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Experimental congenital toxoplasmosis. III. Toxoplasmosis in the offspring of mice infected by the vaginal route. Incidence and manifestations of the disease.

A study has been made of congenital toxoplasmosis in the offspring of mice infected with Toxoplasma by the vaginal route during pregnancy. Some of the young mice were retarded in postnatal development, and some became ill or died in the 2nd to 4th weeks of life while the majority remained symptom-free in spite of the presence of toxoplasmic lesions of varying degrees of severity. Congenital toxoplasmosis developed only in offspring whose mothers had been infected on the 7th to 9th day of pregnancy. Infection of the offspring without active toxoplasmosis in the mother was not observed. The highest incidence of congenital infection (57.6 per cent) was obtained by giving 2 vaginal instillations of Toxoplasma-infected mouse brain on the 8th and 9th days of pregnancy. Mice infected before the 7th day developed placental toxoplasmosis but rarely delivered viable young. When the mother was infected after the 9th day, the offspring were normal. When congenital toxoplasmosis occurred in a litter, a majority or all of the individual offspring were usually infected. Although pathologic changes were not present in the suckling mice at birth, and did not appear before the 9th postnatal day, reasons are stated for excluding the possibility of postnatal contact or milk-borne infection. It cannot be assumed from the experimental disease that the vagina is a portal of entry of Toxoplasma in human congenital toxoplasmosis. Any route of infection leading to a maternal parasitemia during pregnancy might result in toxoplasmosis of the placenta and transmission of the disease to the offspring before birth. Unlike the restricted time interval effective in the mouse, there is a long period during the later months of pregnancy in the human being in which transplacental passage of the infection may occur. When transmission to the fetus takes place shortly before parturition, evidence of disease in the human infant, as in the mouse, may not become manifest until several weeks postpartum, and the prenatal origin of the infection may not be apparent. When the fetus becomes infected well before parturition, symptoms of congenital toxoplasmosis may be present at birth. The asymptomatic character of the infection in many of the young mice would appear to have a counterpart in certain instances of human congenital toxoplasmosis.

Animals↗

[Serodiagnosis of toxoplasmosis developing during pregnancy and of congenital toxoplasmosis].

During the first prenatal serodiagnosis of toxoplasmosis, the test must permit to differentiate between immunized and non-immunized patients and to screen recently contracted toxoplasmosis. In a group of 33 women affected with toxoplasmosis during pregnancy a critical study of serodiagnosis criteria is carried out by comparing the theoretical protocol of the evolution of the serology during acquired toxoplasmosis with the situations observed under usual prenatal monitoring. Seroconversion was noted in 26 women and the variability of the results emphasizes the difficulties in determining the date of the contamination when an evolutive form of toxoplasmosis is suspected at the first examination, which is the case in 7 other patients. In children, 11 congenital toxoplasmosis were diagnosed, all on laboratory examinations. It must be emphasized that 16 children were prematurely lost to follow-up. It should be necessary to devote our energies to screening and information in order to validate the protocol of prevention of congenital toxoplasmosis.

Agglutination Tests↗

Ophthalmological findings in children with congenital toxoplasmosis. Report from a Swedish prospective screening study of congenital toxoplasmosis with two years of follow-up.

UNLABELLED: Congenital toxoplasmosis may lead to severe visual impairment or neurological sequelae in the child. PURPOSE: To study the severity of the primary and late ophthalmological dysfunction during a prospective incidence study of congenital toxoplasmosis in the Stockholm and Skåne counties. METHODS: Blood collected on phenylketonuria (PKU) cards from 40,978 consecutively born children were investigated for antitoxoplasma antibodies. Children with verified congenital toxoplasmosis were treated for 12 months with antiparasitic therapy and followed ophthalmologically, neurologically and serologically every third month. RESULTS: Three children had congenital toxoplasmosis. Two of these were asymptomatic at birth and would have escaped early detection without screening. One child had unilateral severe visual impairment and CNS involvement. The incidence of congenital toxoplasmosis was less than 1:10,000. CONCLUSION: Neonatal screening is of importance to diagnose asymptomatic infected children with congenital toxoplasmosis as treatment has been shown to reduce long-term sequelae. Ophthalmological investigations should start early and continue in co-operation with paediatricians.

Adult↗

Experimental congenital toxoplasmosis. II. Transmission of toxoplasmosis to the placenta and fetus following vaginal infection in the pregnant mouse.

