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Prognosis of pregnancy in patients with toxoplasmic retinochoroiditis.

From the study of 18 pregnancies in 10 patients with toxoplasmic retinochoroiditis, it was concluded that the most important factor to be considered in advising pregnant patients with this disease is whether or not the antibody titer increases during pregnancy rather than the clinical pictures or the absolute values of antibody titer. Periodical titration of the antitoxoplasma antibody during pregnancy was recommended as a preventive measure against congenital toxoplasmosis. Pregnancy may be continued if antibody titer does not increase during pregnancy, and it may be interrupted if the antibody titer increases.

Adolescent↗

Morphology and diagnostics of human toxoplasmosis.

Toxoplasmosis has regained clinical importance. In addition to intrauterine fetal infections, the acquired toxoplasmosis endangers an increasing number of immunocompromised adults. This disease affects not only oncologic patients, but also organ transplant recipients and, above all, AIDS patients. Toxoplasmosis has five clinical subtypes: lymphadenopathy, encephalitis, chorioretinitis, disseminated toxoplasmosis and congenital toxoplasmosis. In biopsies of different organs and autopsies of persons who died as a result of an infectious disease, the pathologist is involved in the diagnostic procedures. The findings of the parasites in tissue specimens still constitute the morphologic feature of toxoplasmosis. Differential diagnosis has been improved by immunohistologic methods for demonstrating toxoplasmas in tissue specimens and by the use of polymerase chain reaction for identification of toxoplasmatic antigens. This review describes the pathomorphology and possibility regarding the diagnosis of toxoplasmosis.

AIDS-Related Opportunistic Infections↗

[Toxoplasmosis in pregnancy: recent acquisitions and new prospects].

Congenital toxoplasmosis may develop after maternal primary infection during pregnancy. The infection is usually asymptomatic in pregnant women but poses a risk of severe effects on the fetus. In Italy the incidence is about 6 per thousand. The infection is transmitted to the fetus in approximately 50 percent of such cases. The risk of transmission rises with growing gestational age at the time of primary infection; on the contrary, the seriousness of the effect on the fetuses becomes less active with more advanced pregnancies. Infants with congenital toxoplasmosis are mostly asymptomatic at birth but long-term studies have indicated that up to 85% of them will develop serious sequelae as severe impairment of vision, mental retardation and deafness during the months or the years after the birth. Preventing congenital toxoplasmosis is fundamental. All seronegative women should be encouraged to observe good dietary and general health regulations until delivery. Today the diagnosis in the mother is more reliable because of the improvements in serological techniques. Moreover, it is possible to identify infected fetuses by prenatal procedures such as ultrasonography, amniocentesis and cordocentesis, of which the last two consent to detect the parasite and/or specific antibodies. Recently a polymerase chain reaction (PCR) assay has been developed for the detection of Toxoplasma in the amniotic fluid. Adequate serological screening of pregnant and prenatal diagnosis can be helpful in reducing the incidence of congenital toxoplasmosis; furthermore abortion should be reserved only to cases with severe toxoplasmosis revealed by ultrasonography. Early recognition of pregnant infection and a specific treatment could reduce the parasitic colonization in the placenta by more than 60% and prevent infection in the fetus. If the fetal infection has already occurred, maternal treatment may modify the fetal disease. Spiramycin as immediate treatment of maternal primary infection is essential in preventing Toxoplasma transmission to the fetus. If the fetus results non-infected, spiramycin should be prolonged until delivery. If the fetus is infected, pyrimethamine-sulphadiazine combination should be given in repeated courses alternated with courses of spiramycin. However, there is an urgent need for more active and safer compounds; it would be useful to evaluate in the pregnant woman other potential therapeutic agents as atovaquone and azithromycin.

English Abstract↗

[Congential toxoplasmosis and ocular involvement. A review with 6 case reports].

A review is presented of the ocular affections in congenital toxoplasmosis. The epidemiological, pathogenetic and pathological conditions are reviewed together with the clinical manifestations and the diagnostic and therapeutic possibilities. On the basis of incidence investigations and knowledge from the literature, it must be assumed that approximately 190 infants with congenital toxoplasmosis are born annually in Denmark. Only approximately 15% of the infections will be symptom-producing and will be diagnosed neonatally, but more than 85% of the children with congenital toxoplasmosis will develop chorioretinitis on delivery or later in life and this will frequently cause reduction in vision or blindness. Congenital toxoplasmosis must be regarded as the commonest cause of chorioretinitis and it is probable that congenital toxoplasmosis and chorioretinitis due to toxoplasmosis are considerably underdiagnosed in Denmark. Treatment of congenital toxoplasmosis from birth improve the prognosis. Toxoplasmosis should be suspected in all cases of chorioretinitis. When antibodies to Toxoplasma gondii are demonstrated and the clinical picture is compatible with toxoplasmosis and when there is no other diagnosis, anti-Toxoplasma treatment should be considered. It is important to inform pregnant women about prophylactic measures. If investigations for toxoplasmosis were introduced in the prenatal or perinatal examinations, treatment could be initiated from birth and the diagnosis could be confirmed by possible activation of the chorioretinitis at a later date. Six case reports are presented.

