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Toxoplasmosis of donor and recipient hearts after heterotopic cardiac transplantation.

Toxoplasmosis of both donor and recipient hearts was diagnosed by means of endomyocardial biopsy specimens after heterotopic cardiac transplantation for dilated cardiomyopathy. Before transplantation, the donor had raised antibody titers to Toxoplasma, and the recipient was negative. When toxoplasmosis was diagnosed on the basis of endomyocardial biopsy specimen, the recipient had a greatly elevated antibody titer of 1:1,027. This suggests that the infection could have been transferred with the donor heart. The mononuclear cell response elicited by disrupted toxoplasmic cysts interferes with the diagnosis of rejection in graft biopsy specimens. Electron microscopy is valuable in confirming a light microscopic diagnosis of toxoplasmosis. Drug therapy eradicated the toxoplasmosis, but the patient died later of tuberculous meningitis.

Diagnosis, Differential↗

[Acquired immunodeficiency syndrome, Kaposi's disease and cerebral toxoplasmosis in a young man. Review of the literature apropos of a case].

We report a new case of acquired immune-deficiency syndrome (AIDS) in a 43 year-old white homosexual man, characterized by the association of disseminated cutaneo-mucous Kaposi's sarcoma and cerebral toxoplasmosis. This man had Kaposi's sarcoma for about 10 years but evolution became quickly extensive in July 1981. Chlorambucil was prescribed at that time and was the cause of a pancytopenia. Death occurred in July 1982 due to a cerebral mass identified as toxoplasmosis on a left temporal biopsy. This observation is typical of AIDS, a new syndrome which suddenly developed in the last 2 years in the United States in homosexual men, Haitians and hemophiliacs, and is characterized by disseminated Kaposi's sarcoma and/or opportunistic infections, with a very high mortality rate. Severe toxoplasmosis of CNS has been reported in AIDS and appears to result from defects in cellular immunity which permit recrudescence of latent infection. Cerebral biopsy is necessary for the diagnosis of cerebral toxoplasmosis as seroconversion occurs infrequently in immuno-suppressed hosts. AIDS appeared in Western Europe in 1982. Most of the cases were reported in France, Denmark, Belgium and Great Britain. These cases differ from reported cases in the USA: fewer drug or poppers users, fewer homosexual men, an important number of people having lived or travelled in the Kaposi's endemic area (Mediterranean basin and Central Africa). The immunological profile of patients presenting AIDS in Europe doesn't seem to differ from the american profile: serious cellular immunodeficiency and marked increase in the suppressor/cytotoxic cell population. As in the United States, one may suspect, among several hypotheses, that it is caused by one or several transmissible agents now present in France. The nature of these agents, transmissible by sexual contacts and blood, is not yet known: the role of the CMV is now less probable and most of the studies look for the role of other factors such as the HTLV.

Acquired Immunodeficiency Syndrome↗

[Toxoplasmosis and rubella in Moroccan women. Results of a serological survey].

A prospective sero-immunological enquiry of the rubella and toxoplasmosis immune status of 200 pregnant women in Casablanca (Morocco) revealed that 66,5% are immune to rubella and 51,5% are immune to toxoplasmosis. A study of the relation between the immune status and age shows that serum conversion takes place most frequently between the ages of 21 and 25. 7 women had high levels of anti-toxoplasmosis antibodies. The authors compare their results with those obtained in other regions of Morocco and in other countries. They also present a range of epidemiological and technical correlations. They conclude that the prevention of congenital toxoplasmosis and rubella must be integrated into a national programme of mother-and-child protection, notably by means of obligatory prenatal serological tests and the continued monitoring of those women who are not immune.

Adult↗

[Preliminary results of the use of an ELISA test for the differential determination of IgG and specific IgM in toxoplasmosis serology].

