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Gestational and neonatal toxoplasmosis: regional seroprevalence in the United Arab Emirates.

Paired maternal/cord blood samples were tested for anti-Toxoplasma IgG or IgM antibodies using Biomerieux Micro-EIA2 IgG and IgM test kits. Of the 1503 women tested at the time of delivery, 344 (22.9%) were IgG seropositive. Three hundred and one maternal sera, including 265 that were IgG positive, were tested for IgM antibodies: 47 were found positive, indicating a gestational toxoplasmosis incidence of 31 per 1000 pregnancies over one year. All but one of the IgM positive maternal sera had tested IgG positive. Cord blood IgG seropositivity was similar to the maternal rate but 18 of the 301 babies had significant levels of anti-Toxoplasma IgM antibodies. As these 18 babies were all born to mothers also positive for IgM antibodies, the calculated rate of transplacental transmission was 38.3% with the estimated prevalence of congenital toxoplasmosis of 12 per 1000 live births. There was no statistically significant positive correlation between maternal seroprevalence and such well-known risk factors as consumption of raw meat and milk, or proximity of cats and other animals. One baby was born with the classical stigmata of congenital toxoplasmosis.

Adolescent↗

[Retinochoroiditis as a diagnostic indication of acute systemic toxoplasmosis in an immunocompetent patient].

HISTORY AND GENERAL INVESTIGATIONS: In February 1993 a 53-year-old immunocompetent man presented at our department with blurred vision on the right eye for 6 weeks. Following a journey to Guatemala in November 1992 he had developed undulating fever up to 40 degrees C (later subfebrile temperature) with loss of weight (15 kg), dysesthesia mainly in the feet and general weakness. He was hospitalized at a general hospital and treated with different antibiotics. Various examinations showed normal results, like cranial computer tomography, and serological tests for virus, bacteria or malaria. Only the transaminases and the borrelia serology (IgG: 1:80, IgM:neg.) were slightly elevated, and the abdominal sonography revealed a moderate hepatomegaly. OPHTHALMOLOGICAL FINDINGS: Visual acuity was 1.0 in both eyes. The right eye showed fatty retrocorneal precipitates, cellular infiltration of the anterior chamber and vitreous and a focal retinochoroiditis next to the superior temporal vessels (Fig. 1a), with corresponding defect in visual field and nerve fiber layer (Fig. 1b, c). Serology established the diagnosis of an acute generalized toxoplasmosis (IgM ISAGA i.S.: 1:1,600; IgM-AK IFT i.S.: 1:128, KBR i.S.: 1:320). THERAPY AND CLINICAL COURSE: After adequate chemotherapy ocular symptoms and dysesthesia improved rapidly. The temperature stayed low and the liver parameters returned to normal. CONCLUSION: The ophthalmoscopic finding of an acute focal retinochoroiditis played an important role for the diagnosis of an acute generalized toxoplasmosis in a patient with fever of unknown origin. Ocular manifestation is rare in acute generalized toxoplasmosis.

Chorioretinitis↗

[Disseminated toxoplasmosis in AIDS].

Within one year a 46-year-old HIV-positive man developed Pneumocystis carinii pneumonia, candida oesophagitis and recurrent mucocutaneous herpes simplex infections. He finally developed a constant fever without any infection-localizing features. There was pancytopenia, increased activities of the transaminases, lactate dehydrogenase, amylase and lipase, as well as diffuse ST-segment changes in the ECG and discrete pulmonary infiltrates. The anti-toxoplasmosis titre was 8 IU/ml. Despite extensive diagnostic tests no firm diagnosis could be established. The pulmonary infiltrate and the fever regressed under antibiotic treatment with co-trimoxazole. Two months later his general condition deteriorated again with some disorientation and subfebrile temperature, epididymitis and renewed rise in abnormal laboratory values. For the first time computed tomography showed some punctate contrast-medium concentrations in the subcortical area and the medulla. The patient died on the same day. Histological material obtained at the time of autopsy revealed pseudocysts with Toxoplasma gondii and necrotizing inflammation in the brain, myocardium and lungs, as well as the entire gastrointestinal and urogenital tracts. In addition, cytomegalovirus infection of the lung and adrenals was demonstrated. Anti-toxoplasmosis IgG titre, determined postmortem, again registered a marked rise to 251 IU/ml. This suggests that there was reactivation of the toxoplasmosis as part of the immunosuppression process.