Pregnant mice infected with Toxoplasma by the vaginal route have been found to transmit toxoplasmosis to the placentas and fetuses in utero. The microorganism entered the blood stream of the mother from primary foci of infection in the vaginal wall and produced disseminated lesions in the labyrinth of the allantoic placenta at the same time as other peripheral maternal tissues were involved. Placental lesions were observed in mice infected with Toxoplasma by vagina between the 3rd and the 9th day of pregnancy. They consisted of microscopic foci of degeneration, without inflammation, in the syncytial trophoblast, and parasites undergoing multiplication were readily identified in them. Here Toxoplasma gained access to the fetal circulation. Following the vaginal instillation of Toxoplasma on the 8th day of pregnancy, subinoculation of test animals revealed the parasites in the maternal peripheral and placental blood on the 13th day and later, while the first histopathologic changes in the placenta were found on the 17th day. Toxoplasma could be demonstrated in suspensions of fetal tissues on and after the 17th day by the injection of normal test animals. However, no lesions of toxoplasmosis, or Toxoplasma, were found in histologic sections of fetuses 11 to 21 days old removed at autopsy from vaginally infected mothers. It is concluded that before birth the parasites were confined to the fetal blood. The experiments provide the first direct histological demonstration of placental toxoplasmosis. The possible bearing of the experimental disease on human placental and fetal toxoplasmosis is briefly considered. It is probable that a maternal parasitemia during the latter part of pregnancy, whatever the portal of entry may be, is an essential factor in the pathogenesis of human congenital toxoplasmosis and that this occurs shortly after exposure to Toxoplasma rather than in a later chronic stage of the infection. The suggestion is offered that some instances of spontaneous abortion or fetal death in man, as in the mouse, may be due to inapparent toxoplasmosis.

Animals↗

First case of toxoplasmosis following small bowel transplantation and systematic review of tissue-invasive toxoplasmosis following noncardiac solid organ transplantation.

BACKGROUND: Toxoplasmosis prophylaxis is standard following heart and heart lung transplantation, when an increased risk of allograft transmitted Toxoplasma is well-recognized. In contrast, prophylaxis and routine serologic evaluation of donors and recipients for Toxoplasma in noncardiac solid organ transplantation (SOT) is not recommended. We report the first case of disseminated toxoplasmosis following small bowel transplantation, presumably transmitted via the transplanted intestine and systematically review reported cases of toxoplasmosis in noncardiac SOT recipients to determine if current guidelines should be reconsidered. METHODS: Systematic MEDLINE review was performed for tissue invasive toxoplasmosis in noncardiac SOT recipients and analysis of clinical features, serologic status, and treatment regimens with respect to mortality. RESULTS: Fifty-two cases of toxoplasmosis in noncardiac SOT recipients were identified. Eighty-six percent developed disease within 90 days of transplantation. Presentation was nonspecific and consisted of fever (77%), respiratory distress (29%), neurologic manifestations (29%), and bone marrow suppression (26%). Multivariate analyses demonstrated that localized disease (odds ratio [OR]=37.36, 95% CI 1.85-754.85), treatment received (OR=1.814, 95% CI 1.193-3.480) and donor and recipient serostatus (OR=1.39, 95% CI 1.068-1.815) were predictors of survival. High-risk recipients (donor seropositive/recipient seronegative) developed disease earlier (16 days vs. 31 days P=0.002) and were less likely to survive (OR=0.14, 95% CI 0.03-0.69) than standard-risk recipients. CONCLUSIONS: Toxoplasmosis is recognized following noncardiac SOT. Reduction of morbidity and mortality necessitates knowledge of donor and recipient Toxoplasma serostatus, prophylaxis, early diagnosis, and treatment. The findings support a reconsideration of pretransplantation evaluation and prophylaxis strategies in SOT recipients.

Child↗

Low incidence of congenital toxoplasmosis in children born to women infected with human immunodeficiency virus. European Collaborative Study and Research Network on Congenital Toxoplasmosis.

