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White blood cells in infants with congenital toxoplasmosis: transient appearance of cALL antigen on reactive marrow lymphocytes.

Existing serological methods for diagnosing congenital toxoplasmosis are inadequate. We have therefore characterized the features of peripheral blood cell counts and smears in a prospective study of 8 affected infants during their first year of life. Enlarged, vacuolated lymphocytes were observed in all patients. Six patients had periods of neutropenia; in 1 patient the neutropenia was severe and prolonged. A bone marrow aspirate from this patient showed enhanced myelopoiesis, and after stimulation with hydrocortisone, but not with adrenaline, his neutrophil count normalized. Phenotyping of his bone marrow cells revealed that approximately 55% of both the immature and mature B lymphocytes were positive for the cALL antigen. Of the 8 patients, 6 had mild eosinophilia, 4 had mild monocytosis and 3 had increased numbers of plasma cells in the peripheral blood. These findings may reflect the activity of the congenital toxoplasma infection and may thus contribute to the diagnosis, particularly in patients with silent serology.

Antigens, Differentiation↗

Congenital toxoplasmosis: eye manifestations in infants and children.

The eye manifestations of congenital toxoplasmosis were investigated in 38 infants and children. Diagnosis of the congenital ocular lesions was established clinically, using also X-ray, computed tomography and ultrasonography, and confirmed by two immunodiagnostic techniques. Infants and children were examined when one or more characteristic manifestations of ophthalmic disorders were present. Typical symptoms and signs can present at birth or appear later in life. The multiplicity of clinical manifestations is characteristic of the disease. The most common symptom was chorioretinitis (92%), associated in 71% of the cases with other ocular lesions, and the second most common symptom was microphthalmia and strabismus. The inflammatory process also involved the anterior segment of the eye: iridocyclitis, cataract, glaucoma. Other rare findings were hydrocephalus, calcification in the brain, paresis, epilepsy and diminished visual acuity. The study showed that transplacental transmission of Toxoplasma to the fetus can have severe clinical consequences and terminate in fatal ocular impairment.

Adolescent↗

Congenital toxoplasmosis: a serologic screening of 963 mothers and their children at birth.

An investigation carried out according to a predetermined serologic screening sought to evaluate the prevalence, level, and quality of fluorescent anti-Toxoplasma antibodies in a population sample of a certain district. The most important issues concern the risk of congenital toxoplasmosis for the above-mentioned subjects, the level of serotiter for expected risk, and the features of our screening protocol as regards thoroughness and the possibility of early diagnosis.

Adolescent↗

Congenital toxoplasmosis--prenatal aspects of Toxoplasma gondii infection.

Toxoplasma gondii (T. gondii) is the cause of toxoplasmosis. Primary infection in an immunocompetent person is usually asymptomatic. Serological surveys demonstrate that world-wide exposure to T. gondii is high (30% in US and 50-80% in Europe). Vertical transmission from a recently infected pregnant woman to her fetus may lead to congenital toxoplasmosis. The risk of such transmission increases as primary maternal infection occurs later in pregnancy. However, consequences for the fetus are more severe with transmission closer to conception. The timing of maternal primary infection is, therefore, critically linked to the clinical manifestations of the infection. Fetal infection may result in natural abortion. Often, no apparent symptoms are observed at birth and complications develop only later in life. The laboratory methods of assessing fetal risk of T. gondii infection are serology and direct tests. Screening programs for women at childbearing age or of the newborn, as well as education of the public regarding infection prevention, proved to be cost-effective and reduce the rate of infection. The impact of antiparasytic therapy on vertical transmission from mother to fetus is still controversial. However, specific therapy is recommended to be initiated as soon as infection is diagnosed.

Adult↗

[Decision analysis of congenital toxoplasmosis in the absence of exact knowledge of the treatment benefits and secondary effects].

