Spiramycin Treatment of Toxoplasma gondii Infection in Pregnant Women Impairs the Production and the Avidity Maturation of T. gondii -Specific Immunoglobulin G Antibodies

Abstract

The aim of the study was to evaluate the influence of treatment with spiramycin on the increase of immunoglobulin G (IgG) titers and IgG avidity indexes (AI) in pregnant women with seroconversion from the beginning of therapy until delivery and after delivery. This group was compared with adult patients with recently acquired untreated toxoplasmosis. One hundred four samples from 32 pregnant women with seroconversion for toxoplasmosis and/or very low IgG AI were followed from the beginning of therapy with spiramycin until delivery. Twenty-nine women were further followed some months after delivery and interruption of therapy. Thirty-eight samples from 16 untreated, nonpregnant patients were evaluated as the control group. The Toxoplasma gondii-specific IgG antibody and the T. gondii-specific IgG AI were significantly delayed in pregnant women receiving therapy compared to nonpregnant, untreated controls, and the findings were consistent with the results of assays from two different manufacturers. The T. gondii-specific IgG AI increased in pregnant women after they gave birth. Avidity maturation is delayed during pregnancy and treatment, and low-avidity antibodies in pregnant women within 3 to 4 months cannot be taken as a sign of infection.After infection, the specific immunoglobulin G (IgG) antibody response matures by the selection of clones of B cells producing antibodies with increasingly higher avidities against a specific antigen from the invading microorganism. In Toxoplasma gondii infections, specific IgM may be present for a long time (14-17), and measurement of the T. gondii-specific IgG avidity index (AI) is the best method to determine the time of infection (24) and is a further development of the differential agglutination assay (3,27).The original method developed by Hedman et al. (4, 5) used serial dilutions tested in enzyme immunoassays with and without 6 M urea, but automated assays calculate the IgG AI from two single measurements with and without urea (22). This introduces uncertainty, although experiments with only two serum sample dilutions showed excellent agreement with IgG AI measurements obtained with four serial serum sample dilutions (9).A persistent, low IgG AI poses a diagnostic problem, at least in some pregnant women receiving treatment during pregnancy (21).The observation that Toxoplasma gondii-specific IgG maturation is delayed in treated pregnant women compared to nontreated, nonpregnant individuals has been reported in two previous studies, which found significantly delayed IgG maturation in treated individuals (13, 26).The maturation of the IgG response varies between individuals and may take months in pregnant, treated women, for whom one study found that a low IgG AI persisted up to 9 months postinfection (20). In a study of T. gondii-infected pregnant women identified prospectively through prenatal screening, one study found that 2 out of 73 women had IgG AI above 0.2 before 20 weeks of gestation, but many continued to have low IgG AI even a year after infection. It is ass...

Epidemiology of and Diagnostic Strategies for Toxoplasmosis

“…In a study by Petersen et al (253), the mean IgG avidity index determined during the 16 weeks following infection was lower in treated pregnant women than in untreated nonpregnant patients (0.092 versus 0.149; P Ͻ 0.01). In that same study, only 2 out of 103 sera from treated women reached a high avidity index after 4 months, underlining again the potential impact of treatment and in accordance with other studies using other assay devices (138,225). Another way to appreciate the age of infection resides in the kinetics of IgG titers analyzed in two serum samples obtained at 3-week intervals in the absence of any specific therapy.…”

Emerging Role of Zika Virus in Adverse Fetal and Neonatal Outcomes

“…Some screened women will present with both IgG and IgM, making the dating of the infection difficult. IgG avidity testing does not provide reliable information, as a low avidity can be observed for many years, especially in pregnant women receiving treatment (62). In cases of suspected infection, amniocentesis should be discussed at least 4 weeks after the suspected time infection and after 18 weeks GA to increase sensitivity.…”

Toxoplasma Seroconversion with Negative or Transient Immunoglobulin M in Pregnant Women: Myth or Reality? A French Multicenter Retrospective Study

“…Toxoplasma seroconversion is thus defined by specific IgG antibodies appearing after IgM antibodies (2). However, the serological diagnosis of toxoplasmosis is very complex and has been discussed extensively in the published literature (13,14,15). The interpretation of serological tests is complicated by the long-term persistence of specific IgM and the detection of either IgM alone or IgG alone in a previously seronegative pregnant woman (2).…”