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An enzyme-linked immunosorbent assay for detection of IgM antibodies to Toxoplasma gondii: use for diagnosis of acute acquired toxoplasmosis.

In an enzyme-linked immunosorbent assay (ELISA) for detection of IgM antibodies to Toxoplasma gondii, sera from individuals with negative results in the Sabin-Feldman dye test (DT) and sera from individuals with chronic toxoplasma infection all yielded negative results, even when tested undiluted. In contrast, of sera obtained from individuals with recently acquired toxoplasmosis, all sera that gave positive results in both the DT and the IgM-immunofluorescent antibody (IgM-IFA) test and 92.8% of sera that gave negative results in the IgM-IFA test yielded strongly positive results in the IgM-ELISA. Thus, the IgM-ELISA is more sensitive than the IgM-IFA test in the diagnosis of recently acquired infection with T. gondii. Moreover, sera that gave negative results in the DT but that contained either antinuclear antibodies or rheumatoid factor and thus caused false-positive results in the IgM-IFA test all yielded negative results in the IgM-ELISA, probably because serum IgM and IgG fractions were separated during the initial step.

Acute Disease↗

Toxoplasmosis acquired during pregnancy: improved serodiagnosis based on avidity of IgG.

Serodiagnostic methods were evaluated in prenatal screening for primary Toxoplasma infections acquired during pregnancy in the Helsinki area. Altogether 44,181 sera were obtained consecutively during each trimester from 16,733 mothers. All IgG-containing samples were first examined by a sensitive mu-capture (IgM) ELISA, and positive results were reassessed by IgM immunoblotting and indirect IgM ELISA. An assay measuring the avidity of toxoplasma IgG was used for the first time under screening conditions. Patients suspected to have recent toxoplasmosis were reexamined by IgA ELISA and selectively by the differential agglutination assay (HS/AC test) and IgE ELISA; 16 women with diagnostic increases in IgG titer, 36 with IgM fulfilling strict specificity criteria, and 25 with IgG of low avidity were identified. The measurement of IgG avidity was a highly specific and sensitive method suitable for verification of acute primary Toxoplasma infections during pregnancy.

Agglutination Tests↗

Response to treatment for an intracellular infection in a T cell-deficient host: toxoplasmosis in nude mice.

To examine the experimental basis of treatment failures in T cell-deficient patients with intracellular infections, euthymic and athymic (nude) BALB/c mice were infected with Toxoplasma gondii and treated with sulfadiazine. All euthymic and nude mice survived during 2 weeks of sulfadiazine therapy. Once treatment was discontinued, 100% of euthymic mice survived while all nude mice died. Post-sulfadiazine treatment survival was enhanced in nude mice by reconstitution with either L3T4+ or Lyt-2+ cells and was reduced in euthymic mice by monoclonal antibody treatment directed at depleting either L3T4+ or Lyt-2+ cells or interleukin-2 (IL-2) or interferon-gamma (IFN-gamma). These results suggest that although T cells and their products are not required for an initial response (survival) to treatment in acute experimental toxoplasmosis, survival off drug is strictly T cell-dependent. Optimal posttreatment survival appears to involve both L3T4+ helper and Lyt-2+ cytotoxic cells, probably acting in concert, as well as the endogenous secretion of at least two T cell-derived lymphokines, IL-2 and IFN-gamma.

Animals↗

Evaluation of the efficacy of prolonged administration of azithromycin in a murine model of chronic toxoplasmosis.

The efficacy of prolonged administration of azithromycin was evaluated in a murine model of lethal chronic toxoplasmosis. Mice were challenged intraperitoneally with cysts of a moderately virulent strain of Toxoplasma gondii, observed for 4 weeks and then allocated to the treatment or control group. All 26 animals given azithromycin 100 mg/kg/day for 100 days were protected compared with 19 of 25 control animals which died (P < 0.001). Nineteen of the 20 mice in the treatment group survived for an additional month while receiving the same azithromycin regimen but viable cysts were identified in the brain tissue of these animals when they were killed. Although there was no significant difference between the groups in terms of the number of cysts in the brain, the administration of azithromycin was associated with a reduction in brain inflammation. The concentrations of azithromycin in the brains of five animals ranged from 0.7 to 2.3 micrograms/g; there was no evidence of accumulation even after 100 doses. Azithromycin merits further evaluation as primary or secondary prophylaxis against toxoplasma encephalitis in individuals at risk of developing this complication.

Animals↗

Marked variation in pyrimethamine disposition in AIDS patients treated for cerebral toxoplasmosis.

