Immunobiology of Schistosomiasis

S. M. Munsaka, BSc., MSc., PhD

Department of Biomedical Sciences
School of Health Sciences
University of Zambia
Outline
Introduction
Epidemiology
Life cycle
Schistosoma species
S. mansoni
S. japonicum focus
S. haematobium
S. mekongi
S. intercalatum
Symptoms
Imunopathogenesis/immunobiology
Diagnosis
Treatment
Prevention/Control/Vaccine
Conclusion and Summary
Introduction
Closely related flukes that inhabit the portal vascular system

Important species:
Schistosoma haematobium
S. japonicum
S. mansoni

Less common:
S. intercalatum found in West Africa
S. mekongi found in Southeast Asia

In addition, other species of schistosomes, which parasitize

birds and other mammals, can cause cercarial dermatitis
(Swimmers’ itch) in humans.
Introduction cont’d

Adult worms differ from other Trematodes

different morphologies
Separate sexes (Diecious)

Female worms are long and slender (1.2-

2.6cm), body almost circular in cross section
http://www.biology.ualbert
a.ca/courses.hp/zool250/
Adaptation to intravascular existence where Labs/Lab04/Schistosoma
they lay eggs -M&F.gif

Male worms are 0.6-2.2cm long, body

dorsal-ventrally flattened but curved
ventrally to form a Gynecophoric canal in
which the female reposes
Introduction cont’d

Eggs have spines

Assist in retention in blood vessels http://images.google.com/images?svnum=10&hl=en&lr=&client=f
irefox-a&rls=org.mozilla%3Aen-
US%3Aofficial&q=shistosoma&btnG=Search

Necrosis and pressure liberates eggs into lumen

of intestines or bladder

Eggs hatch in water releasing Miracidia that infect

snails

Development in snail intermediate host gives rise

to infective cercaria
Epidemiology
Ranks second to Malaria in socio-economic and public health
importance in tropical and sub-tropical areas

Widespread distribution and extensive morbidity

Endemic in 74 developing countries

Infects 200 to 300 million people in

Rural agricultural and peri-urban areas of:
Africa
Middle East
Southeast Asia
the Caribbean and
South America
Epidemiology

20 million suffer severe disease and about 120

million are asymptomatic

1 million people killed annually

Between 500 and 600 million people are at risk of

infection

Most affected age group: under 14 years children

Epidemiology
Presence depends on
Disposal of infected human/vertebrate waste into fresh water
Availability of snail intermediate host
Exposure of humans to infected water with cercaria

Would be stopped by
Modern waste disposal?
Provision of safe drinking water supplies?

Spread to areas of new irrigation projects

Aswan Dam in Egypt
Diama Dam on Senegal River (Senegal and Mauritania)

Refugee movements and displaced populations

Somalia and Djibouti
African Slave trade
Epidemiology
Life cycle
Schistosoma mansoni

Brought to western hemisphere by the African slave

trade
Not public health concern in the west
No appropriate snail intermediate host

Rarely infects other animals

Adults live in the inferior mesenteric veins, lower

colon
egg

Smallest of the Schistosomes that infect humans

Light yellow brown eggs with lateral spine passed in

stool
Schistosoma japonicum

Oriental blood fluke http://www.path.cam.

ac.uk/~schisto/Picture
s/Eggs/S.jap.egg.gif

Found virtually in all vertebrate animals exposed to infested water

Adult worms live in small branches of superior mesenteric veins

adjacent to small intestines

Produce more eggs in stool than other schistosomes, eggs more

smaller and more spherical

Causes hepatic and pulmonary cirrhosis during chronic infection

CNS involvement may occur one eggs are deposited near nerve
tissue
Schistosoma haematobium
Causes urinary schistosomiasis (Bilharzia)
Endemic in the Nile valley
Terminal haematuria

