Serological diagnosis is the main approach for defining the risk of primary Toxoplasma
infection in a pregnant woman. The measurement of IgG, IgM, IgA, and IgG avidity by different methods usually allows doctors to establish the immunologic status of a patient and to diagnose seroconversion (2
). The difficulties encountered in the serodiagnosis of toxoplasmosis in pregnant women have been underlined for a long time (15
). The absence of IgG antibodies before, or early in, pregnancy enables the identification of women at risk for acquiring infection (12
). Thus, in the daily routine, serological results showing positive IgG and negative or transient IgM in previously negative pregnant women can create interpretation difficulties.
Different factors might explain such results: (i) the injection of gamma globulins or a blood transfusion, which might have led to the appearance of exogenous anti-Toxoplasma
); (ii) immune disorders or other pathologies in the patient, which might have led to the presence of unusual antibody subsets; (iii) toxoplasmosis serological reactivation or reinfection in chronically infected patients with previously very low IgG residual titers below the detection threshold; and (iv) toxoplasmosis that was recently acquired but with a very unusual serological profile. The first two factors should be investigated before the others, and if appropriate, the pregnant women should be considered seronegative and be given hygiene recommendations to avoid toxoplasmic infection.
The first factor (injection of gamma globulins) was ruled out for the 26 cases described in our study. Concerning immune disorders or other pathologies, only varicella symptoms were observed in 1/26 cases (, case 18). To our knowledge, while viral infections are known to generate positive anti-Toxoplasma
IgM, no data can be found in the literature about the influence of viral infection on the detection of anti-Toxoplasma
IgG. The third factor is toxoplasmic serological reactivation or reinfection. In chronic toxoplasmosis, IgG could exceptionally decrease to below the cutoff level of the IgG assay, and in such cases, the reappearance of IgG is not a real seroconversion but a serological reactivation. An additional exposure to T. gondii
could trigger an immediate IgG response without an (or with a weak) IgM response (37
In the case of high IgG avidity results and the absence of gamma globulin injection or transfusion, IgG detection is the paramount criterion of chronic toxoplasmosis (12
). In one case of our study (, case 6), the result of the avidity assay was high, but it is necessary to stress that high avidity has been observed, if rarely, in serum sampled 1 month after infection (21
). However, the determination of IgG avidity in an atypical serological profile is necessary (12
The fourth factor (recently acquired toxoplasmosis with an atypical serological profile) is often considered by medical biologists and clinicians. In fact, in our study, 22/26 patients were treated with spiramycin as a consequence of such serological results, and an amniocentesis was performed for 11/26 patients. However, the results of the infants' follow-ups did not reveal any case of congenital toxoplasmosis. In fact, our results definitively excluded toxoplasmosis in 12 cases and revealed no neonatal abnormality or any serological argument for congenital toxoplasmosis at birth in 10 cases.
The results of IgG confirmatory techniques were always the same as those of the IgG screening techniques, i.e., negative on the first serum sample and positive on the other successive serum samples. Moreover, the avidity findings were low in 16/17 cases. Typically, in seroconversion, the appearance of IgG is linked to high IgM and rising IgM levels (15
). In our study, IgM antibodies were not detected in 15 cases, although we cannot totally exclude that they could have been transient and present during only a very short time period so that they were not observed in the samples at the time they were collected. If the interval between two samplings had been shorter, IgM might have been observed. In the 11 other cases, IgM antibodies were detected at low levels by the Liaison and Platelia tests (2 cases) or with a positive index by only the ISAGA test (9 cases). The detection of IgM usually indicated toxoplasmosis. However, considering that these IgM antibodies were detected at low levels for a very short time period and that they tested positive with only one or two techniques (only the ISAGA test or only the Platelia and Liaison tests) and quickly disappeared, anti-Toxoplasma
IgM antibodies were probably not specific. The persistence of IgG in all successive serum samples might have suggested a life-long immunity to toxoplasmosis, but the follow-up time of these women was not long enough (from 2 weeks to 6 months, depending on the patient).
A pregnant woman who tests negative requires regular check-ups for seroconversion (2
). In fact, the frequency of check-ups varies from one country to another, depending on the screening programs adopted in each country. Seroconversion without IgM can be observed in France thanks to monthly routine testing of seronegative pregnant women. Such results in a previously seronegative pregnant woman should motivate further exploratory tests, as defined by the French National Reference Center for Toxoplasmosis (12
). Double-checking IgG results using other techniques is necessary to confirm the first results, and the avidity test is necessary. It is also important to collect all information about the clinical history of a pregnant woman (immune disorders, other pathology, transfusion, and previous results of toxoplasmosis serology). The interpretation of seroconversion with either no IgM or transient IgM levels may then be discussed.
It is noteworthy that the pathophysiology of toxoplasmosis is far from being fully understood, and the pathogenesis mechanism is complex because the parasite and host specificities are interrelated (38
). In such complex serological cases as those that we analyzed, we think that it is cautious to initiate treatment and to follow up with pregnant women (4
). Puncture and analysis of the amniotic fluid may also be discussed, depending on the gestational age at which the IgG antibodies appeared.