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A rapid flow cytometric method to explore cellular immunity against Toxoplasma gondii in humans.

To assess cell-mediated immunity to Toxoplasma gondii, we evaluated the expression of the activation antigens CD69, CD71, and CD25 on T lymphocytes by flow cytometry after specific in vitro stimulation of whole blood from 127 T. gondii-positive and 63 T. gondii-negative patients. T lymphocytes from many seropositive individuals did not express CD69 at 24 h after T. gondii antigen stimulation, but CD71 and CD25 were easily detectable on T cells from seropositive individuals 7 days after specific activation. CD25 was mainly expressed by stimulated CD4(+) T cells, and its detection on total T cells was both a sensitive (98%) and a specific (97%) indicator of prior T. gondii infection. These results make flow cytometric detection of CD25 an excellent candidate for screening cell-mediated immunity to T. gondii in vitro and an interesting tool for the diagnosis of congenital infection.

Adolescent↗

[The effect of toxoplasma antibodies after reinfection with T. gondii. III. Communication: investigations on the question of placental transmission of toxoplasma in immunised pregnant animals (author's transl)].

Investigations on whether theprotective effects of maternal defence mechanisms against T. gondii could prevent a placental transmission of the parasite to the foetus were carried out on pregnant rabbits and mice. With rabbits which were infected 6 to 1 month before the conception and showed a high infection immunity, there was never a transmission to the foetus and likewise at no time after reinfection of such maternal animals during the pregnancy. In mice which were latent infected with 11 different Toxoplasma strains, placental transmission succeeded with only 6 strains intrauterine infection of the foetuses were confirmed in 1 to 3%. After active immunisation of rabbits with non-multiplying antigen before the conception and later primary infection during the pregnancy, intrauterine transmission to the foetus could be detected in 55%. After passive immunisation with hyperimmune serum, infected foetuses could be ascertained in 79% of rabbits and 24% of mice. Possible intrauterine transmission to foetus protected by maternal defence mechanisms is likely to be dependent on various factors. 1. On the host species, 2. the state of immunity (infection immunity), 3. on Toxoplasma strain. An infection immunity with the presence of living parasites in maternal organism is probably dependent on Toxoplasma strain in mice and offers in rabbits an apparently certain protection against congenital infection. On the contrary, serologically detectable humoral antibodies after active or passive immunisation do not prevent a transplacental transmission. On the basis of experimental findings it has been concluded that at least the immunoglobulins of type IgG, IgA and IgM in lower titer ranges offer no protection against congenital transmission after reinfection during pregnancy. Also, the protective effect can not be based on the structure of respective placenta. The roles of cellular immune defence and other possible factors in this connection are discussed.

Animals↗

Pachygyriclike changes: topographic appearance at MR imaging and CT and correlation with neurologic status.

Studies of 23 pediatric patients with pachygyriclike changes (PLCs) examined with computed tomography (CT) and magnetic resonance (MR) imaging were reviewed to determine topographic patterns and correlate them with various clinical syndromes and degrees of neurologic impairment. Three types of topographic distributions were identified: unilateral, diffuse, and bilateral nondiffuse (of which eight of 10 showed frontotemporal predominance). PLCs were an isolated finding in seven patients, were associated with various congenital syndromes in nine patients, and were associated with congenital infection in seven patients, six of whom showed marked white matter abnormalities. Although most patients had severe developmental delay, three with nondiffuse PLCs had less severe impairment, permitting less required care.

Abnormalities, Multiple↗

Characteristics of a pediatric low-vision population.

BACKGROUND: Assessment of the causes of childhood blindness is important to develop preventive and therapeutic strategies that can reduce the incidence of visual impairment. METHODS: A retrospective survey of the clinical records of 395 consecutive children younger than 14 years of age who were attended by the Low Vision Service of State University of Campinas (UNICAMP) was conducted. Data on the age distribution, the causes of low vision, the types of low vision aids prescribed, the follow up of their use, and improvement in visual acuity were obtained. RESULTS: Congenital bilateral toxoplasmic macular scars, optic atrophy, and congenital cataracts were the major causes of low vision in this population. The optical aid most frequently prescribed was a telescope. The improvement of visual acuity with the use of aids was highly significant.

