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HLA typing in congenital toxoplasmosis.

HLA-A, HLA-B, HLA-C, and HLA-D typing was performed in 47 mothers of patients suffering from ocular toxoplasmosis to investigate whether an immunogenetic predisposition exists for developing congenital toxoplasmosis in their offspring. No significant association between any HLA antigen was observed in the mothers of patients with ocular toxoplasmosis, although a total absence of the HLA-B51 antigen was found in this group. HLA-A, HLA-B, and HLA-C typing was also performed in their children (52 patients with ocular toxoplasmosis), to investigate a possible relation between the severity of ocular toxoplasmosis and an eventual immunogenetic factor. In the patients with ocular toxoplasmosis an increased frequency of the HLA-Bw62 antigen was observed in correlation with severe ocular involvement.

Disease Susceptibility↗

Fitness of Toxoplasma gondii is not related to DHFR single-nucleotide polymorphism during congenital toxoplasmosis.

Factors that regulate the pathogenesis of Toxoplasma gondii in humans are poorly understood. When acquired during pregnancy, toxoplasmosis can be disastrous, leading to fetal loss or conversely to subclinical disease. In congenitally infected infants, evolution is highly unpredictable. Genotype based virulence patterns have been described in mice, but in humans this classification does not correlate with the gravity of the disease. Mutations on DHFR-TS loci have recently been reported to confer T. gondii fitness cost. In this study, we investigated the relationship between the virulence of the parasite, as measured by clinical outcome in the fetus or newborn, fitness, as measured by parasitic load in amniotic fluid, and allelic polymorphism in DHFR. Six cases of severe congenital toxoplasmosis and 23 cases of mild congenital infections were included in the study. Quantitative PCR was performed to evaluate total T. gondii DNA load in amniotic fluid and detection of mutations was carried out with a LightCycler using hybridisation probes. Parasitic load was significantly higher in severe infections than in mild diseases. Among isolates from severe or non-severe cases of congenital toxoplasmosis, no polymorphism could be detected at loci 36, 83 or 245 of the DHFR gene. The virulent RH strain presented the same melting temperature as the non-virulent PRU strain for codons 36, 83 and 245. Only mutated clones, M2M3 and M2M4 with allelic replacement at these positions, displayed different profiles allowing a clear distinction between wild and mutant types. We concluded that the DHFR gene mutations we investigated do not regulate T. gondii fitness in humans.

Animals↗

[Follow up of 16 cases with congenital toxoplasmosis treated with azithromycin].

OBJECTIVE: To study the therapeutic effects of azithromycin in treatment of congenital toxoplasmosis in children. METHODS: Definite diagnosis of congenital toxoplasmosis was made on the basis of clinical manifestation combined with one or more positive results of the following laboratory tests and excluded other congenital infectious diseases: toxoplasma DNA (TOX-DNA), circulating toxoplasma antigen (TOX-CAG), and toxoplasma IgM antibody (TOX-IgM). All the patients were given oral azithromycin 10 mg/(kg.d) for 6 days followed by 8 days without medication (one course of treatment), and the regimen was persisted for 2 months and then another 2-month treatment was given at a 1-month interval. The authors continued to provide further treatment according to the state of the illness at one month interval. The patients received 2 to 8 (average 5) courses of treatment. The patients were followed-up for 2.5 to 5 (average 4) years. RESULTS: The treatment was effective in all the patients and the patient's condition was improved. The authors repeated in 12 cases the four tests for toxoplasma (TOX-DNA, TOX-CAG, TOX-IgM, and TOX-IgG) 9 months to one and a half years after treatment. In 10 cases all these tests showed negative results, in 2 cases TOX-IgG was positive and in the other 4 cases symptoms disappeared. CONCLUSION: The results of the study showed that oral azithromycin had significant therapeutic effects with little side effect and was well tolerated. Azithromycin may become an alternative therapy in treatment of congenital Toxoplasma gondii infection in children.

Anti-Bacterial Agents↗

Congenital toxoplasmosis complicated by central diabetes insipidus in an infant with Down syndrome.