Man is the only important host egg

Worms mature in liver and migrate to vesical, prostatic and uterine

plexuses

Females deposit eggs in the walls of the bladder or other adjacent

organs

Eggs may break through the bladder into the lumen and escape with
the urine

Eggs are light yellowish brown and have a terminal spine

Schistosoma mekongi
Endemic in the Mekong river basin of Cambodia

Resembles S. japonicum in structure and ability to

infect other vertebrate hosts

Different snail intermediate host, mild disease

Eggs are smaller than S. japonicum eggs

 Schistosoma intercalatum
Occurs in humans in Western and Central Africa

Adult worms are found in mesenteric veins and eggs

are voided in feaces

Eggs resemble those of S. haematobium but their

terminal spine has a bend and are acid fast

Disease relatively benign, hepatomegaly not quite

marked, severe digestive disturbances accompanied
by pain and bloody stools
Symptoms
Asymptomatic esp. S. mansoni

First stage (24-36 hrs): initiated by penetration of cercaria and

migration of schistosomula
Hemorrhage, edema, pruritus skin rash, fever, headache, cough,
intestinal complaints

Second stage (1-3 months): begins with oviposition and

associated with complex clinical manifestations
Malaise, fever, abdominal pain, liver tenderness, eosinophilia,
fever and chills (Katayama syndrome of S. Japonicum)
diarrhea/dysentery (S. mansoni and S. Japonicum), haematuria
(S. haematobium), lymphadenopathy, splenomegaly

Circulating immune complexes and deposition in tissues

Intestinal inflammation and encephalitis occur acutely

Symptoms

Third stage or chronic stage: granuloma formation,

necrosis, fibrosis and scaring around retained eggs

Hepatosplenic schistosomiasis: portal hypertension,

ascites, Hepatitis (HBV, HCV Co-infection)

Intestinal Schistosomiasis: granulomatus colitis,

abdominal cramps and bloody mucoid stools

Urinary Schistosomiasis: haematuria, obstructive

uropathy, bladder cancer

Pulmonary Schistosomiasis: fibrosis of pulmonary bed

Cerebral Schistosomiasis and transverse myelitis:

lethargy, confusion, seizures, flaccid paralysis of lower
limbs
http://www.medicalhealthcareinfo.com/thumbs/5255_thumb.jpg
Immunopathogenesis

Complex
Antigenic differences between cercaria, schistosomula, adult
worms and eggs

Schistosomula eliminated by IgG, eosinophils,

through eosinophil MBP

Macrophages may play role with IgE and lysosomal

enzymes

Survival/Tolerance
Immunological ‘camouflage’ of adult worms
Immunopathogenesis
Damage is caused by host’s cell mediated
responses
Egg deposition
Abscess formation
Granuloma formation
Necrosis and Fibrosis of submucosa

Modulating mechanisms: Both cellular (T cell

dependent) and humoral immunity
Absent in athymic (Nu/Nu) mice
Different HLA haplotypes and development of
hepatosplenomegaly
Diagnosis

Recovery of characteristic eggs in

Stool (S. mansoni, S. japonicum)
Urine (S. haematobium)
Biopsy specimens (S. mansoni, S. japonicum) for mild
infections

Techniques
Formal-ether concentration
Gravity sedimentation

Determination of egg viability and output useful

Hatching Test
 New infection Vs chronic infection
 Mild Vs Heavy infection

Kato-Katz Thick smear test

Diagnosis
Serology
Conventional serological methods
Can detect antibodies in blood (90%< sensitivity)
Cannot distinguish active infection to inactive infection

Enzyme Immuno Assays (EIAs), Dipstick

Detect adult antigens in blood or urine
Rapid, simple and very sensitive
Useful to diagnose Katayama syndrome
Can distinguish active Vs inactive infection as antigens drop
after therapy
Diagnosis
Treatment

Safe and effective drugs are available for the treatment of Schistosomiasis.

However no drugs for dermal Schistosomiasis and Katayama syndrome

Antihistamines and Cortical steroids may help

The drug of choice is Praziquantel for infections caused by all Schistosoma

species. Dosage: 40mg/Kg body weight
Makes adult worms more susceptible to elimination by immune response of host
 Humoral immunity important

Oxamniquine has been effective in treating infections caused by S. mansoni

in some areas in which Praziquantel is less effective.
Use contraindicated in pregnancy

Metrifonate is an alternative drug used to treat S. Haematobium

Prevention/Control
Education

Mollusciding
Using Niclosamide
Large scale application difficult and expensive

Biological control
Snail eating fish or birds

Proper disposal of urine and feces?

snail-eating fish
Provision of safe drinking water?
Difficult to enforce
Limited by economic status and culture
Prevention/Control

Change in human behavior

Avoid snail infested fresh water streams?

