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[Composition of circulating immune complexes in acute toxoplasmosis].

The circulating immune complexes (CIC) that form in the hot just in early Toxoplasma gondii invasion can be present in the blood bed for a while. At the same time, the data on the antigenic composition of CIC in toxoplasmosis are fragmentary and rather contradictory. The investigation used enzyme immunoassay (EIA) to detect specific CIC that contain antigens to T. gondii tachyzoites in the sera of different populations and studied their antigenic composition by immunoblotting after 2-6% polyethylene glycol 6000-induced deposition. Examining 464 sera from groups of individuals with varying-stage T. gondii invasion indicated CIC in each, but showing their different frequency. CIC were virtually present in all sera from children who had been diagnosed as having congenital toxoplasmosis. In groups of seropositive pregnant women, CIC detection rates were noticeably higher in the samples showing both IgG and IgM antibodies (40.2 and 66.4%, respectively). CIC were also revealed in 9.8% of the seronegative blood donors; however, immunoblotting failed to confirm that they had no components that specifically reacted with T. gondii tachyzoite antigen antibodies. There were some differences in the composition of CIC in the serum yielding positive results in both EIA and immunoblotting. The serum CIC from pregnant women that exhibited only IgG antibodies contained mainly T. gondii antigens having molecular weights of 67 and 30 kD. The serum CIC from children with congenital toxoplasmosis and from pregnant women with serologically detected IgM antibodies to Toxoplasma antigens were found to contain 55-58-, 48-, 44-, 38-, 30-, and 26-kD components. The same molecular weight proteins were detected by electrophoretic studies of Toxoplasma excretory-secretory antigen (ESA). Comparing the findings suggests that in acute toxoplasmosis, the circulating complexes mainly contain ESA of the tachyzoites which appear in human blood just at the onset of invasion. Thus, this study demonstrates that specifically CIC are detectable in the sera of individuals infected with T. gondii and their antigenic composition varies with the stage of disease. In the authors' opinion, the detection of specific CIC and the determination of their antigenic composition may be serve an additional test in diagnosing acute toxoplasmosis.

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↗

Prevention of toxoplasmosis in pregnancy: knowledge of risk factors.

BACKGROUND: Infection with Toxoplasma gondii is common and usually asymptomatic, although it can have catastrophic consequences in a pregnant woman if passed to her developing fetus. Counseling of pregnant women about risk factor reduction may reduce the risk of congenital toxoplasmosis. This study was undertaken to assess and compare the knowledge of obstetricians and internists or family practitioners regarding well-established risk factors for toxoplasmosis infection. METHODS: The study surveyed 102 obstetricians, internists and family practitioners to assess their knowledge of risk factors for toxoplasmosis infection as well as their practices for primary prevention counseling of pregnant women. Responses were analyzed for differences. RESULTS: Obstetricians were more likely than internists or family practitioners to provide appropriate counseling on reducing the two most common risk factors for toxoplasmosis infection (undercooked meat consumption and gardening without gloves). However, over one quarter of all participants inappropriately advised pregnant women to avoid all cat contact. Obstetricians, internists and family practitioners were all likely to fail to identify undercooked meat consumption as the primary risk factor for toxoplasmosis transmission. CONCLUSIONS: Obstetricians appear to provide more appropriate counseling for primary prevention of toxoplasmosis than internists and family practitioners, but both groups of physicians inappropriately advised avoidance of all cat contact. Education of obstetricians, internists and family practitioners on risk factors for toxoplasmosis transmission is needed and may lower the rate of congenital toxoplasmosis as well as decrease the frequency of cat abandonment during pregnancy.

Animals↗

[Toxoplasmosis in pregnancy. Diagnosis and new therapeutic possibilities].

Congenital toxoplasmosis results from contamination of the foetus by Toxoplasma gondii during pregnancy. It is a frequent and severe condition calling for close surveillance of mothers at risk. During the last few years, numerous advances have been made in the diagnosis and treatment of toxoplasmosis. Its diagnosis in the mother is now more reliable due to improvements in serological techniques, while in the foetus the use of foetal vascular techniques has made it possible to detect those who are infected. Owing to a new and effective therapeutic method certain foetuses can now be treated successfully in utero, so that induced abortion is reserved to cases with severe and early toxoplasmosis. The contribution of new molecular biology techniques to advances in this ever moving field is explained.

Adult↗

Current recommendations and future prospects in the treatment of toxoplasmosis.

