Trematodes and Cestodes Flashcards
What are the four major biomedically relevant groups of parasite?
Give an example for each
1. Platyhelminths - Monogeneans, Trematodes, Cestodes
2. Nematodes- Roundworms, pinworms, filarial worms
3. Arthropods- Crustacea, ticks, mites, insects
4. Protists- Amoebae, flagellates, apicomplexans
1 and 2 are also helminths
What are the classes under the Phylum Platyhelminth group and provide examples for each one?
Helminth is another meaning for worm
- Turbellarians are not a single phylum (they are a great model for regeneration)
- Mono and di is the number of posts in their life cycle
Tell me some general facts/ characteristics about Phylum Nematoda
- Planeria- free living many hunters
- Platy- flat, sheet like, broad- playpus
- Monogenetic – one stage in reproductive cycle etc
What are the common structures of platyhelminths?
- Bilaterian, (bilateral symmetry) invertebrates- perfect symmetry
- Flattened dorsoventrally“flat worms”
- Unsegmented- means hox genes behave differently to other organisms
- Triploblastic (has three germ layers: ecto- meso- endo)
- Acoelomates (having no internal body cavity)
- Lack circulatory and respiratory organs, hence flattened shapes
- The digestive system (where present) incomplete has a single opening
- Most are hermaphrodites (not Schistosomal flukes); internal fertilization
- Excretory system with protonephridia (flame cells)
Tell me the features/ characteristics of the Monogenea (monogenic fluke)
- Has a single reproductive stage
- All parasite’s, dont cause disease in high amounts
- Cause problems in fish
- Ectoparasitic flatworms mainly of fish (1000s of species)- Gills /Skin
- A few infect frogs (bladder) and turtles
- Have a head region that contains concentrated sense organs and nervous tissue “brain”.
- Generally, hermaphroditic - oviparous (a few are viviparous)
- Monogenea attach to hosts using hooks, clamps, and variety of other specialized structures. (Have weak suckers)
- Luke – from Germanic (flak) for a flat fish
- Picture shows viviparous version
Simple single host cycle- IE monogenetic fluke
- Produce an egg when reproduce
- Hatches and produces the intermediate (Miracidium)
- This is short living unless breeds
- Attaches to host via skin
Tell me about Gyrodactylus salaris (viviiperous)
- Releases digestive enzymes onto Scales and digests skin
- By digesting the skin it leaves the host open to other Bacterial and fungal infections
- 0.5mm long
- Organism cannot survive in salt water so is geographically restrained
What can freshwater fish destroy?
Whole populations salmonids- notifiable
Name a monogenetic fluke which shows complete monogamy, tell me where it is found and some information about it and its reproduction
One species shows complete monogamy; Diplozoon paradoxum: found in Gills of freshwater fish
External reproductive organisms allow the two organisms to fuse together
In this form they survive for several years
Fusion leads to maturation of internal system
A diporpa juvenile can live for several months, but it cannot develop further until encountering another diporpa; if not, dies.
When one diporpa finds another, each attaches its sucker to the dorsal papilla of the other.
The two worms fuse completely, with no trace of separating partitions. This stimulates maturation, Gonads appear; the male genital duct of one terminates near the female genital duct of the other, permitting cross-fertilization- can apparently live in this state for several years.
Name a monogenetic fluke which is the only known parasite to mammals
Only one know to parasitise a mammal; Oculotrema hippopotami
Found in the hippo eye
Only mammalian monogenetic fluke
How many stages of reproduction does the Trematode- digenetic fluke have?
2 stages of reproduction
Tell me some of the general features/ characteristics of the trematodes
- All parasitic
- Two suckers, one ventral and one oral.
- Adults common related to the digestive tract of the host, but some spp. occur in organ systems of all classes of vertebrates.
- Closer genetically to Cestodes- tapeworms (rather than Monogenea- which they look like!!)
