Disseminated toxoplasmosis following T cell-depleted related and unrelated bone marrow transplantation.
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More than 95% of reported cases of disseminated toxoplasmosis following BMT have occurred following an unmodified transplant. Most have been fatal, diagnosed at autopsy and without antemortem institution of specific therapy. From 1989 to 1999, we identified 10 cases of disseminated toxoplasmosis, in 463 consecutive recipients of a T cell-depleted (TCD) BMT. Transplants were from an unrelated donor (n = 5), an HLA-matched sibling (n = 4) or an HLA-mismatched father (n = 1). In 40%, both the donor and recipient had positive IgG titers against T. gondii pre-transplant; in 30%, only the recipient was sero-positive. Three recipients of an unrelated TCD BMT developed toxoplasmosis despite both donor and host testing negative pretransplant. All 10 patients presented with high grade fever. CNS involvement ultimately occurred in seven patients, with refractory respiratory failure and hypotension developing in nine. Eight of 10 cases were found only at autopsy, involving the lungs (n = 7), heart (n = 5), GI tract (n = 5), brain (n = 8), liver and/or spleen (n = 5). The only survivor, treated on the day of presentation with fever and headache, was diagnosed by detection of T. gondii DNA by polymerase chain reaction (PCR) performed on the blood and spinal fluid. This study demonstrates the similar incidence of toxoplasmosis following TCD BMT and that reported post T cell-replete BMT, and underscores the need for rapid diagnostic tests in an effort to improve outcome. (+info)
Discrimination between patients with acquired toxoplasmosis and congenital toxoplasmosis on the basis of the immune response to parasite antigens.
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Many persons infected with Toxoplasma gondii develop ocular lesions. Immunologic parameters in the response to T. gondii were evaluated in infected persons with and without ocular lesions and in noninfected controls. Subjects were divided into groups on the basis of presence of serum antibodies to T. gondii, presence of ocular lesions, and clinical history. Production of interleukin-2 and interferon-gamma by peripheral blood mononuclear cells from patients with probable congenital toxoplasmosis was decreased, compared with that in persons with presumed acquired infection. Cell proliferation and delayed-type skin reaction induced by soluble toxoplasma tachyzoite antigen followed the same pattern. Asymptomatic persons showed high levels of interleukin-12 and interferon-gamma, whereas persons with ocular lesions had high interleukin-1 and tumor necrosis factor-alpha responses toward soluble toxoplasma tachyzoite antigen. These data suggest that patients with ocular disease due to congenital infection show tolerance toward the parasite. Furthermore, susceptibility to ocular lesions after acquired toxoplasmosis is associated with high levels of interleukin-1 and tumor necrosis factor-alpha, whereas resistance is associated with high levels of interleukin-12 and interferon-gamma. (+info)
Diagnosis of toxoplasmosis in bone marrow transplant recipients: comparison of PCR-based results and immunohistochemistry.
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Toxoplasmosis in bone marrow transplant recipients is a rare but serious complication and if untreated, almost uniformly fatal. The diagnosis, however, remains difficult. We therefore compared serial determination of antibody titers specific for T. gondii before and after transplantation, serial PCR for T. gondii DNA in serum, PCR and nested PCR for T. gondii DNA in various tissues, conventional histology and immunohistochemistry for detection of parasites in three patients with autopsy-confirmed toxoplasmosis after bone marrow transplantation. Immunohistochemistry demonstrated the presence of parasites in 13 out of 20 organs investigated (65%), whereas PCR detected T. gondii-specific DNA in 15 out of 20 organs (75%). Immunohistochemistry revealed concordant results to PCR data in 60% of the specimens. With the use of a nested PCR protocol, eight out of nine samples (89%) were positive for T. gondii-specific DNA. The combination of both methods detected the presence of parasites in 90% of the specimens. Serial PCR in serum did not yield positive results. Neither PCR nor immunohistochemistry was able to detect parasites in all organs investigated, but both methods together improved sensitivity to 90% and consequently, should be used jointly to maximize diagnostic precision. Bone Marrow Transplantation (2000) 25, 1257-1262. (+info)
Enzyme-linked immunosorbent assays using the recombinant dense granule antigens GRA6 and GRA1 of Toxoplasma gondii for detection of immunoglobulin G antibodies.
