Introduction Ophthalmologic complications of congenital toxoplasmosis, such as retino-choroiditis... more Introduction Ophthalmologic complications of congenital toxoplasmosis, such as retino-choroiditis, are particularly feared. Any child with confirmed congenital toxoplasmosis is systematically treated and followed regularly with multiple fundus examinations. The goal of our study is to describe the management and monitoring of a cohort of patients with congenital toxoplasmosis in Alsace, and the impact of this disease in terms of parental anxiety using a standardized questionnaire. Materials and methods Our study recorded 35 children with congenital toxoplasmosis, born between 1990 and 2011 in Alsace. All patients were followed by an ophthalmologist. A standardized questionnaire concerning the experience of pregnancy and post-natal follow-up was administered to the parents. Results At birth, retinochoroiditis was detected in 2 of the 35 children, and only one child developed chorioretinitis detected during follow-up monitoring (follow-up ranged from 1 to 22 years). Brain abnormalitie...
Materno-foetal transmission causes one of the most severe forms of infection with the protozoan p... more Materno-foetal transmission causes one of the most severe forms of infection with the protozoan parasite Toxoplasma gondii. Several studies have shown T. gondii in placental trophoblast cells, which form the barrier between maternal blood circulation and foetal tissue. Parasite multiplication in trophoblast cells is thus a critical step leading to infection of the foetus. Here, we show that multiplication of T. gondii tachyzoites was slow in BeWo trophoblast cells, compared with MRC-5 fibroblast cells. However, unlike MRC-5 cells, even combined stimulation with interferon-gamma and tumor necrosis factor-alpha did not reduce T. gondii replication in BeWo cells. This was associated with a lack of indoleamine-2,3-dioxygenase induction by these cytokines. Neither low availability of iron salts, nor an immunosuppressive action of cyclooxygenase-2 could be attributed to the low T. gondii multiplication rate in BeWo cells. However, treatment with the nitric oxide synthesis inhibitor N(G)-m...
Protective immunity in mice infected with Toxoplasma gondii is mainly mediated by NK cells, CD4 a... more Protective immunity in mice infected with Toxoplasma gondii is mainly mediated by NK cells, CD4 and CD8 T cells, and type 1 cytokines, such as gamma interferon (IFN-gamma). To clarify the roles of NK cells and IFN-gamma in protection against primary congenital toxoplasmosis, we used recombination activating gene 2 knockout (RAG-2(-/-)) mice, which lack T and B lymphocytes, in comparison with the wild-type BALB/c model. RAG-2(-/-) mice had a significantly lower risk of fetal toxoplasmosis than BALB/c mice (25 versus 63.9%; P = 0.003). This protection was associated with an increased number of maternal NK cells, IFN-gamma secretion by spleen cells, and decreased parasitemia. In the RAG-2(-/-) mice, NK cell depletion increased both the rate of fetal infection, to 56.5% (P = 0.02), and the blood parasite burden. Conversely, in the BALB/c mice, this treatment did not modify maternofetal transmission or the blood parasite burden. Neutralization of IFN-gamma in both infected RAG-2(-/-) and...
We evaluated molecular diagnosis of congenital toxoplasmosis (CT) on neonatal amniotic fluid samp... more We evaluated molecular diagnosis of congenital toxoplasmosis (CT) on neonatal amniotic fluid samples from 488 mother-child pairs. Maternal infection during pregnancy was diagnosed and dated or could not be ruled out. Forty-six cases of CT were defined according to the European Research Network on CT classification system and case definitions. Neonatal amniotic fluid testing had an overall sensitivity of 54% (95% confidence interval (CI95): 39-69%) and a specificity of 100% (CI95: 99-100%). Its sensitivity was 33% (CI95: 13-59%) when antenatal diagnosis was positive, and 68% (CI95: 48-84%) when antenatal diagnosis was negative or lacking. This difference in sensitivity may have been due to treatment of antenatally diagnosed cases. Relative to postnatal serology, neonatal amniotic fluid testing allowed earlier diagnosis in 26% of cases (CI95: 9-51%).
We examined 785 placentas, including 51 from documented cases of congenital toxoplasmosis. Toxopl... more We examined 785 placentas, including 51 from documented cases of congenital toxoplasmosis. Toxoplasma was detected in 16 placentas, including 1 in which congenital toxoplasmosis was ruled out. Placental screening had poor sensitivity (25%) but good specificity (99%), positive predictive value (93%), and negative predictive value (95%).