In children born to immunocompetent women, congenital toxoplasmosis almost always results from primary infection during pregnancy. However, reactivation of latent toxoplasmosis during pregnancy could occur in HIV-infected pregnant women, particularly in those who are severely immunocompromised, and result in maternal-fetal transmission of the parasite. This mode of infection has been described in case reports but the risk of transmission is unknown. Findings on toxoplasmosis are presented from the European Collaborative Study, a prospective study of children born to women known to be HIV-infected at the time of delivery. In 1058 children followed for a mean duration of 35 months, only one child developed clinical toxoplasmosis. This child was HIV-infected, severely immunocompromised, and acquired toxoplasmosis postnatally. Congenital infection was excluded serologically in a subgroup of 167 children, of whom an estimated 71 had been at risk of infection. These clinical and serological findings indicate a low general risk of maternal-fetal transmission of Toxoplasma infection in HIV-infected women. It is not possible to draw conclusions about the risk of transmission for severely immunocompromised HIV-infected women because most women in the study were asymptomatic.

Acquired Immunodeficiency Syndrome↗

Outcome of treatment for congenital toxoplasmosis, 1981-2004: the National Collaborative Chicago-Based, Congenital Toxoplasmosis Study.

BACKGROUND: Without treatment, congenital toxoplasmosis has recurrent, recrudescent, adverse outcomes. Long-term follow-up of infants with congenital toxoplasmosis treated throughout their first year of life with pyrimethamine and sulfadiazine has not been reported. METHODS: Between 1981 and 2004, one hundred twenty infants (current mean age +/- standard deviation, 10.5 +/- 4.8 years) with congenital toxoplasmosis were treated with 1 of 2 doses of pyrimethamine plus sulfadiazine; therapy was initiated shortly after birth and continued for 12 months. Children who received treatment were evaluated at birth and at predetermined intervals; the focus of the evaluations was on prespecified end points: motor abnormalities, cognitive outcome, vision impairment, formation of new eye lesions, and hearing loss. RESULTS: Treatment of infants without substantial neurologic disease at birth with pyrimethamine and sulfadiazine for 1 year resulted in normal cognitive, neurologic, and auditory outcomes for all patients. Treatment of infants who had moderate or severe neurologic disease (as defined in this article in the Treatments subsection of Methods) at birth resulted in normal neurologic and/or cognitive outcomes for >72% of the patients, and none had sensorineural hearing loss. Ninety-one percent of children without substantial neurologic disease and 64% of those with moderate or severe neurologic disease at birth did not develop new eye lesions. Almost all of these outcomes are markedly better than outcomes reported for children who were untreated or treated for 1 month in earlier decades (P<.01 to P<.001). Sex and severity of disease were comparable in our 2 treatment groups, and no significant differences in efficacy or toxicity were noted between the 2 treatment groups (P > .05). CONCLUSIONS: Although not all children did well with treatment, the favorable outcomes we noted indicate the importance of diagnosis and treatment of infants with congenital toxoplasmosis.

Antiprotozoal Agents↗

[The results of a serological examination of the population for toxoplasmosis and the estimated incidences of congenital toxoplasmosis in 2 foci in Uzbekistan].

Enzyme immunoassay was used in screening for toxoplasmosis of 500 residents of the town of Ghulistan and of 1074 residents of the town of Shavat in the Khorezm district of Uzbekistan. All the examinees were aged 15 to 40. The share of seropositive subjects in Ghulistan was 24.6%, that in Shavat 14.6%, the toxoplasmosis loimopotentials were 0.87 and 0.62%, respectively. The predicted parameters were as follows: new cases of toxoplasmosis among pregnant women were 4.9% in Ghulistan and 3.9% in Shavat, the incidence of congenital condition 1.7 and 1.3%, respectively, the incidence of manifest congenital toxoplasmosis 0.6 and 0.4%, respectively. The presence of a cat in the house was associated with higher share of seropositive subjects in the town of Shavat as against Ghulistan. An urban focus (Ghulistan) appeared more intensive as against a rural type focus (Shavat) at the expense of a higher intensity of the xenotropic route of the agent transmission.

Adolescent↗

[Toxoplasmosis and pregnancy. Evaluation of 2 years of prevention of congenital toxoplasmosis in the maternity ward of Hôpital Saint-Antoine (1973-1974)].

The authors report the results of prophylaxis of congenital toxoplasmosis in a maternity hospital in Paris for a two years period (1973-1974). 6269 pregnant women were surveyed. 18 toxoplasmosis were detected in evolution at the first prenatal examination, 10 seroconversions were identified among the first examination antibody negative women, when re-examined during the pregnancy. 25 of these 28 women were treated regularly. The seroconversions of the 3 other women were detected only at delivery. In addition 25 women were treated because of high antibody titers (Dye-Test greater than or equal to 300. U.I/ml). 6 congenital toxoplasmosis, 2 of them were manifest, were observed among the children whose mothers were treated for confirmed toxoplasmosis. The extremely low level of seroconversions may be in relation to hygienic and dietetic prescriptions. The difficulties of this prophylaxis are analysed: they are due to studied population and to problems of interpretation or serologic examinations.

