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Management of toxoplasmosis.

Toxoplasma gondii, an intracellular coccidian protozoan, is the causative agent of toxoplasmosis, a widespread infection affecting various birds and mammals including humans. In immunocompetent hosts, the infection is usually asymptomatic and benign. Toxoplasmosis is either congenital or acquired. In general, prenatal therapy of congenital toxoplasmosis is beneficial in reducing the frequency of infant infection. Therapies are based primarily on spiramycin because of the relative lack of toxicity and high concentrations achieved in the placenta. Clindamycin is the standard drug for chemoprophylaxis in newborn infants, and is directed at preventing the occurrence of retinochoroiditis as a late sequel to congenital infection. The standard treatment for acquired toxoplasmosis in both immunocompetent and immunodeficient patients is the synergistic combination of pyrimethamine and sulphonamides. Toxoplasmic encephalitis is the most common manifestation of acquired toxoplasmosis in immunocompromised patients and if not treated is fatal. However, because of toxicity, the therapeutic efficacy of pyrimethamine-sulphonamide combinations may be seriously limited in immunodeficient patients. A number of novel and less toxic agents are being currently studied in clinical settings, including macrolide antibiotics (clindamycin, clarithromycin and azithromycin) and atovaquone, as well as some older anti-infective drugs such as cotrimoxazole (trimethoprim/sulfamethoxazole). Maintenance or prophylactic therapy is essential in many patients with acquired immunodeficiency syndrome (AIDS) where toxoplasmosis is most often the result of a pre-existent latent infection.

Anti-Infective Agents↗

Fuchs's heterochromic cyclitis in congenital ocular toxoplasmosis.

We report a follow-up after 25 years of a patient with a congenital bilateral ocular toxoplasmosis who developed Fuchs's heterochromic cyclitis in her left eye. Whether Toxoplasma gondii can cause the development of Fuchs's heterochromic cyclitis, as our case suggests, or whether the iridocyclitis is a secondary ocular response to other agents, is not yet clear.

Animals↗

Impact of primary prevention on the incidence of toxoplasmosis during pregnancy.

Until now, it was assumed that primary prevention of congenital toxoplasmosis was possible by means of specific hygienic measures. A prospective survey of pregnant women was made at a hospital in Brussels over the period 1979-1986 to assess the impact of such a prevention program. In the first study period (1979-1982), when no prophylactic measures were taught, 2986 consecutive women demonstrated a seroconversion rate of 1.43% among the nonimmunized subjects; 1.07% of the seropositive patients had high antibody levels in their first serum sample. In the second study period (1983-1986), all 3563 patients were instructed to adopt prophylactic measures. The seroconversion rate in seronegative patients and the percentage of patients with high initial antibody level were 0.95 and 1.26%, respectively. Although the percentage of seroconversion was reduced by 34% in the second study period, this difference did not attain significance. These results indicate that the impact of a primary prevention program aimed at reducing congenital toxoplasmosis is limited.

Animals↗

Cerebellar anomalies in congenital murine toxoplasmosis.

Gravid Nya:NYLAR mice, infected with Toxoplasma gondii on gestation day 7, experienced embryo resorptions, abortions, stillbirths, and a reduction in average litter size by one-third. Postnatally, all congenitally infected pups showed growth retardation, cachexia, and hind limb weakness. Some pups developed necrotic petechiae on the ears and tail, and a blood-tinged nasal discharge. Coronal sections of the cerebellum at age 1 month revealed developmental abnormalities including: persistence of remnants of an external granular layer; fragmented and disoriented Bergmann glial foot processes; numerous ectopic granule cells stranded in the molecular layer; focal disorganization and edema of the Purkinje cell layer; and thinning of the internal granular layer. Our working hypothesis is that the cerebellar anomalies originated with parasite invasion of the fetal vascular endothelium leading to vasculitis and microcirculatory dysfunction, perivascular edema, perfusion impairment, and tissue anoxia. In the cerebellar folia, the cellular migration defects are attributed to edema-induced swelling and fragmentation of the Bergmann glial foot processes that guide migrating neurons, whereas the focal loss of Purkinje and granule cells is ascribed to hypoxia-ischemia. Although Toxoplasma cysts were detected in the cerebellum, morphologic evidence of parasite association with neuropathology was not obtained.

Animals↗

[Toxoplasmosis in Poznan region, Poland 1990-2000].

