Trematodes

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Schistosomes and schistosomiasis Medical
Parasitology course, 2008 University of
Georgia Silvia N.J.Moreno
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Schistosomes and schistosomiasis

• Disease schistosomiasis or Bilharzia (in honor
  of Theodor Bilharz)
• Infect 200 millions of the worlds population in
  Africa, Asia and S. America. Population at risk
  600 millions. 20 Million with severe disease
• Live in blood vessels of the definitive hosts
  including humans.
• Pathology is not due to host response against the
  worms but rather to eggs entrapped in tissues

Theodor Bilharz -(1825-1862) Postal stamp
released in Egypt, 1962 Issued on his 100th death
anniversary
Ascites due to portal hypertension, liver
fibrosis. Bilharzia. Schistosomiasis. Schistosoma
mansoni. Photo Dr Van den Enden
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Schistosome biologyimportant points

• They live in the bloodstream
• They live for a long time
• The host can become resistant to infection
• The parasites do not replicate in their
  definitive host
• Have separate sexes-male has pouch which holds
  female

www.icp.ucl.ac.be/opperd/ parasites/schisto1.html
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Transmission

• Pollution of fresh water with excreta containing
  Schistosome eggs

• Presence of the snail host

Snail from genus Biomphalaria http//www.cdfound.
to.it/HTML/sch1.htm

• Human contact with water infested with cercaria

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Geographic distribution

• Schistosoma mansoni
• Africa (52 countries) , Caribbean, Eastern
  Mediterranean, South America
• Schistosoma japonicum
• Asian countries and the Pacific region
• Schistosoma haematobium
• Africa (54 countries), Eastern Mediterranean
• Schistosoma intercalatum
• African Countries (10)

S. hematobium
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Schistosome life cycle
Eggs passed in feces or urine
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Schistosoma mansoni eggs These eggs are large
(length 114 to 180 µm) and have a characteristic
shape, with a prominent lateral spine near the
posterior end.  The anterior end is tapered and
slightly curved.  When the eggs are excreted,
they contain a mature miracidium
S. hematobium egg In this species, the eggs are
large and have a prominent terminal spine at the
posterior end.  Length 112 to 170 µm. 
S. japonicum egg the egg is typically oval and
has a vestigial spine. Schistosoma japonicum
eggs are smaller (68 to 100 µm by 45 to 80 µm)
than those of the other species.
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Schistosome miracidium

• Eggs hatch releasing miracidia
• 200 ?m length and 40 ?? diameter
• Swims at 2 mm/sec by beating of the cilia
• Remain infective for 8-12 h
• Infects the snail
• They accumulate around the snail or in a drop of
  snail-conditioned water

Miracidium Swimming towards Snail Intermediate
Host
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Main intermediate snail hosts that transmit human
schistosomiasis
S. Mansoni S. intercalatum S. hematobium
S. japonicum S. mekongi (Biomphalaria)
(Bulinus) (Bulinus) (Oncomelania)
(Tricula)
Africa B. Pfeifferi B. Alexandrina B.
Sudanica Americas B. glabrata B.
straminea B. tenagophila
B. truncatus B. glabosus B. forskalii B.
africanus
T. aperta
O. hupensis
B. globosus B. forskalii
Bulinus globosus, the intermediate host snail for
Schistosoma haematobium (courtesy
WHO/TDR) www.icp.ucl.ac.be/opperd/
parasites/schisto1.html
Biomphalaria glabrata
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Intramolluscan stages

• The miracidium penetrates the snail
• It sheds the epithelium and remodel its surface
  (2 h approx.)
• A new surface layer appears around the newly
  formed sporocyst
• A new syncytial tegument is formed
• Primary sporocysthollow, fluid filled germinal
  sac
• Daughter sporocysts in less than a week (35-600)
• Cercaria by 3-4 weeks after infection (1500/day
  for 18 days)

SPOROCYST
http//www.personal.leeds.ac.uk/bgy1mjt/sporocyst
.html
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Cercaria in the water

• First escape into the hemolynph and then through
  the snails integument
• Swim into the surrounding water to find their
  definitive host
• Swims by alternating side-to-side rhythmic
  contractions
• It is composed of a body 125 ?m long by 25 ?m in
  diameter to which a 200 ?m long tail is attached

http//www.personal.leeds.ac.uk/bgy1mjt/cercaria.
html
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Cercaria characteristics

