Toxoplasma gondii. Definitive Host adult forms sexual reproduction. Intermediate Host immature forms asexual reproduction

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1 Toxoplasma gondii cosmopolitan distribution seropositive prevalence rates vary generally 20-75% generally causes very benign disease in immunocompetent adults tissue cyst forming coccidia predator-prey life cycle felines are definitive host infects wide range of birds and mammals (intermediate hosts) Definitive Host adult forms sexual reproduction Intermediate Host immature forms asexual reproduction

2 Typical Isospora Life Cycle in Felines

3 Typical Isospora Life Cycle in Felines fertilization within infected host cells immature oocysts in feces sporulation in environment (1-4 d)

4 Tachyzoite Stage sporozoites merogony rapid replication dissemination via macrophages reticuloendothelial cells acute stage infection

5 Endodyogony

6 Tachyzoite Stage sporozoites merogony rapid replication dissemination via macrophages reticuloendothelial cells acute stage infection

7 Tachyzoite Stage sporozoites merogony rapid replication dissemination via macrophages reticuloendothelial cells acute stage infection

8 Bradyzoite Stage dormant, slowly replicating due to host immune response chronic or latent infection tissue cysts in brain and muscle

9 Bradyzoite Stage dormant, slowly replicating due to host immune response chronic or latent infection tissue cysts in brain and muscle

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11 Fatal Attraction in Rats Infected with Toxoplasma gondii non-infected rats (n=32) infected rats (n=23) visits to scented areas own neutral rabbit cat From Berdoy et al (2000) Proc. R. Soc. (Biol.) 267:1591

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13 Human Transmission ingestion of sporulated oocysts (cat feces + incubation) ingestion of zoites (undercooked meat) congenital infection (only during acute stage) organ transplants chronic infection in donor immunosuppression blood transfusions (only during acute stage)

14 Acquired Postnatal Toxoplasmosis 1-2 week incubation period acute parasitemia persists for several weeks until development of tissue cysts often asymptomatic (>80%) a common symptom is lymphadenopathy without fever occasionally mononucleosis-like (fever, headache, fatigue, myalgia) likely persists for life of patient immunosuppression can lead to reactivation (eg., organ transplants)

15 Toxoplasmic Encephalitis common complication associated with AIDS during the 1980's recrudescence of latent infection multifocal disease associated with immunosuppression lesions detectable with CT or MRI little spread to other organs symptoms include: lethargy, apathy, incoordination, dementia progressive disease convulsions

16 Congenital Toxoplasmosis 1 o infection must occur during pregnancy can only occur once 1/3 will pass infection to fetus incidence ~1 per 1000 births severity varies with age of fetus move severe early in pregnancy more frequent later in pregnancy infection can result in: spontaneous abortion, still birth, premature birth, or full-term ± overt disease

17 typical disease manifestations include: retinochoroiditis, psychomotor disturbances, intracerebral calcification, hydrocephaly, microcephaly Prevalences of Outcomes 5-10% death 8-10% severe brain and eye damage 10-13% moderate-severe visual impairment 58-72% asymptomatic at birth, many developing retino-choroiditis or mental impairment

18 Ocular Toxoplasmosis retinochoroiditis: likely due to both active parasite proliferation and immune hypersensitivity generally a recrudescence-- rarely from primary infection congenital infection 20% exhibit ocular symptoms at birth 82% by adolescence most lesions are focal and self-limiting rapidly destructive in AIDS patients

19 Ocular Toxoplasmosis retinochoroiditis: likely due to both active parasite proliferation and immune hypersensitivity generally a recrudescence-- rarely from primary infection congenital infection 20% exhibit ocular symptoms at birth 82% by adolescence most lesions are focal and self-limiting rapidly destructive in AIDS patients

20 Diagnosis seldom by direct parasite demonstration biopsy inoculation into mice or cell culture (only acute stage) various serological tests active (acute) vs chronic infection compare samples at 2 week intervals IgM > IgG; Ab titers

21 Treatment recommended: anti-folates (pyrimethamine + sulfadiazine) clindamycin for children spiramycin for prophylatic use during pregnancy Condition Duration Comments symptomatic disease active retinochoroiditis asymptomatic children (<5) + corticosteriod (antiinflammatory) immunocompromised until symptoms subside and evidence of immunity until symptoms subside and evidence of immunity 3-6 weeks 4-6 weeks after symptoms subside + continued prophylaxis prevents retinochoroiditis + folinic acid in AIDS

22 Prevention Raw Meat cook meat thoroughly (66 o C, 150 o F) wear gloves when handling wash hands after Cat Feces no cats in home clean litter box promptly (<24 hr) wear gloves keep cat in house cover sand box control strays

23 An Enigma Several studies show no correlation between cat contact and Toxoplasma. But dog contact is highly correlated with Toxoplasma transmission. Frenkel et al (1995) AJTMH 53:458