The diagnosis of acute toxoplasmosis usually depends on serology, since clinical and/or histological features are difficult and/or often misleading. IgM titers are the best indicators of infection acquired in the past two to four months. IgG titers are generally correlated with non-active infections as well as previous (symptomatic and/or asymptomatic) illness. In the present paper, results obtained with a new kit for the evaluation of IgG and specific-IgM by micro-ELISA technique, are reported. Optical density values in sera from: a) blood donors; b) miscellany group; c) suspected toxoplasmosis, were at various degree high for IgG. Few sera of the entire sample (in the group of suspected toxoplasmosis and one in miscellany) showed high optical density for specific IgM. Reading of results with spectrophotometer were in agreement with reading to the naked eye. Reproducibility was satisfactory. Unfortunately some sera positive in the first determinations gave equivocal results in successive proofs. For these reasons diagnosis of toxoplasmosis must be based upon the use of at least three tests.

Enzyme-Linked Immunosorbent Assay↗

Vascular anastomoses in ocular toxoplasmosis.

Toxoplasmosis is a frequent cause of uveitis seen in clinical practice and fundus scars typical of ocular toxoplasmosis are common. It has been reported that vascular anastomoses between the retinal and choroidal circulation can occur through the damaged Bruch's membrane in fundus scars resulting from ocular toxoplasmosis. Although it has been stated that these vascular anastomoses are a rare occurrence, it has also been suggested that they are relatively common. In order to determine the prevalence rate of patients with vascular anastomoses in toxoplasmic fundus scars, 3,850 consecutive optometry patient files were studied retrospectively. Seventy-four patients (1.92%) had a clinical diagnosis of ocular toxoplasmosis with typical fundus scars, and two of these patients (2.70%) had documented vascular anastomoses.

Chorioretinitis↗

[Should a preventive congenital toxoplasmosis program be established in Switzerland?].

The Swiss Federal Office of Public Health established a multidisciplinary working group whose objectives were to review the subject of congenital toxoplasmosis (CT), to strengthen, as far as possible, the level of knowledge concerning congenital toxoplasmosis in Switzerland (particularly the epidemiological and economic aspects) and to propose a CT prevention programme acceptable to all concerned medical disciplines. Two main questions were considered: (1.) Does the size of the congenital toxoplasmosis problem justify the cost of a systematic screening programme for pregnant women? (2.) How secure is laboratory diagnosis? Neither the national system of reporting by laboratories and physicians, mortality statistics nor insurance records are adequate to estimate the incidence of congenital toxoplasmosis. A study carried out at the main hospital departments of neonatology and pediatrics in Switzerland provides a more accurate estimate but does not match the number of cases predicted by mathematical models. The discrepancy does not put the seroprevalence studies in doubt but rather the estimate of the rate of transmission of T. gondii to the fetus and its degree of virulence. The implementation of a better surveillance system would provide information for adoption and funding of a prevention programme based on facts rather than estimations. Those who support a generalized screening programme for pregnant women must also make an effort to convince the community of its importance. A prenatal screening programme for pregnant women should resolve problems rather than create new ones. The security of the diagnosis of an infection and the effects to the fetus are of vital importance for the principle primum nil nocere.(ABSTRACT TRUNCATED AT 250 WORDS)

Cost-Benefit Analysis↗

[Cerebral toxoplasmosis with central diabetes insipidus and panhypopituitarism in a patient with AIDS].

Endocrine disorders in the course of HIV infection are often a result of opportunistic infections of endocrine organs. We describe the case of a 30-year-old HIV positive man in whom diabetes insipidus developed initially with no abnormal findings in cranial magnetic resonance imaging. 2 months later the patient presented with symptoms of panhypopituitarism. At this time, neuroradiologic examination was consistent with cerebral toxoplasmosis. Symptoms and neuroradiologic findings improved after treatment for cerebral toxoplasmosis. Toxoplasmosis is the most frequent opportunistic infection of the brain in patients with AIDS. In HIV positive patients with malfunction of the hypothalamic-hypophyseal system cerebral toxoplasmosis must be considered in differential diagnosis. Treatment of this disorder may alleviate symptoms and signs of endocrine malfunction.

