Identification of a sporozoite-specific antigen from Toxoplasma gondii

Authors: Hill, Dolores; COSS, CATHLEEN - Former ARS Employee; Dubey, Jitender; WROBLEWSKI, KRISTEN - University Of Chicago; SAUTTER, MARI - University Of Chicago; HOSTEN, TIFFANY - University Of Chicago; MUNOZ-ZANZI, CLAUDIA - University Of Minnesota; MUI, ERNEST - University Of Chicago; WITHERS, SHAWN - University Of Chicago; BOYER, KENNETH - Rush University Medical Center; HERMES, GRETCHEN - University Of Chicago; COYNE, JESSICA - University Of Chicago; JAGDIS, FRANK - Centers For Disease Control And Prevention (CDC) - United States; BURNETT, ANDREW - Centers For Disease Control And Prevention (CDC) - United States; MCCLEOD, PATRICK - University Of Chicago; MORTON, HOLMES - Clinic For Special Children; ROBINSON, DONNA - Clinic For Special Children; MCLEOD, RIMA - University Of Chicago

Submitted to: Journal of Parasitology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/3/2011
Publication Date: 5/1/2011
Citation: Hill, D.E., Coss, C., Dubey, J.P., Wroblewski, K., Sautter, M., Hosten, T., Munoz-Zanzi, C., Mui, E., Withers, S., Boyer, K., Hermes, G., Coyne, J., Jagdis, F., Burnett, A., Mccleod, P., Morton, H., Robinson, D., Mcleod, R. 2011. Identification of a sporozoite-specific antigen from Toxoplasma gondii. Journal of Parasitology. 97(2):328-337.

Interpretive Summary: Toxoplasmosis causes loss of sight, neurologic function, and life. Frequency with which infections were caused by oocysts and implications of acquisition of oocysts had not been explored. An 18.3 kDa sporozoite specific protein was discovered and an assay developed to determine whether and when serum antibody to this protein detects infection acquired from ingestion of oocysts. Sera from 72 uninfected, 59 chronically infected, and 35 acutely infected persons in 4 North American epidemics [laboratory, N=6; riding stable, N=17; family, N=8; Victoria, Canada, N=3], and 76 mothers of newborn, congenitally infected children in the NCCCTS were studied. Associations with perceived risk factors, demographics, and clinical findings were characterized for the mothers. Serum antibody to the 18.3 kDa sporozoite protein identified primary infection with sporozoites acquired within <8 months. Four North American epidemics and 78% of congenital infections were caused by oocysts. Only 49% of mothers infected by oocysts recognized significant exposure to oocysts [Specificity, 71% (95% CI [44%, 90%]); Sensitivity, 49% (95% CI [36%, 63%]); Positive predictive value, 85% (95% CI [69%, 95%]); Negative predictive value, 29% (95% CI [16%, 45%])].

Technical Abstract: Toxoplasma gondii is an apicomplexan parasite that causes the disease toxoplasmosis. Toxoplasmosis results in the loss of life, sight, cognitive and motor function, and hearing in congenitally infected individuals. While the sources of T. gondii infection have been established, the factors influencing pathogenesis in humans, such as the predominant mode of acquisition and how this might impact its prevention are not well characterized. Existing serologic assays can only determine previous exposure to the parasite. We hypothesized that understanding the epidemiology of the infection would allow for developing the best means to prevent it. Therefore, in this study we developed an assay that differentiates between cat borne and meat borne infection. Detection of serum antibody to an 18.3 kDa sporozoite protein was a sensitive and specific method to identify primary infection by sporozoites within the past 6-8 months in persons infected post-natally. Presence of serum antibody to sporozoite 18.3 kDa protein identifies acquisition of infection with oocysts in the prior ~6 months. Unrecognized exposure to T. gondii oocysts is a significant cause of infection of humans in North America. Although educational programs describing hygienic measures may be beneficial, only systematic serologic testing of pregnant women and newborns and consequent treatment, or vaccines, will prevent congenital toxoplasmosis in North America.