Adolescent↗

Toxoplasmosis in rats (Rattus norvegicus): congenital transmission to first and second generation offspring and isolation of Toxoplasma gondii from seronegative rats.

To study congenital transmission of Toxoplasma gondii during acute and chronic infections, 4 pregnant Sprague-Dawley rats were each fed 10,000 oocysts of the VEG strain. Toxoplasma gondii was recovered from 33, 55, 83 and 57% of rats (F1) when dams were inoculated at 6, 9, 12 or 15 days of gestation, respectively. Progeny of 15 congenitally infected female rats were examined for T. gondii. Toxoplasma gondii was recovered from tissues of 1 of 155 rats (F2) born to congenitally infected dams. A total of 4 (F2) females were mated; 0 of 40 (F3) rats born to them were infected. None of the acutely infected 4 dams that had given birth to congenitally infected litters produced congenitally infected offspring during the second pregnancy. Thus, unlike mice, evidence for repeated congenital transmission of T. gondii in the rat was found in < 1% of cases. Of the 16 congenitally T. gondii infected pups with demonstrable tissue cysts, 5 were seronegative (< 1:4) in the Sabin-Feldman dye test and 5 were seronegative (< 1:20) in the modified agglutination test by the use of whole formalinized tachyzoites and mercaptoethanol.

Animals↗

Anophthalmos. Report of two cases.

Two infants were found to have bilateral anophthalmos and other congenital anomalies. Secondary anophthalmia was diagnosed in one patient who showed malformations of the brain and an absence of ocular tissues including the optic nerves. The other patient had degenerative (consecutive) anophthalmos; fragments of ocular tissues including the optic nerves were found in the orbits.

Abnormalities, Multiple↗

The fractionation of cerebrospinal fluid proteins by cellulose acetate electrophoresis in children with infectious diseases of the central nervous system (author's transl).

The increased permeability of the blood-brain barrier during acute inflammation of the central nervous system leads to changes of the cerebrospinal fluid (C.S.F.) protein pattern. Initially, in the cases of bacterial meningitis, cellulos acetate electrophoresis revealed decreased prealbumin, albumin and tau-globulin fraktion whereas alpha- and gamma-globulin fractions were found increased. In later stages of purulent inflammation a hydrocephalus occurred in five children, associated with an increased amount of albumin in the C.S.F. Cases of viral meningoencephalitis had a characteristic decrease of prealbumin and increase of gamma-globulin, the lowered prealbumin values were found more often. In three cases of congenital encephalitis pathological patterns of C.S.F. proteins were still found 1--1 1/2 years postpartum. Children with acute peripheral facial palsy and febrile convulsions had a normal C.S.F. protein profile.

Acetates↗

Management strategies for congenital infections.

Information on congenital infection is continuously expanding. New diagnostic techniques are making significant contributions to the prenatal diagnosis of several fetal infections. In this review we highlight some of the most recent advances in the diagnosis and management of the most common fetal infections, those caused by cytomegalovirus, human immunodeficiency virus 1, Toxoplasma, varicella-zoster virus, and parvovirus B19.

Chickenpox↗

Endogenous uveitis in Indian children: analysis of 94 cases.

Out of 1086 cases of endogenous uveitis registered in the uveitis clinic of Irwin Hospital, New Delhi, India, over a period of 10 years from 1963-1972, 94 cases (8.6%) were within the pediatric age group 0-15 years. These cases have been analyzed in detail and the data on age, sex distribution, clinical types, course, complications, various etiological factors, and associated conditions have been tabulated. There were 29 cases within the age group 0-10 years. The youngest was six weeks old. Brief clinical data were: boys, 61.7%; bilateral cases, 45.8%, anterior uveitis, 40.4%; posterior uveitis, 47.9%; generalized uveitis, 11.7% and chronic cases 81.9%. Complicated cataract was the most frequent complication (25.5%) followed by band keratopathy (10.6%). The etiology could be determined in 52.1% of the cases. Tuberculosis was the commonest cause (31.9%) followed by toxoplasmosis (10.6%). There was one case of Behcet's disease where the ocular lesions preceded oral and genital lesions by two years. The series is conspicuous by the notable absence of sarcoidosis as a cause of uveitis. Comparative data on the incidence of childhood uveitis and its various etiological factors as reported by other workers have also been tabulated.