Adult↗

[Toxoplasmosis and pregnancy].

The ongoing national project for prevention of congenital toxoplasmosis has created a need for general information on both toxoplasmosis in relation to pregnancy and on congenital toxoplasmosis. This paper presents an up-to-date survey of these facts. It briefly describes the clinical picture and what can happen to the foetus after primary maternal infection. Special emphasis is placed on diagnosis, and recommendations are made for the treatment of infected mothers and babies. Prevention of congenital toxoplasmosis is discussed from both an individual point of view and in a social perspective.

Anti-Bacterial Agents↗

Prenatal screening for toxoplasmosis.

OBJECTIVE: To evaluate the merits of screening for toxoplasmosis in all pregnant women. METHODS: We used decision analysis to compare three strategies for the antepartum management of congenital toxoplasmosis: 1) no testing for congenital toxoplasmosis; 2) current practice, which is to perform targeted screening in cases of incidental abnormalities noted on ultrasound; and 3) universal serologic screening of pregnant women followed by amniocentesis to diagnose fetal infection in cases of maternal seroconversion. For each of the three strategies, we considered the two available treatment options: intrauterine antiparasitic treatment or pregnancy termination. RESULTS: Universal screening reduced the total number of cases of congenital toxoplasmosis compared with no testing or targeted screening. However, compared with no testing, universal screening with medical treatment resulted in 18.5 additional pregnancy losses for each case of toxoplasmosis avoided. If infected pregnancies underwent termination, universal screening resulted in 12.1 additional pregnancy losses for each case avoided. CONCLUSION: Maternal screening reduces the number of cases of disease, but at a substantial clinical cost. The rarity of the disease and limitations in diagnosis and therapy limit the effectiveness of screening strategies. The risks associated with amniocentesis are particularly important. Universal maternal screening for congenital toxoplasmosis should not be performed.

Decision Support Techniques↗

Acquired and congenital ocular toxoplasmosis experimentally induced in Calomys callosus (Rodentia, Cricetidae).

An experimental model for acquired and congenital ocular toxoplasmosis as well as a model to induce experimental autoimmune uveitis (EAU) was investigated in Calomys callosus. Toxoplasma gondii, ME-49 strain, was used to infect males and pregnant- and not pregnant-females while S-antigen, a major glycoprotein of the retinal photoreceptor cell, was used to induce EAU. The ocular lesions elicited by T. gondii were characterized by the presence of cysts, free tachyzoites and inflammatory cells in the retina or related tissues. In the congenital form, 40% of the fetus presented ocular lesions, i.e., presence of cysts in the retina, vitreous, and extra-retinal tissues. In the acquired form, 75% of the females and 50% of the males presented unilateral ocular cysts both at 21 and 47 days post-infection. It was also demonstrated that S-antigen was not uveitogenic in the C. callosus model. No lesion was observed in the animals exclusively immunized with this retinal component, even when jacalin was used as additional adjuvant for polyclonal response to the retinal antigen. It can be concluded that C. callosus may constitute in a promising model for study both acquired and congenital ocular toxoplasmosis, particularly when it is important to make sure that a non autoimmune process is involved in the genesis of the ocular infection.

Animals↗

Detection of IgA specific for toxoplasmosis in serum and cerebrospinal fluid using a non-enzymatic IgA-capture assay.

A non-enzymatic immuno assay was optimized for detection of immunoglobulin A in serum and cerebrospinal fluid specific in acquired and congenital toxoplasmosis. An antihuman IgA monoclonal antibody was coated onto a polystyrene to capture total IgA. Suspensions of Toxoplasma gondii were used as a visible antigen. Eight hundred specimens (sera, cord blood serum, and cerebrospinal fluid) were tested. These were collected from 300 patients with acquired toxoplasmosis and from 28 children with congenital toxoplasmosis. In acquired toxoplasmosis, the assay allowed early detection of specific IgA, with kinetics similar to those of specific IgM expression. In congenital toxoplasmosis, anti-T. gondii IgA could be detected in the neonatal period. This assay was useful for diagnosis, follow-up, and posttherapeutic evaluation of toxoplasmosis. Specific IgA was also detected in the cerebrospinal fluid of infected newborn children. This simple IgA capture assay improves serological diagnosis of acquired and congenital toxoplasmosis when used in combination with analysis of T. gondii specific IgG and IgM.