Mass chemotherapy
Praziquantel

Vaccine?
Cobalt irradiated cercaria of S. bovis have shown protection
against disease

Several schistosome proteins are under investigation as potential

vaccine candidates
WHO’S Strategy
Reduce the amount of disease than to halt transmission entirely.

Controlling morbidity with drug treatment is a feasible and effective

strategy. Other major interventions are health education and provision of
safe water.

Schistosomiasis control is optimal when it is part of the general health

care system and when the primary health care system performs specific
control tasks.

Approaches differ for controlling the various forms of Schistosomiasis

and must be adapted according to the epidemiology, resources and
culture of each country.

Schistosomiasis control is a long-term commitment. While short-term

objectives to reduce prevalence can be achieved (up to 75% within two
years in many endemic areas), surveillance and maintenance must
continue for 10-20 years.

http://www.who.int/mediacentre/factsheets/fs115/en/index.html
WHO’S Strategy

Praziquantel efficacious at three weeks after treatment

95.3% egg reduction, 94.1% heavy infection and 57.9% overall
Cure rate 80.7% at week 41

Re-infection low and seasonal

Occur in hot and rainy summer season

Use of one sample Vs two samples

Regular treatment of school going children

Treatment synchronized with Seasonal transmission
One treatment per year, after the end of summer
Praziquantel still effective in HIV/AIDS
With humoral immunity

Resistance to re-infection is not altered in HIV/AIDS

Co-infected people excrete fewer eggs and had less hematuria

Low sensitivity and positive predictive value of reported hematuria as an indication of heavy
infection

Reason:
Low CD4+ T cell, impaired cell recruitment for granuloma formation
Reduced fecundity of female worms

Implication
Use of hematuria as indicator for rapid diagnosis in areas where HIV prevalence is high
may result in underestimation of heavy infection
Vaccines

Radiated-attenuated cercaria provided protection form S. Mansoni

Interferon gamma and Th-1 response important

Schsitosomule antigens
Disappointing results so far

Shared antigens promissing

63 kD parasite myosin
97 kD paramomyosin
28 kD triose phosphate isomerase (TPI)
23 kD integral membrane protien (Sm23)
26 and 28 kD glutathione-S- transferase (GSTs)

28 kD S. haematobium GSTs (shGSTs) developed by the Pasteur

Institute
Safe
Good immunogenecity in human volunteers in France, Niger and Senegal
Vaccines

None of the above vaccines have shown provided

more than partial reduction worm burden relative to
non-immunized controls

New approach
Target fecundity to diminish egg output
S japonicum 26 kD GST and paramyosin
Mice, large reservoir hosts
Reduce transmission to man

http://www.who.int/vaccine_research/diseases/soa_parasitic/en/index5.html
Conclusion and Summary

Schistosomiasis is second to Malaria in socio-economic and public

health importance in tropical and sub-tropical areas

Widespread distribution and extensive morbidity

Immunopathophysiology centered on the eggs and granuloma formation

Praziquantel
Easily administration, single oral dose
Tolerable side effects
Low cost

Control still a challenge

epidemiology
resources
culture of each country
References

Kenneth j.,et al., Sherris Medical Microbiology, fourth edition

Markell E., et al., Medical Microbiology, Eighth edition

www.who.int/

Mwanakasale, V., P. Vounatsou, et al. (2003). "Interactions between

Schistosoma haematobium and human immunodeficiency virus type 1: the
effects of coinfection on treatment outcomes in rural Zambia." Am J Trop Med
Hyg 69(4): 420-8.

Ross, A. G., P. B. Bartley, et al. (2002). "Schistosomiasis." N Engl J Med 346(16):

1212-20.

Saathoff, E., A. Olsen, et al. (2004). "Patterns of Schistosoma haematobium

infection, impact of praziquantel treatment and re-infection after treatment in a
cohort of schoolchildren from rural KwaZulu-Natal/South Africa." BMC Infect Dis
4: 40.