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PubMed1997

Radiological signs in newborns exposed to primary Toxoplasma infection in utero.

A total of 44 181 serum samples from 16 733 pregnant women were analyzed for findings suggesting primary Toxoplasma infection. Thirty-seven newborns exposed to maternal primary Toxoplasma infection in utero were studied prospectively with ultrasound, CT, and MRI for signs of intrauterine infection. Their mothers had been treated during pregnancy, and all infants were treated. The children were assigned to three groups according to their mothers' serological status, and the radiological results were compared with the clinical outcome. Although radiological signs were scarce, ultrasound findings combined with maternal serology were found to be significantly related to clinical outcome.

Abdomen↗
PubMed1999

Kinetics and differential expression of heat-stable antigen and GL7 in the normal and Toxoplasma gondii-infected murine brain.

The co-expression of various cell surface molecules by cells of the nervous system and the immune system is a remarkable feature. To identify novel molecules that are shared between cells of the neural and hematopoietic lineage, the expression and regulation of heat-stable antigen (HSA, CD24, nectadrin) and GL7, two hematolymphoid differentiation antigens that are involved in antigen presentation, cell adhesion, signal transduction and activation, was studied in the adult normal and Toxoplasma gondii-infected murine brain by immunohistochemistry and flow cytometry of isolated cerebral leukocytes. In the normal brain ependymal cells, plexus macrophages and a fraction of blood vessel endothelial cells were HSA positive (+), whereas the choroid plexus epithelium was GL7+. This basal expression of HSA and GL7 was not further modified on these cell populations in Toxoplasma encephalitis (TE). In acute and chronic TE, HSA and GL7 were strongly induced on resident brain cells, and activated astrocytes were the predominant HSA+ and GL7+ cell type. FACS analysis additionally identified a minor fraction of HSA+ microglia in the normal brain with a small, but significant increase in TE. The differential expression pattern of HSA and GL7 on distinct resident cell populations in various anatomic compartments of the normal adult brain and their up-regulation in TE may indicate that their intracerebral role is diverse and may include both immunological as well as non-immunological functions.

Animals↗
PubMed1985

Macrophage-mediated suppression of immune responses in Toxoplasma-infected mice. II. Both H-2-linked and -nonlinked control of induction of suppressor macrophages.

The suppressive effect of Toxoplasma infection on initiation of memory cells to dinitrophenylated keyhole limpet hemocyanin (DNP-KLH) was drastically different among inbred strains of mice. C57BL/6 (B6), C57BL/10 (B10), and SJL mice showed markedly suppressed secondary anti-DNP responses when infected. In contrast, the suppression did not occur in BALB/c mice. The infected DBA/2 and C3H/He mice produced moderately suppressed responses. In B6 mice, an injection with 1 X 10(2) organisms of T. gondii induced a suppressed elicitation of the memory cells to DNP-KLH. However, in BALB/c mice, the responses were not affected even by inoculation with 1 X 10(4) organisms. The difference in the suppressive effect of infection between B6 and BALB/c mice was also observed in the primary anti-DNP antibody responses to DNP-KLH. Both H-2-linked and -nonlinked genes appeared to be responsible for the regulation of the immunosuppression, since the suppressive effect of infection in B10.D2 mice, which have the B10 background and the same H-2 haplotype as BALB/c, was weaker than that of B10 mice, but stronger than in BALB/c mice. In vitro studies using a primary anti-sheep erythrocytes (SRBC) antibody response system demonstrated that the activation of plastic-adherent suppressor cells by Toxoplasma infection, in which suppressor macrophages have been proved to be the responsible cells for the suppressive activity, was controlled by both H-2-linked and -nonlinked genes.

Animals↗
PubMed1993

Experimental infection with Toxoplasma gondii in farmed mink (Mustela vison S.).

Live Toxoplasma gondii tissue cysts (Strain 119) were administered orally to five mink (Mustela vison S.) and five mink were inoculated with a suspension of ultrasonicated Toxoplasma gondii trophozoites (RH-strain). Seroconversion was observed in all animals administered live T. gondii cysts indicating that infection was established. Likewise seroconversion was observed in three out of four animals administered ultrasonicated T. gondii trophozoites. Faecal shedding of oocysts of T. gondii was not demonstrated in any of the infected animals. Histologically chronic meningitis with calcification was seen in all animals. Cerebral T. gondii tissue cysts were detected in four animals administered live tissue cysts. The study demonstrates that mink can be experimentally infected with T. gondii, thus representing a potential infection source for man, when considering the pelting procedure.