Age Factors↗

High levels of congenital transmission of Toxoplasma gondii in a commercial sheep flock.

Our current understanding of congenital transmission of Toxoplasma gondii from ewe to lamb dictates that infection frequently results in abortion and the death of the developing foetus, that the birth of live infected lambs occurs rarely and that the cat is the predominant source of infection in ewes. Using direct polymerase chain reaction detection of T. gondii, we report high levels of congenital transmission occurring in a commercially managed sheep flock. We sampled foetal-derived placental tissue and tissues from aborted lambs and showed that congenital transmission was detected in these tissues from 61% of all pregnancies. Where pregnancies resulted in the death of one or more lambs, T. gondii was detected in the lamb tissue for all but one of 18 (94%) pregnancies. Of the successful pregnancies resulting in the birth of live lambs we were able to detect T. gondii in foetal-derived placental tissue from 37 of 70 (42%) pregnancies. These results show that congenital transmission is occurring in a high percentage of lambings including normal healthy lambings, at this farm, suggesting that this route of transmission from generation to generation may be much more significant than that reported previously. These results may have implications for sheep husbandry and future epidemiological studies of T. gondii.

Animals↗

Method for avoiding false-positive results occurring in immunoglobulin M enzyme-linked immunosorbent assays due to presence of both rheumatoid factor and antinuclear antibodies.

In a double-sandwich immunoglobulin M (IgM) enzyme-linked immunosorbent assay recently developed for the detection of IgM antibodies to Toxoplasma, the presence of either rheumatoid factor or antinuclear antibodies did not cause false-positive results. We recently noted, however, that in certain sera containing both rheumatoid factor and antinuclear antibodies, false-positive results do occur. In experiments to define the nature of the cross-reaction, these false-positive results were not found to be a consequence of interactions of the sera with Toxoplasma antigens, but rather were due to interactions of rheumatoid factor-antinuclear antibodies with the Fc portion of IgG antibodies used for the enzyme conjugate. This was avoided when the F(ab')2 fragment of IgG was used for the conjugate. The use of such F(ab')2 conjugates did not affect the sensitivity and, thereby, the usefulness of the double-sandwich IgM enzyme-linked immunosorbent assay for the diagnosis of acute acquired or congenital Toxoplasma infections. We concluded that F(ab')2 fragments of IgG antibodies can be used as enzyme conjugates to avoid false-positive results in sera positive for both rheumatoid factor and antinuclear antibodies in either the conventional test or in our double-sandwich IgM enzyme-linked immunosorbent assay.

Animals↗

Multicenter evaluation of a fluorometric enzyme immunocapture assay to detect toxoplasma-specific immunoglobulin M in dried blood filter paper specimens from newborns.

An easy-to-perform fluorometric enzyme immunocapture assay (FEIA) was developed by Labsystems, Helsinki, Finland, to detect toxoplasma-specific immunoglobulin M (IgM) in dried blood spots. Assay materials were distributed to two sites that have programs in place designed to identify infants born with congenital toxoplasma infection: the Statens Serum Institut, Copenhagen, Denmark, and the New England Regional Newborn Screening Program, Boston, Mass. Each site tested over 700 dried blood samples from healthy newborns to define a cutoff at the 99.5 percentile (5 enzyme immunounits for Copenhagen and 4 enzyme immunounits for Boston). Each site then applied its own cutoff of interpret results for dried blood spots prepared from either adults with serology suggestive of acute infection (Copenhagen) or infants determined to be congenitally infected on the basis of serological criteria (Boston). In Copenhagen, 35 of 38 adult samples were either positive to a small degree or borderline positive for IgA. These samples thus may not represent acute infection. In Boston, of 26 congenitally infected infants, 22 were positive by FEIA. The four infant specimens not positive by FEIA were either negative or borderline positive by the standard Boston assay. These results demonstrate that the IgM FEIA is a potential alternative to other filter paper assay for toxoplasma-specific IgM currently in use for newborns.

Adult↗

[Incidence of congenital infections].