Antibodies, Monoclonal↗

Low incidence of toxoplasma infection during pregnancy and in newborns in Sweden.

To estimate the burden of disease due to congenital toxoplasmosis in Sweden the incidence of primary infections during pregnancy and birth prevalence of congenital toxoplasmosis in 40,978 children born in two regions in Sweden was determined. Women possibly infected during pregnancy were identified based on: 1, detection of specific IgG based on neonatal screening of the phenylketonuria (PKU) card blood spot followed by retrospective testing of stored prenatal samples to detect women who acquired infection during pregnancy and follow up of their children to 12 months: 2, detection of specific IgM on the PKU blood spot. The birth prevalence of congenital toxoplasmosis was 0.73/10,000 (95 % CI 0.15-2.14) (3/40,978). The incidence of primary infection during pregnancy was 5.1/10,000 (95% CI 2.6-8.9) susceptible pregnant women. The seroprevalence in the southern part was 25.7% and in the Stockholm area 14.0%. The incidence of infection during pregnancy was low, as the birth prevalence of congenital toxoplasmosis. Neonatal screening warrants consideration in view of the low cost and feasibility.

Algorithms↗

[Occurrence of congenital ocular toxoplasmosis in siblings].

The author points out in connection with the description of two families in which evidently several children suffered damage through toxoplasmosis with which the mother had been infected a long time ago (pseudocoloboma of the macula, changes of the macula similar to juvenile degreneration, abortion and malformations such as anophthalmia, rhinoschisis, cheiloschisis, gnathoschisis and palatoschisis), that low titer levels in the Sabin-Feldmann test and in the complement fixation test are by no means totally insignificant for subsequent pregnancies, as is commonly assumed. In any case, women who have already given birth to children with congenital toxoplasmosis should be subjected to toxoplasmosis treatment, as far as possible, before any new pregnancy.

Adult↗

Cellular immunity to Toxoplasma gondii in congenitally infected newborns and immunocompetent infected hosts.

The aim of this study was to determine the frequency of anergy to Toxoplasma gondii in congenitally infected newborns and immunocompetent infected individuals. Specific anergy to Toxoplasma has been reported previously, especially in cases of congenital toxoplasmosis. Whole blood from 592 immunocompetent patients with suspected toxoplasmosis was cultured in the presence of soluble Toxoplasma antigen for 7 days. Activated T lymphocytes were detected by flow cytometry. In patients over 1 year of age, the percentage of soluble Toxoplasma antigen-stimulated T cells expressing the interleukin-2 receptor CD25 was higher in infected patients than in uninfected subjects (40.0+/-18.3% vs. 1.8+/-2.0%, P<0.0001). No differences were detected between seroconverters, i.e. those with recent rises in IgM and IgG antibodies, and those with acquired or congenital toxoplasmosis. Similar results were observed when congenitally infected ( n=38) and uninfected ( n=89) children under 1 year of age were compared (17.6+/-9.2% vs. 3.0+/-4.9%, P<0.0001). The sensitivity and specificity values of CD25 detection for diagnosis of congenital toxoplasmosis in infants were 95% and 89%, respectively, at a threshold value of 7% above control culture. The results show that specific cellular immunity is detectable in virtually all Toxoplasma-infected patients, including newborns. Detection of CD25 constitutes a simple, sensitive and specific test for diagnosis of congenital toxoplasmosis.

Animals↗

Automated time-resolved immunofluorometric assay for Toxoplasma gondii-specific IgM and IgA antibodies: study of more than 130,000 filter-paper blood-spot samples from newborns.

BACKGROUND: To screen for congenital toxoplasmosis, we developed a time-resolved immunofluorometric assay for the simultaneous detection of Toxoplasma gondii-specific IgM and IgA in filter-paper samples collected from newborns 4-7 days after birth. METHODS: The assay was performed on the AutoDELFIA, and results were calculated based on the ToxoM WHO Third International Reference Serum. Comparison with an in-house mu-capture immunoassay was carried out retrospectively on filter-paper samples from children with confirmed congenital toxoplasmosis. Prospectively the assay was compared with a mu-capture immunoassay on 68 394 samples and a commercially available assay on another 69,467 samples. Before serum was requested from the newborn, positive samples were tested for IgA and IgM separately and in an IgM-immunosorbent agglutination assay developed for filter-paper samples. RESULTS: Intra- and interassay variations (CVs) were 8% and 16%, respectively. The cutoff of 5 units/mL produced a 0.5% retest rate. The assay detected 13 of 18 (72%) samples from newborns diagnosed with congenital toxoplasmosis in the retrospective study. Prospectively, the assay identified 24 newborns who were later diagnosed with congenital toxoplasmosis. Results for all 24 cases were positive by the respective comparison method. No cases were detected solely by the IgA antibodies in the sample. CONCLUSION: Neonatal screening for congenital toxoplasmosis can be automated by use of purified europium-labeled antigen for detection of T. gondii-specific IgM and IgA eluted from filter-paper samples.

