SCHISTOSOME:IMMUNE EVASION AND VACCINATION STRATEGIES SUBMITTED BY : SABIHA BI 14ZYM13 GG-3653 SECTION OF PARASITOLOGY

contents Introduction Classification History Epidemiology Life cycle Immune evasion Progression of disease Prevention and control Vaccination strategies

introduction Schistosomiasis (also called bilharziasis) is a parasitic disease caused by Schistosoma spp. (blood fluke). WORLD HEALTH ORGANISATION defined Schistosomiasis as a neglected tropical disease found commonly across ASIA, AFRICA, and SOUTH AMERICA . Schistosome infection causes great socio-economic impact, as it produces chronic illness, leading to impairments of organs functions and finally cancer.

classification KINGDOM : Animalia PHYLUM : Platyhelminthes CLASS : Trematoda SUBCLASS : Digenea ORDER : Prosostomata FAMILY : Schistosomatidae GENUS : Schistosoma SPECIES : S. haematobium S. mansoni S. japonicum

history First case in humans was reported in 1851 by Theodore Bilharz(1825-1862) . Approximately 200 million people in 74 Countries are infected with Schistosomes. 120 million are symptomatic & 20 million suffer severe illness.

Today 18 species of Schistosomes have been recognised: 1. S. haematobium 7. S. nasale 13. S. sinensium 2. S. bovis 8. S. hippopotami 14. S. spindale 3. S.intercalatum 9. S. curassoni 15. S. leiperi 4. S. magrebowiei 10. S. rodhaini 16. S. indicum 5. S. mansoni 11. S. malthesi 17. S. incognitum 6. S japonicum 12. S. mekongi 18. S. edwardiense

HISTORY Five Schistosome species infect human – S. haematobium Bilharz -1851 S. japonicum Katsurada - 1904 S. mansoni Sambon - 1907 S. intercalatum Fischer - 1934 S. mekongi Voge et al - 1978

Three species of Schistosomes are : S. haematobium S. mansoni S. japonicum MALE SIZE : 1 - 1.5 cm by 1 mm. 1 cm by 1 mm. 1 - 2 cm by 0.5 mm. FEMALE SIZE: 2 cm by 0.25 mm. 1.4 cm by 0.25 mm. 2.6 cm by 0.5 mm. INTERMEDIATE HOST (SNAIL): Bulinus and Planorbarius. Biomphalaria and Australorbis. Oncomelania. DEFINITIVE HOST: Man. Man and domestic animal. HABITAT: Vesical and prostatic venous plexus. Mesenteric plexus of sigmoido-rectal area ( inferior mesenteric vein and its radicles). Mesesnteric plexus of ileocaecal area (superior mesenteric vein and its radicles). EGGS: Terminal spine. Lateral spine. Lateral knob.

eggs S. mansoni S. haematobium S. japonicum

EPIDEMIOLOGY Areas where human schistosomiasis is found include: Schistosoma mansoni Distributed various parts ofAfrica . Nile River valley in Sudan and Egypt. South America: including Brazil. S. haematobium Distributed various parts of Africa. Transmission also occurs in the Nile River valley in Egypt. Middle East S. japonicum Found in China, Japan, some parts of Burma. Philippines.

Distribution of schistosomiasis China Japan Egypt Burma Columbia Arabic peninsula Philippines Brazil

LIFE CYCLE OF SCHISTOSOMES

Progression of the disease cercarae penetrate unbroken skin Cast off tail (schistosomulae) Peripheral venule Right heart schistosomula Pulmonary circulation Left heart

Some shunted in abdominal aorta Systemic circulation Some shunted in abdominal aorta Some mesenteric artery intestine Enter portal circulation (liver)

Taken from K. D. Chatterjee

PROGRESSION OF THE DISEASE ACUTE INFECTION : Cercariae penetrate skin  rash ( cercareal dermatitis) or swimmer’s itch. Eggs laid in target organs release antigens  cause fever (Katayama fever) urticaria malaise chills abdominal pain eosinophilia. 

CHRONIC INFECTION: Symptomatic : Asymptomatic: Many persons are asymptomatic Symptomatic : Bloody diarrhea Hepatosplenomegaly Ascites, haematuria, bladder cancer, kidney problems, CNS lesions. Granuloma formation.

