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Association between congenital toxoplasmosis and parent-reported developmental outcomes, concerns, and impairments, in 3 year old children.

BACKGROUND: Information is lacking on the effects of congenital toxoplasmosis on development, behavior, and impairment in later childhood, as well as on parental concerns and anxiety. This information is important for counselling parents about the prognosis for an infected child and for policy decisions on screening. METHODS: We prospectively studied a cohort of children identified by screening for toxoplasmosis in pregnant women or neonates between 1996 and 2000 in ten European centers. At 3 years of age, parents of children with and without congenital toxoplasmosis were surveyed about their child's development, behavior, and impairment, and about parental concerns and anxiety, using a postal questionnaire. RESULTS: Parents of 178/223 (80%) infected, and 527/821 (64%) uninfected children responded. We found no evidence that impaired development or behavior were more common in infected children, or that any potential effect of congenital toxoplasmosis was masked by prenatal treatment. Parents of infected children were significantly more anxious and reported more visual problems in their children. CONCLUSION: On average, children aged three to four years with congenital toxoplasmosis identified by screening and treated during infancy in this European setting had risks of abnormal development and behavior similar to uninfected children. Parental anxiety about infected children needs to be addressed by clinicians. Future studies with longer follow up and clinician-administered assessments may be better able to detect any subtle differences in child outcomes.

Anxiety↗

[Seroprevalence, epidemiology and ocular evaluation of human toxoplasmosis in the rural zone Jauguapitã (Paraná) Brazil].

Toxoplasmosis is a protozoal zoonosis common among a great variety of species worldwide. The objective of this study was to assess the presence of toxoplasmosis among 345 residents in a rural area in Jagupitã municipality, Paraná state, Brazil. The frequency of titers in human serum samples was compared with the frequency of titers found in 1,420 samples obtained from various animal species with which local residents came into contact. Titers > or = 16 were considered positive. The highest titer found was 65,536 (1%), and the most frequent titer levels were 256 (29%) and 1,024 (19%). The comparisons between humans and animals revealed a positive and significant correlation between humans and felines (r = 0.78; P = 0.01) and humans and canines (r = 0.64; P = 0.05) in terms of titer distribution. Study participants were also tested with the Amsler grid. Seventy-five of the 345 people (22%) reported some type of ocular degradation. Of these 75, 58 of them (77%) were seropositive for toxoplasmosis. Forty-one of these 58 people underwent an ophthalmologic exam. Of these 41, 9 of them, who were between 34 and 78 years old, presented lesions characteristic of healed chorioretinitis, suggesting ocular toxoplasmosis. None of the 9 had ocular inflammation. Six of the 9 patients (67%) had unilateral lesions; 4 of these 6 presented a titer level of 256. The epidemiological survey showed that the probability of presenting ocular problems was 2.06 times as great for reactive patients as for nonreactive ones. No significant differences were observed in terms of sex, contact with felines or other animals, consumption of raw or rare meat and raw milk, and slaughtering of animals for personal consumption. Our results suggest that toxoplasmosis is common in the region, with a significant incidence of ocular lesions caused by Toxoplasma gondii. Health authorities should increase their monitoring and control activities in order to decrease the risk of toxoplasmic infections, especially among pregnant women.

Animals↗

[Composition of circulating immune complexes in acute toxoplasmosis].

The circulating immune complexes (CIC) that form in the hot just in early Toxoplasma gondii invasion can be present in the blood bed for a while. At the same time, the data on the antigenic composition of CIC in toxoplasmosis are fragmentary and rather contradictory. The investigation used enzyme immunoassay (EIA) to detect specific CIC that contain antigens to T. gondii tachyzoites in the sera of different populations and studied their antigenic composition by immunoblotting after 2-6% polyethylene glycol 6000-induced deposition. Examining 464 sera from groups of individuals with varying-stage T. gondii invasion indicated CIC in each, but showing their different frequency. CIC were virtually present in all sera from children who had been diagnosed as having congenital toxoplasmosis. In groups of seropositive pregnant women, CIC detection rates were noticeably higher in the samples showing both IgG and IgM antibodies (40.2 and 66.4%, respectively). CIC were also revealed in 9.8% of the seronegative blood donors; however, immunoblotting failed to confirm that they had no components that specifically reacted with T. gondii tachyzoite antigen antibodies. There were some differences in the composition of CIC in the serum yielding positive results in both EIA and immunoblotting. The serum CIC from pregnant women that exhibited only IgG antibodies contained mainly T. gondii antigens having molecular weights of 67 and 30 kD. The serum CIC from children with congenital toxoplasmosis and from pregnant women with serologically detected IgM antibodies to Toxoplasma antigens were found to contain 55-58-, 48-, 44-, 38-, 30-, and 26-kD components. The same molecular weight proteins were detected by electrophoretic studies of Toxoplasma excretory-secretory antigen (ESA). Comparing the findings suggests that in acute toxoplasmosis, the circulating complexes mainly contain ESA of the tachyzoites which appear in human blood just at the onset of invasion. Thus, this study demonstrates that specifically CIC are detectable in the sera of individuals infected with T. gondii and their antigenic composition varies with the stage of disease. In the authors' opinion, the detection of specific CIC and the determination of their antigenic composition may be serve an additional test in diagnosing acute toxoplasmosis.

