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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 Typical Isospora Life Cycle in Felines Typical Isospora Life Cycle in Felines • fertilization within infected host cells • immature oocysts in feces • sporulation in environment (1-4 d) Tachyzoite Stage • ingestion of oocysts • sporozoites penetrate intestinal epithelium • rapid intracellular replication (any cell) • dissemination via macrophages Tachyzoite Stage • merogony 'merozoites' • typical apicomplexan • motile invasive stages • intracellular replication • 'binary fission' = endodyogony Endodyogony Tachyzoite Stage • repeated rounds of merogony • acute stage infection • primarily in reticuloendothelial cells Bradyzoite Stage • dormant, slowly replicating • due to host immune response • chronic or latent infection • tissue cysts primarily in brain and muscle Bradyzoite Stage • dormant, slowly replicating • due to host immune response • chronic or latent infection • tissue cysts primarily in brain and muscle “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 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) Recent Expansion of Toxoplasma 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) 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 Congenital Toxoplasmosis • 1o infection must occur during or shortly before 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 • 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 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 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 Diagnosis • various serological tests • active (acute) vs chronic infection • compare samples at 2 week intervals • IgM > IgG; Ab titers • seldom by direct parasite demonstration • biopsy • inoculation into mice or cell culture (only acute stage) 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) immunocompromised until symptoms subside and evidence of immunity until symptoms subside + corticosteriod (antiand evidence of immunity inflammatory) prevents 3-6 weeks retinochoroiditis 4-6 weeks after symptoms subside + continued + folinic acid in AIDS prophylaxis Prevention Raw Meat • cook meat thoroughly o o (66 C, 150 F) • wear gloves when handling • wash hands after Cat Feces • clean litter box • • • • • promptly (<24 hr) wear gloves keep cat in house cover sand box no cats in home control strays 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