Thomas Grochow1,2, Britta Beck1,2, Zaida Rentería-Solís2, Gereon Schares3, Pavlo Maksimov3, Christina Strube4, Johannes Seeger1, Lisa Raqué5, Reiner Ulrich6, Arwid Daugschies2, Simone A Fietz7. 1. Institute of Veterinary Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany. 2. Institute of Parasitology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany. 3. National Reference Laboratory for Toxoplasmosis, Institute of Epidemiology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Greifswald-Insel Riems, Germany. 4. Institute for Parasitology, Centre for Infection Medicine, University of Veterinary Medicine Hannover, Hannover, Germany. 5. Veterinary Practice Raqué, Leipzig, Germany. 6. Institute of Veterinary Pathology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany. 7. Institute of Veterinary Anatomy, Histology and Embryology, Faculty of Veterinary Medicine, University of Leipzig, Leipzig, Germany. simone.fietz@vetmed.uni-leipzig.de.
Abstract
BACKGROUND: Toxoplasma gondii is an obligate intracellular parasite with a worldwide distribution. Congenital infection in humans and animals may lead to severe symptoms in the offspring, especially in the brain. A suitable animal model for human congenital toxoplasmosis is currently lacking. The aim of this study is to establish and validate the guinea pig as a model for human congenital toxoplasmosis by investigating the impact of the T. gondii infection dose, the duration of infection and the gestational stage at infection on the seroconversion, survival rate of dams, fate of the offspring, T. gondii DNA loads in various offspring tissues and organs and the integrity of the offspring brain. METHODS: Pregnant guinea pigs were infected with three different doses (10, 100, 500 oocysts) of T. gondii strain ME49 at three different time points during gestation (15, 30, 48 days post-conception). Serum of dams was tested for the presence of T. gondii antibodies using immunoblotting. T. gondii DNA levels in the dam and offspring were determined by qPCR. Offspring brains were examined histologically. RESULTS: We found the survival rate of dams and fate of the offspring to be highly dependent on the T. gondii infection dose with an inoculation of 500 oocysts ending lethally for all respective offspring. Moreover, both parameters differ depending on the gestational stage at infection with infection in the first and third trimester of gestation resulting in a high offspring mortality rate. The duration of infection was found to substantially impact the seroconversion rate of dams with the probability of seroconversion exceeding 50% after day 20 post-infection. Furthermore, the infection duration of dams influenced the T. gondii DNA loads in the offspring and the integrity of offspring brain. Highest DNA levels were found in the offspring brain of dams infected for ≥ 34 days. CONCLUSION: This study contributes to establishing the guinea pig as a suitable model for human congenital toxoplasmosis and thus lays the foundation for using the guinea pig as a suitable animal model to study scientific questions of high topicality and clinical significance, which address the pathogenesis, diagnosis, therapy and prognosis of congenital toxoplasmosis.
BACKGROUND:Toxoplasma gondii is an obligate intracellular parasite with a worldwide distribution. Congenital infectioninhumans and animals may lead to severe symptoms in the offspring, especially in the brain. A suitable animal model for humancongenital toxoplasmosis is currently lacking. The aim of this study is to establish and validate the guinea pig as a model for humancongenital toxoplasmosis by investigating the impact of the T. gondii infection dose, the duration of infection and the gestational stage at infection on the seroconversion, survival rate of dams, fate of the offspring, T. gondii DNA loads in various offspring tissues and organs and the integrity of the offspring brain. METHODS: Pregnant guinea pigs were infected with three different doses (10, 100, 500 oocysts) of T. gondii strainME49 at three different time points during gestation (15, 30, 48 days post-conception). Serum of dams was tested for the presence of T. gondii antibodies using immunoblotting. T. gondii DNA levels in the dam and offspring were determined by qPCR. Offspring brains were examined histologically. RESULTS: We found the survival rate of dams and fate of the offspring to be highly dependent on the T. gondii infection dose with an inoculation of 500 oocysts ending lethally for all respective offspring. Moreover, both parameters differ depending on the gestational stage at infection with infectionin the first and third trimester of gestation resulting in a high offspring mortality rate. The duration of infection was found to substantially impact the seroconversion rate of dams with the probability of seroconversion exceeding 50% after day 20 post-infection. Furthermore, the infection duration of dams influenced the T. gondii DNA loads in the offspring and the integrity of offspring brain. Highest DNA levels were found in the offspring brain of dams infected for ≥ 34 days. CONCLUSION: This study contributes to establishing the guinea pig as a suitable model for humancongenital toxoplasmosis and thus lays the foundation for using the guinea pig as a suitable animal model to study scientific questions of high topicality and clinical significance, which address the pathogenesis, diagnosis, therapy and prognosis of congenital toxoplasmosis.
Authors: Elżbieta Hiszczyńska-Sawicka; Justyna M Gatkowska; Marcin M Grzybowski; Henryka Długońska Journal: Parasitology Date: 2014-05-07 Impact factor: 3.234
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