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 causedby Schistosoma spp. (blood fluke). WORLD HEALTH ORGANISATION defined Schistosomiasis as a neglected tropical disease found commonlyacross ASIA, AFRICA, and SOUTH AMERICA . Schistosome infection causes great socio-economic impact, as it produces chronic illness, leadingto 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( ) . 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 S. japonicum Katsurada S. mansoni Sambon S. intercalatum Fischer S. mekongi Voge et al Three species of Schistosomes are :
S. haematobium S. mansoni S. japonicum MALE SIZE : 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 cmby 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 Rivervalley 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 swimmers 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. hosts RBCs Similar to hosts 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 hosts immune system. Similar to hosts 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. Animproving understanding of immune response to Schistosome infection suggest the develpoment of vaccine is possible . Vaccination against Schistosome can be targeted towardsprevention of infectionandreduction in worm burden. The existance ofimmunity 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 attenuatedforms are used to immunized experimental animalsin which they induce immunity. Such immunized animals are substantially protected from pathogenic effect and shows 60-70% lowerwormcount andtissue egg count than non vaccinatedanimal 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. Usedin a defined vaccine formulation upon administration provided : Protection % Reduction in egg burden % 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 Schistosomeinfection. 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 protectiveeffects: Worm reduction . Antifecundity effect . Protection against acute Schistosomiasis . worm reduction % other candidates are: SOD (SUPEROXIDE DISMUTASE) localised below the tegumentalmembrane and Paramyosin. A number of recent studies, have utilised plasmid DNA vaccines. Generate both T-cell and B-cell immune responses. Particularly appealing for Schistosomevaccines development. Conclusion An effective, protective Schistosomiasis vaccine would be of immense public importance. Theapical 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-leal Scistosomiasis vaccines. Donald P. McManus1* and Alex Loukas Current status of vaccines for Schistosomiasis. Internet sites Global poverty info bank