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PubMed2004

Toxoplasmosis.

Toxoplasma gondii is a protozoan parasite that infects up to a third of the world's population. Infection is mainly acquired by ingestion of food or water that is contaminated with oocysts shed by cats or by eating undercooked or raw meat containing tissue cysts. Primary infection is usually subclinical but in some patients cervical lymphadenopathy or ocular disease can be present. Infection acquired during pregnancy may cause severe damage to the fetus. In immunocompromised patients, reactivation of latent disease can cause life-threatening encephalitis. Diagnosis of toxoplasmosis can be established by direct detection of the parasite or by serological techniques. The most commonly used therapeutic regimen, and probably the most effective, is the combination of pyrimethamine with sulfadiazine and folinic acid. This Seminar provides an overview and update on management of patients with acute infection, pregnant women who acquire infection during gestation, fetuses or infants who are congenitally infected, those with ocular disease, and immunocompromised individuals. Controversy about the effectiveness of primary and secondary prevention in pregnant women is discussed. Important topics of current and future research are presented.

Animals↗
PubMed1999

Feasibility of neonatal screening for toxoplasma infection in the absence of prenatal treatment. Danish Congenital Toxoplasmosis Study Group .

BACKGROUND: The best method for prevention and control of congenital toxoplasma infection is uncertain. Prenatal screening is done in Austria and France, but the effect of treatment during pregnancy is not well documented. The aim of our study was to find out the maternofetal transmission rate and outcome in infants born to mothers who were not treated during pregnancy. METHODS: We analysed 89873 eluates from phenylketonuria (PKU) cards from neonates and paired first-trimester serum samples from the mothers for specific IgG antibodies to Toxoplasma gondii. Children born to mothers who seroconverted during pregnancy were followed-up clinically and serologically to 12 months of age. In addition, 21144 PKU cards were analysed for toxoplasma-specific IgM antibodies during the last 12 months of the study. FINDINGS: In 24989 (27.8%) cases both the PKU eluate and the first-trimester samples were IgG positive, which indicates previous maternal infection. 139 of the 64884 seronegative women acquired toxoplasma infection during pregnancy and gave birth to 141 infants (two sets of twins). 27 of these children were diagnosed with congenital toxoplasma infection. The transmission rate was 19.4% (95% CI 13.2-27.0). Clinical signs and symptoms were found in four (15%) of the 27 children. The additional analysis for toxoplasma-specific IgM antibodies from the PKU card identified seven of nine children with congenital toxoplasma infection. The false-positive rate for the IgM test was 0.19 per 1000, and no false-negatives were found. INTERPRETATION: The risks of transmission of infection and of disease in the infant are low in an area with a low risk of toxoplasma infection. A neonatal screening programme based on detection of toxoplasma-specific IgM antibodies alone will identify between 70% and 80% of cases of congenital toxoplasmosis.

Adult↗
PubMed1993

Toxoplasmosis in pregnancy.

Primary infection with Toxoplasma gondii in pregnant women occurs all over the world with frequencies between 0.1-1%. In approximately 40% of the cases, the unborn child is infected. The risk of fetal infection increases during pregnancy, while at the same time the risk of severe disease decreases. As a result, infants with congenital toxoplasmosis are mostly asymptomatic at birth, but long-term studies indicate that up to 85% of them will develop sequelae including chorioretinitis (leading to severe impairment of vision), hearing loss or mental retardation. Early recognition of maternal infection and treatment with spiramycin or pyrimethamine-sulphadiazine will reduce the parasitic colonization of the placenta by more than 60% and prevent infection in the fetus. If fetal infection has already occurred, maternal treatment modifies the fetal disease. Therapy during the first year of life improves the prognosis. It is possible today to identify infected fetuses by prenatal diagnosis based on detection of the parasite in cord blood, amniotic fluid and placental tissue. Specific antibodies and non-specific signs of infection in fetal blood give additional information. Advances in laboratory techniques have made it feasible to consider serological surveillance of pregnant women. The present recommendation is that each country should provide data on the incidence of toxoplasma infection in pregnancy and thereby decide whether it represents a problem and what measures should be adopted. This paper summarizes the present knowledge of the parasite and its implication for the mother and unborn child. The effect and problems of primary and secondary prevention in pregnancy are discussed as well as the efficacy of treatment. The need for future research including long-term follow-up studies are emphasized.

Female↗
PubMed1991

Evaluating the sensitivity and predictive value of tests of recent infection: toxoplasmosis in pregnancy.