Toxoplasma infection is highly prevalent throughout the world and causes disease in diverse populations. Effective treatment regimens are available for each clinical entity of toxoplasma, but problems of incomplete clinical efficacy, drug potency, drug safety, and length of treatment remain. No well-controlled clinical trials in humans have been performed to evaluate the efficacy and safety of treatment. Primary treatment of toxoplasmosis is with the synergistic combination of pyrimethamine and sulphonamide. This is considered the treatment of choice for severe disease, disease in immunocompromised patients, and congenital toxoplasmosis. Spiramycin, a macrolide antibiotic, is frequently used alone or alternately with pyrimethamine and sulphonamide for pregnant women with the acute acquired infection to prevent congenital toxoplasmosis. Clindamycin is used frequently to treat acute flares of toxoplasmic chorioretinitis and as second-line therapy for toxoplasmic encephalitis in patients with the acquired immunodeficiency syndrome (AIDS). Inadequacies in the treatment of toxoplasmosis in immunosuppressed patients, exemplified by experience with AIDS patients, should provide the impetus for well-designed trials to find and evaluate more potent and better-tolerated agents. Classes of new drugs that have been investigated and show some promise include: (a) macrolides (roxithromycin, azithromycin); (b) folic acid antagonists (piritrexim and trimetrexate), and (c) purine analogues (arprinocid). Immunomodulators have attracted interest, and interferon-gamma alone and in combination with roxithromycin is effective in murine models. Interleukin-2 is also effective in the murine model.

Animals↗

Toxoplasmosis surveillance during pregnancy and quality assurance of methods in Hungary.

In Hungary, screening programs have been performed for the early detection of toxoplasmosis in pregnant women in three different counties. The results of a screening program performed in the town of Szeged are discussed in details. The pregnant women are screened by serological and molecular biological methods (anti-Toxoplasma CFT, IgG, IgM, anti-P30 IgA ELISA, IgG avidity test, PCR amplification). The women are first screened within the first 16 weeks of gestation. Seronegative cases are retested for seroconversion in every second month. Appropriate treatment is immediately started both in the mothers suspicious of acute toxoplasmosis and in their offspring. The urine samples of the babies are examined by nested PCR specific to B1 gene of Toxoplasma gondii. No cases of congenital toxoplasmosis have been detected among the screened and treated children so far. Thus, we consider the program as highly successful for screening of congenital toxoplasmosis. To insure the quality of the applied laboratory diagnostic methods, the QualiCont Company organizes two quality control investigations yearly in the laboratories involved.

Female↗

[Toxoplasma infestation: prevalence, risk of congenital infection and development in Geneva from 1973 to 1987].

Assessment of the risk of toxoplasma infection during pregnancy in the female population of the Geneva area, and of the risk of congenital toxoplasmosis, has shown 9 cases of toxoplasmosis for 1000 pregnancies and 3.5 congenital infections for 1000 newborn infants. These results show that the prevalence of toxoplasma infection has been decreasing constantly during the 15 years of study, but that the risk of infection during pregnancy and of congenital infection has remained steady.

Adolescent↗

Selective antenatal screening for toxoplasmosis and the latex agglutination test.

Recent publicity concerning congenital toxoplasmosis has generated a demand for serological assessment of pregnant women. Many laboratories are requested to undertake primary screening in these cases. We assessed the latex agglutination test (LAT) findings in 158 specimens with detectable toxoplasma specific IgM derived from pregnant women. The LAT titres ranged from 16 to greater than or equal to 4000 reflecting the variable antibody response observed in acute toxoplasmosis. We recommend that non-reference laboratories test specimens from pregnant women using the LAT at a screening dilution of 1:16 and select all reactive samples for detailed investigation.

Agglutination Tests↗

Role of specific immunoglobulin E in diagnosis of acute toxoplasma infection and toxoplasmosis.

Toxoplasma immunoglobulin E (IgE) antibodies were evaluated in an immunosorbent agglutination assay (ISAGA) and an enzyme-linked immunosorbent assay (ELISA) to determine their usefulness in the diagnosis of acute infection with Toxoplasma gondii. IgE antibodies were not detected in serum specimens from otherwise seronegative individuals, individuals with chronic toxoplasma infection, or infants without congenital toxoplasmosis. In contrast, they were detected in pregnant women who seroconverted during gestation (100% by ELISA, 63% by ISAGA), patients with toxoplasmic lymphadenopathy (96% by ELISA, 88% by ISAGA), infants with signs of congenital toxoplasmosis which prompted serologic testing in the postnatal period (92% by ELISA, 67% by ISAGA), children and adults with toxoplasmic chorioretinitis (36% by ELISA, 18% by ISAGA), and adult patients with AIDS and toxoplasmic encephalitis (33% by ELISA, 25% by ISAGA). In many of the serum specimens, the titer of IgE antibodies detected by the ISAGA were close to or at the positive cutoff value. The duration of detectable IgE antibodies in patients with acute infections varied considerably among individuals but showed a trend toward a briefer duration by the ISAGA than by the ELISA. These results reveal that recrudescence of IgE antibodies in patients with reactivated chronic infection (toxoplasmic chorioretinitis and toxoplasmic encephalitis) may be useful diagnostically and that demonstration of toxoplasma IgE antibodies is a useful adjunct to currently available serologic tests for the diagnosis of acute toxoplasma infection and toxoplasmosis.

Acute Disease↗

[Method of polymerase chain reaction in toxoplasmosis diagnosis].

Since introduction of polymerase chain reaction for the detection of DNA Toxoplasma gondii 398 biological samples from 301 patients were examined from 2000 to 2003. Positive finding of toxoplasmosis DNA we noted in 23 cases. Polymerase chain reaction enables exact and fast diagnosis of the actual parasitemia Toxoplasma gondii, which is important especially in the pregnant patients, new-born with suspicion on congenital toxoplasmosis and in the patients with immunosupression.

