1. Protist parasite of human importance Disease : Toxoplasmosis Agent : Toxoplasma gondii Diverse routes of transmission Tissue-inhabiting Apicomplexan. Zoonosis. At risk groups.

2. Life cycle of Toxoplasma

3. Toxoplasma life cycle stages Oocyst Tachyzoites Bradyzoites

4. Bradyzoites within tissue cysts

5. Toxoplasma gondii : Modes of transmission Ingestion of cyst- containing meat (carnivores) Ingestion of oocysts (environmental contamination) Congenital infection Transfusion (rare) Raw goat’s milk, lambing, transplantation

6. Percentage of Toxoplasma infection associated with type of meat consumed CountryBeef (%)Pork (%)Lamb (%) Salami (%) Belgium 6210 Denmark 27284 Italy 12.530.512.5 Norway 193213 Switz. 813105 Adapted from Sukthana, 2006

7. Seropositivity rates Continents and countriesSeropositivity (%) Europe Spain Austria France Norway UK Poland 28.6% 43% up to 75% 10.9% 57-93% 46.4-58.5% USA 16-40% Central and South America Costa Rica Argentina 76% 72% S.E. Asia Indonesia Thailand 58% 2.3-21.9%

8. Symptomatology : Toxoplasma Most infections benign Rarely severe –hepatitis, encephalomyelitis, myocarditis Few cases of retinochoroiditis which can progress to blindness At risk groups (see over)

10. Intra-uterine infections Severe clinical picture : retinochoroiditis, encephalomyelitis, hydrocephalus, microcephaly Most infections result in blindness, severe visual impairment and/or mental retardation Estimates 50-70 seriously affected births UK ; approx 3000 congenital cases USA

11. Toxoplasma in the immunocompromised host Immunosuppression, malignancy, AIDS, organ transplantation Neurological complications - meningoencephalitis or cerebral mass lesions : cerebral toxoplasmosis Headache, confusion, ataxia, hemiparesis, retinochoroiditis Endogenous versus exogenous infection

12. Cerebral toxoplasmosis : Centre for Disease Control (CDC) criteria for diagnosis Recent onset of focal neurological abnormality consistent with intercranial disease or reduced consciousness Evidence from brain imaging of a lesion (CT or MRI) Positive serum antibody to T. gondii or response to treatment

13. Diagnostic tests for Toxoplasma Sabin-Feldman dye test (DT) Enzyme immunoassay for T. gondii specific IgM (EIA) Immunsorbent agglutination assay (ISAGA) Enzyme immunoassay for IgG avidity Isolation and culture of parasite Direct detection by microscopy and PCR

14. Differential Diagnosis Immunocompetent adults (DT, IgM EIA) Pregnant women (maternal serum DT, IgM EIA, IgG avidity; Amniotic fluid culture or PCR) Neonates (DT, EIA, ISAGA for IgM, IgA) Organ transplantation (DT, IgM EIA) Immunodeficiency (serum and CSF : DT, EIA, ISAGA for IgM and IgA; PCR, culture, microscopy)

15. Prevention and control Avoid consumption of raw or undercooked meat Litterpans should be changed daily Wash hands after handling raw meat, litter pans & soil Pregnant women should avoid contact with cats Issue of prenatal screening

16. Program for mass screening and prophylactic treatment of pregnant women for T. gondii Test 1Test 2Test 3Group IgG +ve IgM -ve No test No treat No test No treat Infection before pregnancy no risk IgG +ve IgM +ve Repeat IgG after 3 wks Treat if high or rising Possible infection soon after conception slight risk IgG -ve IgM -ve Treat if IgG +ve No previous infection, if seroconver. high risk

17. Treatment : toxoplasmosis Only accepted treatment pyrimethamine with trisulfapyrimines for 1 month Intravenous clindamycin used to treat encephalitis in AIDS patients In France spiramycin has been used to treat toxoplasmosis in pregnancy Spiramycin is available in the US on a case-by-case basis

18. Seroprevalence of Toxoplasmosis by county of maternal residence % Ferguson et. al. 2009 IMJ

19. Toxoplasma and Schizophrenia Robert H. Yolken, F.B. Dickerson & E. Fuller Torrey (2009) Parasite Immunology 31 (11), 706-715

20. Key points Individuals with schizophrenia higher seroprevalence of Toxoplasma Epidemiology of Toxoplasma and schizophrenia similar Antipsychotic drugs inhibit Toxoplasma Toxoplasma induces elevated levels of dopamine Individuals with schizophrenia higher exposure to cats