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Cerebral toxoplasmosis in Danish AIDS patients.

We estimate the frequency of central nervous system (CNS) toxoplasmosis in Danish AIDS patients and evaluate the diagnostic accuracy using the following criteria for acceptance of the diagnosis: either (1) the demonstration of Toxoplasma gondii in brain tissue or (2) one or more hypodense or ring-enhancing lesions on computerized axial tomography (CAT) scan and a neurologic and CAT scan improvement in response to 2 weeks of treatment. From 1981 until July 1990 266 patients were diagnosed with AIDS at Hvidovre Hospital, Copenhagen and 29 (11%) were treated, suspected for CNS toxoplasmosis. 17 patients had the diagnosis confirmed but since 5 patients, who were never treated, were diagnosed at autopsy, the overall cumulated incidence was 8% (22/266 patients). The overall diagnostic accuracy was 59% (17/29 patients) showing some changes over time. Among patients diagnosed with AIDS in 1988 or later, the accuracy was 83% (10/12 patients) while among patients diagnosed in 1987 or earlier the accuracy was 41% (7/17 patients). Four patients were diagnosed with Pneumocystis carinii pneumonia (PCP) prior to the diagnosis of CNS toxoplasmosis, while among patients with toxoplasmosis as the AIDS-defining diagnosis, 3 later developed PCP. None of these 7 patients had received secondary prophylaxis with a drug containing sulfonamide.

Acquired Immunodeficiency Syndrome↗

DNA amplification on cerebrospinal fluid for diagnosis of cerebral toxoplasmosis among HIV-positive patients with signs or symptoms of neurological disease.

Reactivation of Toxoplasma gondii can lead to a life-threatening intracerebral infection in immunocompromised HIV-positive patients. Due to the current diagnostic limitations for establishing an exact diagnosis of cerebral toxoplasmosis, a nested PCR system was developed for direct detection of T. gondii in cerebrospinal fluid. A storage temperature for samples of -20 degrees C and sample preparation using Proteinase K appeared to be critical for obtaining a high sensitivity of PCR. A total of 56 samples from 38 HIV-positive patients and 12 HIV-negative patients with symptoms or signs of neurological disease were evaluated by PCR. 5 of the 38 HIV-positive patients were diagnosed as having cerebral toxoplasmosis and PCR was positive in samples from all 5 patients. In the remaining 33, PCR was positive in one case and negative in 32. An exact etiological diagnosis other than cerebral toxoplasmosis was established in 5 patients. PCR performed on cerebrospinal fluid samples seems to be a fast, sensitive, specific and valuable tool for establishing the diagnosis of cerebral toxoplasmosis among HIV-positive patients at the time of presentation of symptoms or signs of neurological disease.

Base Sequence↗

Frequency of toxoplasmosis in the appearance of congenital hydrocephalus.

Thirty-eight children with signs of hydrocephalus have been tested for toxoplasmosis. On the basis of clinical data, including roentgenographical and ophthalmological findings, and serological data (Sabin-Feldman and IgM-IFA tests), congenital toxoplasmosis was confirmed in 15 (39%) infants. The diagnosis was established by demonstration of the persistence of Toxoplasma antibodies. In 13 (34%) infants aged 1 to 3 months there was not enough serological data and these were placed in a group of cases with "suspected congenital toxoplasmosis." Ten children with negative serology for toxoplasmosis and with hydrocephalus were considered not to be infected.

Child, Preschool↗

Reactivation of ocular toxoplasmosis after LASIK.

PURPOSE: To report a reactivation of ocular toxoplasmosis after LASIK. METHODS: Case report of a 34-year-old man who underwent bilateral LASIK. The posterior segment examination revealed an old toxoplasmosis scar in the retinal periphery of the right eye. RESULTS: Uncorrected visual acuity improved postoperatively, and the patient was satisfied. However, 52 days after the procedure, he complained of loss of visual acuity in his right eye. Examination revealed signs of anterior uveitis, vitreitis, and active chorioretinal lesion satellite of the old toxoplasmosis scar. The patient was treated with a multidrug regiment with resolution of the vitreous and lesion activity. CONCLUSIONS: Toxoplasmosis reactivation may develop after LASIK.

Adult↗

Congenital toxoplasmosis: a large survey in western Australia.