Acute Disease↗

Comparative value of polymerase chain reaction and conventional biological tests for the prenatal diagnosis of congenital toxoplasmosis.

When toxoplasmosis is acquired during pregnancy, there is a risk of severe congenital defect in the foetus. Maternal treatment with spiramycin limits the transplacental passage of the parasite to the foetus but does not prevent infection in all cases. Prenatal diagnosis should be based on specific and fast methods to prescribe the more potent combination of sulfadiazine and pyrimethamine. This study evaluates PCR in the prenatal diagnosis of toxoplasmosis; PCR was based on the detection of the gene coding for the P30 surface protein. Amniotic fluid from 44 women with suspected foetal infection was tested by PCR and results were compared to those of conventional diagnostic tests on foetal blood and amniotic fluid. PCR was positive in 7 out of 10 samples from proven congenital toxoplasmosis cases. Sensitivity of PCR was similar to cell culture and mouse inoculation of amniotic fluid but was superior to tests carried out on foetal blood (specific IgM, eosinophil and platelet counts, gamma glutamyl transferase, mouse inoculation). In two cases, PCR was positive with no detected infection of the foetus. In this study, the combination of fast detection methods, ie cell culture and PCR of amniotic fluid, eosinophil and platelet counts, GGT activity and specific IgM, enabled us to confirm 10/10 cases of congenital toxoplasmosis in less than a week. PCR therefore appears to be an additional test which improves early prenatal diagnosis of toxoplasmosis.

Amniotic Fluid↗

Pattern of antibodies in toxoplasmosis of pregnant women and their children in Thailand.

The latex agglutination test for toxoplasmosis was performed on 690 blood samples collected from the Veterans and Bang Bua Thong Hospitals in Bangkok. Blood samples were collected in the first- and the third-trimester from pregnant women and from the cord blood. The seroprevalence of toxoplasmosis in the first trimester was 13.14%, 13.60%; in the third trimester was 12.21%, 9.43% and in the cord blood 7.18% and 13.04% for the Veterans Hospital and Bang Bua Thong Hospital, respectively. There was no significant difference between the prevalence of toxoplasmosis for each type of blood from both hospitals. The average prevalence of toxoplasmosis for Thai pregnant women in the first- and third-trimester was 13.38% and 11.41%, respectively, and that for the cord blood was 9.01%. Congenital toxoplasmosis occurred in children of untreated mothers who were seropositive or seronegative in the third-trimester, the infection rates of the fetus being 46.67% and 8.13% respectively.

Animals↗

Toxoplasmosis.

Toxoplasmosis is a common infection of animals and man, yet remains a rare disease. The disease appears in the offspring of mothers first infected during pregnancy and by relapse of chronic infection in immunodeficient animals and man. Toxoplasmosis can be prevented by the simplest of hygienic measures, such as handwashing. Further control can be achieved by widespread education of the public about the dangers of toxoplasmosis and the methods of prevention. Education of veterinary and zoo workers would reduce transmission in an environment where it is most likely to occur because of high concentrations of cats and cat feces. Toxoplasmosis of sheep and pigs on farms may be amenable to vaccination with the ts-4 strain of Toxoplasma. Finally, the new T-263 toxoplasmosis vaccine for cats offers the possibility of drastically reducing environmental contamination with oocysts, especially on farms. The reduction in numbers of viable oocysts in the environment would eventually reduce the infection of bird and rodent intermediate hosts, and ultimately, the infection of humans.

Animals↗

[Detection of the foci of familial toxoplasmosis in rural environment].

