Parasitology 04 Introduction To Trematodes (Flatworms)

Front 1

What are trematodes?

Back 1

Non-segmented flat worms?

Front 2

What are the important species of trematodes?

Back 2

Schistosoma mansoni
Schistosoma haematobium
Schistosoma japonicum
Schistosoma mekongi

Front 3

What areas are endemic for S. mansoni?

Back 3

Sub-saharian Africa
East South America

Front 4

What areas are endemic for S. japonicum?

Back 4

East asia, mainly China

Front 5

What areas are endemic for S. haematobium?

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Throughout Africa and some spots throughout the Arabian peninsula

Front 6

What areas are endemic for S. mekongi?

Back 6

Southeast Asia

Front 7

What is the intermediate host for schistome species?

Back 7

Aquatic freshwater snails

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Back 8

Adult male and female Schistosoma mansoni

Front 9

Describe adult male and female Schistosoma mansoni

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-Several mm long
-The male encompasses the female
-They live as a pair of worms in the mesenteric venules of the small intestine.
-Lives in blood vessel
-Can live up to 30 years

Front 10

Describe the immune response to Schistosoma

Back 10

-They are not harmed by the immune system for long periods of time
-Schistasome is capable of including onto its tegument your serum proteins. It does so at an early stage in its development, so your immune system cant recognize it as being any different.
-It also has a surface molecule similar to beta-2-microglobulin, a macrophage receptor factor, which forces macrophage to recognize the worm as self

Front 11

Describe how Schistosoma mansoni acquires nutrients

Back 11

-Absorbs some nutrients through rough surfaces
-Has a blind gut track
-It sucks in blood through anterior sucker, digests it, and then regurgitates the digested products that are not absorbed.

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Schistosoma mansoni in situ in the venules

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Cross section of a pair of adult schistosomes in situ in a mesenteric venule. The worms are in the venule, not in the tissue.

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Embryonated egg of Schistosoma mansoni (adult female requires TNF for maxium egg production)

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Embryonated egg of Schistosoma japonicum

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Embryonated egg of Schistosoma mekongi

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Embryonated egg of Schistosoma haematobium

Front 18

How does Schistosoma mansoni enter the body?

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-Penetrates unbroken skin, called acercariae
-Acercariae is the free swimming, free living stage
-It swims until it encounters the chemical signature of skin that you shed onto the surface of the water
-Sticks to the skin through little suckers
-Tail breaks off
-The parasite then secretes metalloproteases
-Enters through the hair shaft
-Once in the skin it sits there for a while and undergoes developmental changes
-Renters the circulation

Front 19

What does Schistosoma mansoni do after it enters the circulation?

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-Lungs are first encountered
-Finds its way to the liver
-Then follows different signals given by different organ systems
-Schistosomes mate in the liver
-Male-female pair find each other by secreting pheromones
-They go against the flow of blood into the mesenteric venule
-The worms access the food before it reaches the liver
-Eventually the females start to pass eggs

Front 20

When do Schistosoma disguise themselves as self?

Back 20

When they go to the lungs

Front 21

How long does it take adult Schistosoma mansoni to mature?

Back 21

2-4 months

Front 22

What occurs when female Schistosoma mansoni start to pass eggs?

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-Females have a pore between the anterior and posterior suckers that connects to the reproductive tract
-Female pushes anterior and posterior suckers against the endothelial cells
-Eggs released from pores
-Eggs produce metalloproteases
-Eggs burrow through endothelial cells, muscular layer of venule, and erode to the lumen of the small intestine
-Bleeding and loss of serum proteins occurs
-Peristalsis carries eggs to large intestine
-Excreted in feces
-Must be excreted into freshwater to complete the life cycle

Front 23

What are the reservoir hosts of Schistosoma?

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Many animals including water buffalo

Front 24

What happens when Schistosoma eggs are released into freshwater?

Back 24

-Eggs hatch
-Free swimming stage is released
-Miracidium uses chemoreceptors to detect certain species of snails
-Each species of Schistosoma evolved with a particular species of snail
-Once in the snail the worm can reproduce and make 50,000 parasites
-When the sun shines the snail sheds cercaria
-Cercaria go to the surface and look for host
-If they dont find one in 8 hours they die

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Biomphilaria glabrata, a common intermediate snail host for Schistosoma mansoni

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Miracidium of Schistosoma mansoni caught in the act of hatching

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Miracidium of Schistosoma mansoni

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SEM of a cercaria of Schistosoma mansoni, the infective stage for humans

Front 29

What are the differences between the Schistosoma mancosi and japonicum life cycles?

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-When japonicum is sending eggs to the small intestine, it occasionally moves the sucker
-This releases eggs into the blood
-Eggs wash back into liver
-Eggs get stuck in presinusoidal capillaries
-Eggs still alive and secreting lytic enzymes
-Macrophages accumulate
-Kill parasite, but plug up presinusoidal capillary
-Japonicum egg is slightly smaller and lacks spine, so it can pass through liver and end up in the brain
-Some adult worms end up in places other than mesenteric venules, such as venules surrounding nervous system or in the spinal column

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Oncomelania nosophora, a common snail intermediate host for Schistosoma japonicum in China

Front 31

What causes the majority of the pathological damage from Schistosomes?