The diagnosis of maternal infection in early pregnancy depends on tests which are sensitive to recent infection, such as specific IgM. Two types of test are considered: those where the response persists for a period following infection and then declines, such as IgM, and those whose response increases with time since infection, such as IgG-avidity. However, individuals vary in their response to infection, and it may not always be possible to determine whether an infection occurred during pregnancy or before it. Mathematical methods are developed to evaluate the performance of these tests, and are applied to the diagnosis of toxoplasmosis in pregnancy. It is shown that, based on existing information, tests of recent infection are unlikely to be both sensitive and predictive. More data on these tests are required, before they can be reliably used to determine whether infection has occurred during pregnancy or before it.

Animals↗
PubMed2002

Inoculation with Bartonella henselae followed by feline herpesvirus 1 fails to activate ocular toxoplasmosis in chronically infected cats.

Infection by Toxoplasma gondii is very common in cats although most remain disease free. The factors that trigger development of uveitis in some cats infected with T gondii have not been elucidated, but infection by more than one organism may be contributory. In this study, cats chronically infected with T gondii were inoculated with Bartonella henselae followed by FHV-1 to test the hypothesis that immune stimulation by multiple infections will reactivate ocular toxoplasmosis. Anterior uveitis and chorioretinitis were not detected in the cats with chronic T gondii infection thus allowing rejection of the hypothesis using this experimental design.

Animals↗
PubMed1983

[Incidence of primary toxoplasmosis infection in pregnant women].

Toxoplasma-specific antibodies transferred across the placenta were determined in 1953 blood samples of newborn infants from the Lower Saxony newborn-screening-laboratory using the indirect immunofluorescence test. There were no antibodies demonstrable in 54.4% of the samples. Related to the age of the mothers there was increase of positive findings of about 1% per year. Among 10 000 pregnancies about 70 to 80 mothers can be expected to undergo a primary infection with Toxoplasma gondii. With a fetal infection rate of about 50% derived from the literature 30 to 40 cases of congenital toxoplasmosis of variable severity, three among them serious, may be expected.

Antibodies↗
PubMed1985

Meningo-encephalitis accompanying retinochoroiditis in a murine model of congenital toxoplasmosis.

A histopathological study of the brains of adult mice infected in utero with Toxoplasma gondii and presenting manifestations of ocular toxoplasmosis is reported. All brains contained Toxoplasma tissue cysts. A sub-acute/chronic meningo-encephalitis was the main feature of the inflammatory response in the brain. Microscopical features suggest that autoimmune processes may play a part in the disease. We suggest that our mouse model will provide a simple and inexpensive tool for the investigation of histopathological processes in the CNS resulting from congenital Toxoplasma infection.

Animals↗
PubMed1989

New perspectives in the chemoprophylaxis of toxoplasmosis.

The usual chemoprophylaxis of toxoplasmosis consists of spiramycin or the combination of pyremethamine-sulfamide. This chemoprophylaxis can be used: 1 - In the pregnant woman: spiramycin avoids or has low fetal damage. In case of maternal contamination after 33 weeks of pregnancy, pyrimethamine-sulfadiazine combination should be used in spite of its potential toxicity. 2 - In the newborn infant, chemoprophylaxis prevents the emergence of retinochoroiditis. 3 - In congenital toxoplasmic retinochoroiditis, systematic repetitive cures of pyrimethamine-sulfamide reduce frequency of recurrences. 4 - In immunocompromised patients, the systematic use of pyrimethamine and sulfadoxine prevents neurotoxoplasmosis, in case of kidney, heart, and allogeneic bone marrow transplantations, and also in case of patients with malignant hemopathy or AIDS.

Chorioretinitis↗
PubMed1997

[Congenital toxoplasmosis and seroconversion at the end of pregnancy: clinical observations].

We report seven cases of subclinical congenital toxoplasmosis secondary to maternal primary infections. Mothers were infected between two and four weeks prior to delivery. The diagnostic criteria of congenital infections included: IgM antibody (Ab) (1 case); IgM and IgA Ab (1 case); a real IgG seroconversion in the neonatal and postnatal samples (3 cases); persistence of IgG Ab beyond 6 months post-delivery (2 cases). A treatment was initiated, including a combination of pyrimethamine + sulfadiazine (6 cases); trimethoprim + sulfamethoxazole (1 case). This retrospective study suggests that it is important to screen the non-immune pregnant women until delivery. We confirmed the usefulness of a combination of isotypes of antibodies for the accurate assessment of congenital infection. Finally, infected infants have to be treated and monitored clinically and immunologically during the first year of life.

