Introductory review of human Schistosomiasis

2.  Schistosomiasis is an inflammatory disorder that is
initiated by infection with Schistosoma blood flukes.
◦ Estimated 240 - 450M cases , > 800M at risk esp in LDCs (SSA)
 It causes tissue damage and systemic pathology that
often persist into adulthood, even after infection abates.
 Presentation among residents of endemic areas differs
from that seen among travelers or migrants (naïve
cases).

3. Schistosomiasis; Global Burden

4.  This disease is most commonly found in Asia, Africa, and
South America
 S.mansoni is endemic throughout Africa , Middle East
and South America.
 S. haematobium confined in Africa and Middle East.
 S. intercalatum endemic in Central Africa.
 S. japonicum and mekongi found in Asia only.

5.  The linear rise (with increasing age) in both prevalence and
intensity of infection.
◦ Peak infection among children aged 12 to 15 years.
 S. haematobium- highest prevalence of associated disease.
 Kills 1 to 2 per 1000/yr, estimated to contribute 1 to 3 % of
deaths in LDCs.
◦ Although end organ effects serious, morbidity and DALYs worse
◦ Anemia, cognitive impairment, stunting, reduced QOL (NTDs)

7.  S. haematobium mainly human restricted, although
primates are potential carriers (Bulinus spp)
 S. intercalatum, intestinal variant with similar eggs but
different clinical ppt, and excretion. (B. africanus spp)
 S. mansoni – various mammals & non-human pirates.
◦ Baboons, rats (Biomphalaria spp)
 S. japonicum - mainly buffalo, but various domesticated &
herbivores carry infection. (Oncomelanis spp)
 S. mekongi only dogs demonstrated as reservoirs. (Tricula
aperta snail spp)

8.  Species of the genus Schistosoma are trematodes, family
Schistosomatidae.
 Dioecious, digenean multicellular helminthic parasites,
adult habitat is the vascular system of vertebrates.
◦ Several inter stages; miracidium, sporocyst, cercaria & metacercaria.
 5 infectious spp; Schistosoma haematobium, S.
intercalatum, S. mansoni, S. japonicum & S. mekongi.
◦ Very rarely, other zoophilic species or interspecies hybrid
infections may be found in humans

10.  Cercaria penetrates host skin, loses tail > swimmers rash
◦ Become schistosomulum > invade respective vasculature
◦ More common S. mansoni & S. japonicum
 Dioecious organisms exist in copula as adults
◦ Intestinal parasites in mesenteric vasculature
◦ Urinary occupy vesicle plexus
 Long slender & smooth female encased in gynaecophoric
groove/ canal of shorter, stumpy male.
 Lays unembryonated eggs everyday of adult life (> 10k)

11. • Eggs laid by adult & excreted in host faeces or urine.
• Hatch> miracidia, penetrate snails.
• Develop; sporocysts > (2° sporocysts) >cercariae (in schistosomes
there are no rediae).
• Cercariae emerge from the snail, penetrate definitive host
skin in water > schistosomulae.
• Migrate through host body provoking severe
immunologic response and inflammation (acute)
• Molecular mimicry and expression of host Ag allow mature forms
to exist masked in host tissue; No clinical disease
• Eggs lack immune evasion mech’ms & cause disease
manifestations... Chronic manifestation.

13.  Parasite eggs released into freshwater (from human/
host urine, feces)
 Eggs hatch  ciliated miracidia, free swimming
 Miracidia find & infect snail host (spp specific)
 Each miracidia transforms into many fork-tailed, free
swimming cercariae within 4-6 weeks of entering snail.
 Cercariae leave snail and move into water at a rate of
1500/day for up to 18 days.