Decision analysis seemed the appropriate method to bring out the interest of toxoplasmosis serology in children born from mothers who seroconverted during pregnancy. In particular it provides the possibility to choose between IgA serology, recently introduced in hospital practice, and IgM serology that is the reference test. We study a series of 96 children suspected of having congenital toxoplasmosis who were followed up until the age of one. A decision analysis is thereafter conducted by synthesizing data about clinical efficacy with the RBNCN ratio that is the net benefit of treating an affected person divided by the net cost of treating an unaffected person; these costs and benefits are clinical. The effectiveness of the treatment (sulphonamides in most cases) was not quantified. Therefore, we used the fact that the RBNCN ratio is equal to the number of healthy children likely to be treated unnecessarily in order not to leave untreated a contaminated child. Although data available in the literature and data from our study still remain insufficient to draw a final conclusion, IgA antibodies are significantly more sensitive than IgM antibodies (p < 0.01). Conversely, IgA antibodies are significantly less specific than IgM antibodies (p < 0.001). The sensitivity analysis shows that the IgA test is preferred to the IgM test if the mother is contaminated during the third trimester. On the other hand, for low prevalences, as observed in the first trimester, the IgM serology is more useful.

Anti-Infective Agents↗

Screening for congenital toxoplasmosis in Brazil.

Toxoplasmosis acquired at the end of the pregnancy can produce ocular and neurological sequelae. The detection of IgM anti-Toxoplasma gondii in dried blood spots of newborns is an important tool for early treatment and prevention. In this study we showed results of a pilot study about the prevalence of congenital toxoplasmosis in Brazil and concluded that this disease should be included in the menu of neonatal screening programs.

Animals↗

[Congenital toxoplasmosis with activation of extramedullary hematopoiesis in a premature infant].

An immature neonate surviving for 45 minutes showed a generalized hydrops and hepatosplenomegaly unassociated with blood incompatibility. A marked activation of extramedullary haematopoiesis was observed not only in its liver and spleen, but also in the interstitium of the lungs, pancreas, kidneys, and adrenal glands. In addition, extensive necrosis of the brain and diffuse nonsuppurative myositis and myocarditis were found. All the changes were due to congenital toxoplasmosis, which has been confrimed by the findings of occasional pseudocysts within the placenta, by the result of the parasitologic examination of the brain of the autopsied infant and by serological examination of the mother post partum.

Edema↗

Prenatal diagnosis of congenital toxoplasmosis.

Ninety-three pregnant women with Toxoplasma gondii seroconversion during pregnancy underwent prenatal diagnosis of fetal toxoplasmosis. The following tests were used: (1). amniocentesis for mouse inoculation (93 subjects), (2). amplification of T. gondii DNA by polymerase chain reaction (PCR) (79 subjects), and (3). cordocentesis for the detection of T. gondii-specific IgM antibodies (13 subjects). All patients had serial ultrasonographic scans to detect those fetuses with abnormalities that could be associated with congenital toxoplasmosis. Eighteen pregnancies (19.4%) had evidence of vertical transmission. A total of 11/18 (61.1%) had positive amniotic mouse inoculation test, while 10/12 (83.3%) had positive PCR results. The combination of both tests allowed the prenatal diagnosis in 17/18 infected fetuses (94.4%). All patients who underwent cordocentesis for the detection of T. gondii-specific IgM antibodies had negative results. However, in two of the above cases fetal toxoplasmosis was detected by amniotic fluid studies. In five of the infected fetuses there were abnormal ultrasonographic findings. All pregnancies with evidence of vertical transmission were terminated, whereas the remaining pregnancies proceeded normally to term. The present data showed that amniotic fluid studies, preferably PCR amplification of T. gondii DNA, are the best diagnostic tools for the detection of vertical transmission in pregnancies with seroconversion during pregnancy.

Adult↗

Platelia-Toxo IgA, a new kit for early diagnosis of congenital toxoplasmosis by detection of anti-P30 immunoglobulin A antibodies.

With the aim of achieving earlier diagnosis of congenital toxoplasmosis, anti-P30 immunoglobulin A (IgA) antibodies were assayed by using a Platelia-Toxo IgA kit with samples from 72 children born to mothers who seroconverted during pregnancy. A total of 148 serum samples and 1 cerebrospinal fluid samples were from 23 congenitally infected children (2 serum samples were collected from fetuses), and 74 serum samples were from 49 uninfected children. Among the 23 infected children, anti-P30 IgA antibodies were present in all infants either at birth or in the following weeks, whereas anti-P30 IgM antibodies were present in 13 from the 23 infected children either at birth or in the following weeks. Serum samples collected in utero from two infected children were also tested. One of these samples was positive for both anti-P30 IgA and anti-P30 IgM antibodies, whereas both children were negative at birth for these antibodies. Neither anti-P30 IgA nor anti-P30 IgM antibodies were detected in 47 of 49 uninfected children. These results suggest that detection of anti-P30 IgA antibodies by the Platelia-Toxo IgA kit is a very effective method for early diagnosis of congenital toxoplasma infection.