Adult↗
PubMed2002

Laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis.

For the past 40 years, the Toxoplasma Serology Laboratory at the Palo Alto Medical Foundation Research Institute (TSL-PAMFRI) has been dedicated to the laboratory diagnosis of Toxoplasma gondii infection and toxoplasmosis. TSL-PAMFRI is the "brain child" of Jack S. Remington. Jack's ceaseless devotion to objectivity and uncompromising excellence has made TSL-PAMFRI the Toxoplasma reference laboratory for the Centers for Disease Control and Prevention, the US Food and Drug Administration, and health care providers and clinical laboratories in the United States and other countries. Jack's leadership and vision created, defined, and significantly contributed to the development of laboratory methods for the diagnosis of the infection and diseases caused by T. gondii. A summary of the laboratory tests currently available at TSL-PAMFRI for the diagnosis of infection and disease caused by the parasite is presented here.

Animals↗
PubMed1997

Foodborne outbreaks of human toxoplasmosis.

Two outbreaks of acute toxoplasmosis involving 8 adult patients in Korea were linked to eating uncooked pork. In the first outbreak, 3 patients developed unilateral chorioretinitis within 3 months of eating a meal consisting of raw spleen and liver of a wild pig. In the second outbreak, 5 of 11 soldiers who ate a meal consisting of raw liver of a domestic pig developed lymphadenopathy. All 8 patients had high levels of IgG Toxoplasma gondii antibodies (> or = 1:1024) in the Sabin-Feldman dye test, modified agglutination test incorporating mercaptoethanol, and latex agglutination test. T. gondii IgM antibodies persisted in these patients for several months. Most patients had a favorable response to anti-T. gondii chemotherapy with pyrimethamine and sulfanomides.

Adult↗
PubMed1988

Prophylaxis of congenital toxoplasmosis. Effects of spiramycin on placental infection.

The results of parasitological investigation of the placenta for toxoplasma in 223 cases with documented congenital toxoplasmosis were analysed according to whether the mother had been treated, or not, with spiramycin during pregnancy. The investigation was negative in 10-11% of the cases when the mother had not been treated or had been inadequately treated; in 25% of the cases with a treatment of 3 g spiramycin day; and in 50% with spiramycin plus the combination of pyrimethamine with sulphonamide. This series is compared with a previous group of 321 women whose placental investigation was negative in 50% of untreated cases and 81% of treated women. The treatment categories are not directly comparable, because it is not possible to have a randomly assigned 'no treatment' group, for ethical reasons. Correlation between spiramycin treatment and negative results of mouse inoculation of placental material suggests that spiramycin might decrease the risk of materno-fetal transmission of toxoplasma by reducing the severity and duration of toxoplasmic placentitis. Current use of spiramycin in infected pregnant women is recommended because of its activity and lack of side effects. The dosage must not be lower than 3 g/day. Additional pyrimethamine plus sulphonamide should be restricted to selected cases with fetal abnormality diagnosed during pregnancy. Some data on pharmacology of spiramycin in mothers, placentas and fetuses are reviewed. They suggest that monitoring of maternal serum antibody titres for a dosage more adapted to individual cases may be desirable.

Female↗
PubMedDate not supplied

Retinal vasculitis in ocular toxoplasmosis in nonhuman primates.

Six monkeys had prior systemic immunization followed by intraretinal challenge to each eye with Toxoplasma antigens. All eyes developed iridocyclitis, vitritis, and retinal edema, but no necrotizing retinochoroiditis. One-half of the eyes were then challenged with living organisms and the other one-half with Toxoplasma antigens. All eyes developed iridocyclitis, vitritis, and retinal edema, but no necrotizing retinochoroiditis. Four months later, the right eye of each monkey was challenged with living Toxoplasma organisms injected intraretinally. Each injected eye developed iridocyclitis, vitritis, and retinal edema 24 hours after injection, and all developed a retinal vasculitis 6 days after injection. One injected eye developed a papillitis. A subcutaneous booster of living Toxoplasma organisms in four of the monkeys failed to produce a reactivation of the iridocyclitis, vitritis, and vasculitis. These findings suggest that hyperimmunization provides protection against the development of a necrotizing toxoplasmic retinochoroiditis in nonhuman primates and that it may lead to retinal vasculitis and iridocyclitis. This study also serves as an animal model of retinal vasculitis in ocular toxoplasmosis.

Animals↗
PubMed2006

Real-time PCR targeting a 529-bp repeat element for diagnosis of toxoplasmosis.

