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CONGENITAL TOXOPLASMOSIS AFTER A PRECONCEPTIONAL OR PERICONCEPTIONAL MATERNAL INFECTION

Robert-Gangneux, Florence PharmD, PhD*; Yera, Hélène PharmD, PhD†‡; D’Herve, Dominique MD§; Guiguen, Claude MD, PhD*

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The Pediatric Infectious Disease Journal: July 2009 - Volume 28 - Issue 7 - p 660-661
doi: 10.1097/INF.0b013e3181966020
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Abstract

Toxoplasmosis is a worldwide parasitic disease, acquired mainly through undercooked meat or exposure to cat feces, whether directly or indirectly through contaminated raw vegetables or fruits. Primary acquired Toxoplasma gondii infection is usually asymptomatic in immunocompetent subjects, and is often diagnosed retrospectively by serologic analysis. Toxoplasmosis acquired during pregnancy leads to infection of the fetus in about 30% of cases, causing variable lesions according to the duration of gestation at the time of infection.1 Early seroconversion in pregnancy can be associated with fetal loss or serious damage that usually involves the brain and the eyes, but the risk of transplacental transmission to the fetus is very low.2 Conversely, maximal risk of fetal transmission is observed when maternal infection occurs during the third trimester of gestation, but clinical signs at birth are scarce and mostly minor. Very few cases of congenital transmission following a maternal infection acquired before conception or at the time of conception have been described,3–6 and most cases can be related to a deficient immunity background of the mother.5 We report here a case of asymptomatic congenital toxoplasmosis diagnosed at 10 weeks of life in an infant born to a mother who seroconverted in the weeks around or before conception, and discuss in the light of recent data the performance of maternal and neonatal follow-up.

CASE REPORT

As recommended by the French prevention program of congenital toxoplasmosis, M. underwent a serologic screening test for toxoplasmosis during the first trimester of pregnancy (11 weeks of gestation), that showed significant titers of IgG antibody (157 IU/mL) and the presence of IgM antibody (index, 3.78; positivity threshold, >0.55), using the ELISA technique Vidas Toxo IgG II and Vidas Toxo IgM (BioMérieux, Marcy l’Etoile, France). She had previously been diagnosed as seronegative 1 year earlier. IgG titers remained at a similar level in a second serum sample drawn 3 weeks later. Despite a low IgG avidity index 0.03 (Vidas Toxo IgG Avidity, BioMérieux), the stable IgG titers obtained using differential HS/AC agglutination assay (100 and 400 IU/mL, respectively) (performed at the Laboratoire de la Toxoplasmose, Institut de Puériculture de Paris, Paris, France) were compatible with a maternal infection acquired before pregnancy but an infection acquired in the early weeks of gestation could not be excluded. After questioning the patient, no clinical manifestations were evident at this period.

Treatment with spiramycin in a classic dose regimen of 9 MIU daily was started at 13 weeks of gestation until delivery with a good compliance. Monthly ultrasound monitoring examinations were normal. At 16 weeks of gestation amniotic fluid was analyzed for the presence of T. gondii by quantitative PCR (Genbank AF 146527 sequence on LightCycler, Roche Diagnostics, Meylan, France) and mouse inoculations. Both techniques were negative and the pregnancy continued normally.

Delivery occurred by cesarean section at 38 weeks of gestation. Clinical examination of the newborn (boy; weight, 3360 g) was normal, was also transfontanellar ultrasound and fundal examination. As is the custom in France, the biologic neonatal screening comprised placental examination by PCR and mouse inoculation and cord blood serology. No IgM antibody was detected in the cord blood (Toxo ISAGA, BioMérieux), and IgG titer (Enzygnost Toxo IGG Behring, Siemens, Paris la Défense, France) was similar to that of the mother. The comparison of immunologic profiles of maternal and neonatal sera by immunoblotting (Toxoplasma IgG Western-Blot, LDBio, Lyon, France) showed identical IgG patterns, suggestive of passive transfer in utero. Cord blood PCR was negative. However, the placenta was positive by both PCR and mouse inoculation assay (4/6 seropositive mice, confirmed by the presence of cerebral cysts). Serologic testing of the newborn was repeated at 3 and 10 weeks of life and showed decreasing IgG titers, without IgM. Immunoblotting profiles confirmed the infection of the infant by revealing neosynthesized IgG with contrasting profiles at 10 weeks only. The following serum (15 weeks) gave similar results, with an increase of IgG titers. Treatment with 1 mg/kg/d pyrimethamine and 100 mg/kg/d sulfadiazine was started for the infant. Fundal examination was still normal at 4 months of life, and the infant was asymptomatic at 8 months. The T. gondii isolate was sent for genotyping to the Centre de Ressources Biologiques de Toxoplasma (Limoges, Reims, France), a laboratory support for the Centre National de Référence de la Toxoplasmose. The strain was typed as genotype II, as usually observed in human congenital infections in France.