- Around 20,000 species described
- Oral sucker around mouth and ventral sucker
- GI tract with one entry
- Excretory tubules, some species have a bladder like structure, hermaphrodite, fertilisation internally so there is a uterus, glands for reproduction such as seminal vesicle
- Excretory system releases via bladder to excretory pore
Tell me about the syncytial tegument for tapeworms
Surface- damaging to tissues and antigenic
Single syncytial cell which covers whole of the surface, this can release toxins
Has keratinised spines which allows organism to move through tissue, can cause damage to the tissues
What are the groups that the trematodes are divided into?
Tissue flukes
Blood flukes
Give me some examples of some tissue flukes
E.g., Fasciola hepatica- Liver fluke
Fasciolopsis buski - Intestinal fluke
Paragonimus Westermani- Lung fluke
(poster/talk)
Clonorchis sinensis, - Chinese Liver Fluke
Dicrocoelium dendriticum- (poster/ talk)
Tell me about blood flukes
Blood flukes – defined sexes
Eggs released by release of chemicals form fluke compromising the endothelial cell interaction with each other- and the epithelial integrity – may be disease causing
Tell me the tissue fluke’s basic cycle
- Primary host is typically bovine
- Sexual reproduces and releases large number of eggs (thousands per day), this allows animals to live for years
- Eggs have to go into a damp or wet environment
- Here the eggs will then embryonate and hatch producing miracidium (these are none feeding, no GI tract, have a sucker for feeding, photoactive, ciliated)
- Move to areas where they expect to find their secondary host (specific areas)
- Looking for snail
- Enter Mollusc, attach across tissues epithelium
- Shed outer ciliated surface
- Form sporocyst (germinal cells, stem cells around surface). These can either reproduce asexually or giver certain triggers (life cycle changes and warmth) internally can produce a redia asexually
- The redia can reproduce themseleves
- Radia can form cercaria
- Which goes out to environment and looks for a place to form a cyst (loses tail and forms cyst like structure)
- Attaches to green matter like leaves
- Stays there for long periods of time
- Once ingested, cyst is released, attaches to wall of intestine, or migrates to tissues of host
- Instead of forming cyst directly may look for tertiary host and exist there instead. In this case the organism is eaten by a carnivore
What is the weak point in the tissue flukes basic cycle and why?
Miracidia the weak point in the life cycle
non feeding (no gut), short lived and are in water so easily washed away- but can swim
How do Miracidia find their secondary host?
- Show geotactic, chemotactic, phototactic responses (eye spots) so will swim to position in water were host likely
- Then show swimming in that region ie cover a wide area in a narrow plane
- responds to chemical cues from host snail (many species can recognise specific snail types)
- once contacts snail (usually foot), a sensory apical papilla facilitates attachment to the snail surface: oral sucker is used to hold, and penetration is possibly achieved by release of proteases from glands and mechanical movement.
These are the stages for their “swimming”
How does the tissue flukes Miracidium enter their secondary host? What is this often and how is it achieved?
On entry the miracidium loses its cilia and forms a sporocyst
- germinal sacs containing stem cells, these form more sporocysts and redia
- Redia- have also stem cells and form more redia, but some of these differentiate to cercaria with suckers, mouth and GI tract
Many 100s of cercaria are formed per day
geotactic and phototactic – different species use different Lymnaea mollusc types and will move in the water table so in likely environment
The structure of the Cercaria (found in sporocysts escaping from a Lymnean snail)
A cercaria (plural cercariae) is the larval form of the trematode class of parasites.
GI tract: no reproductive organs here
The life cycle of the Fasciola Hepatica (2M humans infected worldwide)
- Many other flukes have similar life cycle- e.g., Fasciolopsis buski, endemic in Asia wherever pigs kept and fed on freshwater plants
- Lymnaea
- Fluke can live yrs – some to +20 yrs in host
- Clostridea
- Clostridium novyi- black disease
- Cyst goes into duodenum –> wall of duodenum –> migrates through abdomen –> liver –> cycle starts again
What can Fascioliasics affect?
