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Disseminated toxoplasmosis in cardiac transplantation.

The first case of disseminated toxoplasmosis following cardiac transplantation in the UK is described, with details of Toxoplasma antibody tests made on other cardiac transplant patients. Sixteen of 40 (39%) of recipients had Toxoplasma antibody before operation. Eleven of 30 (37%) of donors had Toxoplasma antibody. The were four occasions when a negative recipient received a heart from a positive donor. Three survived the immediate postoperative period and two became infected with toxoplasmosis. The implications of this are discussed. Disseminated toxoplasmosis appears much more often when heart muscle from a dye test positive donor is given to a dye test negative recipient. Antibiotic therapy is limited by the fact that the antitoxoplasma drugs available are static in their effect, and need to be given for prolonged periods postoperatively.

Adult↗

Use of three immunological techniques for the detection of Toxoplasma spIgA antibodies in acute toxoplasmosis.

AIMS: To assess the performance and efficacy of three immunological techniques for the detection of Toxoplasma specific IgA antibodies in acute toxoplasmosis. METHODS: The following techniques were used to examine 128 serum samples (51 cases of acute toxoplasmosis, 50 cases of heterologous infections, and 27 healthy controls): direct enzyme linked immunosorbent assay (ELISA), antibody capture ELISA, and antibody capture agglutination. RESULTS: Direct ELISA had a sensitivity of 98% and a specificity of 97%, antibody capture ELISA of 100% and 99%, respectively, and antibody capture agglutination had sensitivity and specificity of 100%. CONCLUSIONS: All three immunological techniques performed well with similar efficacy. Detection of Toxoplasma specific IgA antibodies is a useful diagnostic marker for acute toxoplasmosis.

Acute Disease↗

Toxoplasmosis of the stomach: a cause of antral narrowing.

Radiographs of the stomach showed narrowing of the antrum, caused by toxoplasmosis, in a patient with acquired immunodeficiency syndrome (AIDS). A biopsy specimen demonstrated numerous cysts containing Toxoplasma gondii and many free trophozoites. A subsequent brain scan, obtained with computed tomography, showed multiple enhancing lesions throughout the cerebrum, cerebellum, and basal ganglia that were characteristic of toxoplasmosis. Radiographic abnormalities of the stomach are not uncommon in patients with AIDS. They are associated with infections such as cryptosporidiosis and cytomegalovirus and neoplasms such as Kaposi sarcoma and malignant lymphoma. To the authors' knowledge, this is the first reported case of toxoplasmosis involving the stomach.

Acquired Immunodeficiency Syndrome↗

Too late prenatal diagnosis of fetal toxoplasmosis: a case report.

OBJECTIVE: We describe a case of severe fetal hydrocephalus due to toxoplasmosis which could not be diagnosed until late gestational age due to the lack of a serologic surveillance program during pregnancy; moreover, this case points to the usefulness of molecular biology tools in the diagnostic process. Abnormal ultrasound in the 2nd trimester was noticed and Toxoplasma gondii was demonstrated in amniotic fluid at the 28th week of gestation both by PCR and by mice inoculation. Fansidar and folinic acid were administered. The newborn suffered from progressive hydrocephalus, seizures, and pathological muscular tonus; ultrasound examination showed massive cerebral calcifications. Ophthalmologic examination revealed bilateral choroidoretinitis. Congenital toxoplasmosis was confirmed by the detection of anti- T. gondii IgM and IgA in the neonatal serum. CONCLUSION: The presented case is an example of severe fetal toxoplasmosis diagnosed and treated in utero.

Adult↗

Juvenile dermatomyositis induced by toxoplasmosis.

A 10-year-old girl from southern Alberta, Canada, who had close contact with cats, developed typical features of dermatomyositis. The diagnosis was confirmed by muscle biopsy. A toxoplasmosis titer was 1:16,384 by indirect fluorescent antibody technique, and the IgM response to toxoplasma was positive. Only minimal improvement followed prednisone and azathioprine administration, but she rapidly improved after 4 weeks of treatment for toxoplasmosis with pyrimethamine and sulfadiazine. A year after the onset of dermatomyositis, she showed no weakness or cutaneous lesions, and a repeat muscle biopsy no longer showed inflammation, perifascicular atrophy, or regeneration of myofibers. She remains asymptomatic more than 2 years after discontinuation of all medications. Investigation for immune deficiency disease 1 year after therapy revealed that lymphocytic response to T-cell and B-cell mitogens was normal, as were immunoglobulin and complement levels. She had mild impairment of natural killer cell activity and a positive antinuclear factor. Her rapid improvement on specific therapy and lack of significant long-term immune deficiency is consistent with acute toxoplasmosis infection in an immunologically competent child.