• Covered by a single continuous syncytial
  tegument 0.5 ?m thick on the body and 0.2 ?m
  thick on the tail
• A trilaminate plasma membrane over a trilaminate
  basement membrane forms the outer surface of the
  tegument
• Glycocalyx (highly antigenic) of 1-2 ?m thick
  cover the surface of the tegument
• Unicellular glands that secrete proteinases that
  digest extracellular proteins

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Cercaria to schistosomula

• Tail is lost
• Shedding of the glycocalyx
• Penetration glands empty
• Formation of a new double-unit membrane on the
  syncytial surface.
• Some glycocalyx remains on the surface of the
  schistosomula
• Several new glycoproteins not found in the
  cercaria
• Loss of resistance to the hypoosmolar stress of
  fresh water
• Change from aerobic to anaerobic metabolism

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Inside the human host Schistosomula

• 3-4 days in the subdermal layers
• Bloodstream briefly passing through the right
  side of the heart into the pulmonary artery
• Pulmonary capillaries around the 4th day and
  remain for 2-3 days
• Schistosomula becomes resistant to the immune
  response
• The fibrous interstitial layer beneath the
  tegument as well as some of the anterior
  musculature, disintegrates and disappears
• After passing through the lungs schistosomula
  come to rest in the hepatic portal vein

http//www.cdfound.to.it/HTML/sch2.htm
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Inside the human host Schistosome adult worms

• Male/female pair copulate throughout
  life-produce eggs
• Females resides in canal-Important for
  maturation
• Some differences among species
• Worm pairs can live for more than 10 years in a
  host
• Pair migrate back against the blood flow to the
  mesenteries around the intestine.

http//www.med.sc.edu85/parasitology/schis8.jpg
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Adult worm characteristics

• No body cavity or circulatory system. The
  internal organs are embedded within a solid
  cellular parenchyma
• Covered by a tegument (skin)
• Ventral and oral suckers
• Reproductive tract differs in different species

Digestive system of schistosomes is very simple
They have only one bifurcated digestive tract.
Their digestion is performed by frame cells, and
they seem to have no excretory pore.
http//www2.ttcn.ne.jp/akky/parasite/digest.htm
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The tegument

• Poor in organelles syncytium with cytoplasmic
  connections with underlying nucleated cell bodies
• The outer surface has folds and is pitted with
  numerous opening of tubular canals
• Males
• Warty tubercles with many spines which help to
  maintain the position of the pair against the
  blood flow
• Female
• Wrinkled annularly and is smooth except for
  dense spination around the excretory pore.
• Underlying the tegument is a basal lamina from
  which mitrotubules extend into the tegumentary
  matrix

Diagram of the ultrastructure of the adult
schistosome tegument (click to enlarge).
www.york.ac.uk/res/ schisto/proteomics.htm
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The egg

• Surrounded by a biopolymer composed of proteins
  crosslinked to each other by quinone bridges
• Contains pores to allow the influx of nutrients
  and efflux of macromolecules
• The shell is a highly organized conglomerate
• Surface proteins with numerous repetitive domains

The egg is eliminated with feces into the water
to release miracidia that http//www.wellcome.a
c.uk/en/labnotes5/animation_popups/schisto.html
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Pathogenesis of Schistosomiasis

• Eggs that do not leave the body are swept to the
  pre-sinusoidal capillaries of the liver and are
  trapped there (or in the bladder wall)
• The immune system responds and walls off the eggs
  with a granuloma, the egg dies
• Continuous stimulation of the immune system leads
  to regulation or fibrosis (less or more
  morbidity)
• Periportal fibrosis leads to portal hypertension
• Portal hypertension leads to collateral
  circulation, eosophageal varices, blood loss
  (Sm Sj)
• Continuous aggravation in the bladder wall leads
  to carcinoma of the bladder (Sh)

Granuloma in a mouse liver formed around a
Sepharose bead coupled with schistosome egg
secreted proteins. http//www.york.ac.uk/res/schis
to/proteomics.htm
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Clinical symptoms

