Introduction to Platyhelminths and Schistosomes Flashcards
Name some parasitic worms
- Nematode
- Nematomorpha
- Pentastomes
- Annelids
- Nemertea
- Platyhelminths
- Acanthocephala
What type of worm is a Nematode and tell me about it
Nematodes – round worms
- Over half known species are parasitic – major human, veterinary and plant parasites
- Lots more on these during the module
What type of worm is a Nematomorpha and tell me about it
Nematomorpha – horsehair worms or gordian worms
All species parasitoids, largely of insects but also of crustacea – up to 2m long!
What type of worm is a Pentastome and tell me about it
Pentastomes – tongue worms
live in the upper respiratory tract of reptiles, birds, and mammals
Mentioned last week – seem, based on molecular sequence data, to be enigmatic crustaceans
What type of worm is a Annelids and tell me about it
Annelids – “ringed or segmented worms”.
But includes echiurids which appear to have secondarily lost segmentation – ie. evolved it and then lost it.
Polychaetes – some commensal, others parasitic – ecto and endo in other polychaetes, rarely in other taxa.
Oligochaetes – earthworm, lugworm – Branciobdella – obligate crayfish ectoparasites.
Hirudinea – leeches -
What type of worm is a Nemertea and tell me about it
Nemertea – ribbon worms / bootlace worm / proboscis worm - unsegmented
Up to 54m long!!! – possibly the longest animal in the world.
Manly marine scavengers and carnivores, some freshwater or damp terrestrial
Some commensals in mantle cavities of mollusc where feed on small organisms filtered out by the host
A few parasitic species – parasitising crustacea, molluscs and ascidians.
Carcinomertes lives on crabs and largely feeds on the eggs carried by the females, causing significant reduction in reproductive capacity.
Pseudocarcinomertes on American Lobster – up to 100% egg loss by direct consumption and promotic epibiotic colonisation by other organisms
Significant impact on some key economic crustacea species
What type of worm is a Platyhelminth and tell me about it
Platyhelminthes – flatworms
Vast group – some 55,000 species, over 44,000 parasitic
Includes many very important human parasites – digenean flukes and tapeworms, and other major veterinary parasites
And the monogenean flukes
Come back to these in a minute
What type of worm is a Acanthocephala and tell me about it
Acanthocephala – thorny headed worms / spiny headed worms
Obligate intestinal parasites of vertebrates
Invertebrate intermediate host, vertebrate definitive host
Very rarely in humans, found in GI tract and likely as accidental and opportunistic infections after ingestion of raw fish or infected insects for dietary or medicinal purposes - rarely matures.
One report from conjunctiva of the eye (from the UK!)
Appear from sequence analysis to be very highly derived rotifers!
Tell me about the genes of the platyhelminth/ flatworm
Why is it not a monophyletic group?
Platyhelminthes
Flatworms
- 18S rRNA gene (complete)
- What considered historically as the flatworms
- Not a monophyletic group – no single evolutionary origin separating them from all other taxa
*
What are Turbellaria?
Tell some some of its general features and where its found?
“Turbellaria”
Free living flatworms – includes all the subgroups that are not exclusively parasitic
Found in marine, freshwater, or moist terrestrial
They are ribbon like or leaf like
They have no respiratory or circulatory systems so rely on diffusion, some quite large.
Where are Turbellaria found?
Mostly predators
In UK only 3 natives terrestrial sp but at least 9 introduced including New Zealand Flatworm –accidental introduced UK early 1960s via containerised plant trade as lives in / on soil. Spread UK, Ireland and Faroe Isles, not yet continental Europe. Voracious predator of earth worms.
Also, Australian flatworm (Australia), Obama flatworm (S. America, spreading across Europe),
Voracious predators, predating of earthworms
very few parasitic sp
Schmidtea, Dugesia model organisms – stem cell biology and regeneration
Tell me about the Platyhelminth, Neodermata
Neodermata – monophyletic derived from one group of turbellaria
What are the three main lineages of the Neodermata?
- Monogenea mono- and polypisthocotylea – skin flukes
- Eucestodes - tapeworms
- Digenea – digenean flukes or trematodes
What are the Platyhelminths, monogenean all characterised by?