The discussions on the pros and cons of obstetric screening for connatal infections have been going on for years. We, therefore, conducted a prevalence study of the most common connatal infections. HIV infection, rubella and syphilis were not subjects of this study. We analysed the relevance of these infections in 512 pregnant women and their newborn infants at the moment of delivery. Further serological tests were run three months post partum, if necessary even for a longer period. Cytomegaly IgG antibodies were found in 46% of the examined women, IgM antibodies in 1.3%. Women under the age of twenty and women of low social standing showed the highest rate of prevalence of infection with CMV. The prevalence of IgG antibodies against parvovirus B 19 was 29%. In 10 mothers, positive IgM titers were found at the time of delivery. In all these women, pregnancies had been uneventful. However, 9 mothers exhibited a significantly raised abortion rate within the last 20 months before delivery. 7 of 512 women turned out to be HBs antigen carriers, 3 women and their babies were anti-HCV positive. The prevalence of toxoplasmosis IgG antibodies was 36%, of IgM antibodies 5.3%. By further investigation (Toxo ISAGA, Toxo IgA) we were able to detect one child with connatal toxoplasmosis. We conclude, that screening for parvovirus B 19 and hepatitis C is required only, if there are contact or clinical hints that the patients might have acquired either one of these infections. But we postulate, that a routine screening programme for hepatitis B and toxoplasmosis should be carried out in all pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Congenital toxoplasmic myocarditis: case report of an unusual presentation.

Extensive calcification of the heart, involving predominantly the right ventricle and interventricular septum, was observed in a 3-h-old baby. The aetiology of the condition was attributed to infection by Toxoplasma gondii, based on the presence of several visceral lesions allied to the identification of the microorganism. The case is reported in view of the rarity of the type of the heart lesion. It is considered that calcification of the myocardium is secondary to vascular, inflammatory or toxic condition. The factors implicated in the pathogenesis of this unusual myocardial lesion are discussed.

Female↗

Lack of evidence for superantigen activity of Toxoplasma gondii towards human T cells.

Toxoplasma gondii is an obligatory intracellular parasite whose life cycle may include man as an intermediate host. More than 500 million people are infected with this parasite worldwide. It has been previously reported that T. gondii contains a superantigen activity. The purpose of the present study was to determine if the putative superantigen activity of T. gondii would manifest towards human T cells. Peripheral blood mononuclear cells (PBMC) from individuals with no previous contact with the parasite were evaluated for proliferation as well as specific Vbeta expansion after exposure to Toxoplasma antigens. Likewise, PBMC from individuals with the congenital infection were evaluated for putative Vbeta family deletions in their T cell repertoire. We also evaluated, over a period of one year, the PBMC proliferation pattern in response to Toxoplasma antigens in patients with recently acquired infection. Some degree of proliferation in response to T. gondii was observed in the PBMC from individuals never exposed to the parasite, accompanied by specific Vbeta expansion, suggesting a superantigen effect. However, we found no specific deletion of Vbeta (or Valpha) families in the blood of congenitally infected individuals. Furthermore, PBMC from recently infected individuals followed up over a period of one year did not present a reduction of the Vbeta families that were originally expanded in response to the parasite antigens. Taken together, our data suggest that T. gondii does not have a strong superantigen activity on human T cells.

Adult↗

Screening small for gestational age babies for congenital infection.

The widespread practice in newborn nurseries of screening asymptomatic small for gestational age (SGA) babies for TORCH infection has been evaluated. In a retrospective review, we found that, in 1979, in our nursery 23 (35%) of the sixty-six SGA babies were investigated for TORCH infection. No asymptomatic baby was investigated adequately to exclude infection. The two proven cases of congenital infection were both apparent on other clinical grounds, and neither would have been detected by our routine serologic screening. A review of published information on asymptomatic TORCH infections showed that, in the absence of other clinical signs of infection, intrauterine growth retardation is an unusual manifestation. Clinical investigation of TORCH infection should be confined to those babies with other clinical evidence of infection.

Canada↗

Autosomal recessive congenital intrauterine infection-like syndrome of microcephaly, intracranial calcification, and CNS disease.

We present data on 10 patients from 5 families with a condition of microcephaly, intracranial calcification, and a clinical course resembling congenital TORCH infection. Repeatedly, negative TORCH investigations are a prerequisite for the identification of this disorder and the value of disturbed liver function and thrombocytopenia as aids to diagnosis is emphasised. Several similar families with recurrence of the disease in sibships are identified in the literature and the genetic implications of our observations are considered.

Brain↗