AIDS-Related Opportunistic Infections↗

Neurologic and developmental outcome in treated congenital toxoplasmosis.

BACKGROUND: Earlier studies have shown that infants with untreated congenital toxoplasmosis and generalized or neurologic abnormalities at presentation almost uniformly develop mental retardation, seizures, and spasticity. Children with untreated subclinical disease at birth have developed seizures, significant cognitive and motor deficits, and diminution in cognitive function over time. OBJECTIVE: To determine neurologic, cognitive, and motor outcomes for children with congenital toxoplasmosis who were treated for approximately 1 year with pyrimethamine and sulfadiazine. DESIGN AND METHODS: Systematic, prospective, and longitudinal neurologic, cognitive, and motor evaluations were performed for 36 individuals with congenital toxoplasmosis. These infants were born between December 1981 and January 1991 and were treated with pyrimethamine and sulfadiazine for approximately 1 year beginning in the first months of life. Compliance with medications was documented. These individuals were evaluated in a standardized manner in a single center in the first months of life and at approximately 1, 3.5, 5, 7.5, and 10 years of age. Their cognitive function was compared with the cognitive function of a nearest-age, same-sex sibling when such siblings older than 3.5 years were available for study. RESULTS: Signs of active central nervous system infection (eg, cerebrospinal fluid [CSF] pleiocytosis, hypoglycorrhachia, elevated CSF protein, and, in some instances, seizures and motor abnormalities) resolved during therapy. Six of the 36 children had perinatal seizures. Four had their anticonvulsant therapy discontinued successfully within the first months of life, and two additional children developed new seizures at 3 and 5 years of age. Tone and motor abnormalities resolved by 1 year of age in 12 of 20 infants who exhibited abnormalities of tone and motor function at their initial neonatal evaluation. By February 1992, 29 of the 36 children had been evaluated when they were 1 year old, and 23 (79%) had a mean +/- standard deviation Mental Developmental Index (MDI) of 102 +/- 22 (range, 59 to 140). Six (21%) had a measure of their cognitive function that was less than 50. Results of sequential IQ tests, performed at 1.5 year intervals or greater, did not differ significantly over time (P > .05). Seven children with MDIs greater than 50 were compared with sibling controls; they had scores of 87 +/- 11 (range, 68 to 97) and their siblings had scores of 112 +/- 15 (range, 85 to 132) (P = .008). Seventeen of 18 children without hydrocephalus and six of eight children with obstructive hydrocephalus responsive to shunting had normal or near-normal neurologic and developmental outcomes. Children with hydrocephalus ex vacuo present at birth, with high CSF protein, and with lack of response to shunting have done less well. CONCLUSIONS: Neurologic and developmental outcomes were significantly better for most of these treated children than outcomes reported for untreated children or those treated for only 1 month (P < .001). Although the level of cognitive function for treated children was less than for their uninfected siblings (P < .008), there was no significant deterioration in neurologic and cognitive function of the treated children tested sequentially. These favorable treatment outcomes justify systematic identification and treatment of pregnant women with acute gestational Toxoplasma infection and young infants with congenital toxoplasmosis.

Child Development↗

[Therapeutic alternatives for cases of cerebral toxoplasmosis in patients with AIDS: clarithromycin and atovaquone].

BACKGROUND: Cerebral toxoplasmosis is the most common opportunistic infection of the central nervous system in AIDS patients. Its rate varies between 3-40% according to the prevalence of toxoplasmosis in the different geographic areas. Conventional treatments used for this pathology are: sulphadiacin or clindamycin plus pyrimethamine, but all can occasionally produce severe side effects. Therefore, the search for new alternative therapies is recommended. METHODS: Two cases of encephalic toxoplasmosis in AIDS patients who developed severe toxicity to conventional treatment with pyrimethamine and sulphadiacin and later to clindamycin are described. RESULTS: The first patient had a complete clinical and neuroradiological curation using clarithromycin 2 g/day and pyrimethamine 50 mg/day for 6 weeks. At 22 months follow up with a maintenance dose of 1 g/day of clarithromycin, the patient still remains asymptomatic. The second patient was successfully treated with atovaquone (750 mg/6 h) for 8 weeks and at 12 months of follow up with a maintenance dose of 750 mg/8 h remains asymptomatic. CONCLUSIONS: The authors believe that clarithromycin and atovaquone may constitute valid alternatives for the treatment of cerebral toxoplasmosis. Nonetheless, their use may, at present, be recommended only as an alternative for the cases of therapeutic failure or severe intolerance when the usual schedules are used.