Animals↗
PubMed2004

Acute acquired toxoplasma retinitis may present similarly to unilateral acute idiopathic maculopathy.

PURPOSE: To describe a patient with acquired toxoplasma retinitis that shared similarities with unilateral acute idiopathic maculopathy. DESIGN: Interventional case report. METHODS: Interventional case report. RESULTS: A 39-year-old woman presented with sudden unilateral vision loss in the right eye after a flu-like illness. She had retinitis involving the fovea, subretinal fluid, thickening of the retinal pigment epithelium, and a few vitreous cells; the retinitis resolved with antitoxoplasma antibiotic treatment. CONCLUSIONS: Acute acquired toxoplasma retinitis may present similarly to unilateral acute idiopathic maculopathy.

Acute Disease↗
PubMed2005

Seroprevalence of Toxoplasma gondii infection among pre-schoolchildren aged 1-5 years in the Democratic Republic of Sao Tome and Principe, Western Africa.

The prevalence status of Toxoplasma gondii infection in children of the Democratic Republic of Sao Tome and Principe (DRSTP), Western Africa, is unknown to date. A serologic survey of T. gondii infection among pre-schoolchildren aged <5 years in the DRSTP was assessed by the latex agglutination (LA) test from November 2003 to March 2004. The overall seroprevalence of T. gondii infection was not low, reaching 21.49% (26/121). No significant gender difference in seroprevalence was found between boys (19.30%; 11/57) and girls (23.44%; 15/64) (chi2 = 0.31, P = 0.58). The older age group of 4-5 years had significantly higher seroprevalence (36.67%; 11/30) than the younger age group of <2 years (10.34%; 3/29) (chi2 = 5.64, P = 0.02). It was noteworthy that the majority of seropositive boys (90.91%; 10/11) or older children aged > or = 2 years (82.61%; 19/23) had high LA titres of > or = 1:1024, indirectly indicating acute Toxoplasma infection. This study is the first report indicating that T. gondii infection is not low in pre-schoolchildren aged <5 years in the DRSTP. Whether the DRSTP pre-schoolchildren acquire T. gondii infection through constant exposure to the parasite from their daily activities owing to poor environmental hygiene should be further evaluated.

Africa, Western↗
PubMed1996

Depression of the N-demethylation of erythromycin, azithromycin, clarithromycin and clindamycin in murine Toxoplasma infection.

The N-demethylation of macrolides was studied in a murine model of infection. Mice were infected with a cystogenic strain of Toxoplasma gondii (20 or 40 cysts/mouse) and microsomes were prepared from liver homogenates and jejunum villus tip enterocytes on day 10 post-infection. The rate of N-demethylation of the anti-Toxoplasma macrolides azithromycin, clarithromycin and clindamycin was investigated and compared to that of the macrolide erythromycin, a marker of activity of the cytochrome P-450 3A (CYP3A) mono-oxygenases. In infected mice (20 cysts/mouse), the rate of N-demethylation fell in the liver and jejunum for erythromycin (-25% and -35%, respectively), azithromycin (-12% and -10%, respectively), clarithromycin (-23% and -21%, respectively) and clindamycin (-20% and -28%, respectively). The degree of hepatic depression was more marked in mice receiving a 40-cysts burden: for erythromycin (-54%), azithromycin (-29%), clarithromycin (-49%) and clindamycin (-47%).

Animals↗
PubMed1999

HLA-class II genes modify outcome of Toxoplasma gondii infection.

Associations between Human Leukocyte Antigen (HLA) (i.e. human major histocompatibility complex [MHC]) genes and susceptibility to infections and inflammatory processes have been described, but causal relationships have not been proven. We characterized effects of HLA-DQ alleles on outcome of congenital toxoplasma infection and found that among Caucasians, the DQ3 gene frequency was significantly higher in infected infants with hydrocephalus (0.783) than infected infants without hydrocephalus (0.444) or published normal controls (0.487). We then developed a novel animal model to definitively determine the effect of these HLA DQ molecules on the severity of toxoplasmosis. Human MHC-Class II transgenes reduced parasite burden and necrosis in brains of mice infected with Toxoplasma gondii. Consistent with the observed association between DQ3 and hydrocephalus in human infants, in the murine model the DQ3(DQ8; DQB1*0302) gene protected less than DQ1 (DQ6; DQB1*0601). Our findings definitively prove a cause and effect relationship between human MHC genes and resistance to infection, provide novel means to characterise human immune responses that are protective or pathogenic in infections, and are important for vaccine development.

Animals↗
PubMed1996

Mycotoxin T-2 and aflatoxin B1 as immunosuppressors in mice chronically infected with Toxoplasma gondii.