Uveitis is a potentially blinding inflammatory disease. Thirty to 50% of uveitis cases are consid... more Uveitis is a potentially blinding inflammatory disease. Thirty to 50% of uveitis cases are considered idiopathic. The present study sought to determine the intraocular cytokine patterns in the different etiological types of uveitis in order to better understand their immunological regulation and to determine whether the cytokine pattern may be a useful diagnostic tool. From a multicenter institutional prospective study, the clinical and biological data from patients with uveitis of various etiologies, determined after a complete workup, were compared with those from a control group of cataract patients. A multiplex assay was used to assess the profiles of 27 cytokines and chemokines in aqueous humor samples from these patients. In total, 62 patients with infectious or noninfectious uveitis and 88 controls were included. After a complete workup, the cause of uveitis remained unknown in 25 patients (40% idiopathic uveitis). Interleukin 1β (IL-1β) levels were markedly increased in viral uveitis, as were IL-10 levels, whereas IL-17A levels were augmented in toxoplasmic uveitis. Based on the cytokine pattern, the patients were reassigned to specific groups. At the end of the study, the diagnosis of idiopathic uveitis was still valid in only 11 patients (18%). The observation that some markers are specific to certain diseases enables a better understanding of the disease pathogenesis and paves the way for new diagnostic methods aimed to identify inflammatory markers, which may perhaps be targeted by therapy.
Ophthalmologic complications of congenital toxoplasmosis, such as retino-choroiditis, are particu... more Ophthalmologic complications of congenital toxoplasmosis, such as retino-choroiditis, are particularly feared. Any child with confirmed congenital toxoplasmosis is systematically treated and followed regularly with multiple fundus examinations. The goal of our study is to describe the management and monitoring of a cohort of patients with congenital toxoplasmosis in Alsace, and the impact of this disease in terms of parental anxiety using a standardized questionnaire. Our study recorded 35 children with congenital toxoplasmosis, born between 1990 and 2011 in Alsace. All patients were followed by an ophthalmologist. A standardized questionnaire concerning the experience of pregnancy and post-natal follow-up was administered to the parents. At birth, retinochoroiditis was detected in 2 of the 35 children, and only one child developed chorioretinitis detected during follow-up monitoring (follow-up ranged from 1 to 22 years). Brain abnormalities were noted in 3 children at birth; none of them have presented with chorioretinitis to this day. An average score of 15 out of 23 was found by our standardized questionnaire, reflecting significant anxiety due to congenital toxoplasmosis. Parental anxiety due to congenital toxoplasmosis is obvious, as demonstrated by our standardized questionnaire. Follow-up, directed by comprehensive pediatric examination at birth, including fundus examination, and good information on functional signs of ocular toxoplasmosis may improve screening, so as to avoid impact on visual function.
Introduction Ophthalmologic complications of congenital toxoplasmosis, such as retino-choroiditis... more Introduction Ophthalmologic complications of congenital toxoplasmosis, such as retino-choroiditis, are particularly feared. Any child with confirmed congenital toxoplasmosis is systematically treated and followed regularly with multiple fundus examinations. The goal of our study is to describe the management and monitoring of a cohort of patients with congenital toxoplasmosis in Alsace, and the impact of this disease in terms of parental anxiety using a standardized questionnaire. Materials and methods Our study recorded 35 children with congenital toxoplasmosis, born between 1990 and 2011 in Alsace. All patients were followed by an ophthalmologist. A standardized questionnaire concerning the experience of pregnancy and post-natal follow-up was administered to the parents. Results At birth, retinochoroiditis was detected in 2 of the 35 children, and only one child developed chorioretinitis detected during follow-up monitoring (follow-up ranged from 1 to 22 years). Brain abnormalitie...
Materno-foetal transmission causes one of the most severe forms of infection with the protozoan p... more Materno-foetal transmission causes one of the most severe forms of infection with the protozoan parasite Toxoplasma gondii. Several studies have shown T. gondii in placental trophoblast cells, which form the barrier between maternal blood circulation and foetal tissue. Parasite multiplication in trophoblast cells is thus a critical step leading to infection of the foetus. Here, we show that multiplication of T. gondii tachyzoites was slow in BeWo trophoblast cells, compared with MRC-5 fibroblast cells. However, unlike MRC-5 cells, even combined stimulation with interferon-gamma and tumor necrosis factor-alpha did not reduce T. gondii replication in BeWo cells. This was associated with a lack of indoleamine-2,3-dioxygenase induction by these cytokines. Neither low availability of iron salts, nor an immunosuppressive action of cyclooxygenase-2 could be attributed to the low T. gondii multiplication rate in BeWo cells. However, treatment with the nitric oxide synthesis inhibitor N(G)-m...