AIDS-Related Opportunistic Infections↗

[Comparison of the diagnostic usefulness of immunoglobulins A and M in acute toxoplasmosis].

We compared the levels of IgA and IgM antibodies in nonimmunosuppressed patients with active toxoplasmosis to evaluate their diagnostic value. In group I (nine patients with toxoplasmosis) we determined the presence of anti-toxoplasma antibodies at the onset of the disease; in four of them we also studied the levels three months later. In group II (control) we tested 50 serum samples from healthy subjects. In both groups we investigated the presence of IgG with indirect enzyme immunoassay (EIA) (Eti-Toxok G, Sorin Biomedica); capture EIA was used to study IgA (Platelia Toxo IgA, Pasteur), and this method (Eti-toxok M, Sorin Biomédica) and the capture agglutination technique were used to study IgM (Toxo-ISAGA, Biomerieux). The nine patients in group I were positive for IgM (Sorin test) but one was negative with the capture agglutination technique and for IGA. All nine were positive for IgG, and IgG titers were increased in the patients studied a second time. In group II, none of the subjects had IgM; the levels of IgG were > 15 IU/mL in 18 subjects, and < or = 15 IU/mL but not absent, in the 32 remaining subjects. IgA was detected in eight of the 18 individuals with IgG levels > 15 IU/mL and in 11 of the 32 with levels < or = 15 IU/mL. The sensitivity of IgA was 88.8% and its specificity 62%; positive and negative predictive values were 29.6% and 96.8%, respectively. The assay of IgA in the course of active toxoplasmosis does not appear to be a more useful marker than IgM detection; however, the study population should be enlarged to include patients with reactivations of toxoplasmosis, before we can be more conclusive.

Acute Disease↗

[Antenatal diagnosis of toxoplasmosis. 176 case reports].

OBJECTIVE: To determine the value of antenatal diagnosis of congenital toxoplasmosis by ultrasound guided aspiration of cord blood for testing. MATERIAL: This is a prospective study of 176 cases. As well as obtaining fetal blood and amniotic fluid the searched for specific IgM and A as well as culturing for the parasites on human fibroblasts and inoculation of mice, as well as researching them for non-specific signs of fetal infection. 149 children were able to be followed up one year after birth. RESULTS: 15% of the children (22/149) were infected with toxoplasmosis. 11 out of these were diagnosed positive antenatally. For the 11 others the diagnosis of fetal infection could only be made after birth, but the non-specific signs made it possible to expect early that they had been contaminated. 59% (13/22) had latent toxoplasmosis which only showed up after a mean interval of 34 months after birth. 41% (9/22) had clinical and/or paraclinical signs of toxoplasmosis (mainly unilateral non-macular chorioretinitis and intracranial calcifications) but they are well after a follow-up period averaging 30 months. COMMENTARY: Ultrasound alone, when it shows up fetal abnormalities, can make the diagnosis of the severity of the condition. The role of taking fetal specimens is to make clear those infants that are infected because of specific signs, and to find those fetuses which are at high risk because of non-specific signs in order to improve the management of the cases. This development has made it possible to avoid carrying out a large number of unnecessary terminations of pregnancy and has resulted in the birth of affected infants that had no functional sequelae from the infection.

Amniotic Fluid↗

Cats and toxoplasmosis risk in HIV-infected adults.