Humans (Fasciola hepatica and Fasciola gigantica)
What happens in the invasive or acute phase of Fascioliasics?
Fluke migration from gut to bile ducts
Can last a number of weeks
With Fascioliasics, the mechanical destruction of the gut, hepatic tissue and the peritoneum by migrating juvenile flukes can cause what and what are some of the symptoms?
(all during the invasive or acute phase)
Can cause localised and or general toxic and allergic reactions
the symptoms include:
- fever
- abdominal pain
- Gastointestinal disturbances
- Hepatomegaly
- Ascites
- Jaundice
How long does the Latent phase of Fascioliasics last?
This phase can last for months or years and may not always progress
(fibrotic material forms)
How long can the chronic or obstructive phase of Fascioliasics last?
Months or years after the initial infection
Tell me what happens during the chronic or obstructuve phase of Fascioliasics
What does this result in?
Adult flukes in the bile ducts cause mechanical obstruction, due to chronic inflammation (cholecystitis) and fibrosis, hyperplasia of the epithelium.
Results in - Biliary colic, Fatty food intolerance, Jaundice, Cholangiocarcinoma
Are flukes are carcinogen?
Yes
This means that they can cause cancer e.g., liver cancer
other flukes modify the lifecycle by having extra intermediate hosts- this increases the liklihood of meeting primary host. Give an example of a fluke which does this
Tell me its life cycle
Paragonimus Westermani
Exists in duodenum –> abdomen –> instead of going to liver it migrates into the lung bronchiole –> mates and produces eggs here –> eggs are coughed up –> can be swallowed and that would go through gut and then excreted
Can cause lung damage
Infection is long lived
Causes snails to become non-reproductive and get larger
Tell me about the trematode Paragonimus Westermani
22 million people -Africa, Asia, South, and Central America. (Where raw seafood popular)
Humans infected eating raw crustaceans eg crayfish
In Asia ~80 % freshwater crabs infected with lung fluke.
Acute and chronic disease
signs like TB
Lung fluke, primary host crustacean eating mammals (including man)
The flukes can also enter other organs and tissues, such as the brain and striated muscles,
but completion of the life cycles fails.
Infections may persist for 20 years in humans
How can such a complex lifecycle of the flukes continue?
- Adult fluke- mostly hermaphroditic and can self-fertilise or show mating behaviour (production – variation trade-off)- long lived (yrs) and can have more than one final host species
- Very fecund eg - F hepatica producing many 1000s eggs per day
- Eggs can be hardy in cold dry conditions
- Miracidia have specific homing behaviours (as do cerceria)
- Secondary and Primary hosts often at high numbers and in proximity
- Many species can act as Primary Host (host where sexual reproduction occurs)
- Very rapid reproduction of snail hosts (snail can hibernate too)
- Asexual reproduction in snail host – snails can form ~1000 cercaria per day
- Cerceria- swim either to encyst at suitable places for secondary host exposure (On plants high in water column) or attracted to tertiary host or where its likely to be light, gravity, temperature, and chemical cues
- Metacercarial cysts hardy, (can survive a year or more), survive repeat freezing and can live years when encysted in tissues. In some tertiary hosts parasites may alter host behaviour to increase likelihood of transfer to primary host
What does the compound Triclabendazole bind to?
What is it used in?
Binds to tubulin and stops their polymerisation
This can be used to inhibit certain stages of the Fasciola hepatica life cycle
Whats the structure of a Benzimidazole?
Whats the mechanism of action that the Triclabendazole will inhibit?
Why is resistance common in triclabendazoles?
What are the types of resistance?
Higher affinity for beta tubulin
Bind to beta tubulin monomers and prevent them polymerising
Resistance to this agents are common; mutation in the tubulin which reduces the affinity, pumps which remove agents of this class from the cell so the conc. in the cell reduces (lowered uptake and reduced secretion), the cells metabolise agent into non-active form (generally by adding an extra oxygen)
Knowledge so far…
- Classes of fluke
- Examples of major parasitic trematodes in UK and world
- Intermediate stages and strategies used to continue the lifecycle
- Some forms of disease induced and how pathology caused
- Examples of treatment and control
Whats the structure of the Platyhelminths?