• Schistosomiasis is an immunologic disease.
• Symptoms are rarely seen except in heavily
  infected individuals.
• Skin penetration-local dermatitis within 24 h
• Migration of the schistosomula chills, fever,
  sweating, cough, diarrhea, leukocytosis
• Acute phase (Katayama diseases by S. japonicum)
• fever, chills, headache, anorexia, urticaria,
  and diffuse megaly, lymphadenopathy and diffuse
  vasculitis lesions
• 2-3 weeks after the infection and usually lasts
  1-2 months (typhoid fever)
• Chronic disease-most important
• Fatigue, bowel and bladder symptoms, hepatic
  dysfunction
• Hepatosplenomegaly because of portal obstruction
• S. hematobium urinary tract infection,
  inflammation, squamous cell epithelioma,
  hydronephrosis and fibrosis of ureters

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The morbidity spectrum of schistosomiasis mansoni
The 2 faces of schistosomiasis
Intestinal asymptomatic schistosomiasis at the
Egyptian village level
Egyptian boy with hepatosplenomegaly, ascites
fluid build-up and superficial collateral
circulation (NAMRU-3 clinical ward in Cairo)
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Then there is the North American
schistosome-induced pathology --- Duck
schistosomes Raccoon schisto etc.
Sign on the door leading out of a resort to Lake
Bemidji, in Minnesota (the advice cant hurt, but
may not help either
Cercarial Dermatitis
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Diagnosis of Schistosomiasis
Microscopic fecal or urine examinations Thick
smear (Kato/Katz) Concentration techniques
(sediment/filter) Polycarbonate filters (urine
S. haematobium) Antibody assays (measure
exposure) Antigen assays (measure active
infection and quantify intensity) The
standard is egg counts but.
ALSO IMPORTANT Clinical signs, symptoms and
history of living in an endemic area
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Treatment of schistosomiasis
Praziquantel Oxamniquine Type
of Isoquinilone
Tetrahydroquinilone Compound Active against
All Species S. mansoni Dosage
40-60mg/kg
15-40mg/kg Single dose
1-2 doses Cure Rate 70-100
80-100 Main Side
Diarrhea,Nausea Dizziness
Effects Abdominal pain Drowziness
Price/adult 0.25 - 3
2 - 5 dose Mode of Calcium Channel
Delayed action Action blocker ?
Alkylation ?
As with egg excretion Effective treatment also
requires host responsiveness
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Factors Contributing to Transmission of
Schistosomiasis

• Water -- Uses Abuses
• Development (Dams Irrigation), Socioeconomic
  (Sanitation)
• Snail hosts
• Habitat (geography weather), Dams, Marshes
• Adult worms -- Longevity Fecundity
• Human animal (Sj) reservoir hosts
• Contamination Contact Patterns Occupational
  aspects
• Age/Prevalence Age/Intensity Curves
• Immunity?
• New data on the topic -- if time permits
• Focal Transmission sites
• Rural -- and now Urban/peri-urban settings
• Location, Location, Location..

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The infection is age-related

• S. haematobium and S. mansoni show age related
  patterns
• Children are nonimmune
• They become infected when old enough to play in
  open water
• Adults gradually acquire immunity

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Washing Clothes or other jobs
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There is also no transmission without fecal
contamination. So, how does fecal
contamination happen???
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Control measures/ Possible Points of Attack

• Sanitation, Water Supply Community
• Health education Hygiene
• Socioeconomic development gt toilets water
  systems
• Snail Control
• Molluscicides Competitors/Predators Habitat
  reduction/closed irrigation Environmental
  modification
• Chemotherapy
• Target, Coverage -- Process Outcome Indicators
• Delivery options/Integration with other control
  programs
• Prevalence/Intensity/Morbidity
• Vaccine (not for a long time)
• Discovery, Process development, Testing
• Re-infection studies immune correlates

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Schistosomiasis Control Initiative
http//www.schisto.org

• 1. To encourage development of a sustainable
  schistosomiasis control programme in sub Saharan
  Africa.
• 2. In the selected countries
• To reach at least 75 of school-age children and
  other high-risk groups with chemotherapy -
  praziquantel and albendazole.
• Reduce schistosomiasis-related morbidity in high
  risk groups.
• Reduce prevalence and intensity of
  schistosomiasis infections.
• Reduce burdens due to intestinal helminths in the
  targeted populations.
• 3. Create a demand for sustained schistosomiasis
  control.
• 4. To promote access to anthelminthic drugs and
  good case management in the regular health system.