We describe an infant with the unusual combination of Down syndrome, congenital toxoplasmosis, and central diabetes insipidus. Hydrocephalus was documented by fetal ultrasonography at 36 weeks' gestation. He developed central diabetes insipidus as a neonate, followed by interstitial pneumonia, anemia, and hepatosplenomegaly. The patient's serum titer for Toxoplasma-specific IgM (ELISA) at 37 days after delivery was negative, but the Toxoplasma SAG1 gene was detected from the cells of the cerebrospinal fluid on the same day using the polymerase chain reaction (PCR) method. Congenital toxoplasmosis can contribute to the development of central diabetes insipidus in infants. PCR was useful in diagnosing congenital toxoplasmosis rapidly and accurately.

Animals↗

[Prenatal diagnosis and treatment of congenital toxoplasmosis: a program of regional surveillance].

Toxo-net is a regional program of survey on congenital toxoplasmosis which has two aims: 1) to estimate the incidence of gestational and congenital toxoplasmosis in our Region (Piemonte); 2) to assess the compliance to our diagnostic, therapeutic and follow-up protocols which are thoroughly described. Thirty-two obstetrical, neonatal and laboratory units of Piemonte Region have been involved. During 18 months (January 1997-June 1998) 365 pregnant women were studied because of suspected seroconversion: in 129 patients infection was confirmed. Amniocentesis for prenatal diagnosis was carried on 11 patients; two fetuses were affected. 35% of the mothers were untreated or inadequately treated. Hydrocephaly was observed in two fetuses. Neonatal follow-up at 12 months is available for 68 of the 129 infected mothers. Four babies (5.8%) were infected, three of them being symptomatic; their mothers had not been treated. It is concluded that the implementation of a screening program for toxoplasmosis during pregnancy seems to be beneficial. However an effort to improve the surveillance system and the education of the gynecologists, general practitioners and of the patients is needed, and economic evaluations are warranted.

Female↗

Antenatal diagnosis of congenital toxoplasmosis: evaluation of the biological parameters in a cohort of 286 patients.

OBJECTIVE: To evaluate the biological parameters obtained by cordocentesis and amniocentesis in the antenatal diagnosis of congenital toxoplasmosis. DESIGN: Nine-year retrospective study. SETTING: Parasitology Laboratory, Department of Obstetrics and Gynaecology and Department of Paediatrics, Centre Hospitalo-Universitaire, Montpellier, France. PARTICIPANTS: Two hundred and eighty-six pregnant women infected with toxoplasmosis between 7 and 34 weeks of gestation. METHODS: Detection of abnormalities by ultrasound examination. Detection in fetal blood of Toxoplasma, of specific IgM and IgA and of nonspecific biological markers. Detection in amniotic fluid of Toxoplasma. RESULTS: Out of 286 antenatal diagnoses, 211 were negative (1st group), 40 were positive (2nd group) and led to 8 medical abortions, and 35 were uncertain (3rd group). In the 1st and 3rd groups respectively, 7 (3.3%) and 5 (14.3%) cases of congenital toxoplasmosis were observed. Overall, 52 cases of congenital toxoplasmosis were detected: 12 were clinically apparent, 36 subclinical (of which 12 were in groups 1 and 3) and 4 were lost to follow up. CONCLUSION: There is substantial importance in making the diagnosis of toxoplasmosis antenatally in order to limit the number of medical abortions. In our series, the most accurate predictor was the detection of the fetal antibody response (specific IgM and IgA) to Toxoplasma.

Animals↗

[Use of the PCR technique for diagnosis of symptomatic congenital toxoplasmosis based on own observations].

UNLABELLED: The aim of our study was to determine the usefulness of PCR technique in postnatal diagnosis of congenital toxoplasmosis in 17 infants aged from 1 week to 10 months. In 13 cases the diagnosis was established. The diagnostic procedures involved: clinical examinations, serological tests, nested-PCR method and neuroimaging examinations. RESULTS: In almost all children (except one) a high level of toxoplasmatic IgG antibodies was found; in 1/3 we identified antibodies IgM and IgA. In 14 cases the PCR test from CSF was positive. In 4 infants the suspicion of congenital toxoplasmosis was ruled out; in 2 of them PCR from CSF was negative, in 2 - a false positive result was stated. CONCLUSIONS: PCR is a valuable technique for diagnosis of congenital toxoplasmosis. Because of the possibility of false positive and negative results - it should be combined with other laboratory methods.