In order to detect centres of family toxoplasmosis in rural environment 24,546 patients, suspected of invasion of T. gondii, 504 healthy persons coming from villages and 1,681 live stock were examined. Among persons suspected of infection of T. gondii, 65 cases of congenital family toxoplasmosis and 19 cases of environment family toxoplasmosis, involving several members of the family were detected. In animals a comparatively high percentage with positive reaction in the direct agglutination test (cattle 55.5%, swine 27.9%, sheep 23.4%) was detected. The following serological tests were applied to humans: complement-binding test (OWD), indirect immunofluorescence test (OIF), direct agglutination test with 2-mercaptoethanol (CA), ELISA IgM and, selectively, immunoperoxidase test IgM (OIP). The results suggest that the environment conditions can play an important role in the occurrence of family toxoplasmosis in our country, especially in the countryside. Detecting active toxoplasmosis in a family member should be a signal to start serological-epidemiological examination of the remaining family members and live stock.

Adult↗

[Toxoplasmosis and ocular pathology].

Toxoplasmosis is the leading cause of posterior uveitis in the immunocompetent adult, and potentially leads to blindness. Ocular Toxoplasmosis is usually considered a recurrence of a congenital infection, and this fact enhances the importance of prevention in pregnant women in order to avoid transplacental passage of free forms of the parasite Toxoplasma gondii. Ocular toxoplasmosis can also be acquired following undiagnosed primary infection in immunocompetent or immunodeficient patients, particularly AIDS patients for whom it indicates a modification of the immunologic pattern. The typical ocular lesion is necrotizing retinitis, satellite of an existing scar, whose situation in the fundus of the eye, number, size, aspect and evolution are variable; more rarely, ocular toxoplasmosis presents in other forms (anterior uveitis, pars-planitis, scleritis, papillitis). The treatment of ocular toxoplasmosis, remains controversial, in particular due to drug side effects. This enhances the importance of alimentary and environmental prevention.

AIDS-Related Opportunistic Infections↗

[Toxoplasmosis in AIDS patients. Pathoclinical study of 78 cases].

We report 78 cases of toxoplasmosis diagnosed between 1987 and 1992, from an autopsy study of 205 patients infected by the human immunodeficiency virus (HIV). Of the 78 patients 22 were females (28%) and 56 males (72%). Risk factors were as follows: intravenous drug addiction (44 cases, 56%), homosexuality or bisexuality (18 cases; 36%) and multiple blood transfusions (6 cases). Cerebral toxoplasmosis (CT) was diagnosed in 73 cases (93%) and was characterized by abscesses (59 cases), diffuse encephalitic lesions (8 cases), isolated cysts without inflammation (3 cases) and hemispheric involvement with ventricular hemorrhage (3 cases). Cerebral involvement were isolated (55/78 cases; 70%) or associated with multi-visceral diffusion (18/78 cases; 23%). Isolated extracerebral localization was observed in 5 cases. The most frequent extracerebral sites were: cardiac (21 cases), pulmonary (14 cases) and pancreatic (7 cases). Immunohistochemical study with anti Toxoplasma gondii antibodies allowed to a diagnosis of extracerebral localization in 8 cases. Ultrastructural features of Toxoplasma gondii were studied on post mortem myocardial samples (2 cases) open lung biopsy (1 case) and bladder biopsy specimen (1 case). Antemortem diagnosis of cerebral toxoplasmosis was performed on CT-scan in 59/73 (80%). Antemortem diagnosis of extracerebral toxoplasmosis was performed or suspected in 8/23 cases (34%): by isolation of trophozoites in bronchoalveolar lavage (2 cases), on an open lung biopsy (1 case) and on a bladder biopsy specimen (1 case), and by clinical and echocardiographic data (4 cases). Anti-toxoplasmic serology allowed to the diagnosis of toxoplasmosis in 12/78 cases (15%) by showing high levels of IgG in the serum.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗

[Value of prevention of congenital toxoplasmosis].

PURPOSE: To verify incidence of toxoplasmosis seroconversion during pregnancy and the interest of treating the mother. METHODS: Among 7044 infants born between January 1989 and December 1993, 78 (1.1%) born to mothers who developped toxoplasmosis seroconversion during pregnancy were followed. RESULTS: Among 69 mothers treated, there were only 9 cases of congenital toxoplasmosis (13.4%) including only 3 cases of patent toxoplasmosis. CONCLUSION: Treating the mother is an effective means of preventing toxoplasmosis. The cost of verifying seronegativity in women during pregnancy could be reduced by primary prevention.

Coccidiostats↗

Fetal immune response following congenital toxoplasmosis.