Antibodies↗

The potential role of azithromycin in the treatment of prophylaxis of toxoplasmosis.

Infection with Toxoplasma gondii is the most common parasitic infection worldwide with an estimated prevalence of 1-2 billion people. The risk of developing severe toxoplasmosis is higher for immunocompromised individuals and fetuses of mothers who have acquired a primo-infection. The current therapy of choice for toxoplasmosis is the synergistic combination of pyrimethamine and sulphadiazine. This therapy is highly effective but its use is complicated in immuno-compromised individuals due to adverse secondary effects. In addition, since pyrimethamine is potentially teratogenic, its use is not recommended during early pregnancy. Clindamycin, a lincosaminide, in combination with pyrimethamine has been shown to be an acceptable therapeutic alternative in patients who are unable to tolerate pyrimethamine plus sulphadiazine. In the search for new, effective compounds with less adverse or toxic effects, recent efforts have focused on the new macrolides and the azalides. Here, the results of the investigations and, in particular, the theoretical considerations for the potential use of azithromycin in the therapy of toxoplasmosis in immunocompromised individuals are reviewed.

AIDS-Related Opportunistic Infections↗

MR and TL-210 spect imaging with pathologic correlation for the assessment of CNS lymphoma vs. toxoplasmosis in AIDS patients.

PURPOSE: Analyze the value of TL-201 (Tl) brain single-photon emission computed tomography (SPECT), to differentiate CNS lymphoma from toxoplasmosis in AIDS patients. MATERIAL AND METHODS: Twenty-four AIDS patients with MR enhancing lesion(s), underwent a brain Tl SPECT. Final diagnosis was established by pathology and clinical/MR follow-up. RESULTS: Nine patients had CNS tumor, 9 toxoplasmosis and 6 other non-tumorous lesions. The sensitivity of T1 to diagnose CNS tumor was 77% and the specificity 93%. Two false negative studies correspond to tumors with significant necrosis. CONCLUSIONS: T1 proved useful for differentiating brain neoplasm from toxoplasmosis. Tumors with significant necrosis, did not show the expected increase in T1 uptake. Determination of T1 uptake ratios help detect tumor with faint tracer uptake.

AIDS-Related Opportunistic Infections↗

Neuroendocrine abnormalities in a neonate with congenital toxoplasmosis.

The central nervous system is often affected in patients with congenital toxoplasmosis. However, hypothalamo-pituitary dysfunction has rarely been reported in children with congenital toxoplasmosis, and no case with prolonged fever of central origin has been documented so far. We describe a newborn with congenital toxoplasmosis who presented with fever due to hypothalamo-pituitary dysregulation and combined hypothalamo-pituitary deficiencies consisting of central diabetes insipidus, hypothyroidism and ACTH deficiency.

Adrenocorticotropic Hormone↗

Isolated central diabetes insipidus in a newborn with congenital toxoplasmosis.

We present a 5 day-old male newborn with isolated central diabetes insipidus due to congenital toxoplasmosis. This patient was referred to us for hydrocephalus. As we investigated the aetiology of the hydrocephalus, the patient's serum and cerebrospinal fluid tested positive for toxoplasmosis via ELISA and polymerase chain reaction. Computed tomography showed obstructive hydrocephalus and disseminated cranial calcifications. Central diabetes insipidus developed on the 10th day, apparently as a result of the toxoplasmosis infection, and was treated successfully with oral desmopressin.

Administration, Oral↗

Sulfadiazine and pyrimethamine in the postnatal treatment of congenital toxoplasmosis: what are the options?

Pre- and neonatal screening for congenital toxoplasmosis rests upon the assumption that treatment is beneficial on either acute symptoms or in preventing later reactivation. Postpartum treatment of congenital toxoplasmosis with sulfadiazine and pyrimethamine has remained almost unchanged for 50 years. More recently, sulfadiazine has been substituted by sulfadoxine, which has a much longer half-life and provides a basis for a dose schedule with higher compliance. Newer drugs with potential effects against Toxoplasma gondii, such as azithromycin, atovaquone and clindamycin, require further evaluation in animal models and human studies. No randomized controlled trials have ever been conducted. The available studies are either observational studies of groups of referred patients or observational studies with historical controls accrued over many years, often decades. Pre- and neonatal screening for congenital toxoplasmosis is performed on more than two million pregnant women every year in Europe, North and South America at the estimated cost of more than 500 million annually. The benefit needs to be documented by a prospective, placebo-controlled randomized study, which needs to be organized and financed by the countries performing nationwide, universal screening programs.