OBJECTIVE: To establish the prevalence and incidence of toxoplasmosis in an adult human immunodeficiency virus (HIV) population, and to determine if cat ownership contributes to the risk of toxoplasmosis. DESIGN: Retrospective record and laboratory review, coupled with a patient survey. SETTING: A tertiary-care military hospital HIV program. PATIENTS: A total of 723 HIV-infected adults, all former or current US military personnel. MAIN OUTCOME MEASURES: Prevalence and incidence of serologic evidence of toxoplasmosis infection. RESULTS: A total of 723 HIV-infected patients had serial Toxoplasma IgG antibody determinations. Seventy patients (9.7%) were positive on their initial screen; the seronegative patients were tested annually for 1 to 5 years (mean duration of follow-up, 2.1 years). Only 13 patients (2.0%) who were initially seronegative acquired antibodies to Toxoplasma gondii. None of the patients who seroconverted developed clinical disease. A pet history was available on 12 of 13 patients who seroconverted; only one (8.3%) had owned or lived in a household with a cat during the period of seroconversion. The calculated attributable risk of cat ownership/exposure for toxoplasmosis seroconversion in this population is -2.9 per 100 persons annually. CONCLUSION: Toxoplasma antibody seroconversion in an adult HIV-infected population is unusual and appears unrelated to cat ownership or exposure.

AIDS-Related Opportunistic Infections↗

Anergic disseminated toxoplasmosis in a patient with the acquired immunodeficiency syndrome.

Cerebral toxoplasmosis is the most common cause of focal brain disease in patients with the acquired immunodeficiency syndrome. A 24-year-old human immunodeficiency virus-infected woman with two previous episodes of Pneumocystis carinii pneumonia presented with diarrhea and fever. Despite antibiotic treatment, septic shock developed, and she died 3 weeks after the symptoms began. Histologic and histochemical studies revealed an anergic toxoplasmosis with dissemination in all examined organs. There were multiple foci of toxoplasmic cysts and free tachyzoites, sometimes with minute areas of necrosis, but no inflammatory reaction at all. Since effective treatment of toxoplasmosis is available, the occurrence of this rare form of toxoplasmosis should be kept in mind.

AIDS Dementia Complex↗

[Ocular toxoplasmosis in human immunodeficiency virus infected patients without concurrent central nervous system infection. Report of two cases].

Ocular toxoplasmosis is an uncommon complication of acquired immunodeficiency syndrome (AIDS), and it is generally described associated with central nervous system (CNS) lesions. We describe two cases of ocular toxoplasmosis in human immunodeficiency virus (HIV) infected patients, without concurrent CNS infection. Both developed bilateral or unilateral choriorretinitis with favorable response to antitoxoplasma therapy. None of them presented toxoplasmosis of the CNS coexisting with ocular lesions. Ocular toxoplasmosis should be considered in HIV infected patients although no involvement of the CNS is found.

Adult↗

[Congenital toxoplasmosis: contribution of postnatal biological follow-up].

OBJECTIVES: The diagnosis of congenital toxoplasmosis includes a postnatal follow-up, often preceded by a prenatal diagnosis. The aim of our study was to assess the performances of the different techniques used and the value of the samples in the postnatal biological diagnosis. METHODS: The methods available between 1985 and 1993 consisted in the detection of: i) Toxoplasma gondii in the placenta; ii) anti-T. gondii IgM in infant's blood by enzyme-linked immuno-sorbent assay (ELISA), immuno-sorbent agglutination assay (ISAGA) and indirect immuno-fluorescence (IFI), and anti-T. gondii IgG by ELISA and IFI; and iii) neo-synthetized anti-T. gondii IgG and IgM by enzyme-linked immuno-filtration assay (ELIFA). RESULTS: Among 400 cases of seroconversion diagnosed during pregnancy, a sure diagnosis with complete follow-up could be established for 104 infants; 37 of them had proven congenital toxoplasmosis (CT+) while 75 had no congenital toxoplasmosis (CT-). Biological arguments supporting congenital toxoplasmosis had been observed as early as birth in 78.4% of CT+ cases and before two months in 94.6%. The serologic tests were positive in 88.2% of CT+ cases by ELIFA, in 73.0% by ISAGA, in 43.3% by ELISA M and in 14.0% by IFI M. ELIFA was the less specific method (91.3%). CONCLUSION: The sensitive techniques (ELIFA and ISAGA), were essential for the instant follow-up to detect toxoplasmic infection as early as birth.