Female↗

[Alzheimer's dementia or cerebral toxoplasmosis? Case study of dementia following toxoplasmosis infection].

Cerebral toxoplasmosis can lead to dementia in AIDS and in immunodeficient patients. We present a case study in which cerebral toxoplasmosis was associated with a dementia of Alzheimer type. Half a year to one year before the cognitive impairment began, the patient suffered a subacute infection of toxoplasmosis at the age of 56. Neuropsychological examination as well as MRI suggested a diagnosis of dementia with infectious genesis. However, serological tests showed only little evidence of infection. Since the results of the PET examination indicated changes in the glucose metabolism typical of Alzheimer's disease, we infer a comorbidity of cerebral toxoplasmosis and dementia of Alzheimer type.

Alzheimer Disease↗

[Epidemiological data on toxoplasmosis. The aspects of congenital toxoplasmosis].

The aim of the present study was to get a real image about Toxoplasma gondii infection of pregnant woman and the consequence for her child in Moldavia area. There were studied: 224 pregnant women with pathological pregnancies comparing with 347 apparently healthy pregnant women; 1422 newborns; 223 children with mental retardation and visual pathology comparing with 129 apparently healthy children. There were used the following serological methods: indirect immunofluorescent assay, direct agglutination test, immunosorbent agglutination assay (ISAGA). The following results were obtained: 1) a high sero-prevalence of T. gondii antibodies among pregnant women (43.9%)--most of them being chronic infections; 2) 0.6% pregnant women with acute toxoplasmosis in the first trimester of their pregnancies, situation with great danger for the unborn child; 3) a 7.1% degrees of participation of T.gondii infection to the etiology of spontaneous abortion; 4) a high seroprevalence of T.gondii antibodies among children with mental retardation (66.4%) and visual pathology (37.4%) comparing with the group of apparently healthy children (9.3%). The conclusion resulting from this data is that toxoplasmosis demands more attention from our medical world, a national program of prophylaxis including a large screening of pregnant women and/or newborns being able to prevent the severe damages due to congenital toxoplasmosis.

Adolescent↗

Indirect hemagglutination using whole mixed antigen for checking toxoplasmosis immunity and for serodiagnosis of human toxoplasmosis, compared with immunofluorescence.

The indirect hemagglutination (IHA) is an easy technic for which it is possible to get commercial reactifs. This methode should be used often for the serodepistage of Toxoplasmosis and control of the immunitry anti-toxoplasmosis. We used a technique with total mixed antigen, that was compared with indirect immuno-fluorescence (I.F.I.), for 623 human serums. The I.H.A. was used with sheep formal hematies and coated with glutaraldehyde, with a total mixed antigen prepared from ultra sonicated parasites. This standardised reactive can be kept one year at 4 degrees C. We worked with U well micro-titration plates and the result is obtained after 2 hours. The I.F.I. technique was made with classical methods using Evans blue counter staining. The reproducibility of the I.H.A., during 366 tests was satisfactory. For the control of the immunity anti-toxoplasmic, the results tallied with both methods in more 95% of cases. Lastly, as test of progression, the I.H.A. with total mixed antigen appear an interesting way for the early diagnosis of the Toxoplasmosis where the reaction seems to be positive as soon as I.F.I.

Antigens↗

Prenatal diagnosis of congenital toxoplasmosis transmitted by an immunocompetent woman infected before conception. Reims Toxoplasmosis Group.

We report a rare case of congenital toxoplasmosis transmitted by an immunocompetent woman infected before conception. Active toxoplasmosis was suspected due to persistent lymphadenitis with specific IgM, IgA, IgE antibodies. Prenatal diagnosis based on amniocentesis and fetal blood sampling at 24 weeks' amenorrhoea was positive on amniotic fluid, and fetal infection was confirmed after termination. In our opinion such cases need the same monitoring as when seroconversion occurs during the first trimester. A pregnancy-free interval of six to nine months is recommended after proven patent toxoplasmosis seroconversion.

Adult↗