PREVENTION AND CONTROL Public education Sanitation of water Diagnosis and treatment Habitat modification. Control of the intermediate hosts (freshwater snails)

TREATMENT AND CONTROL DRUGS: Praziquantel -drug of choice, effective in the treatment of all forms of schistosomiasis, with virtually no side effects. Oxamniquine -used exclusively to treat intestinal schistosomiasis in Africa and South America Metrifonate - effective for the treatment of urinary schistosomiasis

1- Antigenic modification Immune Evasion 1- Antigenic modification Antigen disguise: Adult Schistosoma cover themselves with host proteins to be considered as self and will not be attacked by the immune factors. host’s RBCs

Similar to host’s antigens Surface turnover : Schistosoma mansoni Shed their teguments in abundance can neutralize antibody response at a distance away from the parasite. Antigen mimicry: Schistosoma produce antigens similar to host antigens so they are not recognized by the host’s immune system. Similar to host’s antigens

2- Production of blocking antibodies Antibodies of little protective effect. Schistosoma produce blocking Abs that combine with Schistosoma Ags making them unavailable for antibodies of high protective effect (antibody involved in ADCC).

3- Inhibition of Immune Factors Schistosoma larva , inactivates the complement system through Protease activity . The mechanism of immune evasion is not resolved completely till now.

VACCINATION STRATEGIES Vaccine strategies represent an essential component as an adjunct to chemotherapy for the future control of Schistosomiasis. An improving understanding of immune response to Schistosome infection suggest the develpoment of vaccine is possible . Vaccination against Schistosome can be targeted towards prevention of infection and reduction in worm burden.

The existance of immunity in the presence of active adult infection is considered by Smithers and Terry (1969), to be an example of Concomitant immunity. Phenomena of concomitant immunity is studied in baboon, mice, rats and humans. Live cercarae or Schistosomulae as well as attenuated forms are used to immunized experimental animals in which they induce immunity. Such immunized animals are substantially protected from pathogenic effect and shows 60-70% lower worm count and tissue egg count than non –vaccinated animal

MAJOR CANDIDATE VACCINES AND THEIR PROTECTIVE EFFICACIES Tetraspanin (Sm-tsp-1& Sm-tsp-2) Important vaccine candidate . Present at apical syncytial surface of S. mansoni. Used in a defined vaccine formulation upon administration provided : Protection 29-61% Reduction in egg burden 50-61%

Sm-28-GST (Glutathione S- transferase) It is expressed in subtegumental tissues of developmental stages of parasite. Has been used as the potential vaccine candidate against human Schistosome infection. It has been successfully tested at primate level and ready for human trial.

Sm-p80 (calpain) First vaccine antigen identified on the basis of T-cell activity. Sm-p80 – based vaccine formulation have three protective effects: Worm reduction . Antifecundity effect . Protection against acute Schistosomiasis . worm reduction 60-70%

other candidates are: SOD (SUPEROXIDE DISMUTASE) localised below the tegumental membrane and Paramyosin. A number of recent studies, have utilised plasmid DNA vaccines. Generate both T-cell and B-cell immune responses. Particularly appealing for Schistosome vaccines development.

Conclusion An effective, protective Schistosomiasis vaccine would be of immense public importance. The apical membrane proteins, help in immune evasion are the logical vaccine targets. All above mention candidates based on this idea. One successful human trial is yet to be completed, the vaccine will be available for commercial product in next few year time.

REFERENCE Animal parasitology by J.D.Smyth BOOKS Animal parasitology by J.D.Smyth Parasitology by K.D.Chatterjee Basic clinical parasitology by Belding & Brown Animal parasites in man by N.H.Swellengrebel & M.M.Sterman Immunity to parasites by Derek Wakelin

Journals Afzal A. Siddiqui1* Bilal A. Siddiqui2 and Lisa Ganley-leal3 .2011 Scistosomiasis vaccines. Donald P. McManus1* and Alex Loukas2 2008 Current status of vaccines for Schistosomiasis. Internet sites http://www.google.com http://en.wikipedia.org http://www.nature.com http://www.dpd.cdc.gov/dpdx http:// www.wikipedia.org http://www.who.int/mediacentre/factsheets Global poverty info bank