Serum concentrations of IgA, its subgroups IgA1 and IgA2, IgM, IgG, and IgD were determined in a group of 14 mothers who contracted toxoplasmosis during pregnancy and their 14 offspring. Four newborns developed toxoplasmosis, 10 did not. The 4 infants with congenital toxoplasmosis had evidence of increased immunoglobulin synthesis in utero in sharp contrast to the 10 offspring of toxoplasmosis-infected mothers who failed to develop the disease. Three of these 4 affected children had elevated IgM levels; all 4 had significantly increased IgA values. The use of IgA subclass IgA1 and IgA2 was not helpful in distinguishing infants with congenital toxoplasmosis from unaffected infants. The present series is consistent with other studies from this laboratory, indicating that the fetal immune response to intrauterine infection may include IgA as well as IgM.

Adult↗

Punctate outer retinal toxoplasmosis.

Classic ocular toxoplasmosis initially involves inner retinal layers and is associated with marked vitreous reaction. We encountered three cases of punctate outer retinal toxoplasmosis, a subset of ocular toxoplasmosis that is characterized by multifocal gray-white lesions at the level of deep retina and retinal pigment epithelium and that is associated with little or no overlying vitreous reaction. Acute lesions may resolve to form fine granular white dots. Recognition of this uncommon presentation of toxoplasmosis is important, since there is some evidence that treatment of toxoplasmosis may be effective.

Adolescent↗

Cervical adenopathy secondary to toxoplasmosis.

Toxoplasmosis is not a rare disease. Infestation occurs in 75% of the general world population and in 35% of the US population. Lymphadenopathy, primarily of the cervical type, is one of the most common signs of acquired toxoplasmosis. During the past 15 years a great number of reports have appeared in the medical literature regarding toxoplasmosis. However, it seems that most clinicians do not consider this disease as a possibility when they encounter patients with unexplained cervical adenopathy in whom the usual tests for infectious mononucleosis are negative. In fact, the majority of such patients come to the operating room with a suspected diagnosis of malignant neoplasm, particularly of malignant lymphoma. Thus, a great deal of unnecessary anxiety is generated and, at times, unnecessary surgery is performed. These may be avoidable. A total of 38 cases of acquired toxoplasmosis manifested by lymphadenopathy (82% in the cervical region) are analyzed with respect to symptomatology, differential diagnosis, clinical and laboratory diagnosis, and treatment. Toxoplasmosis should be included in the differential diagnosis of patients with cervical tumors.

Adolescent↗

Treatments for toxoplasmosis in pregnancy.

BACKGROUND: Toxoplasmosis is a widespread parasitic disease and usually causes no symptoms. However, infection of pregnant women may cause congenital infection, resulting potentially in mental retardation and blindness in the infant. OBJECTIVES: The objective of this review was to assess whether or not treating toxoplasmosis in pregnancy reduces the risk of congenital toxoplasma infection and improves infant outcomes. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched. An electronic search was performed using the key words 'congenital and toxoplasmosis' on the following databases: MEDLINE (1966-07/1997), Embase (1993-07/1997), Pascal (French) (1990-1997), Biological Abstracts (1993-1995) and the Cochrane Controlled Trials Register. There was also contact with experts in the field, including those in the European Research Network on Congenital Toxoplasmosis. SELECTION CRITERIA: Randomised controlled trials of antibiotic treatment versus no treatment of pregnant women with proven or likely acute Toxoplasma infection, with outcomes in the children reported. We also inspected relevant reports of less robust experimental studies in which there were (non randomly allocated) control groups, although it was not planned to include such data in the primary analysis. DATA COLLECTION AND ANALYSIS: Reports of possibly eligible studies were scrutinised by two investigators. MAIN RESULTS: Out of the 2591 papers identified, none met the inclusion criteria. REVIEWER'S CONCLUSIONS: Despite the large number of studies performed over the last three decades we still do not know whether antenatal treatment in women with presumed toxoplasmosis reduces the congenital transmission of Toxoplasma gondii. Screening is expensive, so we need to evaluate the effects of treatment, and the impact of screening programmes. In countries where screening or treatment is not routine, these technologies should not be introduced outside the context of a carefully controlled trial.

Female↗

Disseminated toxoplasmosis resulting in graft failure in a cord blood stem cell transplant recipient.

Toxoplasmosis is an infrequent infection with a high mortality rate in hematopoietic stem cell transplant recipients, and is usually caused by reactivation of prior, latent infection upon intensive immunosuppression. We report a case of fatal disseminated toxoplasmosis, diagnosed at autopsy, in a 7-year-old boy who received a cord blood graft for recurrent acute lymphoblastic leukemia. This case represents both the first reported case of toxoplasmosis in an engrafted cord blood recipient, and also of graft failure due to toxoplasmosis. Recommendations for toxoplasmosis diagnosis, treatment, and prophylaxis in stem cell transplant recipients are reviewed.