Animals↗

[Screening for congenital toxoplasmosis: pregnancy outcome after prenatal diagnosis in 211 cases].

OBJECTIVE: To emphasize the importance of follow-up after birth of infants with an antenatal diagnosis of congenital toxoplasmosis. METHODS: Retrospective study from July 1987 through January 31 1995 on 211 women (214 fetuses) who had undergone ovular biopsy for toxoplasmosis seroconversion during pregnancy. RESULTS: Antenatal diagnosis was positive in 13 patients (6.2%). Four pregnancies were terminated during the second trimester. Delivery was triggered at 37 weeks gestation in one woman and in 8 others pregnancy was continued with Fansidar. All infants were born live with infraclinic disease. Two fetal deaths related to biopsy technique occurred (0.95%) and one pregnancy was terminated before the results had been obtained. Only 21.3% of the patients were delivered in our unit. A total of 197 infants were delivered with a negative antenatal diagnosis: 93 were healthy, 5 had congenital toxoplasmosis, 1 died at 3 months and 98 had no or incomplete follow-up. CONCLUSION: Incomplete post-natal follow-up is in contradiction with the excellent performance of antenatal diagnosis of congenital toxoplasmosis. Greater care is needed, especially since now only an amniocentisis is required to detect the parasite genome with polymerase chain reaction.

Adolescent↗

Prenatal diagnosis of congenital toxoplasmosis: comparative value of fetal blood and amniotic fluid using serological techniques and cultures.

The prenatal diagnosis of congenital toxoplasmosis is mainly based on biological tests performed on fetal blood and amniotic fluid. We studied the performance of neonatal diagnosis procedures and the results of fetal blood and amniotic fluid analysis. Of 127 women who contracted toxoplasmosis and underwent prenatal diagnosis, the postnatal serological follow-up was long enough to definitively diagnose congenital toxoplasmosis in 19 cases and to exclude it in 27 cases. Prenatal diagnosis allowed the detection of 94.7 per cent (18/19) of the infected fetuses. The sensitivities of tests in amniotic fluid and fetal blood were equivalent, 88.2 per cent (15/17) and 87.5 per cent (14/16), respectively. In fetal blood, biological techniques were positive in 12/16 cases and in 2/16 cases, serological tests were the only positive sign. The specificities of tests in amniotic fluid and fetal blood were respectively 100 per cent (23/23) and 86.3 per cent (19/22) (three false-positive serological results). These results, added to the lower morbidity of amniocentesis compared with cordocentesis, might lead to cordocentesis being abandoned in the prenatal diagnosis of congenital toxoplasmosis.

Amniocentesis↗

[Use of polymerase chain reaction (PCR) for diagnosis of toxoplasmosis].

The aim of the study was to assess the value of PCR method in laboratory diagnosis of T. gondii infections. The study was based on the identification of a fragment of B1 gene of Toxoplasma gondii 461 base pairs in length in 124 samples of blood, CSF, amniotic fluid and aqueous fluid obtained form humans and experimentally infected animals. Positive PCR results were found with CSF samples and blood sample from men. Moreover, the results were positive with blood samples from mice and rabbits bled on 5, 6, 11 and 12 days after infection. The obtained results showed that PCR is very useful in the laboratory diagnosis of toxoplasmosis, especially in cases suspected of cerebral toxoplasmosis. Furthermore, the results demonstrated that neurotoxoplasmosis occurs in Poland, more frequently that it is realized at present, however, the cases are not recognized because toxoplasmosis is not taken into account in differential diagnosis. Because of short and irregular parasitaemia, PCR is of limited value in the diagnosis of blood samples.

Adult↗