The paper summarizes the results of the interdisciplinary studies on toxoplasmosis carried out in Poznan region, Poland. In the years 1990-2000 the specific Toxoplasma gondii seropositivity rates in pregnant women decreased from 58.9% to 43.7%. Significant was an increase in seropositivity in the age group 15-20 years. Cats were seropositive in 70.6%; relatively high seropositivity rate was observed in cats kept at home only (65.7%). Slaughtered pigs were positive in 13.2% with higher rates in older pigs and those originating from small private farms. Screening newborns with noncommercial tests by using Guthrie cards revealed that the congenital toxoplasmosis occurs in 0.55/1.000 pregnancies at screening for specific IgM and 1.08/1.000 pregnancies at screening for combined IgM and IgA. The prenatal screening for toxoplasmosis has not been introduced in Poland. However, the frequency of individual serological testing for Toxoplasma increased from 2.7% to 4.6% of pregnancies. Active health education was introduced in Poznan region and the awareness of toxoplasmosis risk increased from 24.3% to 45.2%. Still 54.7% of pregnant women were inadequately informed and 44.8% of pregnant women, being aware of the risk or not, did not respect specific hygienic measures. The rational control of congenital toxoplasmosis in Poznan region should be based on a routine newborn screening for congenital toxoplasmosis, continuous education of medical personnel and intensive, modern health education especially in adolescents and pregnant women from rural areas.

Adolescent↗

The prevalence and incidence of Toxoplasma antibodies in pregnant women.

A group of 213 pregnant Jewish women of Israeli and North-African/Asian origin in the Upper Gallilee in Israel were tested for Toxoplasma antibody, first at 4-12 weeks gestation and again 5-6 months later. Immunofluorescent antibody, Sabin-Feldman tests, and specific IgM estimation were used. The prevalence rates for seropositive women were lower in both groups (total 21%) than the rate found in a 1973 study in Israel. The incidence rate for infection acquired in pregnancy was 1.4%. There were no cases of congenital toxoplasmosis, as far as is known up to 3 years of age. More information on the prevalence and incidence of seropositivity, and on congenital toxoplasmosis, is required before a policy decision can be taken as to whether an antenatal screening program for toxoplasmosis should be instituted in Israel.

Adult↗

[Childhood toxoplasmosis today].

The comparative study of two groups of children suffering from acquired or congenital toxoplasmosis, being in hospital during two different decades (1979-1985--39 children and 1991-1997--117 children) proved: the fact that atypical or subclinical manifestations of the acquired toxoplasmosis (54%) draws our attention to the systematic research of the infection with Toxoplasma gondii, especially at the groups with increased risk now that the frequency of the diseases generating immunodeficiency; the increased frequency of congenital toxoplasmosis (5% in the first group, 8% in the second group) and especially of the invalidating of screening tests to the pregnant women; the therapeutic arsenal limited by the rate price/toxicity/medical resistance, must be individualized for each case, taking into account the increased number of other associated diseases (chronic hepatitis B 7%, TB 17%, HIV infection 5%); Rovamicine treatment at the second group had similar results to those obtained by administrating Pirimetamine--Trimetoprim to the children from the first group.

Adult↗

Prevalence of antibodies to Toxoplasma gondii in the female population of the County of Split Dalmatia, Croatia.

The prevalence of IgG antibodies reactive with Toxoplasma gondii in the female population of the County of Split Dalmatia was investigated by enzyme linked immunosorbent assay. Of a total of 1109 serum samples collected from female subjects, 423 (38.1%) reacted with T. gondii. The frequency of positive sera increased with age. Theoretical incidence of congenital toxoplasmosis was calculated from the annual increase in cumulative prevalence of antibodies between different age groups among the women of childbearing age. The estimated theoretical incidence of congenital toxoplasmosis was 1.4 per 100 pregnancies of adolescents (16-20 years) and decreased to 0.1% in seronegative pregnant women aged 41-45.

Adolescent↗

[Diagnosis of materno-fetal toxoplasmosis].

The antenatal diagnosis of congenital toxoplasmosis represents today an important application of molecular diagnostic methods such as PCR. Done directly in amniotic fluid, the PCR for T. gondii is able to detect in utero infected foetus with high probability. Doing so, it precludes to obtain foetal blood and to use more cumbersome and lengthy procedures such as inoculation to cell lines or to mice. Although it is use today in many centres, the molecular diagnosis of T. gondii by PCR is neither commercialized nor standardised. The objective of this report is to present the methodology used in our institution and to establish its degree of validation.

Female↗

[6 cases of toxoplasmosis in twins].

