Contribution of serology in congenital toxoplasmosis diagnosis: results from a 10-year French retrospective study

Abstract

This study aimed to evaluate different serological strategies for the postnatal diagnosis of congenital toxoplasmosis (CT) and establish a biological algorithm for CT diagnosis. The study analyzed serological data of immunoglobulins M, A, and G (IgM, IgA, IgG) performed by immunoenzymatic and compared immunological profile (CIP) assays in 668 newborns with CT diagnosis across four testing periods: P1 (D0- D10), P2 (D11-D35), P3 (D36-D45), and P4 (>D45). Forty-nine percent of the 668 CT cases were diagnosed during P1 and 34%, 4%, and 12% during P2, P3, and P4, respectively. CIP assays detected neosynthetized IgMs/IgGs in 98% of CT cases diagnosed during P1, while IgMs and IgAs were detected in 90% and 57% of CT cases diagnosed during P2 and in 88% and 67% of diagnoses made during P3, respectively. Detection of neosynthesized IgMs/IgGs, IgMs, and IgAs by immunoassay contributed to CT diagnosis in 81%, 77%, and 60% of cases, respectively. In total, 46% of serum samples were positive for all three parameters, 27% for two, and 27% for one of the three. The study recommends using the CIP assay as standard during P1 for CT diagnosis and IgM and IgA immunoassays after P1. A clinical and biological follow-up in a specialized center with a close collaboration between biologists and clinicians is highly recommended to increase the chances of early diagnosis. Overall, this study provides useful information for the development of a biological algorithm for CT diagnosis, which can aid in early detection and appropriate treatment of this disease.

Keywords: CIP assay; IgA; IgM; congenital toxoplasmosis; immunoblot; serological diagnosis.

Fig 1

Study design. *We noticed 18 late CT diagnoses:10/18 with no CIP, IgM and IgA serological monitoring according to good practice (negative serology on P1 with no control before D90), and 8/18 with a correct but negative serological follow-up.

Fig 2

Categorization of the serum samples that led to CT diagnosis according to the period. CT, congenital toxoplasmosis; P, period (P1 = D0–D10; P2 = D11–D35; P3 = D36–D45; P4 = D46–D90).

Fig 3

(A) Positivity rates of the total of compared immunological profile, IgMs, and IgA on sera that led to the CT diagnosis (positive sera/number of sera for which the technique was performed) immunoanalyses. (B) Proportions of positive techniques by combination on the sera that led to the CT diagnosis. Tests were considered positive or negative/not realized. P, period (P1 = D0–D10, n = 331; P2 = D11–D35, n = 230; P3 = D36–D45, n = 26; P4 = D46–D90, n = 81).

Fig 4

Venn diagram. Contributions of the CIP assays, IgM, and IgA serological tests to CT diagnosis. (A) For the four periods (n = 299 CT, i.e., 518 serum samples). (B) For the P1 period (n = 208 CT, i.e., 208 serum samples). (C) For the P2 period (n = 69 CT, i.e., 69 serum samples). Ig, immunoglobulin.

Fig 5

Recommandations from National Reference Center to CT serological diagnosis on an infant with negative or no prenatal diagnosis. *Risk of contamination by maternal immunoglobulins. **IgG must be measured in parallel on successive sera with the same technique.