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PubMedDate not supplied

Possible reasons for failure of conventional tests for diagnosis of fatal congenital toxoplasmosis: report of a case diagnosed by PCR and immunoblot.

Diagnosis of subclinical congenital toxoplasmosis has to rely on serological methods or isolation of the parasite. We present a case of congenital toxoplasmosis, in which conventional tests failed to establish the diagnosis. It was shown that this infant developed an intrathecal antibody response that was directed only against one of two Toxoplasma gondii strains used for routine diagnosis. In contrast to conventional tests, the diagnosis of cerebral toxoplasmosis could be established by using immunoblot and polymerase chain reaction (PCR). We therefore suggest that in unclarified cases, PCR and immunoblot, using at least two different strains of T. gondii, should be considered as additional tools for diagnosis of an infection with Toxoplasma and that examination of cerebrospinal fluid may be critical.

Adult↗
PubMed1992

Synergistic combination of azithromycin and sulfadiazine for treatment of toxoplasmosis in mice.

Experiments were performed in vivo in a mouse model of acute toxoplasmosis to evaluate the effectiveness of the combination azithromycin/sulfadiazine. Azithromycin alone or sulfadiazine alone, at doses that did not provide any protection against death due to toxoplasmosis, were remarkably and significantly synergistic against murine toxoplasmosis when administered in combination.

Animals↗
PubMed1985

Enzyme-linked immunosorbent assay for detection of soluble Toxoplasma gondii antigen in acute-phase toxoplasmosis.

Sixty-two sera from 51 patients with lymphadenopathy presumed to be due to acute-phase toxoplasmosis were tested for specific IgM class antibodies by both the immunofluorescence antibody to Toxoplasma gondii in sera were first dissociated in 3 M NaSCN. Antigen attached to the solid phase was detected with enzyme-coupled IgG antibody to Toxoplasma antibody to Toxoplasma gondii in sera were first dissociated in 3 M NaSCN. Antigen attached to the solid phase was detected with enzyme-coupled IgG antibody to Toxoplasma gondii. Neither hepatitis B surface antigen nor antigen of Mycoplasma pneumoniae, rubella, cytomegalovirus or herpes simplex virus interfered with this ELISA. Soluble antigen was detected in 13 (30%) of 42 IgM-positive acute-phase toxoplasmosis patients and in only one of 20 sera cleared of IgM. None of an additional 44 IgM-negative patients with low IgG titres had a positive result in the antigen ELISA. Follow-up studies in four acute-phase toxoplasmosis patients showed that the soluble antigen cleared in all cases before the specific IgM antibodies. Simultaneous detection of IgM antibodies to Toxoplasma gondii and soluble antigen would thus seem to indicate an early stage of the infection.

Antibodies↗
PubMed1989

Ocular toxoplasmosis; common and rare symptoms and signs.

The common and rare symptoms and signs of congenital, childhood and adult ocular toxoplasmosis are discussed together with the differential diagnosis of the retinal lesions. A choroidal coloboma in connection with congenital toxoplasmosis is described. The occurrence of an optic pit with congenital macular toxoplasmosis, growth of subretinal new vessels as well as disappearance of arteriolar and venular sheathing is demonstrated.

Adult↗
PubMed1989

Ocular toxoplasmosis in the immunocompromised host.

Disseminated toxoplasmosis is a well-known complication of immunodeficiency states, including those induced by malignancies, steroid and cytotoxic drug therapy, and AIDS. In immunodeficient patients, toxoplasmic infections of the eye are less common than toxoplasmic infections of other organs for unknown reasons. When ocular toxoplasmosis does occur in the immunodeficient host, or if immunosuppressive therapy is administered to patients with active disease, widespread tissue destruction by proliferating organisms may result. Immunodeficiency alone may not be sufficient, however, to cause reactivation of encysted organisms in retinochoroidal scars. Ocular toxoplasmosis in the immunocompromised host presents difficult problems in diagnosis and management. There may be a variety of clinical lesions, including single foci of retinochoroiditis in one or both eyes, multifocal lesions, or diffuse areas of retinal necrosis. The majority of lesions do not arise from the borders of preexisting scars, which suggests that they result from acquired infection or dissemination of organisms from nonocular sites of disease. Toxoplasma gondii may infect iris, choroid, and vitreous-tissues that are not usually infected in the immunocompetent host. Ocular lesions appear to respond to standard antiparasitic drug therapies, but continued treatment is probably necessary to prevent reactivation of disease in the most immunocompromised patients. The best treatment regimens have yet to be determined. Histopathologic studies show little retinal inflammation; therefore anti-inflammatory drugs, such as oral steroids, probably have no role in the management of infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Prevention of Pneumocystis carinii pneumonia and of cerebral toxoplasmosis by roxithromycin in HIV-infected patients.