We have characterized the disposition of pyrimethamine in 20 adults with advanced AIDS. After the first dose, the area under concentration versus time curves (corrected for dose-size) varied 13-fold. This marked variation in drug levels was also noted during accumulation towards steady-state: pyrimethamine levels were consistently below the suggested lower end of the therapeutic range (750 mg/L) in three severely ill patients with perturbed consciousness (two of whom received the drug by nasogastric tube). Possible mechanisms for these observations are discussed. Pyrimethamine levels may be an important determinant of the rate of response to treatment by AIDS patients with toxoplasmosis: therapeutic drug monitoring may have a role.

Acquired Immunodeficiency Syndrome↗

Evaluation of two inhibitors of invasion: LY311727 [3-(3-acetamide-1-benzyl-2-ethyl-indolyl-5-oxy)propane phosphonic acid] and AEBSF [4-(2-aminoethyl)-benzenesulphonyl fluoride] in acute murine toxoplasmosis.

We examined the effect of an inhibitor of secretory phospholipase A2 type II (LY311727) and of a specific inhibitor of serine proteases (AEBSF) in a murine model of acute toxoplasmosis. LY311727 did not afford any significant protection and produced earlier mortality compared with untreated mice at a dose of 100 mg/kg. In contrast, AEBSF demonstrated a significant increase in length of survival, and this effect was enhanced when AEBSF was administered with non-protective doses of pyrimethamine.

Animals↗

Modeling age- and time-specific incidence from seroprevalence:toxoplasmosis.

New forms of catalytic epidemic models were developed to estimate the incidence of primary toxoplasmosis infection from age- and time-specific seroprevalence data collected from persons aged 0-100 years in South Yorkshire, England, 1969-1990. Piecewise constant and exponential polynomial functions were used to assess the way in which incidence depended on age and time, and to guide the choice of parametric models suitable for prediction. Incidence estimates were biased unless both age- and time-dependence were allowed for. New findings on the epidemiology of this infection emerged. Incidence appears to have fallen sixfold between 1915 and 1970, but has remained stable for the last 20 years. There is a marked peak in incidence in childhood. The incidence throughout the childbearing period is currently estimated to be 0.07 or less per 100 susceptible persons per year. However, these predictions were highly sensitive to assumptions about incidence in childhood, and the 95% confidence limits for a range of models were between 0.003 and 0.32% per year. Age- and time-specific seroprevalence data can be collected inexpensively on a mass population basis, and, with appropriate incidence modeling, may prove to be a powerful method for the study of infectious disease and for incidence prediction.

Adolescent↗

Diagnosis of cerebral toxoplasmosis using fluorescein-labeled antitoxoplasma monoclonal antibodies.

The direct immunofluorescence technique using monoclonal antitoxoplasma antibodies was used to detect Toxoplasma organisms in 13 brain touch preparations and six smears of cerebrospinal fluid. For comparison, Giemsa-stained smears and histologic sections of the same cases were also studied. Positive results were obtained from two cases of acquired immunodeficiency syndrome (AIDS) with all three methods. Toxoplasma cysts, pseudocysts, and tachyzoites were easily identified by the immunofluorescence technique, and no false-positive results were encountered in nine cases of AIDS with different kinds of encephalitides. It was difficult to identify tachyzoites in histologic sections and time-consuming to search for pseudocysts and cysts. The parasite was even more difficult to recognize in Giemsa-stained brain touch preparations due to the easy distortion of the organisms. In the present study, immunofluorescence technique was more sensitive than hematoxylin--eosin or Giemsa staining in terms of the number and range of forms demonstrated in tissue. Therefore, immunofluorescence technique using monoclonal antibodies appears to be the preferred method for a rapid diagnosis of cerebral toxoplasmosis as compared to Giemsa staining and histology.

Antibodies, Monoclonal↗

Sulphadiazine desensitization in patients with AIDS and cerebral toxoplasmosis.

The objectives of this study were to evaluate the efficacy of a sulphadiazine desensitization protocol to treat patients with AIDS and cerebral toxoplasmosis (CT) and known sulphonamide allergy, to ensure that an adequate dose of sulphadiazine (2-4 g/day) was achieved rapidly (within 4-5 days), and to assess the effect of concurrent corticosteroid (CS) administration on the success rate of the regimen. Sixteen patients with CT and a past history or current manifestations of sulphonamide allergy were desensitized to sulphadiazine from October 1988 to December 1989. The protocol employed the oral administration of gradually increasing increments of sulphadiazine 3-hourly over 5 days. Success was defined as tolerance of 2-4 g oral sulphadiazine per day for at least 7 days until death or the present time without any allergic reactions. Our success rated overall was 10 out of 16 patients (62%). Seven patients achieved a final dose of 4 g/day and three a dose of 2 g/day. Concurrent CS administration did not appear to affect the outcome in the small number of patients studied. Our sulphadiazine regimen rapidly, successfully and safely desensitized patients with CT and sulphonamide allergy, allowing the optimal first-line treatment to continue. The aetiology of allergy in HIV-infected patients and the mechanisms by which desensitization works are unknown.