OBJECTIVE: To determine the birth prevalence of congenital toxoplasmosis in Western Australia. DESIGN: A prospective serological study of randomly selected pregnant women and their newborn infants. Paired sera collected from the mothers at their first antenatal visit and cord blood specimens taken from their infants were tested for toxoplasmosis by the direct agglutination test and Toxoplasma IgM-capture enzyme-linked immunosorbent assay. SETTING: A major Perth metropolitan obstetric teaching hospital where approximately one-quarter of infants born in Western Australia during January 1986 to December 1989 inclusive were delivered. PARTICIPANTS: Sera were obtained from 10,207 pregnant women presenting for routine clinical evaluation at their first antenatal visit. Cord blood specimens were taken from 18,908 infants; 7523 of these could be paired to maternal specimens. MAIN OUTCOME MEASURES: Maternal infection was indicated in cases where Toxoplasma specific IgM antibody was present or where an initial maternal specimen gave negative results for Toxoplasma antibody but the paired cord blood specimen gave positive results. Toxoplasma specific IgM antibody in a cord blood specimen indicated fetal infection. RESULTS: Of the 10,207 women 3544 (35%) were Toxoplasma immune at their first antenatal visit; in 11 Toxoplasma specific IgM antibody was detected. There was no serological or clinical evidence of congenital toxoplasmosis in any of the offspring of these 11 mothers. The rate of maternal infection in susceptible pregnancies was 1.6 per 1000; the maternal-fetal transmission rate was estimated to be no greater than 24%. Three of the 18,908 cord blood specimens tested gave positive results for Toxoplasma specific IgM antibody giving a birth prevalence of congenital infection of 0.23 per 1000 births to non-immune mothers. There were no clinical features of congenital infection in these three infants but they will require long-term follow-up. Thirteen of the 14 mothers infected during pregnancy were interviewed retrospectively and in only three was a known risk factor for infection present. CONCLUSIONS: a toxoplasmosis screening programme for pregnant mothers is not justifiable in Western Australia. A public education programme is also likely to have limitations.

Agglutination Tests↗

Changes in the personality profile of young women with latent toxoplasmosis.

Latent toxoplasmosis is the most widespread parasite infection in developed and developing countries. The prevalence of Toxoplasma gondii infection varies mostly between 20 to 80% in different territories. This form of toxoplasmosis is generally considered to be asymptomatic. Recently published results, however, suggest that the personality profiles of infected subjects differ from those of uninfected controls. These results, however, were obtained on non-standard populations (biologists or former acute toxoplasmosis patients). Here we studied the personality profiles of 191 young women tested for anti-Toxoplasma immunity during gravidity. The results showed that the differences between Toxoplasma-negative and Toxoplasma-positive subjects exits also in this sample of healthy women. The subjects with latent toxoplasmosis had higher intelligence, lower guilt proneness, and possibly also higher ergic tension. The difference in several other factors (desurgency/surgency, alaxia/protension, naiveté/shrewdness, and self-sentiment integration) concerned changes in the variances, rather than the mean values of the factors.

Adolescent↗

Acute toxoplasmosis following renal transplantation in three cats and a dog.

Three cats and 1 dog that had undergone renal transplantation because of end-stage renal disease were examined because of complications 3 to 6 weeks after surgery. One cat died prior to treatment of the complications; Toxoplasma cysts were found in sections of the renal allograft, and Toxoplasma tachyzoites were found in other organs. The other 2 cats and the dog died despite treatment, and protozoal cysts, as well as tachyzoites, were identified in other organs but not within the allografts, suggesting that reactivation of latent infection following immunosuppression was the most likely cause of disseminated toxoplasmosis. These cases illustrate that toxoplasmosis can be a fatal complication in renal transplant recipients. We currently recommend that feline and canine donors and recipients undergo serologic testing for toxoplasmosis prior to surgery. In addition, we suggest that seropositive donors not be used for seronegative recipients and that seropositive recipients and that seropositive recipients be monitored closely after surgery for clinical signs of toxoplasmosis.

Acute Disease↗

[Immunoblot applied to the diagnosis of congenital toxoplasmosis].