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The potential of the dense granule antigens GRA1 and GRA6 of Toxoplasma gondii to be used as diagnosis reagents in a recombinant form was evaluated. Both proteins were expressed in Escherichia coli as glutathione-S-transferase (GST) fusions. The GST-GRA1 fusion comprises the entire GRA1 sequence devoid of its N-terminal signal peptide. Separate expression of the two N- and C-terminal hydrophilic regions of GRA6 showed that only the N-terminal hydrophilic part of the protein was recognized by a pool of positive human sera in an immunoblot. One hundred T. gondii-positive and 98 negative human sera were tested in two separate immunoglobulin G (IgG)-direct enzyme-linked immunosorbent assays (ELISAs) using either GST-GRA1 or GST-GRA6-Nt recombinant protein. Whereas the sensitivity of the GST-GRA1 IgG ELISA was low (68%), the GST-GRA6-Nt IgG ELISA reached a sensitivity of 96%. The reactivity to GRA6-Nt was shown to be high even with human sera of low IgG titers. In addition, comparison of the optical density values for each serum revealed that GRA1 may complement GRA6-Nt to reach an overall sensitivity of 98%. Therefore, the GST-GRA6-Nt ELISA could be used together with another antigen like GRA1 for the development of a recombinant antigen-based test for serodiagnosis of toxoplasmosis. (+info)
Lack of utility of specific immunoglobulin G antibody avidity for serodiagnosis of reactivated toxoplasmosis in immunocompromised patients.
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The avidities of Toxoplasma-specific immunoglobulin G serum antibodies were measured in immunocompromised patients presenting with cerebral or extracerebral toxoplasmosis and/or serological reactivation. Since avidity remained high and stable in 39 of 40 patients with toxoplasmosis and 27 of 28 patients with serological reactivation, we conclude that this test cannot help diagnose toxoplasmosis in these patients. (+info)
Sources of toxoplasma infection in pregnant women: European multicentre case-control study. European Research Network on Congenital Toxoplasmosis.
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OBJECTIVE: To determine the odds ratio and population attributable fraction associated with food and environmental risk factors for acute toxoplasmosis in pregnancy. DESIGN: Case-control study. SETTING: Six large European cities. PARTICIPANTS: Pregnant women with acute infection (cases) detected by seroconversion or positive for anti-Toxoplasma gondii IgM were compared with pregnant women seronegative for toxoplasma (controls). MAIN OUTCOME MEASURES: Odds ratios for acute infection adjusted for confounding variables; the population attributable fraction for risk factors. RESULTS: Risk factors most strongly predictive of acute infection in pregnant women were eating undercooked lamb, beef, or game, contact with soil, and travel outside Europe and the United States and Canada. Contact with cats was not a risk factor. Between 30% and 63% of infections in different centres were attributed to consumption of undercooked or cured meat products and 6% to 17% to soil contact. CONCLUSIONS: Inadequately cooked or cured meat is the main risk factor for infection with toxoplasma in all centres. Preventive strategies should aim to reduce prevalence of infection in meat, improve labelling of meat according to farming and processing methods, and improve the quality and consistency of health information given to pregnant women. (+info)
Seroprevalence of toxoplasmosis in the residents of Cheju island, Korea.
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This study was performed to evaluate the epidemiological status of toxoplasmosis among the residents of Cheju island. The sera of local students from 18 high schools (boys 2110, girls 2460) and those of adults (474 admitted to Cheju Chungang General Hospital) were collected and checked for the IgG antibody titers against Toxoplasma gondii. Serum samples collected from both the students and adults showed sero-positive rate of 5.5% and 12.9%, respectively. Although the rates were not significantly different between the sexes (5.4% for the boys and 5.5% for the girls attending school), the geographical difference showed a significant difference between the urban (4.6-6.9%) and rural areas (5.6-8.8%) (p < 0.05). Based on the high positive rates, it should be necessary to control toxoplasmosis in Cheju island. (+info)
Seroprevalence of Bartonella henselae and Toxoplasma gondii among healthy individuals in Thailand.
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The seroprevalence of Bartonella henselae and Toxoplasma gondii among apparently healthy individuals, mainly blood donors, in Thailand was investigated by an indirect fluorescent antibody technique and by a latex agglutination test, respectively. Of 163 serum samples examined, 9 (5.5%) were found to be positive for B. henselae-IgG, 2 (1.2%) for B. henselae-IgM, and 5 (3.1%) for the T. gondii antibody. No significant difference was observed between male and female samples in the serological test with either B. henselae or T. gondii. The age of individuals with B. henselae-IgG was distributed from the 20s to the 70s, and B. henselae-IgM was found in the individuals of the 30s and 60s. The age of T. gondii positive samples ranged from the 20s to the 60s. In this study, the prevalence of B. henselae infection among healthy individuals in Thailand was serologically demonstrated for the first time. (+info)