AIDS-Related Opportunistic Infections↗

Prevention of congenital toxoplasmosis in Slovenia by serological screening of pregnant women.

A programme for the prevention of congenital toxoplasmosis in Slovenia involving the screening of pregnant women for Toxoplasma infection is presented. Of 21,270 pregnant women screened for toxoplasmosis between, 1996 and the end of 1999, 13,987 (66%) were seronegative, 7,151 (34%) seropositive and 132 had primary infection; approximately 9/1,000 women were at risk of acquiring the primary infection. One hundred live-born infants of primary infected women were available for follow-up. Nine infected but asymptomatic children were born to mothers who were screened and treated in time and two congenitally infected babies were born to mothers in whom infection was detected too late in pregnancy and who therefore received no adequate treatment. It is suggested that the results obtained in this study outweigh the cost of screening for toxoplasmosis in pregnancy. Pregnant women should always be tested at the beginning of pregnancy and, in cases of seronegativity, should be re-tested in the second and third trimesters of the pregnancy. Toxoplasma primary infected pregnant women and neonates should be treated as soon as possible. However, long-term follow-up of children born to primary infected women would be necessary for an accurate evaluation of the effectiveness of the screening because of the possibility of late onset of symptoms.

Animals↗

Screening and prevention of congenital toxoplasmosis: an effectiveness study in a population with a high infection rate.

OBJECTIVES: Secondary prevention of congenital toxoplasmosis has been attempted by screening pregnant women or by screening neonates. We compared the results of these two approaches, in order to evaluate the effectiveness of these strategies and of the antibiotic treatment of infected women. METHODS: A prenatal serological screening program for toxoplasmosis enrolled 8061 pregnant women; 9730 neonates were screened during the same period. RESULTS: Out of 5288 susceptible pregnancies, 188 were identified as infected by Toxoplasma gondii (35/1000). The transmission rate was 11.3%, with a higher rate for neonates exposed in the last trimester (relative risk 10.6); four neonates were affected. Out of 9730 screened neonates, four tested positive (0.4/1000) and one was affected. Out of a total of 163 exposed neonates, 12 were clinically affected. The rate of clinical sequelae was 31.6% among those infected and 7.4% among all exposed to infection; neonates born of women who had not been treated were more likely to be affected than treated neonates (odds ratio 4), but after adjustment for trimester of infection no significant association was found. CONCLUSIONS: Neonatal screening for toxoplasmosis seems to be less effective than pregnancy screening. Observational data do not support the effectiveness of treatment during pregnancy to prevent clinical disorders.

Animals↗

Toxoplasmosis in AIDS patients.

In patients with AIDS, toxoplasmosis is the most common cause of CNS mass lesions. Diagnosis is made on the basis of clinical presentation and CAT scan findings and confirmed by demonstration of tachyzoites and/or cysts in tissues obtained by needle aspiration or brain biopsy. Response to therapy with pyrimethamine and sulphadiazine is usually prompt but therapy has to be continued for the lifetime of AIDS patients with CNS toxoplasmosis. To date, no alternative regimens of single or combination drugs appear to be effective in patients who fail, or are unable to tolerate pyrimethamine and sulphadiazine therapy. Relapse rate is high. Clearly, there is a need to organize prospective controlled studies to assess the role of agents such as clindamycin, trimetrexate and other drugs in the treatment of CNS toxoplasmosis in patients with AIDS.

Acquired Immunodeficiency Syndrome↗

An outbreak of toxoplasmosis on an Illinois farm.

Two siblings residing on a farm in Illinois were concurrently hospitalized with cervical lymphadenitis. Clinical and serologic evidence indicated that the etiology of the lymphadenitis in each case was toxoplasmosis. The simultaneous occurrence of two cases of toxoplasmosis in a household prompted a prospective investigation of 11 other immediate family members for evidence of disease. During the next month seven of the other family members developed serologic evidence of acute toxoplasmosis. Four of these seven individuals were symptomatic. Investigation of the family's home environment failed to unequivocally identify a common source of infection, but epidemiologic evidence suggested that this outbreak was related to contact with sick cats.

