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Lymph node toxoplasmosis. Follow-up of 237 histologically diagnosed and serologically verified cases.

The clinical features, histology and follow-up of lymph node toxoplasmosis are presented in the light of 237 histologically and serologically verified cases. Lymph node toxoplasmosis is a disease with mild symptoms, and in most patients the enlarged lymph nodes were the only sign. Three fourths of the patients were women and the majority were under 40 years of age. The clinical picture was not specific, but suggestive features included a relatively short history, presence of the nodes in the neck and relative lymphocytosis in peripheral blood. Histological changes in the lymph nodes were characteristic. The most important features were strong hyperplasia but preserved general structure with small groups of epithelioid cells both in the paracortical area and in the germinal centers. Strands of monocytoid cells were usually found. 80% of the cases with typical histology also had high antibody titers, and in more than 85% of the cases with high antibodies, the lymph nodes presented a typical picture of toxoplasmosis. The follow-up revealed that lymph node toxoplasmosis. The follow-up revealed that lymph node toxoplasmosis is a disease without complications, nor is there any connection with malignant lymphomas.

Adolescent↗

Survey of local policies for prevention of congenital toxoplasmosis.

District policies for the primary and secondary prevention of congenital toxoplasmosis in England, Wales, Jersey, and the Isle of Man were surveyed in 1992. Consultants in communicable disease control were asked to describe past, present, and proposed prenatal screening programmes and current health education policies. One hundred and eighty-seven out of 196 districts responded to a postal questionnaire. One district had a prenatal screening programme for toxoplasmosis and five were discussing possible programmes. Over half (55%) had never had a programme or considered introducing one and 68 (36%) districts had decided against screening. Fifty-four per cent of districts had health education policies on toxoplasmosis, and most of these provided leaflets in antenatal clinics. A sample of districts that in 1992 were considering or had not ruled out screening was followed up in February 1994. None had implemented a screening policy. All but one district, therefore, are following the recommendation by a working group of the Royal College of Obstetricians and Gynaecologists that prenatal screening for toxoplasmosis should not be introduced in the United Kingdom. The value of current health education policies in the primary prevention of congenital toxoplasmosis needs to be assessed.

Female↗

A survey of health education material for the primary prevention of congenital toxoplasmosis.

We have assessed health education material for the prevention of congenital toxoplasmosis in terms of its epidemiological and clinical information and preventive advice. Nineteen leaflets and booklets were evaluated: fourteen were produced locally, ten for patients and four for professionals; and five were distributed nationally, including two sponsored booklets and one produced by the Department of Health. Material was compared with 'standards' derived from recently published reviews of toxoplasmosis and the Department of Health's booklet. The amount of information about toxoplasmosis, and the advice on how to avoid it, differed widely. Some booklets contained factual errors and some of the advice was impractical and even hazardous. Booklets contained on average between a fifth and a half of the standard desired for epidemiological and clinical information and preventive advice. Leaflets devoted to toxoplasmosis were more informative than general guides. Presentation was assessed informally: medical terminology inappropriate for a 'lay' audience was used, booklets were published in English only, and the date of publication was not printed. Health education is an important means of primary prevention of disability caused by congenital toxoplasmosis. Our study suggests that it has not received the scientific appraisal and commitment needed to make it effective.

Health Education↗

Persistent enhancement after treatment for cerebral toxoplasmosis in patients with AIDS: predictive value for subsequent recurrence.

PURPOSE: To determine the predictive imaging (CT and/or MR) features of brain toxoplasmosis recurrences in acquired immunodeficiency syndrome. METHODS: The imaging studies of patients with brain toxoplasmosis were retrospectively reviewed. Forty-three patients with significant decrease or disappearance of brain lesions under specific treatment on follow-up imaging examinations were included. MR examinations were performed using T2- and T1-weighted sequences, before and after intravenous administration of gadolinium-DOTA. RESULTS: A recurrence occurred in 11 (26%) of 43 cases. Ten (91%) of these 11 patients with recurrence showed focal persistent enhancement after the initial treatment of toxoplasmosis abscess. One of the 11 patients with recurrence showed no persistent enhancement; 3 patients showed persistent enhancement but had no recurrence. CONCLUSIONS: Recurrences of brain toxoplasmosis in our series correlated with persistent contrast enhancement. We hypothesize that demonstration of persistent areas of contrast enhancement after treatment for initial toxoplasmosis may be a valuable sign for identifying patients at risk for recurrence.