Sensitive and rapid detection of infection with Toxoplasma gondii in transplanted immunocompromised patients is crucial for a good prognosis. Two DNA fragments are used currently for detecting T. gondii infection by PCR, i.e., the B1 gene and a 529-bp repeat element that exists in 200-300 copies/genome. This study investigated whether targeting the 529-bp repeat element gives better sensitivity and accuracy than can be obtained when targeting the B1 gene (35 copies) when concentrations of T. gondii DNA are low. The results demonstrated that detection of the 529-bp repeat element increased diagnostic sensitivity and accuracy. Addition of an internal amplification control did not affect the PCR performance and was useful in order to monitor PCR inhibition by non-specific DNA in the LightCycler instrument. The real-time PCR was used successfully in a clinical context to monitor parasitaemia in the blood of a transplant recipient suffering from toxoplasmosis.

Animals↗
PubMedDate not supplied

Congenital toxoplasmosis.

Infection with Toxoplasma gondii, which occurs in both men and women, is usually subclinical and benign. Infection during pregnancy, however, may be a serious and even life-threatening event for the fetus. Antenatal education should focus on avoidance of contact with the sources of infection: the domestic cat and raw or rare meats. A review of toxoplasmosis is presented, and means for its primary prevention through antenatal education are outlined.

Animals↗
PubMed2004

CD4+ T cells in the pathogenesis of murine ocular toxoplasmosis.

The role of CD4(+) T cells in the pathogenesis of ocular toxoplasmosis was investigated in murine models utilizing inbred C57BL/6 mice deficient either in CD4(+), CD8(+), or B cells (microMT). Severe necrosis and inflammation with replicating parasites were observed in the eyes of control mice after primary ocular infection, and near-normal histology with few tachyzoites was observed in the eyes of mice immunized intraperitoneally with the avirulent ts-4 strain followed by intraocular challenge with the RH strain of Toxoplasma gondii. In contrast, mild inflammation without evidence of necrosis associated with increased parasite burdens were observed in the eyes of CD4 knockout (KO) mice after both primary ocular infection and challenge with RH tachyzoites. CD8 KO mice, as well as microMT mice, demonstrated increased ocular necrosis in response to either primary ocular infection or challenge. The parasite burden was increased in the eyes of both CD8 KO and microMT mice in which the parasite load was even higher. As expected, there were no increases in the levels of immunoglobulin G in serum or aqueous humor in microMT mice, and there was no increase in the levels of gamma interferon and tumor necrosis factor alpha in the sera of CD4 KO mice after both infection and challenge. These results suggest that the ocular inflammatory response to the parasite is mediated primarily by the CD4(+)-T-cell response. CD8(+) T cells and B cells may play an important role in limiting tachyzoite proliferation in the eyes. Mice deficient in CD8(+) CD4(+) T cells or B cells exhibit diminished vaccine-induced resistance and increased ocular parasite burden after challenge.

Animals↗
PubMed2005

Diagnosis of congenital toxoplasmosis by two-dimensional immunoblot differentiation of mother and child immunoglobulin g profiles.

Differentiation between the specific immunoglobulin G (IgG) response to Toxoplasma gondii by a mother and her newborn child is helpful in the diagnosis of congenital infection with T. gondii in newborns without T. gondii-specific IgM and/or IgA antibodies at birth. Previous methods include immunoblotting and complexing T. gondii antigen with the sera from the mother and child and comparing the bands after electrophoresis. We developed a two-dimensional immunoblotting (2DIB) method with T. gondii RH strain tachyzoite antigen and validated the method with sera from 11 children identified through the neonatal screening program for congenital toxoplasmosis in Denmark. The children were identified by using Toxoplasma-specific IgM antibodies at the screening test, but the presence of T. gondii-specific IgM and/or IgA antibodies could not be confirmed at the subsequent serum sample tested. The children were monitored for at least 12 months, and in seven of eight patients monitored for 12 months the results of the 2DIB-predicted congenital infection were confirmed by the presence of persistent Toxoplasma-specific IgG antibodies. 2DIB is a sensitive technique that allows early differentiation between passively transferred maternal T. gondii-specific IgG antibodies and antibodies synthesized by the newborn child.

Animals↗
PubMed1978

Acquired toxoplasmosis in children.

Nine cases of acquired toxoplasmosis, 8 from rural backgrounds, are described, illustrating the wide variety of clinical pictures. Evidence of familial infection was found whenever sought, and was also found in cattle in one case. The availability of an easily performed screening test should make diagnosis of this common disease more frequent.

Animals↗