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Toxoplasmosis.

Toxoplasma gondii is a unicellular protozoan. The definitive hosts, cats, produce hardy oocysts and sporozoites. Ingestion by a nonfeline leads to the formation of tachyzoites acutely, which cause parasitemia and further dissemination, and bradyzoites, which lead to latent infection with the formation of tissue cysts in skeletal muscle, heart muscle, and central nervous system (CNS) tissue. Toxoplasmosis can be transmitted to humans by ingestion of tissue cysts in raw or inadequately cooked infected meat or in uncooked foods that have come in contact with contaminated meat, by inadvertent ingestion of oocysts and sporozoites in cat feces, or transplacentally. Immunocompetent adults and adolescents with primary infection are generally asymptomatic, but symptoms may include mild malaise, lethargy, and lymphadenopathy. Specific treatment for nonpregnant adults and adolescents is not required. Immunosuppressed patients may experience more severe manifestations, including splenomegaly, chorioretinitis, pneumonitis, encephalitis, and multisystem organ failure. These patients are also prone to reactivation of latent infection involving the CNS. All patients with human immunodeficiency virus infection and CD4 counts <100 cells per cubic millimeter should be treated prophylactically with pyrimethamine-sulfonamide. Congenital toxoplasmosis is marked by the classic triad of chorioretinits, intracranial calcifications, and hydrocephalus. Current studies have determined that prolonged treatment (1-2 years) of neonates with fansidar is important to prevent serious sequelae. Diagnosis of acute toxoplasmosis is mainly by antibody detection and generally only undertaken in pregnant patients with risk factors for transplacental transmission. All positive screening tests in pregnant women must be confirmed at a toxoplasma reference laboratory. Recent studies have shown that polymerase chain reaction testing of amniotic fluid is useful for identification or exclusion of fetal T. gondii infection. Ultrasound can be used as an adjunct to serological screening but cannot itself definitively diagnose disease. Early-first-trimester maternal infections are less likely to result in congenital infection, but the sequelae are more severe. Transplacental passage is more common when maternal infection occurs in the latter half of pregnancy, but fetal injury is usually much less severe. Typically, infected pregnant patients are treated with pyrimethamine-sulfonamide for positive PCR-amniotic-fluid testing and with spiramycin for negative PCR-AF testing.

Journal Article↗

[The importance and validity of anti-Toxoplasma gondii IgG, IgM, IgA antibodies and IgG avidity tests in the diagnosis of Toxoplasmosis infection during pregnancy.].

Detection of specific IgG, IgM and IgA antibodies by enzyme immunoassay (EIA) tests are not always sufficient in the diagnosis of early and late Toxoplasma gondii infection during pregnancy. For this reason, the specific IgG avidity test should be used to detect primary toxoplasmosis infection. In this study, an investigation was made of the serological status of pregnant women who were suspected of having primary or late toxoplasmosis as well as the importance and relationship of specific anti-Toxoplasma gondii IgG, IgM and IgA antibodies and specific IgG avidity in their sera. TORCH panels were also used for these patients. A total of 52 pregnant women who were admitted in the Dokuz Eylül University Gynecology and Obstetrics Clinic were included in this study. The sera were sent to the serology and immunology laboratory for investigation of the anti-Toxoplasma gondii IgG, IgM and IgA antibodies by the EIA (Cobas Core, Roche, Germany and ETI-TOXOK-A, DiaSorin, Germany) technique. The anti- Toxoplasma gondii IgG avidity test was performed on IgG as well as IgM and/or IgA in positive sera with the EIA (Toxoplasma IgG Avidity EIA Well- RADIM, Italia) technique. The anti-Toxoplasma gondii IgG avidity test was not performed on sera from 21 pregnant women negative for anti-Toxoplasma gondii IgG, IgM and IgA antibodies. Borderline and high IgM levels showed a good correlation with the IgG avidity results. The ratio for the IgM and IgA positivity was 32.3% and both the IgM positivity and IgA negativity were 29%. In conclusion, anti- Toxoplasma gondii IgG avidity and anti-Toxoplasma gondii IgM antibody tests should be used together. However, positivity or high avidity of IgA was limited in the diagnosis of active toxoplasmosis infection of pregnant women.

English Abstract↗

Congenital ocular toxoplasmosis. Possible occurrence in siblings.