14. Schistosomiasis requires 3 major conditions:
 Pollution of fresh water with excreta containing
Schistosome eggs.
 The presence the right species of snail;
◦ Geo distribution of specific snail hosts determines epidemiology
of disease
 Human contact with water infested with cercaria.
◦ Cercariae must penetrate human skin or mucosa due to direct
contact.
◦ No redial stage, metacercaria susceptible to stomach acid

15. B. truncatus
B. glabosus
B. forskalii
B. africanus
Biomphalaria glabrata
S. Mansoni S. intercalatum S. haematobium S. japonicum S. mekongi
(Biomphalaria) (Bulinus) (Bulinus) (Oncomelania) (Tricula)
Africa
B. Pfeifferi
B. Alexandrina
B. Sudanica
T. apertaO. hupensis
B. globosus
B. forskalii
Americas
B. glabrata
B.straminea
B.tenagophila

16.  Cercariae find a human host, penetrate skin, and
differentiate into larval forms called schistosomulae.
 Migrate through the host’s skin, gain access to the
lymphatic system.
 Travel to the lungs (stay 3-8 days and ~70% are
eliminated)
 Migrate to liver portal system, mature into male &
female adults.

18.  In liver, m & f pair up  female inserts herself into the
gynecophoral canal of male.
 Migrate to favoured sites:
◦ S. mansoni; mesenteric venules of large bowel &
rectum.
◦ S. japonicum; mesenteric veins of the small intestine.
◦ S. haematobium; perivesical venous plexus
surrounding the bladder.

19.  Females release eggs.
Egg characteristics
◦ Covered in microbarbs  cling to vascular endothelium.
◦ Pores, which allow the release of
1) Antigens
2) Enzymes (aid in passage of eggs through host tissues)
 Eggs enter lumen of excretory organs/ trapped.

20.  S.haematobium
 Causes urinary schistosomiasis
1. Prepatent period 10-12 wks
2. Egg deopistion :
1. painless haematuria
2. Inflammation of bladder &burning
micturition
3. Tissue proliferation & repair
 Fibrosis , papillomata in bladder &
ureter > obstructive uropathy.
 Periportal fibrosis
 Lung and CNS involvement
 S.mansoni, japonicum,
intercalatum, mekongi
Causes intestinal schistosomiasis
1. Prepatent period 5-7 wks
2. Egg deposition:
1. dysentery (blood & mucus in stools),
2. Hepatomegaly > splenomegaly
3. Tissue proliferation & repair
 Fibrosis, Papillomata in intestine,
Periportal fibrosis, hematemesis
 Lung and CNS involvement.

21.  Each stage expresses Ag stimulate host immune
response.
 Adult worm evades host immune mechanisms.
◦ Ability deteriorates with age of parasite
 Specific antigens are also released by the eggs.
 Immune response vs Ags causes granuloma formation
around the egg itself.
 Tissue granulomas main lesion in Schistosomiasis.

22. Pathogenesis

23.  Pathogenesis eggs (rather than larvae or adults)
◦ Cercarial dose of inoculation
◦ Site of infection/ localisation (mode of inoculation).
◦ Host immune status
 Most of the pathology is caused by host immune
responses.
 The course of infection is often divided into three
phases:
◦ Migratory
◦ Acute
◦ Chronic.

24.  Occurs when cercariae penetrate and migrate through the
skin.
 Often asymptomatic.
 In sensitized patients it may cause; Cercarial dermatitis
◦ transient dermatitis (swimmers itch, kabure itch)
◦ and occasionally pulmonary lesions and pneumonitis.
 Katayama syndrome [appear 3-6 weeks after the
penetration of cercariae.
◦ Fever, cough, headache, sweating, abd pains, hepato-
splenomegaly, high eosinophilia

25.  Coincides with first egg release;
◦ allergic responses (serum sickness due to overwhelming
immune complex formation),
 IgE mediated Type I hypersensitivity (vs type 3/4 for chronic)
◦ fatigue
◦ lymphadenopathy
◦ gastrointestinal discomfort
◦ and eosinophilia.

26. Portal hypertension in
chronic schistosomiasis

27.  Occurs in response to the cumulative deposition of eggs
in tissues and the host reactions that develop against
them.
 Not all the eggs successfully penetrate the gut or bladder
walls into excreta.
 Some trapped in organs where they elicit strong
granulomatous responses.
◦ Typically cause delayed or Ag-Ab cpx hypersensitivity rxns
◦ Significantly reduced in immuno-compromised patients

28.  Eggs become surrounded by inflammatory cells forming
characteristic pseudotubercles.
◦ May coalesce to form larger granulomatous reactions (polyps).
◦ Intestinal polyposis, abdominal pain, diarrhoea,
glomerulonephritis, pulmonary arteritis, cardiovascular
problems including heart failure, and periportal fibrosis.