Animals↗

Induction of a protective antibody-dependent response against toxoplasmosis by in vitro excreted/secreted antigens from tachyzoites of Toxoplasma gondii.

Toxoplasma gondii is a worldwide protozoan parasite which causes severe disease in congenitally infected children and in immunocompromised patients. Besides the well-defined cytoplasmic and membrane antigens of tachyzoites, we felt that excreted/secreted antigens could play a major role in the immune response. We first report the development of a well-controlled procedure for obtaining tachyzoite excreted/secreted antigens (E/SA) in cell-free incubation media. The E/SA immunogenic in human, rat and mouse toxoplasmosis were then characterized. The major E/SA recognized by human sera from the chronic phase of toxoplasmosis had molecular weights of 108, 97, 86, 69, 60, 57, 42, 39, 28.5, 27 and 26 kD. When injected into +/+ Fischer rats, E/SA elicited high antibody titres. In addition, passive transfer of these sera to highly susceptible nu/nu littermates induced a significant degree of protection towards the virulent RH strain of T. gondii. This work, which demonstrates the key role played by E/SA in the protective immune response, suggests that these antigens should be of value both for diagnostic purposes and for the development of new strategies for immunization against toxoplasmosis.

Animals↗

Congenital toxoplasmosis: efficacy of maternal treatment with spiramycin alone.

PROBLEM: The evidence supporting an additional benefit of a combined regimen of pyrimethamine-sulfonamides compared with spiramycin alone in the secondary prevention of congenital toxoplasmosis was critically evaluated. METHOD OF STUDY: We reviewed the series of cases published in the English literature on antiparasitic treatment of acute toxoplasmosis infection in pregnancy, using spiramycin until fetal infection is documented, then using cycles of spiramycin alternated with combined pyrimethamine-sulfonamide therapy. We then compared the occurrence of overt disease among infected offspring (both severe, represented by ophthalmologic or cerebral abnormalities, and mild occurrences, represented by asymptomatic intracranial calcifications and retinal scars without visual impairment) between the published case series and our consecutive series of cases treated during a 10-year period (January 1986-December 1995) with spiramycin alone. RESULTS: The prevalence of fetal infection in our series was 7.8% (12/154), similar to that reported after alternated regimens (7.0%). The rate of overt disease among infected fetuses is not different after treatment with alternated regimens than after continuous antibiotic spiramycin therapy [23% (19/82) vs. 10% (1/10); relative risk, 2.3; 95% confidence interval, 0.4, 47.0]. The pharmacokinetics of the drugs used may account for this finding. CONCLUSION: The treatment of acute toxoplasmosis in pregnancy with an alternated antibiotic regimen of pyrimethamine-sulfonamide is not more efficacious at preventing overt neonatal disease than treatment with continuous spiramycin alone.

Anti-Infective Agents↗

Rifabutin is active in murine models of toxoplasmosis.

Rifabutin, a semisynthetic derivative of rifamycin S, was examined alone and in combination with other drugs for activity in treatment of systemic toxoplasmosis and toxoplasmic encephalitis in murine models. One hundred percent of the mice infected with a lethal inoculum of tachyzoites or cysts of Toxoplasma gondii were protected against death by treatment with doses of 400 or 300 mg of rifabutin per kg administered alone for 10 days. Doses of 200 mg/kg protected at least 80% of the mice, and doses of 100 mg/kg protected 10 to 40% of the infected mice against death. Doses of 50 mg/kg were not protective but caused a delay in time to death. Combination of nonprotective (50-mg/kg) or slightly protective (100-mg/kg) doses of rifabutin with doses of sulfadiazine, pyrimethamine, clindamycin, or atovaquone that did not confer any protection against death from toxoplasmosis when administered alone resulted in remarkable enhancement of the in vivo activities of all of these drugs. Seventy-five percent of the infected mice survived when treated with 100 mg of rifabutin per kg per day combined with the ineffective dose of 10 mg of pyrimethamine per kg. A dose of 50 mg of rifabutin per kg in combination with the ineffective dosages of clindamycin (25 mg/kg/day), atovoquone (5 mg/kg/day), and sulfadiazine (80 mg per liter of drinking water) protected at least 80, 60, and 60% of the mice against death, respectively. The inflammatory responses in the brains of mice treated for 30 days with 200 mg of rifabutin per kg per day were significantly reduced compared with those in the brains of untreated controls. These observations suggest that clinical trials with rifabutin for treatment and prevention of human toxoplasmosis may be justified, particularly when the drug is used in combination with other drugs with activity against T. gondii.