Back 31

The eggs wash back into the liver

Front 32

Describe the pathogenesis of Schistosomes

Back 32

1. Miracidium inside egg in small intestine releases proteases, dissolves tissues, induces bleeding and diarrhea

2. Eggs (50% of those produces) wash back into liver, lodge in pre-sinusoidal capillaries, eventually blocking flow of blood

3. Blockage of portal circulation results in portal hypertension

4. Portal hypertension leads to induction of embryonic circulatory paths, eggs then bypass liver. Toxic brain syndrome ensues

5. Adults avoid immune detection by
a. camouflage strategy - incorportating host serum proteins on tegumental surface
b. synthesizing beta-2 microglobulin like molecule on tegumental surface

Front 33

What occurs when Schistosome eggs block most of the presinusoidal capillaries?

Back 33

Triggers the blood supply to figure out a way around the liver.

You develop some very fragile veins that can carry blood around the liver and place it into the heart. If this occurs the eggs start to accumulate in the capillaries of the lungs. As that occurs more and more pressure is placed on the right side of the heart and you develop cor-pulmonale. You can die from heart failure as a result. You can also get esophageal varices due to the portal hypertension. When you look at the reason why the patient is sick you can trace it back to these common pathological consequences. While this is occuring your liver parenchymal cells are fine. Bypassing the liver can lead to toxic brain syndrome because you are bypassing the liver's detoxifying effect.

Front 34

What is the clinical disease associated with Schistosomes?

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Acute Phase
1. Katayama fever
2. Paralysis (when Japonicum locates in the spinal column)
3. CNS involvement

Chronic Phase
1. GI bleeding and diarrhea
2. Portal hypertension due to blockage of presinusoidal capilalries
3. Esophageal varices
4. Ascites
5. Rupture of varices, bleeding, death
6. Cor pulmonale, right sided heart failure, death
7. Toxic brain syndrome

Eggs don’t just wash into the liver, they wash into the spleen, so you get hepatosplenomegaly. When the spleen swells up with eggs and starts to exhibit dysfunctional behavior the platelet levels go down. As a result of that the moment that the esophageal varices bleed there is no mechanism for clotting

Front 35

Describe the relationship between granuloma formation and age of infection

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The older the infection the smaller the area of tissue involved in granuloma. There is some sort of immunomodulation that lowers the size of the granulomatous response.

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Schistosome egg in tissue of the small intestine. Note the intense granuloma

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Pipe stem fibrosis in liver due to heavy infection with Schistosoma mansoni. Note the normal liver next to the fibrotic vessels

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Granuloma in liver surrounding eggs of Schistosoma mansoni

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Granuloma surrounding an egg of Schistosoma mancosi in liver tissue

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How do you diagnose Schistosomiasis?

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1. Microscopic examination of feces, urine, rectal "snip" for eggs.

2. Capture ELISA for detecting circulating antigens (experimental)

3. Serological tests (e.g. ELISA): indirect measure of exposure, not active disease,

The ELISA test tell syou that the eggs are still in the tissue. Finding the antigen doesn’t tell you that the infection is ongoing at that moment. If you find eggs it is a live infection.

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Biopsy of rectal tissue revealing eggs of Schistosoma mansoni

Front 42

What is the drug of choice for Schistosomiasis? How does it work?

Back 42

Praziquantel

It interferes with Ca2+ ion channels, leading to disrupted tegument. This drug is more effective if the patient has already developed antibodies against tegumental antigens.

The worm uses this as a second messenger. This paralyzes worms and they are washed into the liver. It hits the presinusoidal capilaries, sticks, worms die, and there is a granulomatous response in the liver.

Front 43

What is special about the life cycle of Schistosoma haematobium?

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-This worm escapes the liver and goes to the venous plexus of the bladder.
-In order to get eggs into the bladder they have to do the same thing that the eggs do to get into the small intestine. -Eroding your way through the bladder is complicated. These worms contain in their eggs the stage that secrete metalloproteases.
-The insult to the bladder over 15-20 years can be significant. As your immune system begins to kick in and kill off the egdgs and they die and calcify you can get calcification of the dome of the bladder.
-This means that the bladder can no longer contract fully. It starts to back up.
-Urine backs up into the ureters until it gets to the kidneys. This can cause hydronephrosis. Because the urine doesn’t exit fully toxins associated with whatever you eat and whatever you drink can accumulate to a level that can induce squamous cell epitheliomas.

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Histological section of bladder with pseudopolyp due to chronic infection with Schistosoma haematobium

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Schistosoma haematobium eggs in bladder wall

Front 46

Describe the pathogenesis of Schistosoma haematobium

Back 46

Eggs lodge in bladder wall, induce cellular changes associated with granuloma formation

Front 47

Describe the clinical disease associated with Schistosoma haematobium

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1. Squamous cell epitheloma
2. Calcification of dome of bladder due to accumulation of dead eggs
3. Hydronephrosis

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Calcification of the dome of the bladder with Schistosoma haematobium

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Squamous cell epithelioma associated with Schistosoma haematobium

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Swimmers itch caused by bird Schistosomes.

It can't complete the life cycle in humans. The parasite cant distinguish people skin from bird skin. The worm penetrates the skin and is killed. The first time it is not a big deal. You go back and you get a rash. This is the hypersensitivity reaction that developed.

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Cercaria of Schistosoma mansoni in skin surrounded by eosinophils.

Even for the human parasites the immune system can adapt and begin to kill off the worms.

The TH2 protective mechanism is that eosinophils and specific IgE antibodies combine to kill the parasite

Front 52

What encourages transmission of Schistosomas?

Back 52

1. Dam building, irrigation projects
2. Reservoir hosts (primates, oxen)
3. Indiscriminate dispersal of feces and urine into the environment

Front 53

How do you prevent and control Schistosomas?

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1. Sanitary disposal of feces
2. Public health education
3. Snail control
4. Community-based drug programs
5. Vaccine development for reservoir hosts