Acquired Immunodeficiency Syndrome↗

Tc-99m colloid lung uptake in a rare case of toxoplasmosis with liver involvement.

Intensive lung accumulation of colloid (Tc-99m phytate) was demonstrated in a child suffering from acquired toxoplasmosis with a rare manifestation of severe liver damage. The possible mechanism and clinical importance of colloid lung concentration in this case is briefly discussed, including a review of the literature on this subject.

Child, Preschool↗

Cerebral toxoplasmosis in the adult.

We report a case of cerebral toxoplasmosis in an adult patient. The diagnosis was established by demonstration of Toxoplasma gondii in the cerebrospinal fluid, and the patient was evaluated by computed tomography.

Adult↗

Computed tomography in the evaluation of congenital cerebral toxoplasmosis.

This report deals with the contribution of computed tomography (CT) to the diagnosis of congenital toxoplasmosis in two infants. Computed tomography revealed diffuse hydrocephalus and confirmed the periventricular nature of the brain calcifications. The clinical, radiographic, and CT findings are discussed.

Brain Diseases↗

Hyperdense CT foci in treated AIDS toxoplasmosis encephalitis: MR and pathologic correlation.

Five AIDS patients with previously diagnosed and treated toxoplasmosis presented with hyperdense precontrast CT approximately 6 months after the CNS infection. An MR study was performed in all cases. The CT hyperdensities were characterized on MR by a high signal intensity on T1 images in four cases. In two of these, pathological correlation confirmed hemorrhage. In the fifth case, MR findings were consistent with calcification, which was verified by pathological examination.

Acquired Immunodeficiency Syndrome↗

Coincidence of congenital toxoplasmosis and biliary atresia in an infant.

A 4-week-old infant presenting with neonatal cholestasis was found to have congenital toxoplasmosis and biliary atresia. This is the first patient in which their coincidence is reported. Because biliary atresia can coexist with either congenital infection or inborn errors of metabolism, evaluation for an obstructive etiology of jaundice in infants with a recognized cause of intrahepatic cholestasis is necessary.

Biliary Atresia↗

Acute acquired toxoplasmosis.

A case of acute acquired toxoplasmosis presenting as a fever of unknown origin is described in a 62-year-old man. The diagnosis was prompted by the presence of Toxoplasma gondii in lymph nodes obtained at abdominal laparotomy. The unusual features of the case include the patient's age, the presence of cysts in the lymph node, and itc clinical presentation as a prolonged remittent fever.

Acute Disease↗

Disseminated toxoplasmosis as a cause of diarrhea.

Disseminated toxoplasmosis in patients with acquired immunodeficiency syndrome is often a central nervous system disease but may be seen as myocarditis or pneumonitis. Toxoplasmic colitis is a rarity. We report a case of toxoplasma colitis in a patient with diarrhea and hypokalemia. The microorganisms were identified in the colonic mucosa on H&E sections and confirmed by immunoperoxidase study.

Adult↗

Congenital toxoplasmosis in twins: a report of fourteen consecutive cases and a comparison with published data.

BACKGROUND: The combined influence of congenital toxoplasmosis and twin pregnancy on the duration of gestation has not been previously examined. Similarly little is known about the influence of genetic factors on the clinical course of this disease. The present study addresses these issues. PATIENTS AND METHODS: Fourteen consecutive twin pairs born of mothers with Toxoplasma seroconversion during pregnancy were monitored after birth and during childhood, and the relevant data were compared with those already documented for similar cases. RESULTS: The presumed time of gestation at which women became infected was earlier in noninfected than in infected twins (P = 0.007). Congenital infection did not influence the duration of pregnancy either in our own cases [36.2 +/- 4.3 weeks for noninfected children and 37.4 +/- 1.8 weeks for infected ones (P = 0.45)] or in previously published ones [35.4 +/- 3.6 weeks (P = 0.69)]. The infection status was identical for monozygotic twins (with one exception) but different for dizygotic ones (19 of 20 vs.35 of 45 cases). The clinical course through childhood corresponded more closely for monozygotic twins than for dizygotic ones [17 of 20 vs.20 of 45 cases (P = 0.007)]. CONCLUSION: Twin pregnancy is not a risk factor either for premature birth or for Toxoplasma infection in contaminated twins. The closely corresponding infection status between monozygotic twins highlights the crucial role played by the placenta in disease transmission. However, the substantial proportion of discrepant clinical courses suggests that other, as yet unknown, factors may be involved.

Adult↗