DISCUSSION

The prevention of congenital toxoplasmosis in France by routine screening of mothers and newborns and by early specific treatment has lead to a decrease of the frequency of severe congenital infections.7 Thanks to this program instituted 30 years ago and to multicenter studies assessing diagnostic techniques and practice,8–10 we have now a more precise idea of the fetal risk associated with maternal seroconversion, and of the value of the biologic techniques carried out, as well as the factors that could influence their results. The question of the efficacy of antenatal treatment remains unanswered11 and despite efficient serologic techniques combining IgM detection and comparative immunologic profiles,12 the diagnosis cannot be ruled out until several months of life in a small percentage of infants.

In the case we describe here, IgM antibody was not detected in the successive samples, as it is the case in many (20%–56%) proven infected newborns.8,13 It has been previously shown that this lack of IgM detection could be related to infection in early pregnancy or to treatment of the mother during pregnancy,8 as was the case here.

The first sign of congenital infection in our case was the observation of a positive placental examination. Since a positive placenta result, taken alone, is not widely agreed by all authors as a definitive criterion for congenital infection, and given the pre or periconceptional dating of maternal seroconversion, we waited for further serologic-based evidence of infant infection, which occurred at about 3 months of life. Consequently, the fact that placental tissue was positive for Toxoplasma detection both by PCR and mouse inoculation indicated in utero transmission of the parasite. Despite a low sensitivity in some series,13 the placenta has an excellent positive predicted value for diagnosis of congenital infection, especially when mouse inoculation is positive.8,13 A peculiarity of our case resides in the latent character of the fetal infection. It is usually considered that periconceptional seroconversions rarely lead to congenital infection, or if any, mostly result in fetal damage or loss.2 To our knowledge, only a few observations of congenital transmission following a maternal infection having occurred within 2 months before pregnancy have been published.3,4,6 In the first 2 reports,3,4 mothers were not treated during pregnancy, and the diagnosis of congenital infection was made on evocative clinical signs at several months of life (2 cases) or on ultrasound abnormalities in utero (1 case). In the case described by Villena et al,6 the mother had prolonged lymphadenopathy, in relation with a Toxoplasma infection acquired in the 2 months before pregnancy and the amniocentesis was positive despite spiramycin treatment. Four other cases were reported by Desmonts et al5 in women with previous immunity against Toxoplasma, but carrying various factors of immunodeficiency. In our patient, the mother had no history of immunodeficiency. She was treated throughout pregnancy with spiramycin, and was carefully monitored. No abnormality developed in the fetus and nor were clinical signs observed at birth in the neonate. In addition, the prenatal diagnosis was negative, a fact that could be due to a low parasite load9 or delayed transplacental transfer of parasites. The parasite strain (genotype II) had no characteristics of hypervirulence, which correlates with the absence of clinical manifestations reported by the mother within the weeks around conception.

In conclusion, in the light of this atypical case of congenital toxoplasmosis, we emphasize as others14 the need for careful ultrasound monitoring of mothers with periconceptional toxoplasmic infection and highlight the value of placental analysis. Additionally, repeated postnatal serum screening is recommended, for early detection of infected newborns who need specific treatment to reduce the onset of long-term sequelae.7,15

ACKNOWLEDGMENTS

The authors thank the Centre de Ressources Biologiques de Toxoplasmes (Limoges, Reims, France) for typing the isolate.

REFERENCES

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Keywords:

congenital toxoplasmosis; periconceptional infection; postnatal diagnosis; Western blotting

© 2009 Lippincott Williams & Wilkins, Inc.