Monogenea
All characterised by posterior attachment organ (opisthaptor) equipped with hooks, bars, suckers, or clamps
Monopisthocotyleans – hooks and suckers
Polyopisthocotyleans clamps and suckers
What are the monogenean predominantly?
Predominantly ectoparasitic skin flukes of aquatic vertebrates (fish, amphibia, reptiles) – some in natural body orifices like gut, bladder, lungs.
A few terrestrial and internal (bladder, lungs, mouth or nasal cavities amphibia and reptiles)
Whats the basic life cycle of the monogenean?
Monogenean – 1 generation – simple, direct life cycle on single host type
Give an example of a monogenean and tell me some general information about it?
Gyrodactylus salaris
salmon fluke on Atlantic Salmon
everts pharynx and secreates digestive solution to dissolve skin and mucus which it then feeds on – skin damage and secondary infection.
Live birth with next generation already developing – Russian doll
Introduced into Norway by imported Baltic Sea salmon for aquaculture in 1970s – wiped out Salmon in 41 rivers by 2001
Shown to survive away from a live fish host for five-seven days at ambient river temperatures and for 42 hours at salinities of 20 ppt.
It is also indigenous to, or has been spread to RUSSIA, FINLAND, SWEDEN, GERMANY, FRANCE, SPAIN and PORTUGAL, largely through fish-farm movements of Rainbow Trout
Notifiable disease in UK – currently absent due to strict biosecurity control measures.
What are the two subclasses of Cestode (a class of parasitic worm in the flatworm phylum)?
How are they distinguished?
Cestodaria – decacanth - 10 hooked larvae
Eucestodes – hexacanth 6 hooked larvae
Tell me the body plan of the cestode?
Digestive tract or associated ducts of vertebrates
Body plan consists of a head (scolex), generative neck region producing the strobila (tape) comprised of segments or prolottids, each of which has a fully equipped reproductive system which matures as it progresses along the tape due to new proglottids being formed in the neck region – breaks off the end of the tape
Huge difference in size and morphology Diphyllobothrium latum / Echinococcus granulosus
Platyhelminth Digenea
Schistosoma and Schistosomiases/ bilharzia
2019 WHO data for estimated # of individuals in the country requiring preventative chemotherapy for schistomiasis
Severe public health problem in many parts of the world,
Present in 78 countries, with 52 countries requiring preventive chemotherapy. Includes parts of Caribbean.
Particularly in sub–Saharan Africa Africa where 92% of all the people requiring preventive chemotherapy for schistosomiasis live.
2018 WHO data
almost 290,000,000 people required preventative treatment, only 42% needing it got it, but 63% of school age children needing it got it.
WHO target to reach >75% all school-aged children who are at risk by 2020 – but new evidence suggests that still need to treat adults as well?
WHO 78 countries considered endemic for schistosomiasis,
Estimated 24,000 – >250,000 deaths per year – simply don’t know
660 million at risk
In sub-Saharan Africa alone 436 million at risk of S. haematobium infection, 393 million at risk of S. mansoni infection.
DALY
disability-adjusted life years (, a time-based measure that combines years of life lost due to premature mortality and years lived with a disability
- 7-4.5 million disability adjusted life years – possibly many times higher (10.4 million estimate by Pan Americann Health Organisation
http: //www.thiswormyworld.org/worms/global-burden
Return to pathology of how it causes disease once we understand the life cycle
WHO transmission status 2020
most affected areas need proactive control.
Since 2016, China, Algeria and Saudi Arabia have gone green.
Tell me the life cycle of Schistosoma and schistosomiasis/ bilharzia
Transmission occurs when eggs from infected individuals contaminate freshwater in which the snail intermediate hosts live and where individuals encounter infective cercariae released from the snails through water contact because of normal human activities – collecting water, washing clothes, agriculture, fishing, playing etc.
Therefore, primarily a disease of rural communities with poor sanitation (raw sewage entering water bodies) and no treated water supplies so much contact with natural water systems. But with increasing and uncontrolled migration to urban areas, resulting in “shanty town” development with no facilities
Water development programs which create large new water bodies and increased opportunity for water contact also important.
From western perspective, With the rise in eco-tourism and travel “off the beaten track”, increasing numbers of tourists are contracting schistosomiasis
How many species are recongised in the Schistosomiasis/ bilharzia genus?