Animals↗

Congenital toxoplasmosis associated with acquired oculomotor nerve (CN III) palsy.

A nine-week-old Caucasian male presented with right ptosis and right exotropia due to a third cranial nerve palsy. Symmetrical macular lesions and a paramacular hyperpigmented lesion with overlying vitreous cells in the left eye were compatible with congenital toxoplasmosis. Computer tomography demonstrated calcifications in the periventricular and midbrain regions where the oculomotor nerve exits the brainstem. The diagnosis was confirmed by the toxoplasma indirect fluorescent antibody titer greater than 1:2048 for the infant and greater than 1:512 for the mother. Treatment was instituted with pyrimethamine, sulfadiazine and folinic acid. Neurologic sequelae included a right hemiparesis, infantile seizures, and generalized developmental delay. A Mueller's muscle resection (RUL) combined with 9-mm recession of the right lateral rectus and 7-mm resection of the right medial rectus muscles produced minimal ptosis and right exotropia one year later. the child now prefers to fix with the right eye and a vertical nystagmus is evident in the left eye. To our knowledge this is the first reported case of an infant with noncomitant strabismus due to congenital toxoplasma cranial nerve involvement. The finding of an acquired third cranial nerve palsy accompanied by progressive neurologic sequelae warrants consideration of congenital toxoplasmosis.

Blepharoptosis↗

Prenatal diagnosis of congenital toxoplasmosis in 261 pregnancies.

Two hundred and sixty-one pregnant women underwent prenatal screening by cordocentesis and/or amniocentesis between 1987 and 1994. The following tests were used: (i) detection of anti-Toxoplasma gondii IgM, IgA, and IgE antibodies by immunocapture and the comparative immunological profile method based on enzyme-linked immunofiltration assay of fetal blood and (ii) direct detection of the parasite in cell culture and by mouse inoculation with fetal blood (FB) and/or amniotic fluid (AF). Of the 31 cases of congenital toxoplasmosis, 24 (77 per cent) were detected prenatally. Overall, the FB and AF inoculation methods were the most effective (50 per cent sensitivity with FB inoculation to mice and/or cell culture and 74 per cent with AF). However, antibody detection in FB was the only positive test in three cases. Of 18 surviving children diagnosed prenatally, only one developed chorioretinitis (9 months of age). Seven newborns (23 per cent) with negative prenatal tests were diagnosed by postnatal laboratory monitoring, but none of these children developed clinical toxoplasmosis. There may have been more false negatives, as only 48 per cent of unaffected children were followed up for at least 12 months. All the tests had a specificity of 100 per cent. Fetal blood sampling has considerable value but also carries some risks and is currently being abandoned in favour of amniocentesis alone with gene amplification and mouse inoculation.

Amniocentesis↗

Congenital toxoplasmosis in Tasmania.

In a prospective study, 9037 cord sera from Tasmanian children were tested using the Toxoplasma indirect fluorescent antibody test (IFAT). There were 494 positive reactors at the screening titre of 1:64. These reacting sera were titrated out and were also tested in the immunoglobulin M (IgM) Toxoplasma IFAT. No specific IgM antibodies were detected, but, even so, 33 of the sera had titres of 1:512 or greater. Repeat samples from 20 of the children with high titres revealed a substantial decline in titre. It is believed that these results indicate that congenital toxoplasmosis is not an important cause of perinatal morbidity in Tasmania.

Antibodies↗

[Prospective study of pregnants and babies with risk of congenital toxoplasmosis in municipal district of Rio Grande do Sul].

This study followed up 2,126 pregnant women cared for at SUS day-care clinics (Public Health Insurance System) of the northwest of the State of Rio Grande do Sul, Brazil. After serological screening we performed a follow up of all pregnant women and their babies. Serologic tests included: IgG, IgM, IgA and IgG avidity levels, mice inoculation and polymerase chain reaction (PCR) also placentas and umbilical materials were tested using immunoperoxidase as well as clinical evaluation. Of all the pregnant women screened, 74.5% were reactive to toxoplasmosis, and 3.6% presented IgM seropositivity. At ophthalmic evaluation ten women had ocular lesions and one infant presented eye lesions and brain calcification. The presence of anti-T.gondii specific IgM throughout the entire pregnancy did not characterize acute phase infection, for this, complementary tests were necessary. The importance is underscored for attendance of the newborn of mothers presenting serology compatible with this infection even in the absence of signs and symptoms of congenital toxoplasmosis.