Animals↗

Presence of gamma interferon in human acute and congenital toxoplasmosis.

The production of gamma interferon in acute acquired and congenital toxoplasmosis was studied. Gamma interferon was produced at significant titers (P less than 0.001) in the course of both congenital toxoplasmosis and acquired toxoplasmosis at an early stage of infection, when Toxoplasma gondii was multiplying. Its presence in fetal blood was correlated with the positive inoculation of fetal blood or amniotic fluid into mice (95%). The data suggest that the fetus is able to synthesize gamma interferon as early as week 21 of pregnancy. This test, easily and rapidly performed, could be included among those useful for diagnosing fetal toxoplasmic disease.

Acute Disease↗

Long term ocular and neurological involvement in severe congenital toxoplasmosis.

AIMS: This study was set up to determine the long term ocular and systemic sequelae in patients with severe congenital toxoplasmosis. METHODS: Cross sectional and retrospective study of 17 patients with severe congenital toxoplasmosis. RESULTS: In addition to chorioretinitis (100%), the most common abnormal ocular features were optic nerve atrophy (83%), visual acuity of less than 0.1 (85%), strabismus, and microphthalmos. In 50% of cases we observed iridic abnormalities and about 40% developed a cataract. Overt endocrinological disease, diagnosed in five of 15 patients, included panhypopituitarism (n = 2), gonadal failure with dwarfism (n = 1), precocious puberty with dwarfism and thyroid deficiency (n = 1), and diabetes mellitus and thyroid deficiency (n = 1). The observed endocrinological involvement was associated in all cases with obstructive hydrocephalus with a dilated third ventricle and optic nerve atrophy. CONCLUSION: The recognition of long term ocular, neurological, and endocrinological sequelae of congenital toxoplasmosis is important for medical management of these severely handicapped patients.

Adolescent↗

Congenital toxoplasmosis: systematic review of evidence of efficacy of treatment in pregnancy.

OBJECTIVE: To summarise the evidence that treating toxoplasmosis in pregnancy reduces the risk of congenital toxoplasma infection and improves infant outcomes. DESIGN: Systematic review of studies comparing at least two concurrent groups of pregnant women with proved or likely acute toxoplasma infection in which treatments were compared with no treatment and outcomes in the children were reported. SUBJECTS: Studies were identified from Medline (1966-97), Pascal (1990-7), Embase (1993-7), and Biological abstracts (1993-5) plus contact with experts in the field, including the European Research Network on Congenital Toxoplasmosis. MAIN OUTCOME MEASURE: Proportion of infected children at 1 year born to infected pregnant women who were or were not treated. RESULTS: Out of 2591 papers identified, nine met the inclusion criteria. There were no randomised comparisons, and control groups were generally not directly comparable with the treatment groups. Congenital infection was common in treated groups. five studies showed that treatment was effective and four that it was not. CONCLUSION: It is unclear whether antenatal treatment in women with presumed toxoplasmosis reduces congenital transmission of Toxoplasma gondii. Screening is expensive, so the effects of treatment and impact of screening programmes need to be evaluated. In countries where screening or treatment is not routine, these technologies should not be introduced outside carefully controlled trials.

Acute Disease↗

Resolution of intracranial calcifications in infants with treated congenital toxoplasmosis.