What are the main roles of the segments?
Platyhelminth, so is a flat worm
Scolex at the top end (attachment part), neck with stem cells in the scolex which are used to form the segments
Immature proglottids; no functioning reproductive organs in this section
Mature proglottid: Reproduction in the other segments of the proglottids. This occurs in a phased manner (testis develop first, the degrade before the ovaries form)
Gravid proglottids; contain fertilised eggs
All of the segments are known as the strobila
Whats a scolex?
The anterior end of a tapeworm, bearing suckers and hooks for attachment
Tell me about the scolex
- What many species have
- The main nerve centre
- Its body plan
- Genes
Many species have bothrina, or “sucking grooves” other species have hooks, spines, tentacles, and suckers that aid attachment
The main nerve centre is a pair or cerebral ganglion in the scolex (smaller nerves supply the body)
The muscles, nerves and tegument are continuous and run down the whole animals so there is not true segmentation as in insects or vertebrates
Has a series of hooks called the Rostellum (these suckers can be round and this is known as the acetabula)
Strong attachment given can be meters long
Do have some hox genes – scolex definition but many homeobox gene families missing when compared to C elegans or Dros.
Reproductive structure: Taenia-a hermaphrodite organism
Tell me about its sensory function
Excretory canal
After fertilisation the eggs are stored…
Sperm when released moves down and then used to fertilise other proglottids when ovaries start to produce mature eggs
Responds to touch and chemoreceptor at the pore
The structure of the reproductive tract is very variable but what are most cestodes?
Hermaphroditic
Tell me about gonad maturation in the cestodes and what this means about its fertilisation
The gonads mature at different stages- so self (same stroblae) and cross fertilisation (different animal) may occur but fertilisation from the same proglottid is unlikely
Some species lack a vagina and traumatic insemination occurs
Don’t want to self-fertilise if they don’t have to (hence why mature at different stages)
Unlikely for same animal (not same proglottid) with mature sperm and egg to reproduce
Fertilisation from same proglottid is unlikely as they mature at different rates
??? Testis develops first and then degenerates as ovaries mature
In Cestodes, as the proglottid ages after fertilisation, what happens to the gonads?
They go through atrophy and the uterus fills with eggs
These may have a shell
What are the different ways in which eggs can be released from the cestodes
From the intact attachment proglottid
After detachment the proglottid degenerates
The proglottid is motile is defecates and then migrates from the faeces shedding eggs)
What is Dipylidium caninum?
- Dog tape worm – cats and dogs (flea as second host)
- Humans can be infected but rare though underreported – 10s cases per yr– kids eat fleas
What is a tape worms basic cycle?
Embryonated eggs have hooks, and these can survive long periods
Released
Ingested via secondary host
Hatches and hooks are released, attach to gut wall, release enzyme (some in vesicles), break through gut wall and enter tissues
Can stay locally or enter circulatory system to other areas such as muscle
Typically, in muscle but can go elsewhere
Cysticercus can stay as it is or can show asexual reproduction and produce more of itself
Must then have death of the organism in order for the cycle to continue
What are Cycsticicoids and how long can they survive?
A cysticercoid is the larval stage of certain tapeworms, similar in appearance to a cysticercus, but having the scolex filling completely the enclosing cyst. In tapeworm infections, cysticercoids can be seen in free form as well as enclosed by cysts in biological tissues such as the intestinal mucosa.
They can survive many years, though may start to die after roughly 9 months
Whats the life cycle of
- *Taenia saginata**
- *T. solium**
Really human tapeworm as we are the primary host, and the cows and pigs are secondary hosts
- Up to 10 proglottids lost per day
- T saginata (will use other ruminants as secondary host) - Estimate ~400M people infected with adult tape worms!
