Abstract
BackgroundToxoplasma 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.MethodsPregnant 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.ResultsWe 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.ConclusionThis 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.Graphical abstract
Highlights
Toxoplasma gondii is an obligate intracellular parasite with a worldwide distribution
This study provides the basis for the proposed use of the guinea pig as an animal model for the investigation of scientific aspects of high medical importance, the pathogenesis of congenital toxoplasmosis in humans
We investigated whether the amount of T. gondii Deoxy‐ ribonucleic acid (DNA) in the guinea pig offspring corresponded to its survival and compared Quantification cycle (Cq) values of various tissue and organs of stillborn offspring and those born asymptomatic, all obtained from dams infected for the same infection duration, i.e. 34–51 days
Summary
Toxoplasma gondii is an obligate intracellular parasite with a worldwide distribution. Congenital infec‐ tion in humans and animals may lead to severe symptoms in the offspring, especially in the brain. Toxoplasmosis is a zoonosis caused by Toxoplasma gondii, an obligate intracellular parasite with a worldwide distribution [1,2,3]. Due to the reaction of the immune system, the parasite is pushed back into the chronic stage, and intracellular tissue cysts containing bradyzoites are formed about 10–14 days after infection. The pathological changes occur in the developing central nervous system [9, 18] In this regard, the clinical picture in humans depends on the time of infection during pregnancy, i.e. the earlier the time of infection, the more severe the symptoms caused by T. gondii. When infection occurs in the third trimester of pregnancy, cerebral calcifications and hepatosplenomegaly predominate [19, 20]
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