AIDS-Related Opportunistic Infections↗

Detection of circulating antigens in the diagnosis of acute toxoplasmosis.

Using an enzyme-linked immunosorbent assay, we have found circulating antigens of Toxoplasma gondii in three models of murine toxoplasmosis: mice infected with trophozoites of the RH strain (acute toxoplasmosis), the Beverley strain (subacute toxoplasmosis), and the T626 strain (chronic toxoplasmosis). Circulating antigens were detected 48 hr after infection in the mice infected with the RH strain, and all mice had antigenemia by the fourth day. In those infected with the Beverley strain, circulating antigens were detected from the second day after inoculation until the end of the study, with a peak (71% of the infected mice) on day 10. Of those infected with the T626 strain, 40% had antigenemia at 13 days after infection. The detection of circulating antigens in serum is directly related to the presence of toxoplasmosis in the acute phase in the three models studied and, therefore, may prove very useful in the rapid diagnosis of this disease.

Acute Disease↗

[Toxoplasmosis in pregnancy. Prevention, diagnosis, and therapy].

Toxoplasmosis is a worldwide health problem. Infection of a pregnant woman can result in severe fetal morbidity or in subclinical neonatal infection; most subclinical cases will develop ocular and neurological sequelae. Fetal infection and clinical outcome is related to when in pregnancy toxoplasmosis was acquired. The risk of transmission increases from 14% in the first trimester to 29% in the second and 59% in the third. Conversely, clinical damage decreases from about 80% in the first to 10% in the third trimester, but up to 50% of patients with subclinical congenital toxoplasmosis will develop neurologic and ocular sequelae. Congenital toxoplasmosis can be prevented by identification of non immune women at the beginning of pregnancy, by giving information on how to avoid the infection and by a serological follow-up until the delivery. Serological follow-up is based on repeated testing for specific IgG and IgM, but other serologic methods are necessary to differentiate between acute and chronic infections and possibly on a single serum sample. Procedures to detect fetal infection are ultrasound examination, cordocentesis and amniocentesis; prenatal diagnosis relies on demonstration of toxoplasma in fetal blood or amniotic fluid by mouse inoculation. Very promising results have recently obtained by the PCR-method applied to amniotic fluid samples. All strongly suspected cases of acquired toxoplasmosis in pregnancy have to be treated.

Animals↗

[Value of the study of IgG avidity for the diagnosis of toxoplasmosis].

The usefulness of IgG avidity analysis for dating acquired toxoplasmosis was documented by a study of 145 serial sera from 39 patients with acute toxoplasmosis and 104 sera from patients with chronic toxoplasmosis. ELISA measurement of IgG avidity involved comparison, for each serum at limit dilution, of optical densities obtained with and without washing with a urea solution to disrupt antigen-antibody bonds. A significant correlation was found between time since onset of toxoplasmosis and IgG avidity. Furthermore, comparison of IgG avidity of sera from patient with chronic infection or with acute infection monitored serologically for less than 20 weeks showed that an avidity index of 0.5 or more was inconsistent with toxoplasmosis of less than 20 weeks duration.

Antibody Affinity↗

Systematic serologic screening for toxoplasmosis in pregnancy.

OBJECTIVE: To determine which serologic method or combination of methods could most effectively identify acute toxoplasmosis during pregnancy and to assess whether systematic screening is practical and cost-effective. METHODS: Using basic serologic tests (direct agglutination test and immunosorbent agglutination assay), we screened 2104 women for toxoplasmosis. Immunoglobulin M (IgM)-reactive patients (IgM immunosorbent agglutination assay score of at least 3) were studied by differentiating serologic tests performed sequentially. RESULTS: Specific immunity was found in 874 pregnant women (41.6%); 155 (7.4%) were IgM-reactive and 12 (0.6%) had acute toxoplasmosis. Using a reduced immunosorbent agglutination assay score of at least 3 (normally a score of at least 6 is used), acute toxoplasmosis was identified in 11 women at their first prenatal visit, including two in whom acute infection would not have been detected by a score of 6 or more until 9 weeks later. One additional nonimmune patient with acute infection was identified only by follow-up serologic testing. CONCLUSION: Systematic screening followed by sequential differentiating serologic tests is practical and cost-effective for the diagnosis of acute toxoplasmosis during pregnancy.