22
The Schistosomiasis/ bilharzia are historically characterised into 4 species groups based on what?
- snail host
- egg morphology
- geographical distribution
What are the 4 species groups of Schistosomiasis/ bilharzia and what characterises each to be distinct?
S. mansoni group – lateral spined eggs Biomphalaria
S. haematobium group – terminal spined eggs – Bulinus Planobarius
S. japonicum group – spineless or minutely spined eggs – Oncomelania and Tricula
S. indicum group – oddballs – variable egg morphology and snail hosts
How many species are involved in human schistosomiasis?
7 species involved in human schistosomiasis, with different and very specific snail host requirements. S. guineensis very recently described, S. malayensis – little studied),
What are the 2 main forms of Schistosomiasis/ bilharzia disease and what determines each?
2 main forms of the disease
- Intestinal
- Urogenital
Depending on where adult worms live and therefore where eggs must escape from
What is the pathology of Schistosomiasis/ bilharzia due to/ not due to?
Pathology not primarily due to adults – small don’t replicate within human host, long lived
Pathology primarily due to eggs – eggs getting out – or eggs not getting out
How do the eggs ‘get out’ with Schistosomiasis/ bilharzia. Tell me about these eggs
Eggs getting out – “burrow through” from blood stream to gut or bladder lumen – eggs are metabolically active and highly antigenic, producing immune-mediated inflammation that results in a granuloma around the egg which is required for passage through into the lumen of gut or bladder.
What are some contraindications/ symptoms of Schistosomiasis/ bilharzia?
Fibrosis / scarring, abdominal pain, diarrhoea, blood in stool – interestingly, sepsis is rare as the immunological activity of the granuloma is host protective and the physical environment of the granuloma protects the host from exaggerated immune responses against eggs.
Fibrosis and calcification of bladder and ureter and blood in urine, accumulation of fluid in kidneys
What happens if the Schistosomiasis/ bilharzia eggs get trapped and not getting out
Eggs not getting out
100s to 1000s eggs per day per female worm
Accumulate in liver – granuloma formation – portal hypertension, hepatosplenomegaly – fibrotic liver damage, ascites.
Interestingly, the composition of granulomas formed in the liver and gut wall seems to be different – intestinal granulomas contain more macrophages but less eosinophils and T and B cells and less collagen.
Even, more interestingly, Omega-1 is a hepatotoxic egg glycoprotein. Recombinant Omega-1 has been shown to have therapeutic activity in diabetes development in Non obese diabetes mouse models – which ties in with the old friend’s hypothesis we talked about last week, where schistosome infection modulated autoimmune diabetes in mice.
Tell me about some other complications with Schistosomiasis/ bilharzia
- systemic effects of chronic inflammation on patient metabolism
- Impaired cognitive development
- Intestinal Schisto
- Urogenital schisto
What can the systemic effects of chronic inflammation with Schistosomiasis/ bilharzia lead to?
- Impaired growth
- Nutrition
- Anaemia
- Iron deficiency
How can the complication of Schistosomiasis/ bilharzia affecting cognitive development effect an individual?
Has an effect on the following…
- School attendance
- Scholastic achievement
- Learning
- memory
How does the complication of Schistosomiasis/ bilharzia effect the intestinal schisto?
- Polyposis- fatal haemorrhage
- Growth retardation in pubescent males
How does the complication of Schistosomiasis/ bilharzia effect the urogenital schisto?
bladder cancer especially in N Africa and Arabia – still little understood – only cancer associated with schisto.
- ova provoke an intense inflammatory reaction, associated with the production of oxygen-derived free radicals.
- these may induce genetic mutations or promote the production of carcinogenic compounds
- often accompanied by chronic bacterial super-infection, which may predispose to squamous cell (SC) neoplasia possibly via bacterial metabolites – especially in smokers.
What system can Schistosomiasis/ bilharzia affect and what does this cause?
Can affect the whole urinogenital system with lesions, bleeding, nodules etc., female genital schistomiasis increasingly recognised (est. 56 million) – urinogenital leasions lead to decreased fertility and increased HIV susceptibility in women (2.8x).
All – katayama fever – acute hypereosinophilia at onset of egg laying due to circulating immune complexes provoking serum sickness
Eggs accumulating in “wrong places, like CNS – cerebral schistosomiasis
Swimmer’s itch / cercarial dermatitis
How is Schistosomiasis/ bilharzia diagnosed?