Studies of congenital toxoplasmosis in twins confirm the definite role of the placenta in the modalities and mechanism of fetal contamination. In single-chorion twin pregnancies, clinical manifestations are generally identical in both infants. Conversely, twins from double-chorion pregnancies usually have different clinical patterns; occasionally, only one of the twins is affected (1 case). The diagnosis can be ascertained antenatally by sampling blood from each of the fetuses (2 cases). The cases reported herein illustrate some of the diagnostic pitfalls that may lead to inappropriate discontinuation of monitoring and treatment: negative placental studies, absence of specific IgM antibodies, transient fall in IgG antibody titers, delayed fetal contamination after a negative fetal blood study, and need for routine tests for increased CSF albumin levels.

Adult↗

[Dynamics of the immune response in a familial focus of toxoplasmosis].

Immunoepidemiological investigations were carried out in a family in which a child with congenital toxoplasmosis was born in 1972. The following were determined: total fluorescent antibodies and their G and M fractions and G and M serum immunoglobulins. The results showed: --the existence of a familial focus if infection with T. gondii, the risk of infection in the course of pregnancy and its consequences on the product of conception; --the normal evolution of the following pregnancy in the presence of anti-T. gondii fluorescent antibodies and the birth of a normal child; --value of the indirect immunofluorescence test for the diagnosis of congenital toxoplasmosis and of the longitudinal immunologic investigation; --determination of the antibody M fraction and serum immunoglobulins did not prove as useful as expected; --persistance of fluorescent antibodies in significant titers over a long period in the absence of a clinical symptomatology or with clinical manifestations of another etiology might lead to a false diagnosis of toxoplasmosis -- hence the necessity of a test for differentiating the carrier of specific antibodies from the toxoplasmosis patient.

Adult↗

Epidemiology of toxoplasmosis among pregnant women in the Paris area.

A survey was performed using a sample of pregnant women selected at one of the biggest test centres in the Paris area. These women were serologically screened for toxoplasmosis between October 1981 and September 1983 (according to the prevention protocol for congenital toxoplasmosis established by the French health ministry). The prevalence rate of specific antibodies for toxoplasmosis was estimated from the 1074 women who were tested for the first time during the study. The prevalence rate among pregnant women in the Paris area was derived by direct standardization according to age and geographical origin. A standardized prevalence rate of 71% +/- 4% among French women, of 51.4% +/- 5% among immigrant women and a global adjusted prevalence rate of 67.3% +/- 3% for pregnant women in the Paris area was found. An incidence rate of 1.6% was estimated for the 2216 non-immune pregnant women included in the sample. There is no significant difference between the probabilities of seroconversion among French and immigrant women (2.3% +/- 1% and 1.6% +/- 0.8% respectively). Comparison of the data with previous study results show a decrease in the prevalence rate of specific antibodies for toxoplasmosis in the Paris area over the last 20 years that cannot be explained by changes in age and geographical origin. No data were available to support an aetiological hypothesis for a decrease in toxoplasma transmission to humans. Since immigration and a decrease in toxoplasma transmission to humans has led to a larger population of women at risk of infection during pregnancy in France, it is therefore important to perform studies to investigate risk factors and markers of acquired toxoplasmosis during pregnancy in order to improve the prevention of congenital toxoplasmosis.

Adolescent↗

Cholestatic jaundice due to congenital Toxoplasma gondii infection.

A case of congenital toxoplasmosis manifesting as hepatosplenomegaly and cholestatic jaundice in a 4 month old child is reported. To the best of our knowledge this is the first report of cholestatic jaundice due to congenital toxoplasmosis from India. The child was successfully treated with sulphadiazine and pyremethamine combination.

Cholestasis, Intrahepatic↗

Newborn screening for congenital infectious diseases.

To estimate the prevalence of congenital toxoplasmosis, Chagas disease, cytomegalovirus, and rubella, blood samples on dried blood spot (DBS) from neonates (day 3-20 of life) were screened for immunoglobulin (Ig) M against Toxoplasma gondii, cytomegalovirus, rubella virus, and IgG against Trypanosoma cruzi by methods used for serum and adapted for use with DBS. Positive samples were further analyzed for IgM and IgG in serum from neonates and mothers. DBS samples from 364,130 neonates were tested for Toxoplasma gondii-specific IgM, and 15,873 neonates were also tested for IgM against cytomegalovirus and rubella virus and for Trypanosoma cruzi-specific IgG. A total of 195 were diagnosed with congenital toxoplasmosis, 16 with cytomegalovirus, and 11 with congenital rubella. One newborn had a confirmed result for Chagas disease, and 21 mothers had positive serum antibodies. These results suggest that infectious diseases should be considered for future inclusion in programs for newborn screening of metabolic diseases in disease-endemic areas.

