplies, and incredibly resistant to chlorine disinfection.

So standard water treatment might not kill it?

Not always reliably, no.

And the infectious dose is really low, maybe just 10 to 100 oocysts.

This led to huge outbreaks, like the one in Milwaukee in 1993.

Wow.

And giardiasis.

Giardia intestinalis, probably the most common intestinal parasitic disease diagnosed in the U .S.

It's another flagellated protist.

Why does this cause problems?

It has these unique sucking discs on its underside.

It uses them to latch onto the lining of your small intestine.

Like little suction cups.

Exactly.

By covering the intestinal lining, it interferes with nutrient absorption.

This leads to the characteristic symptoms.

Severe diarrhea, cramps, bloating,

and, well, famously,

lots and lots of gas.

Voluminous flash lines.

Definitely a memorable symptom.

Okay, last major category, opportunistic diseases.

These are the ones that take advantage of a weakened host, right?

Precisely.

We're talking about pathogens that might be harmless or easily controlled in a healthy person.

But in someone immunocompromised, maybe due to HIV, cancer therapy, organ transplant drugs, even long -term antibiotic use.

The defenses are down, and these guys see their chance.

Exactly.

The ecosystem is disrupted, or the immune surveillance is weak, and they can cause severe, often life -threatening disease.

Let's start with a really common one, candidiasis.

Caused by Candida species, most often Candida albicans.

And here's the thing.

Candida is often part of our normal microbiota.

It lives in us harmlessly.

Where?

Yeah.

Common in the GI tract, mouth, vagina.

It's usually kept in check by competing bacteria in our immune system.

So what lets it overgrow?

A classic trigger is broad -spectrum antibiotics.

They wipe out the bacteria that normally compete with Candida, giving it room to multiply unchecked.

And then it becomes pathogenic.

How?

See, albicans has a specific virulence factor.

It secretes a peptide toxin called Candida lysin.

Candida lysin.

What does that do?

You mentioned it permeabilizes membranes.

That's the key.

It literally punches holes in our host cell membranes,

disrupts them, damages them, allows the fungus to invade tissues more effectively.

Leading to?

Things like oral thrush, common in newborns or denture wearers, vaginal yeast infections linked to antibiotics, pregnancy, birth control pills, but also really severe systemic infections, candidemia if it gets into the bloodstream, especially in hospitalized patients.

Mortality can be quite high, close to 50 % for systemic cases.

Grim.

Okay, next opportunist, aspergillosis.

Aspergillus species.

These molds are absolutely everywhere.

Soil, dust, decaying plants, building materials, air conditioning systems.

You cannot avoid inhaling aspergillus spores.

So why aren't we all sick?

Healthy immune systems clear them out constantly, but in someone with weakened immunity, especially lung issues or low neutrophil counts.

Problems start.

Like what?

It can cause allergic reactions, chronic lung disease, allergic bronchopulmonary aspergillosis, or it can form these dense masses of fungal hyphae in lung cavities called aspergillomas or fungus balls.

Fungus balls.

Yikes.

And in severely immunocompromised patients, it can cause invasive aspergillosis, spreading rapidly through the lungs and bloodstream, very high mortality rate.

And the last major one, cryptocircosis.

Cryptococcus neoformans, primarily.

This one has a well -known association with soil contaminated by pigeon droppings.

Pigeons, again, like histoplasma and guano.

Similar environmental link, yeah.

Again, healthy people usually inhale the spores and clear the infection without even knowing it.

Maybe a mild lung infection.

But in the immunocompromised.

Especially individuals with advanced HIV AIDS, before effective antiretroviral therapy became widespread.

Cryptococcus has a strong tendency to spread to the central nervous system.

Causing meningitis.

Exactly.

Cryptococcal meningitis.

It was, and still is in many parts of the world, a leading cause of death in AIDS patients.

It has a characteristic thick polysaccharide capsule that helps it evade immune defenses.

We've really covered a huge range today.

From fungi that literally change shape inside us.

Like the YM shift.

To protozoa that have these incredibly complex life cycles involving multiple hosts.

Like malaria.

And others that just stick to us with suction cups or punch holes in our cells.

Like giardia or candida with its candida lysin.

The synthesis here, I think, is that while these are all eukaryotes, sharing some basic biology,

their strategies for causing disease are incredibly diverse and specialized.

You really have to appreciate the specific mechanism for each one.

The YM shift, the vector cycles, the toxins, the physical attachments,

the immune evasion like antigenic variation.

These aren't just infections.

They're evolutionary masterpieces of parasitism.

Well put.

And it underscores that huge global health disparity.

Diseases like malaria, chagas, leishmaniasis.

They disproportionately affect the world's poorest populations.

Absolutely.

So as we wrap up this deep dive, here's something to ponder, building on what we discussed.

We talked about how trypanosomes use antigenic variation, constantly changing their surface proteins to evade our antibodies.

Right, staying one step ahead.

Okay, so think about how long it takes our immune system to mount a primary response, to recognize a new antigen, and produce specific antibodies in large amounts.

Usually days, maybe a couple of weeks, right?

Yeah, that's the general timeframe.

So the question is,

how fast do those trypanosomes need to switch their surface coats to consistently beat that immune response?

What does that tell you about the speed and efficiency of their genetic switching mechanisms compared to our adaptive immunity?

Something to think about.