Blood in urine
Urine egg counts - microscopy
Urine dipstick assays for heme proteinurea at low infection rates where egg counts unreliable
Faecal egg counts - microscopy – Kato Katz technique – youtube video
Elisa for anti schisto antibodies – can’t distinguish present and past infection
Detection of circulating schisto antigen in urine (circulating cathodic antigen dipstick and point of use cassette) – commercial product
Detection of schisto DNA in urine using isothermal amplification (Rosser et al. 2015) – 30˚c- 100 fg DNA
Detection of schisto DNA in eDNA samples for site monitoring (Alzaylaee et al. 2020)
Is there any treatment such as chemotherapy for Schistosomiasis/ bilharzia?
Only current drug PZQ – since 1980 – also veterinary and aquatic helminth – safe, effective single dose against all human flukes
Tell me about the use of PZQ?
2 isomers, one effective (R), other ineffective and bitter (S) – 50% of pill useless – not licenced for under 6 years but will already be infected by water contact. Recent studies suggest that young children may need a higher dose than previously expected.
Merck donation program as of 30/Jan 2020, the billionth tablets donated, 400,000,000 school age children treated
Developing single isomer production – smaller, more palatable pill
Only effective against adult worms – immature worms unaffected and rapid reinfection likely. Therefore, repeated treatment needed without other interventions.
Schisto resistance to PZQ can be generated in mouse models and there are rare reports from nature but no strong evidence yet. WHAT IF?
Despite decades of extensive use, much remains unknown about PZQ, in, its exact mode of action, it’s in vivo metabolism, and its molecular target(s)!!!!!!
Are there any other drugs for use aganist Schistosomiasis/ bilharzia?
Very costly and time consuming – 3rd world problems – looking at repurposing drugs from other areas already approved as safe.
schistos eat RBCs so must have haem degradation pathways as does malaria so some attempts to use anti malarials for schisto control – by themselves or alongside PZQ
Mefloquine – against both adult and larvae – but safe?
Artemesins – Chinese traditional medicine and synthetic derivatives
Clerodendrum umbellatum leaf extract
Schistosoma genome analysis
Schistosoma Genome Analysis
Genome Sequence released 2009 – complete coverage – gene prediction and analysis.
Repurposing existing drugs
Schistosoma Genome Analysis
Metabolic and signalling choke points
Genomics – published first draft – 607 predicted enzymes – 120 choke points – many already drug targets in other organisms
30-50% of genes are “unknown”
Computational drug repurposing
Lots of other “omics”
2020 (Wendt et al) single cell RNA-seq atlas of S mansoni adult cells based on 43,000 cells identified 68 distinct cell types
(Diaz Soria et al) single cell RNA seq atlas of S. mansoni schistosomulae
2020 (Wang et al) large scale RNAi of 2216 genes on adult worms in vitro and in vivo.
Are there any vaccines for Schistosomiasis/ bilharzia?
What helps with vaccine design with this parasite?
What are some key challenges?
Whats the aim for the vaccines?
The fact that the different stages reside in different host niches and have different expression patterns can help in the design of possible vaccines to prevent the migration of schistosome parasites and their maturation to adult worms.
The fact that schistosomes do not replicate in the definitive host makes partial reduction of the parasite burden an effective strategy – fewer worms reaching maturity = fewer eggs = reduced pathology
It is prudent to select key schistosome molecules in the live parasite that are
(a) exposed to the host immune system; and
(b) are essential for parasite survival. Such components may, for example, function in migration, immune evasion, nutrient uptake or attachment.
key challenges – different species, different geographic strains
Many targets – over 22 being worked up for S mansoni alone, some by multiple strategies
S. japonicum – targeting reservoir hosts.
Protective immunity to S. mansoni and S. haematobium infection in humans is documented to be dependent on type 2 immune responses, yet formulations of schistosomiasis vaccines destined for use in humans still aim to induce predominant type 1-related cytokines and antibodies.
Clinical trial for vaccine development
Whats some snail control that can be done for Schistosomiasis/ bilharzia?
Molluscicides
Fish
Clearing vegetation from canals – concrete lining
Flushing of rivers
Sokolow et al. 2015
Diama dam on Senegal river blocked annual migration of native river prawns that are voracious predators of snail intermediate hosts.