The aim of this study was to determine whether repeated ingestion of mycotoxin T-2 (T2) or aflatoxin B1 (AFL) at low doses could contribute to the activation of toxoplasmosis in experimentally infected mice. Mice were divided into two groups: Control (C) and Infected (I). The cyst-forming Beverley strain of Toxoplasma gondii was used to produce the infection one month before treatment with mycotoxins. Mycotoxins were given intragastrically for a 50-day period. The average weight gain was reduced in the groups treated with mycotoxins. Mice developed specific IgG to T. gondii. Histopathological studies showed severe encephalitis in all groups infected. The number of unruptured and ruptured cysts was established and the severity of the lesions was evaluated, the groups treated with mycotoxins being the most severely affected. Immunohistochemical studies of the brain showed free antigen in tissues surrounding ruptured cysts. It is suggested that low and repeated doses of mycotoxins, necessary to produce a subclinical intoxication, precipitate Toxoplasma cyst rupture and consequently the activation of chronic toxoplasmosis.

Aflatoxin B1↗
PubMed1984

Toxoplasma cyst with toxoplasmic lymphadenitis.

A toxoplasma cyst and the distinctive histopathologic changes of toxoplasmic lymphadenitis in a non-immunosuppressed patient with acute acquired toxoplasmosis are described. This is the third reported case in which the cyst form of toxoplasma has been observed in nodal tissue, and the first to be confirmed by electron microscopy.

Adult↗
PubMed1996

Response to oral and intravenous azithromycin in a patient with toxoplasma encephalitis and AIDS.

We present a patient with AIDS and toxoplasma encephalitis who was unable to tolerate established therapy with sulphadiazine or clindamycin but responded to oral azithromycin and pyrimethamine. The patient was maintained on oral azithromycin but subsequently relapsed after 8 months. The recurrence was successfully treated with intravenous azithromycin. The case illustrates that azithromycin can be used to treat patients with toxoplasma encephalitis who are unable to tolerate or fail to respond to other therapeutic agents. Failure of oral azithromycin may be due to inadequate tissue concentrations and patients may further benefit from intravenous administration.

AIDS-Related Opportunistic Infections↗
PubMed1997

Interleukin-10 downregulates the intracerebral immune response in chronic Toxoplasma encephalitis.

The expression of the immunosuppressive cytokine interleukin (IL)-10 in the normal and Toxoplasma gondii-infected murine brain was analysed. Microglia/macrophages expressed IL-10 at the mRNA and protein level in the normal brain. In Toxoplasma encephalitis (TE), CD4+ and CD8+ T-cells also contributed to the upregulated IL-10 production. Neutralization of endogenous IL-10 in chronic TE reduced the intracerebral parasitic load and increased the number of immune cells and the production of protective cytokines. These findings indicate that intracerebral expression of IL-10 interferes with the immune response in TE and may contribute to parasite persistence in the brain.

Animals↗
PubMed1997

Speculation on possible life cycles for the clonal lineages in the genus toxoplasma.

Recent evidence suggests that the strains currently classified in the genus Toxoplasma, ie. within the species Toxoplasma gondii, may actually comprise at least two clonal lineages correlated with their virulence in mice. Here, Alan Johnson reviews these data in the context of evolution and speciation within the genus, and raises hypotheses on how the virulent lineage may undergo an asexual life cycle in nature, similar to that found for the very closely related coccidian, Neospora camnum. The putative vertical transmission life cycle of this mouse virulent lineage of T. gondii could involve passage to the foetus late in pregnancy, or transmission in milk to the neonate after birth.

Journal Article↗
PubMed1998

Double maternal seroconversion to cytomegalovirus and Toxoplasma gondii.

BACKGROUND: We report the first case of a double maternal seroconversion for Toxoplasma gondii (TG) and cytomegalovirus (CMV) diagnosed during pregnancy. CASE: One case is reported of a female patient referred for seroconversion in response to TG in the 27th week of gestation. A search for foetal involvement revealed signs of non-specific foetal infection without any TG-related lesions. Tests were carried out for another foeto-maternal infectious disease and maternal seroconversion in response to CMV was discovered with virus in the amniotic fluid. The foetus developed hydrocephalus and intracranial calcifications and the pregnancy was terminated at the parents' request. CMV-induced multiple organ involvement without any signs of Toxoplasma gondii-related involvement were noted in the foetus. CONCLUSIONS: This case indicates that a search should be made for another infectious disease likely to involve the foetus when non-specific signs of infection in the foetus are present, even though maternal seroconversion has been recognized.