29.  Eggs carried by portal circulation to the liver.
 Granulomatous response
 Granulomas are walled off with fibrous tissue
◦ fibrosis obstructs portal veins
◦ portal hypertension.
 Splenomegaly
 enlarged spleen, due to fibrosis

31.  Eggs lodge themselves in wall of bladder & can develop
into polyps.
◦ Erode, ulcerate & cause hematuria
 In ureters and urethra, cause lumps and lesions, kidney
failure
 Ovaries, uterus, cervix, fallopian tubes – Female Genital
Schistosomiasis (FGS)
◦ Lumps, complications including infertility
◦ For the men: eggs can also lodge into the testes and the prostate

32.  <5% of patients develop CNS symptoms
 Cerebral complications more prevalent than spinal.
 Cerebral complications include:
◦ headache, visual impairment, delirium, seizures, motor
deficits and ataxia.
 spinal symptoms comprise:
◦ lumbar pain, lower limb radicular pain, muscle weakness,
sensory loss and bladder dysfunction.

33. Microscopic Detection
 Take stool or urine sample to
detect eggs
 S. haematobium eggs are
oval and have terminal spine
at the posterior end.
 S. japonicum eggs small and
almost spherical, has no
spine but show a lateral knob.
 S. mansoni eggs have a
lateral spine.
S. mansoni S. japonicum
S. haematobium

35. Antibody tests
 An earlier and more sensitive form of detection
 Some complications
◦ Cross-reactivity with platyhelminthic infections
◦ Can’t differentiate between current and old infections as
antibodies persist.
 CCA & CAA Ag tests can ID active infections with speciation
option
 Both lack load association

36.  I.V.U.
 Chest x-ray
 Barium studies
 Myelography
 Immunodiagnostic tests [skin test, complement fixation
test, gel diffusion] provide supportive evidence
 Haemogram [eosinophilia in early stages of the disease
but constant finding in the bone marrow]

38.  Praziquantel : Most widely used drug.
◦ Extremely well tolerated, few side effects, safe in preganancy.
◦ Broad-spectrum antihelminthic drug.
◦ Artemether may be used in both control and treatment of
schistosomiasis in areas where there is no regular malaria
transmission
◦ Combination of both Praziquantel and Artemether
◦ Praziquantel -adult worms while Artemether kill Schistosomula
◦ Ectopic infections (CNS, Skin) may lead to worse symptoms

39.  Oxamniquine
◦ used exclusively to treat intestinal Schistosomiasis in
Africa and South America
◦ S. mansoni specific, 2° alternative. Resistance noted
 Metrifonate
◦ Effective for the treatment of urinary Schistosomiasis
◦ Shows reduced efficacy over time
 NO known 2° for S. japonicum.

40.  Avoid contact with water known to contain cercariae by
◦ Providing safe water supplies
 Waste disposal management; toilets, sanitation
 Health education and mass
 Trials of specific Ag vaccines (murine success)

41.  Destroying snail intermediate hosts mainly by
◦ Using molluscides, clear vegetation, drain swamps
 Treating water supply by using chlorine disinfectant
where possible.

42.  Effective vaccine against Schistosomiasis .
 Drug resistances
 Environment impacts
◦ destroying freshwater snails using chemicals

43.  Aubrey Manning and Marian Stamp Dawkins, An
introduction to Animal Behaviour, 5th edition, Cambridge
university Press.
 Chapman R.F. (2007), The Insects: Structure and
Function, 4th Ed. Cambridge University Press, USA.
 Harjinder Singh, A textbook of Animal Behaviour (1995),
1st edition, Anmol Publications Pvt. Ltd, New Delhi.
 Prasad S, Animal Behaviour (2004), CBS Publishers and
Distributors, New Delhi
 www. nhptv.org/natureworks/nwep3.htm
 http://www.cbc.ca/quirks/episode/2011/01/08/january-
8-2011/