PURPOSE: To determine the natural history of intracranial calcifications in infants with treated congenital toxoplasmosis. MATERIALS AND METHODS: Between January 1982 and March 1994, cranial computed tomography was performed in 56 infants with treated congenital toxoplasmosis when they were newborns and approximately 1 year old. Locations and sizes of intracranial calcifications were noted. RESULTS: Forty newborns had intracranial calcifications. By 1 year of age, calcifications diminished or resolved in 30 (75%) and remained stable in 10 (25%) of these treated infants. Ten (33%) of the 30 infants whose calcifications diminished versus seven (70%) of the 10 infants with stable calcifications received less intensive antimicrobial treatment than the other treated infants. In contrast, a small number of infants who were untreated or treated 1 month or less had intracranial calcifications that increased or remained stable during their 1st year of life. CONCLUSION: Diminution or resolution of intracranial calcifications was an unexpected and remarkable finding in infants with treated, congenital toxoplasmosis, consonant with their improved neurologic functioning.

Anti-Infective Agents↗

Retinochoroiditis associated with congenital toxoplasmosis in children: IgG antibody profiles demonstrating the synthesis of local antibodies.

PURPOSE: Retinochoroiditis is generally diagnosed after the first year of life and the association with congenital toxoplasmosis presents a diagnostic dilemma. The detection of local intraocular specific antibodies could be useful for diagnosis. METHODS: We studied six patients (mean age 7 +/- 5 years) with retinochoroiditis which appeared after the first year of life. Aqueous and serum were analysed by immunoblotting for anti T. gondii IgG to diagnose toxoplasmosis. RESULTS: All serum samples were positive only for anti T. gondii IgG. The retinochoroiditis was active in three patients and inactive in the others. Immunoblot analysis of serum and aqueous from the patients with active lesions showed IgG versus the specific antigen of T. gondii. In the patients with inactive lesions the pattern was the same in the two compartments. In active forms, aqueous and serum Western blot patterns differed in proteins lower than 16kDa and higher than 116kDa: in aqueous the findings were typically positive for 30kDa. CONCLUSIONS: Aqueous humour analysis by the Western blot technique may be useful in the diagnosis of congenital toxoplasmosis. In the present small series, we nevertheless detected different patterns for inactive and active retinochoroiditis, confirming the diagnosis in the latter. Aqueous humour paracentesis may be indicated in a child with active retinochoroiditis with unusual clinical features, appearing after the first year of life, and with no clinical or serological evidence of congenital infection.

Animals↗

Determinants of response to a parent questionnaire about development and behaviour in 3 year olds: European multicentre study of congenital toxoplasmosis.

BACKGROUND: We aimed to determine how response to a parent-completed postal questionnaire measuring development, behaviour, impairment, and parental concerns and anxiety, varies in different European centres. METHODS: Prospective cohort study of 3 year old children, with and without congenital toxoplasmosis, who were identified by prenatal or neonatal screening for toxoplasmosis in 11 centres in 7 countries. Parents were mailed a questionnaire that comprised all or part of existing validated tools. We determined the effect of characteristics of the centre and child on response, age at questionnaire completion, and response to child drawing tasks. RESULTS: The questionnaire took 21 minutes to complete on average. 67% (714/1058) of parents responded. Few parents (60/1058) refused to participate. The strongest determinants of response were the score for organisational attributes of the study centre (such as direct involvement in follow up and access to an address register), and infection with congenital toxoplasmosis. Age at completion was associated with study centre, presence of neurological abnormalities in early infancy, and duration of prenatal treatment. Completion rates for individual questions exceeded 92% except for child completed drawings of a man (70%), which were completed more by girls, older children, and in certain centres. CONCLUSION: Differences in response across European centres were predominantly related to the organisation of follow up and access to correct addresses. The questionnaire was acceptable in all six countries and offers a low cost tool for assessing development, behaviour, and parental concerns and anxiety, in multinational studies.

Child Behavior↗

Options for the pharmacotherapy of toxoplasmosis during pregnancy.