- Humans are the only final host in this life cycle
- Common and generally only causes minor diseases
What is Cysticercosis infection caused by?
Larval cysts of the tapeworm Taenia solium
What does Cysticercosis infect?
How does one get the infection?
What animals does it affect?
- These infect brain, muscle, or other tissue, (most common cause of adult epilepsy worldwide) producing cysts
- Infection from swallowing eggs found in faeces of a person who has an intestinal tapeworm
- People do not get cysticercosis by eating undercooked pork.
- Pork tapeworm is common in Asia, Sub-Saharan Africa, and Latin America.
- Cysticercosis affects pigs and cows but rarely causes symptoms as don’t live long enough
- Can put man in place of the pig in the life cycle above
- Form cysts in the brain, or muscles, or other tissues
- Most common cause known genetically induced epilepsy in the world
- May have cyst within meat but they aren’t necessarily pathological
Taenia saginata and Taenia soleum
Taenia saginata
- US, roughly 25% of cattle sold are infected
- The total global human infection is estimated to be roughly 50 million
Taenia soleum
- About 25% of the planet has seroconverted
- In latin America, roughly 400,000 people have symptomatic disease (commonest in Central and South America
What are some controls that can be put into place in order to reduce the infection with cysticercosis?
- Adequate cooking (56˚c for 5 minutes) of cattle/ pig meat destroys cysticerci
- Freezing (-10˚c for 9 days) or long period of salting is lethal to cysticerci- drying is not
- Vaccines may become used in secondary hosts
- Meat inspection and proper disposal of human excreta are important control measures
- Estimated that 2% of PMs in south America show T solium cysts
- Salami – charcuterie needs to be done properly –
- Dried meats need curing
Whats the Diphyllobothrium latum life cycle?
What kind of parasite is Diphyllobothrium latum?
Who is at high risk from this parasite?
Diphyllobothrium latum- is a human (Other fish eating mammals) parasite with 3 or more intermediates- disease is minor GI, diarrohea, colic and Vit B12 def
–this parasite produces ~ 1,000,000 eggs per day, reaches 20 m long and lives >20 yrs
People at high risk consume raw fish. sushi and sashimi in Japan, carpaccio di persico in Italy, tartare maison in French-speaking populations, ceviche in Latin American cuisine and marinated herring in Scandinavia
Found in ~50% wild salmon
Up to 20 million humans are estimated to be infected worldwide
These mature in wet conditions, produce embryonated egg which hatches differently to before, like the flukes they can move
Lots of intermediate hosts
Eat uncooked, undercook or raw meat
Cestodes have evolved to be very efficient parasites and in doing so what have they removed?
Cestodes have evolved to be very efficient parasites and in doing so have removed gene groups they have lost their digestive tract, (lost specific Hox and Parahox genes) so have altered to absorb nutrients from the host across their tegument
What does cestodes have extra transporters for?
Have extra transporters for AAs, carbohydrates, short and long chain fatty acids, nucleosides. But have lost pathways to synthesise fatty acids, cholesterol, many amino acids lost the genes needed for peroxisomes
What genes do tapeworms also lack?
How do they adapt to this?
What can’t tapeworms make?
What dirves their development and growth?
Tapeworms also lack the ParaHox genes (Gsx, Pdx, Cdx) ancestrally involved in specification of a through-gut
Many Aas become essential Aas for tapeworms 16 are essential (semi essential) cf human 8/9
Can’t make nucleotides/ nucleosides
Tapeworms, like flukes, lack the ability to synthesise fatty acids and cholesterol de novo-m, they scavenge essential fats from the host using fatty acid transporters
Bile acids (remember sterol derivatives) drive development and growth
Even though they have lost genes, they have also gained some. For instance, types of AA transporters
Uses bioacids which produce cholesterol and hormones made by the host to tell the tapeworm that large amounts of nutrients are coming and to use them
Whats the treatment for Diphyllobothrium latum ?