Animals↗

Screening programme for congenital toxoplasmosis in France.

The high prevalence of Toxoplasma gondii infection in France led to the establishment of a national screening programme. Preventive measures were progressively introduced, and these became compulsory in 1978 with the result that the incidence of congenital toxoplasmosis is now markedly reduced. Further improvements may include more systematic sampling from women before pregnancy, better and adequate health education and centralized notification of both maternal and congenital cases of toxoplasmosis.

Antibodies, Protozoan↗

[Problems of congenital toxoplasmosis. Evolution over four decades].

EFFECT OF PREVENTIVE MEASURES: The development of reliable routine serology tests and the demonstration of the high prevalence of toxoplasmosis in France led to mandatory prospective screening of pregnant women in 1978, followed by prenatal screening in 1985. In addition, in utero diagnosis, first on fetal blood and now with the reliable and safe method using polymerase chain reaction on amniotic fluid, formally identifies the parasite. THE SITUATION TODAY: A comparison of the experience of a specialized center in Paris during three different periods over the last 40 years showed that currently 71% of all cases of congenital toxoplasmosis are infraclinical at birth and only 5% are severe. Mean incidence of seroconversion during pregnancy is 1.48%, with a 40% risk of fetal contamination if no treatment is given. The risk of overt fetopathy predominantly concerns maternal infections occurring prior to 26 weeks gestation. IN UTERO TREATMENT: Positive PCR diagnosis on amniotic fluid imposes serial ultrasound examinations to identify any fetopathy and an in utero treatment by giving the mother the pyrimethamine-sulfadiazine combination. Biological results are favorable. POST-NATAL TREATMENT: Post-natal treatment is indicated even in latent forms and should be continued for the first year of life. The pyrimethamine-sulfadiazine combination is the only pharmaceutical regimen with well-proven efficacy. New compounds should allow better prophylaxis against maternofetal contamination or improved post-natal treatment. RECURRENCE: In 70% of the cases, serology tests become positive again, but are not associated with significantly increased risk of ocular recurrence.

Female↗

[Evaluation of the usefulness of serological examinations in the prophylaxis of congenital toxoplasmosis in the materials of CM UJ Parasitology Department].

A total of 9661 persons, mainly from southern region of Poland, were tested by using Sabin-Feldman dye test and ELISA test to determine the IgG class in the years 1991-2000. The tests were positive in 5297 persons (54.8%). The study included 320 pregnant women: 141 with low and mean titres of IgG class antibodies: 8-300 UM/ml and 62 with high titres, exceeding 300 UM/ml, who were tested only once. There were 117 seronegative pregnant women; the test was performed only once in 108 of them and twice in 9. The test was not repeated third time in any women of this group. According to the guidelines of congenital toxoplasmosis prophylaxis, the tests do not meet the expectations.

Animals↗

Coincidence of congenital toxoplasmosis and biliary atresia in an infant.

A 4-week-old infant presenting with neonatal cholestasis was found to have congenital toxoplasmosis and biliary atresia. This is the first patient in which their coincidence is reported. Because biliary atresia can coexist with either congenital infection or inborn errors of metabolism, evaluation for an obstructive etiology of jaundice in infants with a recognized cause of intrahepatic cholestasis is necessary.

Biliary Atresia↗

[Congenital toxoplasmosis and cerebral involvement inspite of prenatal treatment].

BACKGROUND: Maternal toxoplasmosis seroconversion during the first trimester of pregnancy raises an important risk of toxoplasmic fetopathy. CASE REPORT: Primary toxoplasmosis was identified between 9 and 17 weeks of gestation. PCR analysis of the amniotic fluid confirmed fetal infection. The mother was given a sulfadoxine-piremythamine combination and monthly ultrasonographic surveillance was initiated. At birth, the female infant was found to have diffuse cortical lesions and a chorioretinitis compatible with toxoplasmic fetopathy. She was given sulfadoxine-piremythamine. At 2 years, the clinical and neuroradiological course has been favorable. CONCLUSION: Despite antenatal and postnatal treatment and despite ultrasonographic surveillance, it is difficult to predict the course of congenital toxoplasmosis. This case illustrates the importance of informing parents of the risk and the requirement for careful follow-up after antenatal diagnosis of first-trimester toxoplasmosis.

Adult↗