Animals↗

Multiple organ dysfunction in congenital murine toxoplasmosis.

Infection of gravid Nya: NYLAR (NYLAR), C57BL/6J (C57), and BALB/c mice with Toxoplasma gondii, on gestation day 7, resulted in fetal resorptions, abortions, and stillbirths. Fetal wastage (estimated) was 35 and 40% in the NYLAR and C57 strains and 55% in the BALB/c strain. Postnatally, pups were cachectic and growth-retarded, with some developing hind limb weakness, petechial lesions on ears and tail, and a blood-tinged nasal exudate. Only 13 of 97 BALB/c pups, 14 of 41 C57 pups, and 46 of 153 NYLAR pups survived the first month of life. At necropsy, swollen, blotched livers, enlarged spleens, pallid kidneys and pulmonary hemorrhages were observed. Cysts of T. gondii were detected in every pup, via press-smears of brain. Histologic examination revealed mineralizing cavitations, ventricular deformations, and periventricular edema in the central nervous system; extensive liver pathology marked by hepatocellular necrosis and calcification, sinusoidal dilatation, and giant cell granulomas; congestion of the spleen with blurring of red and white compartments and cavitations in the white pulp; and tubule and glomerular necrosis and calcification in the kidney. The pulmonary hemorrhages and dermal petechial lesions may reflect a bleeding diathesis due to hepatic insufficiency. The pathogenesis of congenital toxoplasmosis, in the 3 strains of mice, appears due to microvascular dysfunction characterized by dysregulation of hemostasis, perfusion failure, and multiple organ dysfunction, rather than to parasite-mediated cytopathology. We suggest that hematogenous dissemination and endothelial invasion by the parasite induced a systemic inflammatory response syndrome (i.e; toxoplasmic sepsis) leading to the microvascular dysfunction.

Animals↗

Detection of Toxoplasma gondii in 94 placentae from infected women by polymerase chain reaction, in vivo, and in vitro cultures.

The biological diagnosis of congenital toxoplasmosis at birth is important to determine the infant's treatment. The aim of this study was to evaluate the placenta results in the congenital toxoplasmosis diagnosis and to compare them with those obtained with other samples collected at birth (cord blood and newborn blood). A total of 94 placentas, of which 33 came from fetuses suspected of or with proven congenital toxoplasmosis (CT+) and 61 from definitely or probably non-infected fetuses (CT-), was analysed by in vitro culture, mouse inoculation and polymerase chain reaction (PCR). The PCR sensitivity was higher (60.9 per cent) than that of cell culture (29.6 per cent) and mouse inoculation (51.5 per cent) but the number of PCR positive results in CT - patients was also higher (9.5 per cent). The presence of Toxoplasma gondii in the placenta tissues was the only argument at birth (IgM and neosynthesized Ig were negative) in three out of the 33 CT+ cases. The detection of IgM by ELISA and ISAGA and the detection of neosynthesized Ig by immunoblotting were more satisfactory to diagnose congenital toxoplasmosis but the placenta analysis was important to improve the sensitivity of the diagnosis at birth, especially when the prenatal diagnosis was negative or not performed.

Adult↗

Cranial disjunction and visual failure in a slit ventricle syndrome with patent shunt.

A 6.5-year-old child who received a shunt at 3 weeks of age for triventricular hydrocephalus related to his congenital toxoplasmosis developed symptoms of intracranial hypertension and papilloedema. Computed tomographic scan demonstrated slit ventricles. The shunt device was shown to be patent on isotope transit study. Spontaneously the cranial sutures widened and headaches disappeared, but loss of vision occurred and did not reverse despite optic nerve sheath fenestration. We suspect that a rapid drop in intracranial pressure played a role in the pathogenesis of our patient's blindness. This possible complication should be taken into account when calvarial expansion is planned in a patient with an intracranial hypertension syndrome with papilloedema in the presence of slit ventricles and a patent shunt.

Blindness↗