In two siblings, we saw bilateral macular lesions that were consistent with the diagnosis of congenital toxoplasmosis. Although the congenital nature of this type of infection cannot be proven conclusively, there is considerable evidence that the lesions in our young patients were scars from congenital toxoplasmic retinochoroiditis. To our knowledge, congenital ocular toxoplasmosis in siblings has not previously been reported.

Adolescent↗

Fuchs' heterochromic iridocyclitis is not associated with ocular toxoplasmosis.

To analyze the association between Fuchs' heterochromic iridocyclitis (FHI) and toxoplasmosis, we performed ocular examinations and used various specific laboratory tests to establish a role for Toxoplasma gondii in the pathogenesis of FHI. Results were compared with those for other types of uveitis and healthy controls. Of the 88 patients with FHI, nine (10.2%) had toxoplasmosislike scars, but an association could not be proved by the indirect immunofluorescence antibody test or enzyme-linked immunosorbent assay, or by a test for cellular immunity to Toxoplasma antigen. Analysis of aqueous humor samples for Toxoplasma antibodies in patients with FHI also yielded negative results. On the basis of the negative results of these laboratory tests, we concluded that FHI is not associated with ocular toxoplasmosis.

Adolescent↗

Encephalitis in mice with congenital ocular toxoplasmosis.

The brains of mice with congenital ocular toxoplasmosis were examined histologically. Toxoplasma tissue cysts and a subacute/chronic meningo-encephalitis were present in the brains of all infected mice. The findings were very similar to those seen in human congenital toxoplasmosis. The murine model of congenital toxoplasmic encephalitis described in this paper will be valuable in the study of the pathogenesis, natural history and treatment of this condition.

Animals↗

The role of cytokines in toxoplasmosis.

Infection with Toxoplasma gondii is normally asymptomatic, but as a consequence of the AIDS epidemic the incidence of symptomatic disease and especially toxoplasmic encephalitis (TE) has grown in frequency. The high frequency of adverse reactions to conventional therapeutic regimens for toxoplasmosis highlight the need to develop new strategies for the management of this disease. The importance of cytokines in resistance against T. gondii has been shown primarily in murine models of toxoplasmosis and a number of cytokines (e.g., IFN-gamma, TNF-alpha, IL-2 and IL-12) have been proposed for trials in patients with TE. One mechanism by which these cytokines produce their effects is through stimulation of macrophages and/or NK cells. However, there are problems with immunological intervention in immunocompromised patients with TE since the infection is present primarily in the central nervous system (CNS), an immunoprivileged site, and because certain cytokines may down regulate the immune response. While much valuable information has been obtained from studies conducted in immunocompetent strains of mice their relevance to an immunocompromised host is unknown. The development of genetically altered mice with immune deficiencies offers promising new models that may allow for more rational development of new treatment regimens.

AIDS-Related Opportunistic Infections↗

Onset of ocular complications in congenital toxoplasmosis associated with immunoglobulin M antibodies to Toxoplasma gondii.

Four patients with congenital toxoplasmosis serologically diagnosed by the Sabin-Feldman test (SFT) and the IgM-indirect fluorescent antibody test (IgM-IFAT) in the first year of life presented with eye disease between the age of 21 months and ten years. Repeated serological testing revealed increasing levels of specific antibodies as measured by the SFT. IgM antibodies to Toxoplasma gondii were detected in all four patients by the immunosorbent agglutination assay, in two by the IgM-IFAT and in three by the IgM-indirect haemagglutination test. Findings suggest that specific IgM antibodies reappear at the time of reactivation of congenital toxoplasmosis later in life, or possibly persist for an extraordinary long period (up to ten years).

Age Factors↗

Toxoplasmosis, old stories and new facts.

In this introductory paper some general opinions are presented regarding the parasite Toxoplasma gondii, toxoplasma infection and toxoplasmosis. The transmission of the parasite through oocysts and/or infected meat is discussed with regard to possible prevention. Old stories have been replaced by new facts in the epidemiology of toxoplasma infection. Veterinary measurements in the field of prevention are not likely to be accepted in the near future. It is stressed that laboratory diagnosticians should clearly differentiate between diagnostic support in suspected cases of clinical toxoplasmosis or screening for certain characteristics such as IgG antibodies to toxoplasma in a healthy population.

Animals↗

Treatment of toxoplasmosis in pregnancy: concentrations of spiramycin and neospiramycin in maternal serum and amniotic fluid.