Humans↗

Diagnosis of human toxoplasmosis by a Dot enzyme-linked immunosorbent assay.

A Dot enzyme-linked immunosorbent assay (Dot-ELISA) was standardized and evaluated for the serodiagnosis of human toxoplasmosis. Out of 538 serum samples tested by the immunofluorescence test for toxoplasmosis (IFAT-IgG) as reference test, 183 (34%) were positive at cut off 1:16 and 192 (36%) were positive for Dot-ELISA-IgG at cut-off 1:256. For Dot-ELISA, co-positivity was 0.94, co-negativity 0.94 and concordance 0.88 in relation to IFAT-IgG. These results suggest the usefulness of Dot-ELISA (cut-off titer of 1:256) for the serodiagnosis of human toxoplasmosis. The main advantage of this technique is simplicity, positive test can be visually identified (colored precipitate). It does not require a special equipment and it can be used as a qualitative test to screen large numbers of samples or as a quantitative assay to determine end-point titration of individual sera.

Antibodies, Protozoan↗

Identification of Toxoplasma gondii antigens involved in the IgM and IgG indirect hemagglutination tests for the diagnosis of toxoplasmosis.

Crude Toxoplasma gondii antigens represent raw material used to prepare reagents to be employed in different serologic tests for the diagnosis of toxoplasmosis, including the IgM and IgG indirect hemagglutination (IgG-HA and IgM-HA) tests. So far, the actual antigenic molecules of the parasite involved in the interaction with agglutinating anti-T. gondii antibodies in these tests are unknown. The absorption process of serum samples from toxoplasmosis patients with the IgG-HA reagent (G-toxo-HA) demonstrated that red cells from this reagent were coated with T. gondii antigens with Mr of 39, 35, 30, 27, 22 and 14 kDa. The immune-absorption process with the IgM-HA reagent (M-toxo-HA), in turn, provided antibody eluates which recognized antigenic bands of the parasite corresponding to Mr of 54, 35 and 30 kDa, implying that these antigens are coating red cells from this reagent. The identification of most relevant antigens for each type of HA reagent seems to be useful for the inspection of the raw antigenic material, as well as of reagent batches routinely produced. Moreover the present findings can be used to modify these reagents in order to improve the performance of HA tests for the diagnosis of toxoplasmosis.

Animals↗

Incidence of congenital toxoplasmosis in southern Brazil: a prospective study.

The study aimed to determine the incidence of congenital infection by Toxoplasma gondii and to describe neonatal and maternal characteristics regarding newborn infants treated at a teaching hospital in the town of Passo Fundo, State of Rio Grande do Sul, Brazil. Cord blood samples collected from 1,250 live newborns were analyzed. The laboratory diagnosis was established by the detection of Toxoplasma gondii IgM using an enzyme linked fluorescent assay. Gestational age, intrauterine growth, anthropometric measures, and prenatal characteristics were assessed. The incidence of congenital toxoplasmosis at birth was 8/10,000 (95%CI 0.2-44.5). Mean birthweight was 3,080 +/- 215.56 grams and mean gestational age was 38.43 +/- 1.88 weeks. With regard to prenatal care, 58% of the pregnant patients visited their doctors five times or more and 38.9% were serologically tested for toxoplasmosis in the first trimester of pregnancy. The incidence of congenital toxoplasmosis was similar to that found in most studies conducted in our country and abroad. Our study sample is representative of the town of Passo Fundo and therefore it is possible to consider the frequency observed as the prevalence of the disease in this town during the study period.

Animals↗

Seroepidemiology and occupational and environmental variables for leptospirosis, brucellosis and toxoplasmosis in slaughterhouse workers in the Paraná State, Brazil.

Leptospirosis, brucellosis and toxoplasmosis are widely-distributed zoonosis, being the man an accidental participant of their epidemiological chains. The aim of this paper was to make a seroepidemiological report and identify occupational and environmental variables related to these illnesses in 150 workers in a slaughterhouse in the Northern region of Paraná. For the diagnosis of leptospirosis a microscopical seroagglutination test was applied; for brucellosis, the tamponated acidified antigen test and the 2-mercaptoetanol tests were used, and for toxoplasmosis the indirect immunofluorescence reaction test. For each employee an epidemiological survey was filled, which investigated occupational and environmental variables which could be associated with these infections. Positive results for leptospirosis were found in 4.00% of the samples, for brucellosis in 0.66% of samples and toxoplasmosis in 70.00%. From the three diseases researched, only the results for leptospirosis suggest occupational infection.