Western blot was evaluated for the neonatal diagnosis of congenital toxoplasmosis based on a comparison of antibody profiles between serum samples obtained from the mother at delivery and from the neonate. Passively transferred antibodies can be distinguished from antibodies produced by the neonate, thus allowing early postdelivery diagnosis of congenital toxoplasmosis before the results of other tests are available. This method was developed at the Parasitology-Mycology laboratory of the Pitié-Salpêtrière Teaching Hospital, Paris, France, then evaluated in a retrospective study of 52 mother-infant pairs. The diagnosis of congenital toxoplasmosis was ruled out in 34 cases, confirmed in ten cases, and doubtful in 8 cases. Sensitivity was higher than with conventional serological tests. Antibody profile differences were found between mothers and affected infants; these differences usually involved IgGs (8 of 9 cases). Importantly, in two cases Western blot would have provided the diagnosis of congenital toxoplasmosis two months before the secondary elevation in IgM titers in one case and three weeks before the result of mouse placenta inoculation in another case. In conclusion, Western blot deserves to be used to complement established methods (serology and direct demonstration of the parasite by gene amplification, cell cultures, and mouse inoculations) as a means of rapidly (within 24 hours of receipt of the specimen) providing clinicians with information relevant to treatment decisions.

Antibodies↗

[Toxoplasmosis and chronic myeloid leukemia].

A patient suffering from chronic myeloid leukemia and used as a donor of leucocytes was found to have toxoplasmosis associated with a high level of IgG without an elevation of IgM which was maintained for several months. This case raises several points for discussion. Toxoplasmosis is a frequent complication of malignant hematological disease, it is often severe with neurological complications in more than half the patients affected. It is often difficult to diagnose. The parasite is arduous to isolate and serology is problematic to interpretate without reference to previous samples. This suggests it would be wise to measure the titre of anti-toxoplasma antibodies as part of the initial investigations of every malignant hemopathy and to repeat the measurements during the evolution of the disease. Any patient showing a high serological titre, even though it is stable and without IgM should be given systematically a specific treatment for toxoplasmosis, for as in the patient presented in this paper, such a serological picture is compatible with an increasing infection. The frequence of high serological titres seems to be greater among patients suffering from chronic myeloid leukemia than among another people. Then, transfusion of leucocytes of such patients may be the source of parasite transmission; this paper relates one case of post-transfusional toxoplasmosis.

Antibodies↗

An investigation into the incidence of toxoplasmosis in pregnancy in New Zealand.

AIM: To estimate the incidence of toxoplasmosis in pregnancy in New Zealand and consider whether there is a case for screening women in pregnancy. METHODS: The risk of maternal and fetal infection with toxoplasmosis was derived by first determining the rate of maternal seroconversion based on seroprevalence studies. The age-specific number of seroconversions in pregnancy was then estimated from the birth rate. Using reported fetal infection rates after primary maternal infection, the expected number of congenitally infected infants in one year was estimated. These incidences were compared with the number of recognised cases of toxoplasmosis infection in pregnancy and the actual number of positive IgM results at the Wellington Hospital laboratory. Using national births data, this incidence was extrapolated to estimate the number of expected cases in New Zealand. RESULTS: The annual seroconversion rate was 0.62% (95% confidence interval 0.39-0.86). On this basis, 164 primary maternal infections are expected annually with 66 fetuses being infected. Ten patients tested positive for IgM in Wellington, which averaged only one case per year being identified over the time examined in this study. CONCLUSIONS: Very few of the expected cases in pregnancy are diagnosed. Reporting rates were low when toxoplasmosis was a notifiable disease. Other means of improving detection, reporting and the avoidance of infection are discussed. More information is required before screening can be recommended in New Zealand.

Adolescent↗

[Evaluation of the usefulness examination of IgG avidity for serodiagnosis of toxoplasmosis].

An assay measuring the avidity of T. gondii-specific IgG is a useful serological indicator of toxoplasmosis which in many cases allows on the basis of single serum sample testing to confirm or exclude acute infection. IgG antibodies against T. gondii produced in the recent primary infection are of low-avidity while IgG antibodies in the chronic toxoplasmosis are of high-avidity. In the present study 80 sera: 47 sera of patients with suspected acute toxoplasmosis, 23 sera of pregnant women and 10 sera of healthy blood donors, were evaluated for the presence of IgM, IgA and IgG antibodies and for the avidity of IgG. Among the 80 tested sera IgM antibodies were present in 34 (42.5%) cases of which 22 (64.7%) showed low-avidity of IgG and the presence of IgA antibodies confirming acute toxoplasmosis. In the rest of these 34 sera three of them showed low avidity index and nine other high avidity in spite of the presence of IgM antibodies. In these 12 sera IgA antibodies were not present. In 46 (57.5%) examined sera IgM or IgA antibodies were not detectable and the present the IgG antibodies showed high-avidity what is characteristic of chronic infection. An assay for evaluation of avidity of IgG antibodies specific for T. gondii is valuable in complementing existing tests and in many cases it has decisive value for interpretation of results.

