[Coexistence of congenital toxoplasmosis, congenital malformations and other anomalies].
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Congenital toxoplasmosis is still one of the most frequent causes of fetal death. Despite a significant improvement in diagnosis, particularly in utero diagnosis, maternal treatment is only partially effective in preventing transmission to the fetus and treating fetal infection. Maternal treatment is based on drugs developed 50 years ago, which may have limited efficacy (spiramycin) or serious side-effects (pyrimethamine). Data on the use of cotrimoxazole in mouse models of toxoplasmosis and for preventing toxoplasmic encephalitis in patients suffering from AIDS have led Francis Derouin and colleagues to consider the potential of cotrimoxazole for prenatal prevention and treatment of toxoplasmic fetal death.
Congenital toxoplasmosis is still a concern, particularly in France, where the seroprevalence is high. For an efficient prevention program, reliable techniques are necessary. During the past ten years, biological advances have been made to improve the performance of antenatal diagnosis as well as the postnatal detection of infected neonates. In this review we will touch on three main points: 1) the dating of seroconversion during the course of pregnancy, 2) the value of antenatal diagnosis, 3) the new modalities for postnatal serological follow-up of newborns.
Congenital toxoplasmosis is characterized by the classical triads: hydrocephaly, chorioretinitis and intracerebral calcifications. In fact it is an uncommon manifestation of congenital infection with the parasite Toxoplasma gondii, that is generally subclinical in the neonatal period. But there is a substantial risk of delayed clinical manifestation due to exacerbation of infection: chorioretinitis with loss of vision. With some case histories the interpretation of serodiagnostic techniques is explained and the necessity of repeated tests up to the age of one year in order to exclude a congenital infection definitely, is emphasized.
Many persons infected with Toxoplasma gondii develop ocular lesions. Immunologic parameters in the response to T. gondii were evaluated in infected persons with and without ocular lesions and in noninfected controls. Subjects were divided into groups on the basis of presence of serum antibodies to T. gondii, presence of ocular lesions, and clinical history. Production of interleukin-2 and interferon-gamma by peripheral blood mononuclear cells from patients with probable congenital toxoplasmosis was decreased, compared with that in persons with presumed acquired infection. Cell proliferation and delayed-type skin reaction induced by soluble toxoplasma tachyzoite antigen followed the same pattern. Asymptomatic persons showed high levels of interleukin-12 and interferon-gamma, whereas persons with ocular lesions had high interleukin-1 and tumor necrosis factor-alpha responses toward soluble toxoplasma tachyzoite antigen. These data suggest that patients with ocular disease due to congenital infection show tolerance toward the parasite. Furthermore, susceptibility to ocular lesions after acquired toxoplasmosis is associated with high levels of interleukin-1 and tumor necrosis factor-alpha, whereas resistance is associated with high levels of interleukin-12 and interferon-gamma.
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UNLABELLED: Congenital toxoplasmosis may lead to severe visual impairment or neurological sequelae in the child. PURPOSE: To study the severity of the primary and late ophthalmological dysfunction during a prospective incidence study of congenital toxoplasmosis in the Stockholm and Skåne counties. METHODS: Blood collected on phenylketonuria (PKU) cards from 40,978 consecutively born children were investigated for antitoxoplasma antibodies. Children with verified congenital toxoplasmosis were treated for 12 months with antiparasitic therapy and followed ophthalmologically, neurologically and serologically every third month. RESULTS: Three children had congenital toxoplasmosis. Two of these were asymptomatic at birth and would have escaped early detection without screening. One child had unilateral severe visual impairment and CNS involvement. The incidence of congenital toxoplasmosis was less than 1:10,000. CONCLUSION: Neonatal screening is of importance to diagnose asymptomatic infected children with congenital toxoplasmosis as treatment has been shown to reduce long-term sequelae. Ophthalmological investigations should start early and continue in co-operation with paediatricians.
BACKGROUND: Without treatment, congenital toxoplasmosis has recurrent, recrudescent, adverse outcomes. Long-term follow-up of infants with congenital toxoplasmosis treated throughout their first year of life with pyrimethamine and sulfadiazine has not been reported. METHODS: Between 1981 and 2004, one hundred twenty infants (current mean age +/- standard deviation, 10.5 +/- 4.8 years) with congenital toxoplasmosis were treated with 1 of 2 doses of pyrimethamine plus sulfadiazine; therapy was initiated shortly after birth and continued for 12 months. Children who received treatment were evaluated at birth and at predetermined intervals; the focus of the evaluations was on prespecified end points: motor abnormalities, cognitive outcome, vision impairment, formation of new eye lesions, and hearing loss. RESULTS: Treatment of infants without substantial neurologic disease at birth with pyrimethamine and sulfadiazine for 1 year resulted in normal cognitive, neurologic, and auditory outcomes for all patients. Treatment of infants who had moderate or severe neurologic disease (as defined in this article in the Treatments subsection of Methods) at birth resulted in normal neurologic and/or cognitive outcomes for >72% of the patients, and none had sensorineural hearing loss. Ninety-one percent of children without substantial neurologic disease and 64% of those with moderate or severe neurologic disease at birth did not develop new eye lesions. Almost all of these outcomes are markedly better than outcomes reported for children who were untreated or treated for 1 month in earlier decades (P<.01 to P<.001). Sex and severity of disease were comparable in our 2 treatment groups, and no significant differences in efficacy or toxicity were noted between the 2 treatment groups (P > .05). CONCLUSIONS: Although not all children did well with treatment, the favorable outcomes we noted indicate the importance of diagnosis and treatment of infants with congenital toxoplasmosis.
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In children born to immunocompetent women, congenital toxoplasmosis almost always results from primary infection during pregnancy. However, reactivation of latent toxoplasmosis during pregnancy could occur in HIV-infected pregnant women, particularly in those who are severely immunocompromised, and result in maternal-fetal transmission of the parasite. This mode of infection has been described in case reports but the risk of transmission is unknown. Findings on toxoplasmosis are presented from the European Collaborative Study, a prospective study of children born to women known to be HIV-infected at the time of delivery. In 1058 children followed for a mean duration of 35 months, only one child developed clinical toxoplasmosis. This child was HIV-infected, severely immunocompromised, and acquired toxoplasmosis postnatally. Congenital infection was excluded serologically in a subgroup of 167 children, of whom an estimated 71 had been at risk of infection. These clinical and serological findings indicate a low general risk of maternal-fetal transmission of Toxoplasma infection in HIV-infected women. It is not possible to draw conclusions about the risk of transmission for severely immunocompromised HIV-infected women because most women in the study were asymptomatic.
In congenital cases, ocular toxoplasmosis often presents as a focal whitish fluffy lesion in the retina adjacent to an inactive chorioretinal scar. We examined a girl who has visible floaters in the right eye. The patient had focal active retinitis in the right fundus, a focal chorioretinal scar in the left fundus, a positive enzyme-linked immunosorbent assay (ELISA) for IgG anti-Toxoplasma antibodies and a negative ELISA for IgM antibodies. We believe that active focal retinitis in one eye and a focal chorioretinal scar in the fellow eye in congenital toxoplasmosis, as demonstrated in our patient, may be rare.
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