Abattoirs↗

[Outbreak of acute toxoplasmosis transmitted thru the ingestion of ovine raw meat].

The authors present 17 cases of symptomatic acute toxoplasmosis acquired by the ingestion of raw mutton offered during a party in September 1993. The incubation period carried from 6 to 13 days (10.9 +/- 7.0). Sixteen (94.5%) patients presented fever, headache, myalgia, arthralgia, and adenopathy (cervical or cervical/axilar). Hepatomegaly was found in 6 patients, splenomegaly in 4 and rash in 2. One patient presented clinical picture of chorioretinitis confirmed by ophthalmological exam. All patients showed increased serum levels of specific antibodies (IgG and IgM) on indirect immunofuorescence assay evidencing acute phase of toxoplasmosis. The patients were treated with specific drugs for toxoplasmosis and presented satisfactory clinical and laboratory response.

Acute Disease↗

Analysis of Toxoplasma gondii antigens with sera from toxoplasmosis patients.

Some proteins of the Toxoplasma gondii are recognized by IgG, IgM and IgA antibodies in patients with acute and chronic toxoplasmosis, depending on the strain and stage of the Toxoplasma. Sixty-nine sera from immunocompetent individuals were studied through the Western-Blot Test: 20 has an acute infection, 29 has a chronic toxoplasmosis infection and 20 were healthy (seronegatives). The protein analysis revealed by IgG and IgM antibodies were performed through the immunoplot method in order to know their recognition frequency (f) and be valued as infection markers. In the acute phase, the IgM antibodies showed a recognition frequency (f = 0.60) for the 60 kDa protein, and in the chronic phase the IgG antibodies showed a recognition frequency (f = 0.68) for the 12 kDa protein. Seronegatives revealed no type of band. The protein of 12 kDa can be a diagnostic marker of the chronic phase while protein 60 kDa of the acute phase of toxoplasmosis.

Acute Disease↗

Prenatal toxoplasmosis diagnosis from amniotic fluid by PCR.

Toxoplasmosis is one of the most common infections all over the world. Most cases are asymptomatic, except in immunosuppressed individuals and fetuses, which can be seriously damaged. Prenatal diagnosis should be made as soon as possible since treatment of the mother can minimize fetal sequelae. Our aim in this study was to test the polymerase chain reaction technique (PCR) in 86 samples of amniotic fluid from women who seroconverted during pregnancy. DNA was amplified using external primers and, in a second step, internal primers, in a nested PCR system. Samples were also inoculated into mice and the newborn were evaluated by T. gondii serology, skull x-ray, transfontanel ultrasound, fundoscopic examination, lumbar puncture and clinical examination. PCR was positive in seven cases and negative in 79. Among PCR-positive cases, two were negative by inoculation into mice and by clinical evaluation; among PCR-negative ones, three had clinical evidence of toxoplasmosis and one was positive after inoculation into mice. PCR showed values of sensitivity = 62.5% and specificity = 97.4%; the values of inoculation into mice where 42.9% and 100%, respectively. Although PCR should not be used alone for prenatal diagnosis of congenital toxoplasmosis, it is a promising method and deserves more studies to improve its efficacy.

Adult↗

Toxoplasmosis and mental retardation--report of a case-control study.

A case-control study evaluating the association between mental retardation and toxoplasmosis was conducted among 845 school children in Belo Horizonte, MG, Brazil. Cases (450) were mentally retarded children attending a public school for special education. Controls (395) were children from the regular public school system. Clinical and anthropometric examinations and interviews were carried out to determine risk factors for toxoplasmosis and mental retardation. Diagnosis of Toxoplasma gondii infection was based upon an indirect immunofluorescent test (IFA); 55% of cases and 29% of controls were positive. The Relative Odds of mental retardation in children with positive serology was 3.0 (95% CI 2.2-4.0). Maternal exposure to cats and contact with soil were associated with an increased risk of mental retardation. Retinochoroiditis was fourfold more prevalent among cases than controls and was only diagnosed in T. gondii IFA positive participants. Congenital toxoplasmosis, in its subclinical form, appears to be an important component in the etiology of mental retardation, especially in high risk (lower socio-economic) groups. The population attributable risk was estimated as 6.0-9.0%, suggesting the amount of mental retardation associated with this infection.

Adolescent↗