Toxoplasma infection during pregnancy is widely treated with oral spiramycin to reduce the risk of congenital toxoplasmosis in the infant. Failures of therapy have been observed, however. In this study, a sensitive high-performance liquid chromatography technique was used to measure concentrations of spiramycin and neospiramycin, one of the major metabolites of spiramycin, in maternal serum and amniotic fluid. Samples were obtained from 18 women who underwent amniocentesis for polymerase chain reaction (PCR) diagnosis of fetal infection 5-109 days following the prescription of spiramycin therapy (3 g/day). Concentrations of spiramycin and neospiramycin in both serum and amniotic fluid were highly variable, ranging from nondetectable values to 1 microg/ml. None of the concentrations measured were within the range reported to inhibit growth of the parasite in vitro. Consistent with previous reports, part of the observed variability in maternal and fetal drug concentrations could be explained by individual differences in several pharmacokinetic parameters: intestinal absorption, tissue distribution, cellular uptake, metabolism, transfer across the placenta, drug accumulation in fetal tissue, and maternal and fetal drug elimination. The heterogeneity of the data could also be related to differences in patient compliance with the medication prescribed. By addressing factors that could impair adequate treatment of toxoplasmosis during pregnancy, the data presented call for a larger-scale controlled study to determine individual and diurnal variations in maternal drug levels, patient compliance, and outcomes of the offspring. The activity of neospiramycin against Toxoplasma gondii should be assessed.

Adolescent↗

What can be done to prevent congenital toxoplasmosis?

There is a great deal of confusion within the medical and lay communities regarding Toxoplasma infection in the pregnant woman. Many physicians are not aware of the significance of this infection in pregnant women or of measures that may decrease the likelihood of the birth of an infant with congenital toxoplasmosis. Data regarding the morbidity, incidence, cost, and measures for the prevention of congenital toxoplasmosis are discussed.

Antibodies↗

A prospective study of acquired toxoplasmosis among 8,043 pregnant women in the Oslo area.

A prospective serologic study of acquired toxoplasmosis has been carried out among 8,043 pregnant women in the Oslo area by means of the DT and IgG-IFAT tests on paired blood samples collected on an average in gestational weeks 13 and 35. The screening results indicated that 54 women had to be considered as having potential "risk pregnancies" and they were selected for special follow-up studies. Thirteen women were found to have acquired a toxoplasma infection during pregnancy. The outcome of these pregnancies was: two spontaneous abortions and probably four congenitally infected children. In three of these cases parasites could be demonstrated in the placenta and/or amniotic fluid. This gives a transmission rate of 46% and an incidence of congenital toxoplasmosis of nearly 1/1,000 births.

Female↗

Toxoplasmosis in pregnancy.

Pregnant women who acquire infection from Toxoplasma gondii usually remain asymptomatic, although they can still transmit the infection to their fetuses with severe consequences. Given the asymptomatic nature of most Toxoplasma infections, primary prevention in pregnant women may lower the risk of congenital toxoplasmosis. Both consumption of undercooked meat and unprotected contact with soil are independent risk factors for T. gondii seroconversion during pregnancy, while contact with cat litter may pose a risk in certain situations. However, many pregnant women lack knowledge of these risk factors. This article reviews toxoplasmosis infection in pregnancy, with an emphasis on risk factors and appropriate counseling of pregnant women.

Animals↗

Diagnosis and management of toxoplasmosis.

This article discusses the diagnosis and management of toxoplasmosis. Congenital toxoplasmosis continues to be a tragic outcome of a preventable and treatable infection. Education of patients, physicians and health policy makers on the primary and secondary preventive measures of the disease, and their execution, will undoubtedly result in lower incidence, morbidity, and mortality rates from congenital disease due to Toxoplasma gondii.

Animals↗

Congenital toxoplasmosis from an HIV-infected woman as a result of reactivation.

Congenital toxoplasmosis usually results from acquired infection in non-immune pregnant women. However, severely HIV-infected women with a latent Toxoplasma infection can transmit the parasite as a result of reactivation. We report a case of toxoplasmic reactivation in an HIV-infected woman with moderate immunosuppression resulting in a severe congenital toxoplasmosis.

Adult↗

Congenital toxoplasmosis--prenatal aspects of Toxoplasma gondii infection.