Adult↗

[Seroprevalence of toxoplasmosis in Dakar (Senegal) in 1993: study of women in their reproductive years].

To establish the seroprevalence of toxoplasmosis in women during their reproductive years, we examined 720 women, of whom 404 were pregnant and 306 were not, all residing in and around Dakar. Of the serum tested by indirect immunofluorescence, 40.3% contained antibodies recognizing toxoplasmosis. The seroprevalence did not vary significantly with the age of the women, the number of previous pregnancies, the place of residence or the length of residence in Dakar. It was higher in the pregnant women (44.4%) than in the nonpregnant women (37.2%), but this difference is not statistically different. The titers of antibodies were generally weak, varying between 10 and 320 IU/ml of serum. Also, IgM specific antibodies were absent. These results indicate that the seroconversion had occurred previously, probably at a young age. We observed seroprevalences higher than those obtained by authors using comparable techniques twenty years ago. This indicates an increase of the transmission of toxoplasmosis in the population. Few women during their reproductive years had antibodies against toxoplasmosis. Thus, they are at risk of developing a primary infection during a pregnancy. This undergoes the necessity of promoting measures to prevent toxoplasmosis infection in pregnant women.

Adolescent↗

Angiographic findings in eyes with active ocular toxoplasmosis.

Clinical findings in 5 cases of active ocular toxoplasmosis were documented by fluorescein angiography. The diagnosis was based upon the ophthalmoscopic findings of white, fluffy, retinal exudative lesions with or without overlying vitreous inflammatory cells, and positive serologic tests for toxoplasma and responsiveness to clindamycin therapy. Three cases were considered as recurrent ocular toxoplasmosis and the other 2 cases, acquired ocular toxoplasmosis. Angiographic characteristics of these 5 cases of acute ocular toxoplasmosis consisted of the following: 1) hypofluorescence in the center of the hyperfluorescent lesion, 2) black silhouette of the artery corresponding to the arterial occlusion traversing the necrotic lesion, 3) venous dilation, venous wall staining and dye leakage from the vein, 4) optic disc staining and dye leakage. These angiographic findings reflect either tissue necrosis or hypersensitivity reaction and are helpful in the correct and prompt diagnosis of acute ocular toxoplasmosis.

Adolescent↗

[Serodiagnosis of toxoplasmosis].

Generally, toxoplasmosis has mild symptoms, or is asymptomatic, in patients with intact immune system. The infection, however, may have serious consequences in immunodeficient or immunosuppressed patients, as well as in the off-springs of pregnant women. If the mother has acute toxoplasmosis during the pregnancy, the passage of parasites through the placenta may result in the death of the fetus, or, in the severe damage of the fetus or neonate. All these consequences can be prevented by the early detection of the disease followed by the immediate therapy of the mother. Contrary to the most infectious diseases, however, the high specific IgM level has not proved to be a reliable marker of the acute infection in the case of toxoplasmosis. Therefore, in the case of infections discovered in the "plateau" period [i.e. with persistent IgM ("residual" IgM) and/or persistent high level of IgG antibody), the "acute" and the "chronic" phases can be distinguished more reliably by the detection with ELISA of the IgA antibody response to the so called P30 protein of Toxoplasma gondii. The anti-P30 IgA antibody response appears very early and generally disappears in 3-9 months. Thus, it is possible to discriminate the acute phase of the disease from the harmless chronic phase. Between 1987 and 1996, practically all pregnant women in Szeged and its region (altogether 21,952 women), underwent serologic toxoplasma screening. Among them, 124 pregnant women were found highly suspicious for having acute toxoplasmosis. Appropriate counselling, followed by spiramycin therapy during pregnancy and regular ultrasound examination were their antenatal management. No clinically manifested fetal or neonatal infection was observed. The screening and treatment schedule seems to be promising in the prevention of fetal and neonatal toxoplasmosis.