Adult↗

[Prevention of congenital toxoplasmosis].

Toxoplasma gondii can be transmitted from mother to fetus during primary maternal infection acquired after or, possibly, slightly before conception. The incidence of congenital infection is highest in the third trimester, while severity is greatest when maternal infection is acquired during the first trimester. About 50 per cent of mothers who acquire the infection during gestation, if not treated, will give birth to infected infants. Incidence of congenital toxoplasmosis varies from 0.5 to 6.5 cases per 1000 live births. Serologic screening before or very early in pregnancy is required to identify seronegative women who are at risk to acquire the infection during pregnancy. Prevention of congenital toxoplasmosis is obtained by educating pregnant women at risk about how to prevent the infection and by diagnosing acute infection of mother. Every mother who demonstrates seroconversion for toxoplasmosis during pregnancy has to be treated as soon as possible. Therapy is based on spiramycin that achieves high concentrations in the placenta; if the fetus is infected pyrimethamine plus sulphonamides are administered since fourth month. Chemotherapy of the infected pregnant mother reduces the incidence of congenital toxoplasmosis and the severity of the disease in the newborn. Intrauterine infection can be detected by fetal blood sampling, by amniocentesis and ultrasound examination; prenatal diagnosis is mandatory if an abortion is being considered.

Adult↗

The evaluation of new services: possibilities for preventing congenital toxoplasmosis.

We examine the resource implications of two potential health services aimed at preventing congenital toxoplasmosis: a screening service involving serological surveillance for toxoplasma infection in pregnant women and its prophylactic treatment; and a health education campaign to help pregnant women avoid acquiring toxoplasma infection, through advice about special precautions regarding hygiene. Measuring the costs and benefits of prevention is complicated by uncertainty of the incidence of congenital toxoplasmosis in the United Kingdom, the extent of its harmful manifestations--mental and visual handicap--and the effectiveness of preventive measures. Hence an important aspect of this study is that it exemplifies the use of 'sensitivity analysis' as an aid to evaluation in the absence of hard data. We find that a screening service would seem unlikely to save resources, but that a health education campaign would seem much more likely to do so and further assessment of its potential effectiveness would be valuable.

Blindness↗

[Congenital toxoplasmosis: possibilities for laboratory diagnosis].

A case history and the steps taken in diagnosing congenital toxoplasmosis in a child whose mother experienced asymptomatic infection with the protozoon Toxoplasma gondii are presented. At pregnancy week 35, amniocentesis was performed because of fetal hydrops, ascites, hepatosplenomegaly and dilated left lateral brain ventricle on sonography. Laboratory tests showed high titers of IgM, IgE and IgA antibodies (acute infection markers) against Toxoplasma gondii in serum of the pregnant woman. Congenital toxoplasmosis in the new-born spontaneously delivered at week 41 was confirmed by detection of Toxoplasma gondii DNA in blood, acute infection markers in serum and hydrocephalus and calcifications on brain sonography. The woman received intensive treatment for toxoplasmosis during the last pregnancy trimester and her new-born child's treatment started immediately after delivery. The accurate diagnosis and early institution of therapy in both the pregnant woman and her child led to progressive normalization of laboratory tests (decreased titers of antibodies and Toxoplasma gondii DNA negativity) and significant regression of the brain lesions in the child.

Adult↗

An electron microscope and immunohistochemical study of the intracellular location of Toxoplasma tissue cysts within the brains of mice with congenital toxoplasmosis.

The wall of intact Toxoplasma tissue cysts within the brains of mice with congenital toxoplasmosis was investigated. Smaller cysts were identified within the soma of neurones. With larger cysts, the contained cystozoites were shown by ultrastructural examination to be surrounded by a layer of microtubules; immunohistochemical staining revealed that this layer contained neurofilament protein. Interior to this layer was a much convoluted parasitophorus vacuole membrane; exterior was the host cell membrane. In most cases, synaptic plates were noted on the outer plasma membrane. In no instance were tissue cysts observed either within neuroglial cells or in the absence of host cells. These observations are discussed in relation to the pathogenesis of congenital toxoplasmosis in the brain.

Animals↗