Adult↗
PubMed2003

Effect of timing and type of treatment on the risk of mother to child transmission of Toxoplasma gondii.

OBJECTIVE: To determine the effects on mother to child transmission of the timing and type of prenatal treatment, taking into account gestational age at maternal seroconversion. DESIGN: Prospective cohort study. SETTING: European centres offering prenatal screening for toxoplasmosis. POPULATION: Children born to a cohort of pregnant women with toxoplasma infection. METHODS: We determined the effects on mother to child transmission of the interval between seroconversion and start of treatment (treatment delay), and the type of treatment, taking into account gestational age at maternal seroconversion. MAIN OUTCOME MEASURE: Congenital infection status confirmed by toxoplasma IgG results at one year postnatal age. RESULTS: Of 1208 women analysed, 72% were first prescribed spiramycin, 19% pyrimethamine-sulphonamide and 9% (mostly infected during the last trimester) were untreated. The odds ratios for mother to child transmission for all women treated after a delay of four to seven weeks was 0.77 (95% CI 0.34-1.69), and after eight weeks or more was 1.33 (0.56-2.89) compared with less than four weeks. The odds ratio per week of treatment delay was 1.01 (0.93-1.08). There was no evidence that transmission risk differed in women first treated with pyrimethamine-sulphonamide versus spiramycin: odds ratio 1.10 (0.63-1.91) or in untreated versus treated women: odds ratio 0.57 (0.27-1.17). CONCLUSION: We were unable to demonstrate a beneficial effect of the timing or type of prenatal treatment on the risk of mother to child transmission but we could not exclude a clinically important effect. Randomised controlled trials are required to determine the effect of prenatal treatment on mother to child transmission.

Adult↗
PubMed1999

Incidence of symptomatic toxoplasma eye disease: aetiology and public health implications.

Ocular disease is the commonest disabling consequence of toxoplasma infection. Incidence and lifetime risk of ocular symptoms were determined by ascertaining affected patients in a population-based, active reporting study involving ophthalmologists serving a population of 7.4 million. Eighty-seven symptomatic episodes were attributed to toxoplasma infection. Bilateral visual acuity of 6/12 or less was found in seven episodes (8%) and was likely to have been transient in most cases. Black people born in West Africa had a 100-fold higher incidence of symptoms than white people born in Britain. Only two patients reported symptoms before 10 years of age. The estimated lifetime risk of symptoms in British born individuals (52% of all episodes) was 18/100000 (95% confidence interval: 10.8-25.2). The low risk and mild symptoms in an unscreened British population indicate limited potential benefits of prenatal or postnatal screening. The late age at presentation suggests a mixed aetiology of postnatally acquired and congenital infection for which primary prevention may be appropriate, particularly among West Africans.

Adolescent↗
PubMed1998

Risk factors for Toxoplasma infection in a reproductive age female population in the area of Belgrade, Yugoslavia.

The contribution to Toxoplasma infection of known transmission risk factors such as consumption of undercooked meat, contact with soil, and contact with cats, as well as that of age, degree of education, residence in central vs. suburban city communities, and year of entry into the study, has been investigated in a group of 1157 female residents (age range 15 to 45 years) of a defined geographic area (Belgrade) during a 4-years period (1988-1991). The rate of infection increased with age, ranging from 57% to 93%, with an overall mean of 77%. However, it decreased significantly over the study period (p < 0.01). Of the potential risk factors examined, regression analysis showed that the following: age (relative risk (RR): 1.18, 95% confidence interval (CI): 1.02-1.37, p = 0.022), undercooked meat consumption (RR: 2.22, 95% CI: 1.2-2.86, p = 0.001), and the year of entry into the study (RR: 0.69, 95% CI: 0.6-0.8, p = 0.000) were significantly associated with infection. However, while the consumption of undercooked meat contributed to the frequency of infection in the whole group, its significance increased with the degree of education but decreased with age, and was greater in women residing in the suburbs. In addition, in women below age 20, exposure to soil (farming, gardening) was significantly associated with infection (RR: 1.38, 95% CI: 1.12-1.97, p = 0.037). Since cats are the single source of toxoplasma oocysts, the above finding indicates that cats are an epidemiologically significant source of environmental contamination in Belgrade. However, cat ownership itself as a criterion of contact with cats was not associated with infection (p = 0.326). In the absence of a general screening in pregnancy program in Yugoslavia, these data point out the groups of pregnant women at the highest risk of infection and provide a basis for a region-appropriate educational program to prevent congenital toxoplasmosis.

Adolescent↗