Adolescent↗

Cerebral toxoplasmosis and AIDS. Clinical, neuroradiological and immunological findings in 15 patients.

Cerebral toxoplasmosis is the most common cause of focal CNS disease complicating AIDS and its incidence ranges from 3% to 40% of such patients. This opportunistic infection is generally due to reactivation of chronic toxoplasmosis as a consequence of severe immune deficiency. We present the clinical, neuroradiological and immunological findings of 15 AIDS patients with cerebral toxoplasmosis. All patients had focal neurological signs. CT-scan (13 cases) and NMR (2 cases) showed single or multiple mass lesions and edema. Serum IgG anti-Toxoplasma antibodies were positive in 14 patients; CSF specific IgG were positive in 5 out of 7 studied patients, while serum and CSF specific IgM were negative in all subjects. The intrathecal synthesis of anti-Toxoplasma antibodies were high in all 7 patients. A presumptive diagnosis of cerebral toxoplasmosis is based on the focal cerebral signs and neuroradiological findings. It is more frequently confirmed by the improvement of the clinical and neuroradiological picture during the treatment with pyrimethamine-sulphadiazine or clindamycin.

AIDS-Related Opportunistic Infections↗

Depletion of CD4+ T cells but not inhibition of the protective activity of IFN-gamma prevents cure of toxoplasmosis mediated by drug therapy in mice.

Toxoplasmosis is a frequent opportunistic infection in patients with AIDS. In these patients the major immune deficiencies are a severe depletion of CD4+ T lymphocytes and an impaired capacity to produce IFN-gamma. A mouse model was developed and used to study the effects that depletion of CD4+ T cells and/or inhibition of the protective activity of IFN-gamma have on the effectiveness of the drug therapy for toxoplasmosis. Infection of mice with a lethal inoculum of Toxoplasma gondii cysts followed by treatment with the hydroxynaphthoquinone 566C80 or with sulfadiazine resulted in 100% survival whereas untreated controls had 100% mortality within 15 days of infection. Administration of antiserum to IFN-gamma resulted in early death of untreated mice and in 30% mortality in those treated. Administration of mAb to CD4+ T cells followed by infection with T. gondii prevented the development of both antibody and cell-mediated immune responses against the parasite. These mice resisted the acute infection while undergoing specific treatment. Discontinuation of the treatment, however, resulted in reactivation of the infection and the majority of the animals died within 17 days of suspension of the treatment. Administration of antiserum to IFN-gamma or to CD4+ T cells 24 h but not 15 days after conclusion of the treatment also resulted in mortality. These results indicate that successful treatment of toxoplasmosis depends on the status of the immune system, particularly of CD4+ T cells. Although it is speculative to compare results obtained in mice to the situation in humans, our work suggests that restoration of a competent immune response is of crucial importance for a successful treatment of toxoplasmosis in immunocompromised individuals.

Animals↗

[Predictive value of non-specific signs of fetal infection in congenital toxoplasmosis].

AIMS: To study the predictive value of 9 non-specific signs for congenital toxoplasmosis. METHOD: The work was carried out as a prospective study comparing non-specific signs in 22 fetuses infected with toxoplasmosis and 59 fetuses free of the disease. RESULTS: Four of the nine parameters were found to be statistically higher in the group of infected fetuses. These are the level of leucocytes (p < 0.05) gamma glutamyl transferase (p < 0.001) total M immunoglobulin (p < 0.0001) and C4 fraction of complement (p < 0.0001). This last sign which is non-specific for infection has never been looked at until now in congenital toxoplasmosis but is seems to be of great importance because its sensitivity is much greater than of all the other parameters that have been used up till now (81%) and the positive predictive value is excellent (72%). On the other hand the value of a raised leucocyte count is a matter for discussion. CONCLUSION: The presence of even one abnormally raised feature in the fetal blood of these non-specific signs is enough to screen for a population which is of high risk for congenital toxoplasmosis and sufficient to change our attitude to treating the condition.

Complement C4↗

Use of IgG Avidity test in case definitions of toxoplasmosis in pregnancy.