Adult↗

[Simultaneous occurrence of Toxoplasma gondii and Borrelia burgdorferi antibodies in patients with suspected toxoplasmosis or borreliosis].

In 1995-1997 the frequency of concurrent antibodies against Toxoplasma gondii and Borrelia burgdorferi was assessed in two groups of patients with different clinical symptoms. In 485 subjects the dermatological form (erythema migrans) of borreliosis was suspected, 877 subjects had clinical symptoms suggesting the nodular form of toxoplasmosis. The group of 485 subjects with suspected borreliosis comprised 199 (41%) subjects with the diagnosis confirmed by the serological finding and 286 (59%) subjects were serologically negative. During concurrent examination for toxoplasmosis a statistically significantly higher incidence of antitoxoplasmatic antibodies was recorded in patients with suspected borreliosis but without detected antibodies against Borrelia burgdorferi (29%) than in the group with both types of antibodies (11.5%), p < 0.001. The expected values of the incidence of antibodies against Toxoplasma gondii in the population (25%) were however not substantially surpassed by the actual values. In the group of 877 patients with suspected toxoplasmosis there were 114 subjects (13%) with acute toxoplasmosis, 300 subjects (34%) with anamnestic titres suggesting the chronic form of infection and 463 (53%) subjects where the infection with toxoplasmosis was not confirmed by serological tests. In the whole group, regardless whether the acute or chronic form of infection was involved, but also in the group without antitoxoplasmatic antibodies a significantly elevated number of subjects with antiborrelia antibodies (18-25%) was recorded as compared with the expected values of the incidence of antibodies against Borrelia burgdorferi in the population (10%), p < 0.001. In the discussion the authors deal with the possible causes of these phenomena.

Adolescent↗

Bax-induced apoptosis not demonstrated in the congenital toxoplasmosis in mice.

A prominent neuropathological change observed in a murine model of congenital toxoplasmosis is cerebral cortical hypoplasia. In the early embryonic life of toxoplasmosis mice, the number of apoptotic cell observed in cerebral cortex is increased, indicating that increased number of apoptotic cells might relate to the pathogenetic mechanism of the cortical hypoplasia. Immunohistochemical expression of apoptosis-related factors, Bcl-2 and Bax has been studied in fetal murine brains infected with toxoplasma and in controls. Paraffin sections of the fetal brains on embryonic day (ED) 10, 12, 14, 16 and 18 were applied for the immunostains of Bcl-2 and Bax. Totally, 47 experimental animals (ED10: n=8, ED12: n=6, ED14: n=12, ED16: n=6, ED18: n=15) and 48 control animals (ED10: n=6, ED12: n=8, ED14: n=9, ED16: n=9, ED18: n=16) were examined. Bcl-2 positive cells were detected on ED10, whereas Bax positive cells appeared on ED14. No difference of Bcl-2 and Bax expression between toxoplasmosis and control groups was detected, suggesting that there is no clear relation between Bax-induced apoptosis and cortical dysplasia in congenital toxoplasmosis.

Animals↗

Effect of prenatal treatment on the risk of intracranial and ocular lesions in children with congenital toxoplasmosis.

BACKGROUND: Hydrocephalus, intracranial calcification and retinochoroiditis are the most common manifestations of tissue damage due to congenital toxoplasmosis, but the effect of prenatal treatment on these outcomes is unclear. We aimed to determine the effect of prenatal treatment for toxoplasmosis on the risk of intracranial and ocular lesions in congenitally infected children at 3 years of age. METHODS: A cohort of mothers identified during pregnancy with toxoplasma infection and their 181 liveborn children with confirmed congenital toxoplasmosis was retrospectively analysed to determine the presence of intracranial and ocular lesions. As few women are not treated, we compared the effects of the treatment potency (pyrimethamine-sulfadiazine versus spiramycin or no treatment), and the timing of treatment, on the risks of intracranial lesions, time to detection of ocular lesions, and detection of any lesions (intracranial or ocular) by 3 years of age. Analyses took account of the gestation at maternal seroconversion. RESULTS: There was no evidence for an effect of pyrimethamine-sulfadiazine on intracranial, ocular or any lesions by 3 years: odds ratio (OR) for any lesions 0.89 (95% CI : 0.41, 1.88). There was no evidence of an effect of delayed treatment on ocular lesions (hazard ratio = 0.69, 95% CI : 0.28, 1.68) or any lesions by 3 years of age (OR = 0.44, 95% CI : 0.16, 1.19). CONCLUSIONS: Our study failed to detect a beneficial effect of early or more potent anti toxoplasma treatment on the risks of intracranial or ocular lesions in children with congenital toxoplasmosis. However, larger, prospective studies, which determine the effect of prenatal treatment on long-term developmental outcomes are required to justify changes in clinical practice.