Toxoplasmosis infection during pregnancy can cause stillbirths, severe mental retardations or ocular disorders that can also occur later in life and have a potential to relapse. As the disease is generally asymptomatic, diagnosis relies on serological tests. Primary prevention intends to prevent the infection of the fetus, while secondary prevention aims at reducing the severity of sequelae. Preventive attitudes regarding congenital toxoplasmosis differ according to countries. In Austria and France, a nationwide programme based on the screening of seronegative pregnant women and the treatment of all seroconversions has been implemented. The UK and Norway have rejected such a screening due to the lack of evidence of its efficacy. A review of published studies showed that no randomised controlled trials have been conducted. The only available data come from retrospective studies and are methodologically flawed. The impact of chemotherapy on primary and secondary prevention still needs to be assessed. This lack of evidence results in conflicting attitudes that increase the anxiety already raised in pregnant women and doctors by the occurrence of a maternal toxoplasmosis during pregnancy. Before making any change in preventative strategy, it is of utmost importance to increase our knowledge on treatment efficacy through proper randomised trials of existing drugs and of new potentially active compounds.

Antiprotozoal Agents↗

[Identification of risk factors for infection with Toxoplasma gondii in Serbia as a basis of a program for prevention of congenital toxoplasmosis].

BACKGROUND: Toxoplasmosis has long been known as a major cause of perinatal morbidity. Acute infection in pregnancy may lead to fetal infection and subsequent fetal loss or birth of a manifestly or latently infected infant. However, it is a preventable disease. In Europe, significant variations have been shown to occur not only between countries but also within a given country indicating local variations in the influence of epidemiological factors contributing to infection. Thus, many European countries have implemented prevention programs in measure with the respective estimated risk of congenital toxoplasmosis. Since in view of its cost, a general screening-in-pregnancy program is at present not an option in Serbia & Montenegro, insight into the risk factors of particular local significance may therefore improve the quality of and the compliance with the hygienic and dietetic advice given to pregnant women as a preventive measure, as well as identify the particular subpopulations at an increased risk of infection, who may then be selectively screened. SUBJECTS AND METHODS: A retrospective study of risk factors for Toxoplasma gondii infection based on serological and epidemiological data (questionnaire) was performed in a series of 2936 women aged 15-49 years from throughout Serbia tested in our laboratory between 1988 and 1997. Inclusion criteria included availability of serological and epidemiological data (as specified below). Specific anti-Toxoplasma antibodies were detected by the reference Sabin-Feldman dye test as modified by Desmonts into the lysis test. The questionnaire included questions on age (stratified into five-year groups), degree of education (modalities: grade school, secondary or university level), and community of residence (urban/suburban), as well as on life-style habits pertaining to infection transmission risk factors: consumption of undercooked meat, exposure to soil, and exposure to cats (pet cat ownership). In addition, the year of entry into the study was taken as a variable per se. STATISTICS: The difference in the rates of infection between groups was evaluated by the chi-square test (chi 2). Logistic regression (univariant and multivariant approaches) was used to analyze the association between Toxoplasma infection and the specific demographic and epidemiological factors. RESULTS: The overall prevalence of infection was 69%, but with very wide variations both over time (decreasing from 86% in 1988 to 39% in 1997) and region (40-90%). The risk of infection increased from the south to the north (RR = 0.97, CI = 0.94-0.98). Within Belgrade, the risk was higher in urban than in suburban zones (RR = 0.79, CI = 0.64-0.93). The single infection transmission factor that was shown to be a predictor of infection in the whole study group was undercooked meat consumption (RR = 1.6, CI = 1.2-2.1), while exposure to soil was a predictor only in women aged 15-19 (RR = 10.3, CI = 2.7-38.6). Owing pet cats had no influence. While T. gondii infection was not associated with pathological pregnancies (p = 0.51) in the whole study population, it was significantly associated with pathological pregnancies in women exposed to both undercooked meat consumption (p = 0.009) and in those aged 15-19 in contact with soil (p = 0.022), as well as in women residing in highly urban communities (p = 0.048). CONCLUSION: The dramatic decrease in the prevalence of T. gondii infection over the nineties resulted in a rising proportion of women exposed to infection in pregnancy and consequently in an increased risk of congenital toxoplasmosis. Since the financial status of the country's health system does not allow for a general screening-in-pregnancy program, we propose, based on the above data, health education of all pregnant women in combination with serological testing of those exposed to predictors of infection as an epidemiologically sound and financially sustainable alternative.

Adolescent↗