Deliberate reintroduction
80% decrease in infected snails
18% reduction in prevalence in villagers
50% decrease in egg burden where reintroduced freshwater prawns
What has mass schistosomiasis control over 40 years helped to do in China?
Mass schistosomiasis control over 40 years has reduced S. japonicum in China from 12 to 7 provinces
12 million to 1 million infected
100 million to 50 million at risk
Still major problem with major foci along Jangtze River
What poses a threat to the progress made on reducing S. japonicum in China?
3 gorges dam – world’s largest hydroelectric power scheme threatens to undo much of this
Several well documented instances in Africa and China where large scale hydroelectric dam projects have impacted on schisto transmission
Created 600 km long reservoir – flood 115,000 acres and relocate 2 million people
Between 2 key transmission zones, area was previously schisto free as water flow too rapid for snails.
Change water flow and sediment rates, large impacts on downstream lakes – predicted likely to prevent annual flooding (which kills snails) and create extra marshy habitat.
BUT
Dongting Lake, a 1,600-square-mile body of water, downstream, home to 48% of the snails in China, including the Oncomelania host of Schistosoma japonicum. The snails live in the lake’s vast marshlands, but their populations have plummeted since the Three Gorges Dam - between 2003 and 2015, the area saw a reported 87% reduction in schistosomiasis.
BUT
water buffalo reservoirs being replaced by tractors, mass drug treatment, expanded use of molluscicides.
What is some interesting biology about Schistosomes?
Adult worms
Blood - Immune evasion
Longevity – several years, decade, 43 years!!!
Separate sexes
Male required for female sexual maturation
chromosomally determined sex ZZ male / ZW female
Hirai, paint probes from individual scrapped chromosomes
BAC probes
The W chromosome of Schistosoma mansoni has evolved how?
It has evolved by at least four inversion events and heterochromatinisation
Nine of 93 BAC clones hybridised with both the Z and W chromosomes, but the locations were different between Z and W chromosomes. What are the two types of hybridisation and tell me a bit about them?
Lab hybridisation
- inc. with Schistosomatium and Heterobilharzia – other members of the Family Schistosomatidae
- Maturation stimulus
- Parthenogenesis haploidy, diploidy restored at next generation.
Natural hybridisation
- Huyse et al. 2009 - Stable hybridisation and introgression – S. haematobium and S bovis in Senegal - mitoch seq bovis, nuclear seq haematobium - new parasite species with hybrid vigour?
- Webster et al. 2013 – another natural cross – haematobium and curassoni
- Leger et al (2016) - child in Niger infected with hybridised and introgressed bovis and curassoni
Cercaria to somule – rapid change in environment (temp, osmolarity etc.) how does it do it?
Roquis et al. (2015)
Whole genome analysis to compare the methylation state of human infective larvae (cercariae), the first developmental stage after infection of the vertebrate host (schistosomula) and adults of S. mansoni
Cercariae transcriptionally dormant – bivalent histone H3 methylation around the beginning of genes (transcription start sites) –
removed on transformation to somule and stays absent in adults
Whats the traditional taxonmy based on?
Egg groups
snail hosts
Whats the molecular phylogeny of Schistosomes?
Orientobilharzia (previously a separate genus) monophyletic within Schistosoma
Phylogenetics and evolution- cryptic species
Biogeography and evolution of Schistosomes
- S mansoni Africa, S America C America and Caribbean
- Biomphalaria snail host – evolved in S America but also pan-Africa distribution with lots of species
- Map the trees of parasite and host
- Long distance colonisation of Africa by Biomphalaria from S America somewhen in last 2 million years through transoceanic colonisation
- Once in Africa, spread as self-fertile hermaphrodite and became permissive host for endogenous schisto which evolved and speciated.
- S. mansoni in new world – very recent
- Webster, Gower, CO1 and microsatellite analysis:
- 600 S. mansoni samples, very diverse and rapidly evolving
- links S. mansoni isolates from Brazil to W African isolates.
- Origin of S. mansoni in E Africa
- 2000 S. haematobium samples –– 2 major groupings E and W Africa, Island populations not uniform, so no obvious bottlenecks and regular genetic exchange through human movement.