Anti-Bacterial Agents↗

Detection of specific immunoglobulin E during maternal, fetal, and congenital toxoplasmosis.

Toxoplasma immunoglobulin E (IgE) antibodies in 664 serum samples were evaluated by using an immunocapture method with a suspension of tachyzoites prepared in the laboratory in order to evaluate its usefulness in the diagnosis of acute Toxoplasma gondii infection during pregnancy, congenital infection, and progressive toxoplasmosis. IgE antibodies were never detected in sera from seronegative women, from patients with chronic toxoplasma infection, or from infants without congenital toxoplasmosis. In contrast, they were detected in 86.6% of patients with toxoplasmic seroconversion, and compared with IgA and IgM, the short kinetics of IgE was useful to date the infection precisely. For the diagnosis of congenital toxoplasmosis, specific IgE detected was less frequently than IgM or IgA (25 versus 67.3%), but its detection during follow-up of children may be interesting, reflecting an immunological rebound. Finally, IgE was detected early and persisted longer in progressive toxoplasmosis with cervical adenopathies, so it was also a good marker of the evolution of toxoplasma infection.

Adolescent↗

Circulating immune complexes in toxoplasmosis: detection and clinical correlates.

The 125I-C1q binding test was employed to detect circulating immune complexes in serum of 27 subjects with acute toxoplasmosis. The subjects had no known underlying disease. Elevated C1q binding activity (C1q-BA) was found in the serum of each of three adults with the systemic febrile form of toxoplasmosis, seven of 19 patients with the lymphadenopathic form, and one of four infants with congenital infection. The patients with the systemic form of illness had significantly greater mean C1q-BA than did those with the lymphadenopathic form (P less than 0.001). In six episodes of symptomatic toxoplasmosis associated with elevated C1q-BA, follow-up sera were obtained after resolution of all signs and symptoms. Each of these sera showed normalization of C1q-BA. We conclude that immune complex like material is frequently present in the serum of patients with toxoplasmosis and parallels disease activity.

Adolescent↗

Polyomyositis and myocarditis associated with acquired toxoplasmosis in an immunocompetent girl.

BACKGROUND: Acquired toxoplasmosis more frequently goes unrecognized. Immunocompetent adults and adolescents with primary infection are generally asymptomatic, but symptoms may include malaise, fever, and lymphadenopathy. By contrast, immunocompromised patients may experience severe manifestations including encephalitis and multisystem organ failure. CASE PRESENTATION: We report a case of polymyositis and myocarditis in a 13-year old immunocompetent girl with toxoplasmosis. The patient presented with proximal muscle weakness, dysphagia, palms and soles rash and elevated serum levels of muscle enzymes, with liver and myocardial involvement. The diagnosis of toxoplasmosis was confirmed by serology. The patient was treated with prednisolone and had an excellent outcome. During a follow-up period of four years no relapses occurred and antibody levels to the T. gondii significantly decreased. CONCLUSIONS: Although several previous cases of toxoplasmosis occuring in association with polymyositis have been described in the literature such a wide spectrum of acute toxoplasmosis is rather unusual in immunocompetent adolescents. The relationship between T. gondii and polymyositis remains obscure. Appropriate investigation should be performed in every case of polymyositis not only for the appropriate treatment but also for further elucidation of this relationship.

Journal Article↗

[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↗