Animals↗

[Toxoplasmosis seroconversion in pregnant women. The differing attitudes in France].

INTRODUCTION: Since 1992 France has been running a toxoplasmosis prevention program based on the serological detection of infections during pregnancy. In the absence of a consensus, the seroconversions discovered are managed in different ways, varying from one centre to another. OBJECTIVE: To describe the habits of the specialised centres in France and propose means to reduce the heterogeneity. METHODS: A survey using a questionnaire mailed to the centres of parasitology in France specialised in the management of toxoplasmosis seroconversion during pregnancy. RESULTS: All the 30 centres surveyed replied. Five of them do not provide recommendations for treatment and were excluded from analysis. The attitudes of the 25 other centres varied greatly with regard to the indications for therapeutic abortion and amniocentesis, treatment protocols with pyrimethamine and sulfamides, as well as in the frequency of sonographical monitoring. CONCLUSION: In the absence of National guidelines, the management of seroconversions discovered during the prenatal prevention of congenital toxoplasmosis program is left to the discretion of the specialised centre. This results in variations from one town to the next. This heterogeneity underlines the lack of knowledge on the most efficient and acceptable means of preventing and treating congenital toxoplasmosis. In order to improve this situation, the French parasitologists have launched a program of consensual meetings aimed at harmonising the treatment protocols and identifying the points that require further studies.

Adult↗

Toxoplasmosis, behaviour and personality.

The clinical sequelae of acute and congenital toxoplasmosis are well established, but that of chronic toxoplasma infection remains uncertain. In rodents, chronic toxoplasma infection is associated with altered behaviour leading to an enhanced risk of feline predation and a putative selective advantage to the parasite. It is proposed that neurotropic cysts of toxoplasma exert an effect on animal behaviour, either directly or via the release of metabolic products. Long-standing toxoplasma infection in humans has been linked to cerebral tumour formation and personality shift. In view of the vast population with chronic toxoplasma infection, further studies of the clinical sequelae of this condition are required.

Animals↗

Serodiagnosis of toxoplasmosis. The impact of measurement of IgG avidity.

The development of IgG avidity assays has revolutionised serological diagnosis of Toxoplasma infections. The measurement of IgG avidity has shown its power in various clinical settings, especially in situations where timing and differentiation of primary and secondary infections is crucial. However, no laboratory test performed alone is self-sustained, whereby the diagnostic strategy of choice is sequential (or combinatorial) use of high-quality IgG, IgM, IgA and IgG-avidity assays. The impact of IgG avidity measurement will be discussed in five clinical scenarios: acute acquired infection, primary infection during pregnancy, congenital toxoplasmosis, ocular toxoplasmosis and Toxoplasma infection in immunocompromised patients. All in all in toxoplasmosis, superior diagnostic performance is achieved by appropriate combinations of serological, culture-based and PCR techniques.

Acute Disease↗

An unusual CT presentation of congenital cerebral toxoplasmosis in an 8 month-old boy with AIDS.

We report on a 8-month-old boy with AIDS, born of an asymptomatic mother with positive HTLV-III serology. He was hospitalized in the Intensive Care Unit because of anemia, fever and hepatosplenomegaly. Chest X-ray showed pneumonia and subsequent blood cultures were positive for Candida albicans. After 3 days of Amphotericin B treatment, the patient was transferred to Infectious Disease Department. After 30 days of hospitalization, the patient developed a rapid neurological impairment evolving into coma. CT scan showed a round, ring-shaped low density lesion with hyperdense and enhancing haemorrhagic centre in the left basal ganglia and a smaller hypodense lesion on the right. There was also evidence of cortical atrophy and mild ventricular dilatation. Such lesions are more commonly described in children with AIDS and congenital cytomegalic inclusion virus (CMV) encephalitis. In this case toxoplasma cysts were shown microscopically reinforcing the contention that in patients with AIDS, toxoplasma gondii infection may occur with atypical manifestation.

Acquired Immunodeficiency Syndrome↗

Molecular diagnosis of toxoplasmosis.

Toxoplasmosis is an anthropozoonotic disease endemic world-wide, caused by the apicomplexan Toxoplasma gondii. Although the course of infection is generally benign, it can cause significant morbidity and mortality in the developing fetus and in immunocompromised individuals. Biological diagnosis classically relies upon serology and direct detection of the parasite by inoculation to laboratory animals. In the past decade, the use of the polymerase chain reaction (PCR) has made a significant improvement in both the prenatal diagnosis of congenital toxoplasmosis and the detection of acute disease in the immunocompromised patient. Nevertheless, like many 'in-house' PCR assays, the PCR-Toxoplasma suffers from lack of standardization and variable performance according to the laboratory. A wide variety of primers has been used in different assays, but few comparative tests have been performed. Moreover, in contrast to other parasitic diseases, PCR-Toxoplasma has not yet attained a sufficient level of sensitivity, regardless of the clinical condition considered. These drawbacks are discussed, together with the undoubted gain that PCR has brought to this difficult diagnosis.

Humans↗