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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.    Graphical abstractSupplementary Information  The online version contains supplementary material available at 10.1186/s13071-021-04890-4.

Establishment and validation of a guinea pig model for human congenital toxoplasmosis