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

Abstract

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.

Figure 1

Details of search and study selection procedure. (a) The PRISMA flow diagram describing the study design process. (b) Venn diagram constructed to identify common and exclusive samples used in the included studies.

Figure 2

Forest plot of the sensitivity and specificity estimates and 95% confidence intervals (CI) for PCR and bioassay in amniotic fluid or placenta samples according to the single study sets. Estimates of sensitivity and specificity from each study are shown as solid yellow squares for PCR in amniotic fluid, solid yellow circle for bioassay in amniotic fluid, solid purple squares for PCR in placenta, and solid purple circle for bioassay in placenta.

Figure 3

Schematic model represents the types of samples and methods used to T. gondii detection before and after birth. Maternal peripheral blood (M-PB), prenatal cord blood (P-CB), and amniotic fluid (AF) are the samples collected for gestational and congenital toxoplasmosis diagnosis before birth. After birth, the samples that can be collected are maternal peripheral blood (M-PB), colostrum (CL), placenta (PL), amniotic fluid (AF), neonatal cord blood (N-CB), and neonatal peripheral blood (N-PB) to confirm the congenital toxoplasmosis. The target and methods most used to detect the infection are Toxoplasma DNA by PCR; the parasite by bioassay (culture and/or mouse inoculation); and antibodies anti-Toxoplasma by immunoassay. PCR: polymerase chain reaction. Figure created using images from Servier medical art by Servier licensed under creative commons attribution 3.0 France (CC BY 3.0 FR).