Child↗

Long-term follow-up of patients with AIDS on maintenance therapy for toxoplasmosis.

To assess potential interactions of multiple drug regimens administered to patients with AIDS for toxicity and efficacy, we reviewed the charts of 35 patients on maintenance therapy for toxoplasmosis. Seven relapses of toxoplasmosis occurred in 6 of 35 (17%) patients, and seven episodes of pneumocystosis occurred in 6 of 35 (17%) patients. Four relapses of toxoplasmosis and 5 relapses of pneumocystosis were seen in 20 patients treated with pyrimethamine/clindamycin; 2 relapses of toxoplasmosis and 2 relapses of pneumocystosis were seen in 11 patients treated with pyrimethamine alone, and 1 relapse of toxoplasmosis was seen in 13 patients treated with pyrimethamine/sulfadiazine. Adverse effects were related to pyrimethamine in 10 patients, to clindamycin in 7 patients, and to sulfadiazine in 8 patients. These results must be compared with those of prospective trials to determine the efficacy and safety of various maintenance regimens.

Acquired Immunodeficiency Syndrome↗

Performance of a Western blot assay to compare mother and newborn anti-Toxoplasma antibodies for the early neonatal diagnosis of congenital toxoplasmosis.

The aim of this study was to retrospectively evaluate the performance of a Western blot assay to compare mother and newborn anti-Toxoplasma gondii antibodies for the early neonatal diagnosis of congenital toxoplasmosis. Since specific anti-Toxoplasma IgM or IgA is detected inconstantly at birth in the neonate, the diagnosis of congenital toxoplasmosis is often delayed until 6-9 months, after IgG titers have been observed persistently. In this study, 81 paired samples from 60 mother/child pairs were tested for IgG and IgM patterns. All mothers had (or were strongly suspected to have) acquired toxoplasmosis during pregnancy. Specific IgM and IgA were simultaneously detected by immunocapture tests, and IgG was titrated. A serological and clinical follow-up of infants was conducted during the first year of life until the diagnosis of congenital toxoplasmosis could be either confirmed or ruled out. Seventeen of the 60 newborns were congenitally infected. Specific IgM or IgA was detected by immunocapture at birth in 76.5% and 70.6% of cord sera from infected neonates, respectively, with an equal specificity of 77.5%. Comparative Western blot allowed the detection of neosynthesized IgG and IgM in the cord blood of 50% and 78.6% of infected infants, respectively, with a specificity of 100%. The combination of IgA and IgM immunocapture tests, the analysis of IgG and IgM Western blot patterns, and the combination of both techniques allowed the detection of 94%, 94%, and 100% of cases within the first 3 months of life, respectively. In conclusion, Western blotting seems to be a useful complementary tool for the early postnatal diagnosis of congenital toxoplasmosis.

Animals↗

Clinical features and prognosis in ocular toxoplasmosis.

PURPOSE: To evaluate retrospectively the clinical characteristics, complications, and prognosis in patients with ocular toxoplasmosis. PATIENTS AND METHODS: We reviewed the records of 189 patients (243 eyes) with ocular toxoplasmosis who were examined between 1972 and 1999. Color fundus photography and, in some patients, fluorescein angiography and indocyanine green angiography were performed. There were 98 male (52%) and 91 female (48%) patients with a mean age of 22.8 +/- 8.9 years. RESULTS: Of the patients, 140 (74%) had congenital and 49 (26%) had acquired toxoplasmosis. At the initial examination, there were active lesions in 65 eyes and inactive lesions in 178 eyes. Active lesions included retinochoroiditis in 59 (91%), papillitis in 2 (3%), and neuroretinitis in 4 (6%) eyes. There was also an inactive scar in 17 eyes with active retinochoroiditis. Localisation of the active retinochoroiditis was the macula in 44 (74%), the macula and peripheral retina in 3 (5%), the peripheral retina in 9 (15%) and the peripapillary retina in 3 (5%) eyes. Optic atrophy, pigment epithelial detachment, choroidal neovascularization, lamellar macular hole, and retinal neovascularization were seen during the follow-up period. CONCLUSIONS: Ocular toxoplasmosis commonly affects the macula and seriously impairs visual acuity. The prevention of acquired and congenital infections is very important in controlling ocular toxoplasmosis. Patients should be followed to avoid late complications.

Adolescent↗