Adult↗

Antibodies to Toxoplasma gondii in eluates from filter paper blood specimens.

Blood and serum samples were tested directly for antibodies to Toxoplasma gondii, or as eluates from filter paper using the dye test, IgM enzyme-linked immunosorbent assay (ELISA) and IgM immunosorbent agglutination assay (ISAGA). The specificity and reproducibility of all three assays based on filter paper eluate was satisfactory. The sensitivity of testing eluates was 10 IU by the dye test and 53 EIU by IgM ELISA. IgM ISAGA findings, using eluate or sera, were comparable. Seroprevalence studies of congenital toxoplasmosis can be based on IgM measurement by ISAGA using eluates of filter paper stored infants' blood. Dye test and IgM ISAGA testing of eluate can be used to reduce the frequency of venepuncture when investigating infants for suspected congenital toxoplasmosis.

Animals↗

New prospects in immunology of toxoplasmosis: skin-tests for control of immunity and immuno-assays and agglutination tests for the detection of specific IgM antibodies.

An excretory-secretory (ES) antigen was extracted from supernatants of cell cultures infected with Toxoplasma gondii, purified and controlled according to current standards. In 638 volunteers, the correlation with fluorescent antibody was 94.2% and no false positive skin tests were noted. The skin test did not transform an originally negative serological test into a positive one. For the prevention of congenital toxoplasmosis, this sensitive, specific and inexpensive skin test can be widely used for the detection of immunity to Toxoplasma in women before their first pregnancy. During pregnancy, the detection of specific IgM is very important for the diagnosis of a recently acquired toxoplasmosis and allows for an immediate treatment. For this detection and for the diagnosis of congenital toxoplasmosis, five different serological tests were compared: Indirect Fluorescent Antibody-test (IFA), ELISA test, ELISA test After Capture of IgM (ACCAs), Reverse Enzyme Immuno Assay R-EIA), Double-Sandwich Enzyme Linked ImmunoSorbent Assay (DS-ELISA) and ImmunoSorbent AGglutination Assay (ISAGA). For 37 sera of recently acquired toxoplasmosis, IgM were detected in 98.7% with ISAGA, in 89.5% with DS-ELISA and ELISA in 83% with R-EIA and in 59% with IFA test. The best specificity is obtained with ISAGA, DS-ELISA and R-EIA, from controls with non immune patients (99 cases), patients with chronic toxoplasmosis (77 sera), rheumatoid factors (35 sera) or anti-nuclear antibodies (7 sera). In 21 sera from infants with congenital toxoplasmosis, ISAGA was positive in 13 cases (62%), IFA in 5 cases (24%), ELISA and R-EIA in 2 cases (9.5%) and DS-ELISA in 9 cases (43%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Diagnostic significance of immunoglobulin M antibodies to Toxoplasma gondii detected after separation of immunoglobulin M from immunoglobulin G antibodies.

Failure to demonstrate immunoglobulin M (IgM) antibodies by indirect immunofluorescence (IgM-IFA) in sera from some patients with acute acquired toxoplasmosis has recently been attributed to an inhibitory effect of high titers of IgG antibodies in these sera (Pyndiah et al. J. Clin. Microbiol. 9:170-174, 1979). To confirm these findings and define their importance for diagnosis, we used gel filtration to separate IgM from IgG antibodies in a series of sera that were negative in the IgM-IFA test. A total of 68 sera were from patients with acquired toxoplasmosis, 13 were from uninfected adults, 13 were from infants with congenital toxoplasmosis, and 7 were from uninfected neonates. Of the 68 sera from patients with acquired toxoplasmosis, IgM preparations (from the separated sera) were positive in the IgM-IFA test in 36 (53%). There was a significant (P = 0.00003) association between high titers of IgM-IFA antibodies in the IgM preparations (corrected for dilution of IgM antibodies by the gel filtration procedure) and recent acquisition of infection. IgM antibodies were also detected in 5 (38%) of the IgM preparations of 13 sera from congenitally infected infants but not in any of the IgM preparations of sera from uninfected neonates. IgG antibodies to Toxoplasma gondii were shown to interfere with demonstration of IgM antibodies in the IgM-IFA test. Treatment of sera with protein A resulted in greater dilution of IgM antibodies and less efficient separation of IgM from IgG antibodies than did separation of sera by gel filtration. Treatment of sera with protein A did not result in increased detection of IgM antibodies to T. gondii. Testing of IgM preparations (obtained by gel filtration) resulted in a significant increase in sensitivity of the IgM-IFA test for the diagnosis of recently acquired and congenital toxoplasmosis.

Adult↗