Toxoplasma gondii (T. gondii) is the cause of toxoplasmosis. Primary infection in an immunocompetent person is usually asymptomatic. Serological surveys demonstrate that world-wide exposure to T. gondii is high (30% in US and 50-80% in Europe). Vertical transmission from a recently infected pregnant woman to her fetus may lead to congenital toxoplasmosis. The risk of such transmission increases as primary maternal infection occurs later in pregnancy. However, consequences for the fetus are more severe with transmission closer to conception. The timing of maternal primary infection is, therefore, critically linked to the clinical manifestations of the infection. Fetal infection may result in natural abortion. Often, no apparent symptoms are observed at birth and complications develop only later in life. The laboratory methods of assessing fetal risk of T. gondii infection are serology and direct tests. Screening programs for women at childbearing age or of the newborn, as well as education of the public regarding infection prevention, proved to be cost-effective and reduce the rate of infection. The impact of antiparasytic therapy on vertical transmission from mother to fetus is still controversial. However, specific therapy is recommended to be initiated as soon as infection is diagnosed.

Adult↗

Evaluation of protective effect of DNA vaccination with genes encoding antigens GRA4 and SAG1 associated with GM-CSF plasmid, against acute, chronical and congenital toxoplasmosis in mice.

To develop a multiantigenic vaccine against toxoplasmosis, two Toxoplasma gondii antigens, SAG1 and GRA4 selected on the basis of previous immunological and immunization studies, were chosen. We showed that DNA-based immunization with plasmids expressing GRA4 (pGRA4) or SAG1 (pSAG1mut) reduced mortality of susceptible C57BL/6 mice upon oral challenge with cysts of the 76K type II strain (62% survival). Immunization with pGRA4 and pSAG1mut, enhanced the protection (75% survival). This protection was further increased by co-inoculation with a plasmid encoding the granulocyte-macrophage colony-stimulating factor (GM-CSF) (87% survival). This latter DNA cocktail provided significant protection of less susceptible outbred Swiss OF1 mice against the development of cerebral cysts. A significantly higher survival of newborns from immunized outbred mice exposed to infection during gestation was observed (4.25+/-3.77 live pups/litter) in comparison to non-immunized mice (1.08+/-2.15 live pups/litter) without preventing parasite vertical transmission. Analysis of the immune response showed that protected animals developed a specific humoral and cellular Th1 response to native T. gondii SAG1 and GRA4 antigens. Our data demonstrated that protection was improved by associating antigens (SAG1 and GRA4) and cytokine (GM-CSF) for further development of a multiantigenic vaccine against toxoplasmosis.

Animals↗

Treatment of toxoplasmosis during pregnancy: a multicenter study of impact on fetal transmission and children's sequelae at age 1 year.

OBJECTIVE: Toxoplasmosis during pregnancy can cause fetal infection, with unpredictable sequelae in later life. We measured the effects of prenatal antibiotic therapy on the fetomaternal transmission of Toxoplasma gondii and on the appearance of sequelae in the congenitally infected child at age 1 year. STUDY DESIGN: In a multicenter study we investigated consecutive women with Toxoplasma seroconversion during pregnancy. Data were obtained from 144 women recruited in 5 different Toxoplasma reference centers. Through multivariate analysis we assessed the association between transmission and appearance of sequelae as a function of the following parameters: estimated gestational age at infection, administration of antibiotic therapy, duration of antibiotic therapy, and time lapse between infection and the start of antibiotic therapy. RESULTS: Sixty-four of the 144 women (44%) gave birth to a congenitally infected infant. Multivariate analysis showed that transmission was predicted neither by whether antibiotics had been administered nor by the time lapse between infection and the start of antibiotic therapy, but only by the gestational age at which maternal infection occurred (P <.0001). Sequelae were found in 19 children (13%), 9 of whom (6%) had severe sequelae. Administration of antibiotics was predictive of the absence of sequelae (P =.026, odds ratio 0.30, 95% confidence interval 0.104-0.863), in particular the absence of severe sequelae (P =.007, odds ratio 0.14, 95% confidence interval 0.036-0.584). The sooner antibiotics were given after the infection, the less frequently sequelae were seen (P =. 021). CONCLUSION: Prenatal antibiotic therapy after toxoplasmosis during pregnancy had no impact on the fetomaternal transmission rate but reduced the rate of sequelae among the infected infants. The early start of treatment resulted in a significant reduction in the number of severely affected infants.

Animals↗

Eye manifestations of congenital toxoplasmosis.

PURPOSE: To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision. METHODS: In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients). RESULTS: Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median) and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy. CONCLUSION: Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.

Adolescent↗