Systematic Review and Meta-Analysis of Congenital Toxoplasmosis Diagnosis: Advances and Challenges.

Objective: To understand how congenital toxoplasmosis (CT) diagnosis has evolved over the years, we performed a systematic review and meta-analysis to summarize the kind of analysis that has been employed for CT diagnosis. Methods: PubMed and Lilacs databases were used in order to access the kind of analysis that has been employed for CT diagnosis in several samples. Our search combined the following combining terms: "congenital toxoplasmosis" or "gestational toxoplasmosis" and "diagnosis" and "blood," "serum," "amniotic fluid," "placenta," or "colostrum." We extracted data on true positive, true negative, false positive, and false negative to generate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Random-effects models using MetaDTA were used for analysis. Results: Sixty-five articles were included in the study aiming for comparisons (75.4%), diagnosis performance (52.3%), diagnosis improvement (32.3%), or to distinguish acute/chronic infection phases (36.9%). Amniotic fluid (AF) and placenta were used in 36.9% and 10.8% of articles, respectively, targeting parasites and/or T. gondii DNA. Blood was used in 86% of articles for enzymatic assays. Colostrum was used in one article to search for antibodies. In meta-analysis, PCR in AF showed the best performance for CT diagnosis based on the highest summary sensitivity (85.1%) and specificity (99.7%) added to lower magnitude heterogeneity. Conclusion: Most of the assays being researched to diagnose CT are basically the same traditional approaches available for clinical purposes. The range in diagnostic performance and the challenges imposed by CT diagnosis indicate the need to better explore pregnancy samples in search of new possibilities for diagnostic tools. Exploring immunological markers and using bioinformatics tools and T. gondii recombinant antigens should address the research needed for a new generation of diagnostic tools to face these challenges.

Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection.

Toxoplasma gondii (T. gondii) is an intracellular parasite responsible for causing toxoplasmosis. When infection occurs during pregnancy, it can produce severe congenital infection with ocular and neurologic damage to the infant. From the oral infection parasite reaches the intestine, causing inflammatory response, damage in tissue architecture and systemic dissemination. Macrophage migration inhibition factor (MIF) is a cytokine secreted from both immune and non-immune cells, including gut epithelial cells. MIF is described to promote inflammatory responses, to be associated in colitis pathogenesis and also to play role in maintaining the intestinal barrier. The aim of the present study was to evaluate the influence of the pregnancy and MIF deficiency on T. gondii infection in the intestinal microenvironment and to address how these factors can impact on the intestinal architecture and local cytokine profile. For this purpose, small intestine of pregnant and non-pregnant C57BL/6 MIF deficient mice (MIF-/-) and Wild-type (WT) orally infected with 5 cysts of ME-49 strain of T. gondii were collected on day 8th of infection. Intestines were processed for morphological and morphometric analyses, parasite quantification and for cytokines mensuration. Our results showed that the absence of MIF and pregnancy caused an increase in T. gondii infection index. T. gondii immunolocalization demonstrated that segments preferentially infected with T. gondii were duodenum and ileum. The infection caused a reduction in the size of the intestinal villi, whereas, infection associated with pregnancy caused an increase in villi size due to edema caused by the infection. Also, the goblet cell number was increased in the ileum of MIF-/- mice, when compared to the corresponding WT group. Analyses of cytokine production in the small intestine showed that MIF was up regulated in the gut of pregnant WT mice due to infection. Also, infection provoked an intense Th1 response that was more exacerbated in pregnant MIF-/- mice. We also detected that the Th2/Treg response was more pronounced in MIF-/- mice. Altogether, our results demonstrated that pregnancy and MIF deficiency interferes in the balance of the intestinal cytokines and favors a Th1-immflamatory profile, which in turn, impact in the development of pathology caused by T. gondii infection in the intestinal microenvironment.

Erratum to "Macrophage migration inhibitory factor (MIF) and pregnancy may impact the balance of intestinal cytokines and the development of intestinal pathology caused by Toxoplasma gondii infection" [Cytokine: X 2 (2020) 100034].

[This corrects the article DOI: 10.1016/j.cytox.2020.100034.].