A survey network for congenital toxoplasmosis (TOXO-NET) was set up in December 1996 in Piedmont (Italy). Participants were asked to classify the infections in pregnant mothers and newborns by the criteria of the European Network on Congenital Toxoplasmosis published by Lebech in 1996. Because the IgG Avidity test is largely employed as a 2nd level test in toxoplasmosis diagnosis and it could be helpful to date infection, the co-ordinators of TOXO-NET suggested including it in the "case definition" of "probable" infection and "unlikely" infection. 117 cases of toxoplasmosis in pregnancy divided into the risk categories under Lebech's criteria were re-examined using the "new" case definitions. 77 out of 117 (65.8%) Toxoplasma gondii infections during pregnancy could be defined with only one serum sample using the IgG Avidity test. The IgG Avidity test proved a useful method to classify the Toxoplasma gondii infections in pregnancy, especially when we had only one serum sample.

Animals↗

Seroepidemiological study of toxoplasmosis in rural areas in the eastern region of Saudi Arabia.

Serum from 1400 human subjects of different age, occupation, life style of both sexes was collected. Serological analysis for inactive toxoplasmosis (levels of IgG) and active toxoplasmosis (IgM) was done using the Microparticle Enzyme Immuno-Assay (MEIA) IMx-Toxo, IgG and IgM assays. In Al-Nereiyah and Al-Qurain, the overall seroprevalence of inactive toxoplasmosis was almost similar (26.36% and 25.0% respectively), while active toxoplasmosis was higher in Al-Qurain (4.91%) than in Al-Nereiyah (3.78%). The seroprevalence of IgG was similar in males and females in both areas, but increased with age and was higher in housewives, employees and farmers than in students and children. Almost a similar result was recorded for IgM in respect to age and occupation except that seroprevalence was higher in females than in males in Al-Qurain area.

Adolescent↗

Anti-toxoplasma serotitres in uveitis and ocular toxoplasmosis.

This study was based on anti-toxoplasma serotitres obtained from 80 normal healthy adults and 103 consecutive patients with anterior, posterior and panuveitis over a 42 month period. Twelve out of 80 (15%) normal healthy sera were found to have low titres (1:64 to 1:256), while 3 (3.8%) had high titres (1:1024 or higher). The distribution of serotitres in patients with clinical toxoplasmosis was significantly different from the population sample (p less than 0.001, chi-squared test). Similarly, the distribution of serotitres in patients with posterior uveitis (of which 28 out of 54 were clinically ocular toxoplasmosis) having serotitres of 1:1024 or greater, was found to be significantly different from the normal population (p less than 0.001, Chi-squared test), but not statistically different from those with clinical ocular toxoplasmosis. Hence, anti-toxoplasma serotitre is useful as a diagnostic screening tool only in patients with posterior uveitis. It is also useful in confirming cases of suspected clinically positive ocular toxoplasmosis in our local population.

Adolescent↗

Performance of the immunoglobulin G avidity and enzyme immunoassay IgG/IgM screening tests for differentiation of the clinical spectrum of toxoplasmosis.

Toxoplasmosis has been well known as an important human infection to consider especially in pregnant women. Although many serologic methods are available, the diagnosis of toxoplasmosis can be extremely difficult. The presence of increased levels of Toxoplasma-specific IgG antibodies indicates an infection, but it does not differentiate between a recent and past infection. The purpose of our study was to compare the performance of the ELISA T. gondii IgG/IgM test, a widely used enzyme-linked immunosorbent assay, to the ELISA IgG avidity method. One hundred and four serum samples (from 38 males and 66 females) were tested and evaluated from symptomatic patients (chorioretinitis, lymphadenopathy), and from women in their first trimester of pregnancy who were suspected of having toxoplasmosis. The high IgG avidity and ELISA IgG antibody levels were in agreement for 51 of the specimens (49.0%). Thirty-eight discrepant (borderline) results from the IgG avidity method were positive for IgM (3 specimens) and IgG (37 specimens). Interestingly, out of the eight serum samples that were positive for both IgG and IgM antibodies, two samples were low IgG avidity, and three samples were borderline. There was no statistically significant relation observed between the results of the IgG avidity method and the ELISA IgG test, and the IgG avidity method and ELISA IgM test (chi2 = 1.987; p = 0.370 and chi2 = 2.152; p = 0.341, respectively). The IgG avidity method was considered easy to perform and an acceptable approach for the differentiation of discrepant results (recent/chronic) and for the current detection of T. gondii antibodies. We concluded that the determination of IgG avidity is a helpful tool for the diagnosis of the ocular form of toxoplasmosis and it is a safe method for screening this disease in the first trimester of pregnancy.

Animals↗