Praziquantel and benzimidazole, corticosteroids
PZQ alters binds and activates voltage operated Ca2+ channels (non- binding to mammalian VOCC)
- Adults’ flatworms – paralysed and loose hold of gut wall
- Also used in cysticercosis, though how functions unknown (?Ca mediated changes ) –, does cause blebbing of cells
corticosteroids needed in cysticercosis as dying parasites in tissues cause a major immune response and inflammatory damage
… cysticercosis may require surgery (treatment could sometimes be worse than the cysts themseleves so sometimes it is more beneficial to choose surgery)
Main problem is the cycticeroid stage – adults are destroyed to prevent the cycle or for cosmetic reasons
Surgery…
Sold as Droncit in uk.
PZQ may act in other unknown ways
PRZ – also functions against trematodes (adult not intermediate forms) and nematodes
Cestodes have prolonged survival, what does this suggest?
Cestodes have prolonged survival— (some cysticerci sutvive over 50 yrs in the host, suggesting that they selectively produce components to moderate the host immune response)
The parasites (Echinococcus granulosis (EG) a sheep/ fox tapeworm –long lived as cysticercus)
What do these form, where is it expressed and whats its role?
These form EG-AgB a secreted antigen, highly expressed in cyst fluid that alters both innate and adaptive host immune responses.
1. Can inhibit neutrophil activation (innate)
- AgB impairs the Th1/Th2 balance towards a Th2 cells (Th2 is more inflammatory and damaging) (innate)
- lower inflammatory and non-clearing immune response
- PBMC stimulated with AgB produced IL-4, IL-13 and low IFN-γ and no IL-12 (both pro-inflammatory and Th1 inducers)
- (IL-12 drives differentiation of naive T cells into Th1 cells and stimulates the production of IFN-γ both highly proinflammatory) - Blocks IL5-R so stops path needed for strong Ab response and eosinophil activation
EG-AgB is highly antigenic (hence the name), how does it escape and prolong its activity?
EG-AgB is highly antigenic itself (hence the name) – to escape and prolong its activity the antigen encoded by seven different genes, each showing variation.
Expression regularly switches between the seven and so it escapes the immune response
EG – well studied as causes major pathology
peripheral blood mononuclear cell (PBMC)
Point out Th2 responses also less damaging to the host
What are some other evasion strategies for cestodes(?)?
Other evasion strategies
- Include the production and release of cysticercoid proteases and protease inhibitors
- Proteases destroying host proteins (e.g., Leukotriene A4 hydrolase protease destroys the leukotrienes needed for host immune response)
- and specific protease inhibitors to avoid protease digestion by the host macrophages and eosinophils
Are vaccines possible?
Vaccination of intermediate host blocking the cysticercoid stage
- Taenia solium vaccine pigs
- Echinococcus vaccine sheep and goats
- None of them are yet tried in humans
- 90%+ efficacy of those which work
- Not widely used due to financial reasons
… knowledge
- Examples of major parasitic Cestode in UK and world
- Intermediate stages and strategies used to continue to the lifecycle
- Some forms of disease induced and how pathology caused (mainly intermediate host)
- Example of treatment and control
Out of the following, which are the most genetically similar?
- Turbellarians
- Monogenea
- Trematodes
- Cestodes
Cestodes and Trematodes
Another variation of the Fasciola Hepatica life cycle is the life cycle of Fasciolopsis buski
Tell me the life cycle for this and how it differs
Found in gut of pig
Similar life cycle
Humans can be affected with this
Adult does migrate to tissues, it stays within bowel
Because not doing migration, it is much less damaging
What does Triclabendazole bind to?
Tubulin and stops their polymerisation
What is Triclabendazoles role in the Fasciola hepatica life cycle?
For the microtuule inhibitors that are used in the life cycles, give some examples of Benzimidazoles that have this role?
Albendazole
Mebendazole
Triclabendazole
What is the structure of the Benzimidazoles?