Protective immunity in mice infected with Toxoplasma gondii is mainly mediated by NK cells, CD4 a... more Protective immunity in mice infected with Toxoplasma gondii is mainly mediated by NK cells, CD4 and CD8 T cells, and type 1 cytokines, such as gamma interferon (IFN-gamma). To clarify the roles of NK cells and IFN-gamma in protection against primary congenital toxoplasmosis, we used recombination activating gene 2 knockout (RAG-2(-/-)) mice, which lack T and B lymphocytes, in comparison with the wild-type BALB/c model. RAG-2(-/-) mice had a significantly lower risk of fetal toxoplasmosis than BALB/c mice (25 versus 63.9%; P = 0.003). This protection was associated with an increased number of maternal NK cells, IFN-gamma secretion by spleen cells, and decreased parasitemia. In the RAG-2(-/-) mice, NK cell depletion increased both the rate of fetal infection, to 56.5% (P = 0.02), and the blood parasite burden. Conversely, in the BALB/c mice, this treatment did not modify maternofetal transmission or the blood parasite burden. Neutralization of IFN-gamma in both infected RAG-2(-/-) and...
We evaluated molecular diagnosis of congenital toxoplasmosis (CT) on neonatal amniotic fluid samp... more We evaluated molecular diagnosis of congenital toxoplasmosis (CT) on neonatal amniotic fluid samples from 488 mother-child pairs. Maternal infection during pregnancy was diagnosed and dated or could not be ruled out. Forty-six cases of CT were defined according to the European Research Network on CT classification system and case definitions. Neonatal amniotic fluid testing had an overall sensitivity of 54% (95% confidence interval (CI95): 39-69%) and a specificity of 100% (CI95: 99-100%). Its sensitivity was 33% (CI95: 13-59%) when antenatal diagnosis was positive, and 68% (CI95: 48-84%) when antenatal diagnosis was negative or lacking. This difference in sensitivity may have been due to treatment of antenatally diagnosed cases. Relative to postnatal serology, neonatal amniotic fluid testing allowed earlier diagnosis in 26% of cases (CI95: 9-51%).
We examined 785 placentas, including 51 from documented cases of congenital toxoplasmosis. Toxopl... more We examined 785 placentas, including 51 from documented cases of congenital toxoplasmosis. Toxoplasma was detected in 16 placentas, including 1 in which congenital toxoplasmosis was ruled out. Placental screening had poor sensitivity (25%) but good specificity (99%), positive predictive value (93%), and negative predictive value (95%).
Uveitis is a potentially blinding inflammatory disease. Thirty to 50% of uveitis cases are consid... more Uveitis is a potentially blinding inflammatory disease. Thirty to 50% of uveitis cases are considered idiopathic. The present study sought to determine the intraocular cytokine patterns in the different etiological types of uveitis in order to better understand their immunological regulation and to determine whether the cytokine pattern may be a useful diagnostic tool. From a multicenter institutional prospective study, the clinical and biological data from patients with uveitis of various etiologies, determined after a complete workup, were compared with those from a control group of cataract patients. A multiplex assay was used to assess the profiles of 27 cytokines and chemokines in aqueous humor samples from these patients. In total, 62 patients with infectious or noninfectious uveitis and 88 controls were included. After a complete workup, the cause of uveitis remained unknown in 25 patients (40% idiopathic uveitis). Interleukin 1β (IL-1β) levels were markedly increased in viral uveitis, as were IL-10 levels, whereas IL-17A levels were augmented in toxoplasmic uveitis. Based on the cytokine pattern, the patients were reassigned to specific groups. At the end of the study, the diagnosis of idiopathic uveitis was still valid in only 11 patients (18%). The observation that some markers are specific to certain diseases enables a better understanding of the disease pathogenesis and paves the way for new diagnostic methods aimed to identify inflammatory markers, which may perhaps be targeted by therapy.
Ophthalmologic complications of congenital toxoplasmosis, such as retino-choroiditis, are particu... more Ophthalmologic complications of congenital toxoplasmosis, such as retino-choroiditis, are particularly feared. Any child with confirmed congenital toxoplasmosis is systematically treated and followed regularly with multiple fundus examinations. The goal of our study is to describe the management and monitoring of a cohort of patients with congenital toxoplasmosis in Alsace, and the impact of this disease in terms of parental anxiety using a standardized questionnaire. Our study recorded 35 children with congenital toxoplasmosis, born between 1990 and 2011 in Alsace. All patients were followed by an ophthalmologist. A standardized questionnaire concerning the experience of pregnancy and post-natal follow-up was administered to the parents. At birth, retinochoroiditis was detected in 2 of the 35 children, and only one child developed chorioretinitis detected during follow-up monitoring (follow-up ranged from 1 to 22 years). Brain abnormalities were noted in 3 children at birth; none of them have presented with chorioretinitis to this day. An average score of 15 out of 23 was found by our standardized questionnaire, reflecting significant anxiety due to congenital toxoplasmosis. Parental anxiety due to congenital toxoplasmosis is obvious, as demonstrated by our standardized questionnaire. Follow-up, directed by comprehensive pediatric examination at birth, including fundus examination, and good information on functional signs of ocular toxoplasmosis may improve screening, so as to avoid impact on visual function.
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Papers by Odile Villard