The prevention of cerebral toxoplasmosis and of Pneumocystis carinii pneumonia is an essential objective in the management of patients infected with HIV. Given that roxithromycin is active in vitro against Toxoplasma gondii and that in 1989 Dolermann reported the effective treatment of P. carinii respiratory infections with erythromycin, a randomized pilot study was undertaken in 52 patients infected with HIV. Patients were treated with either: a monthly dose of pentamidine aerosol (300 mg); roxithromycin once a week (300 mg t.i.d.); or a combination of pentamidine aerosol and roxithromycin. Intention to treat analysis was applied to these 52 patients, all of whom received at least one treatment dose. Five out of 18 patients treated with pentamidine aerosol, 1/17 patients treated with pentamidine aerosol + roxithromycin and none of the 17 patients treated with roxithromycin developed cerebral toxoplasmosis (p = 0.038). P. carinii pneumonia was diagnosed in one patient in the pentamidine aerosol-treated group, in one patient treated with roxithromycin and in none of the patients treated with pentamidine aerosol + roxithromycin (non-significant difference). Four cases of Mycobacterium tuberculosis and Mycobacterium avium-intracellulare infection were seen in the pentamidine aerosol-treated group (p = 0.028) and none in the roxithromycin groups. Adverse events leading to the discontinuation of treatment occurred in 5/34 (14.7%) patients treated with roxithromycin. Nausea, abdominal pain and raised transaminases occurred in four patients and a skin allergy in the final patient. Roxithromycin appears to be effective in the prevention of pulmonary pneumocystis infection and of cerebral toxoplasmosis in HIV-infected patients. However, these results require confirmation in a larger study.

AIDS-Related Opportunistic Infections↗
PubMed1999

[Acute toxoplasmosis in coexistent non-Hodgkin lymphoma].

There are many reasons for cervical lymph node enlargement. In particular, the large group of infectious diseases must be considered along with malignant diseases. The coexistence of an uncommon infectious disease with malignant disease is a rare event. We report the case of an otherwise healthy 69-year-old man with marked enlargement of his cervical lymph nodes. A diagnosis of a recent toxoplasmosis infection was made based on positive IgG and IgM toxoplasma titers and the results of fine-needle aspiration from a lymph node. Since the enlarged lymph nodes persisted for more than weeks, the lymph node was excised. Histological examination revealed a non-Hodgkin's lymphoma. IgM titers in toxoplasmosis can persist up to 1 year. In cases with rare infectious diseases like toxoplasmosis in immunocompromised patients, swollen lymph nodes that persist or grow should lead to the suspicion of additional disease. A diagnosis can be confirmed by removing a lymph node for histology.

Aged↗
PubMed2005

Imaging characteristics of toxoplasmosis encephalitis after bone marrow transplantation: report of two cases and review of the literature.

Toxoplasmosis encephalitis is a severe, but often misdiagnosed complication in patients after bone marrow transplantation (BMT). We describe the unique computed tomography (CT) and magnetic resonance (MR) imaging features of cerebral toxoplasmosis in two bone marrow recipients and compare them to the cases in the literature. To our knowledge, this is the first report analyzing the appearance of cerebral toxoplasmosis on diffusion-weighted MR imaging (DWI).

Adult↗
PubMed2002

[Ocular toxoplasmosis antibodies in aqueous humor and serum].

BACKGROUND: The diagnosis of ocular toxoplasmosis is mainly based on ophthalmological examination but might be difficult to establish in some cases. The purpose of our study was to evaluate the value of aqueous humor and serum analysis in ocular toxoplasmosis. PATIENTS AND METHODS: We analyzed the avidity of toxoplasma-specific IgG in aqueous humor and serum samples from 50 patients with toxoplasmic retinochoroiditis, with 25 patients with uveitis posterior or panuveitis serving as controls. RESULTS: Specific intraocular antibody synthesis could be confirmed in 49 patients (98%). In two patients (8%) of the control group, antibody synthesis was detected (false positive). Forty-nine patients with diagnoses of ocular toxoplasmosis were positive for serum anti-T. gondii IgG, but only three patients had increased IgM levels. CONCLUSIONS: Analysis of local antibody production is a reliable method for confirming or excluding a suspected clinical diagnosis of toxoplasma retinochoroiditis. The determination of toxoplasma antibodies in the patients' serum is of limited value.

Adolescent↗
PubMed2006

Fluorescein and indocyanine green angiography in ocular toxoplasmosis.

PURPOSE: To document fluorescein and indocyanine green angiographic findings in patients with ocular toxoplasmosis. METHODS: Charts of patients with ocular toxoplasmosis who were evaluated with fluorescein and indocyanine green angiograpy were reviewed. RESULTS: In this study, eight (38%) females and 13 (62%) males with a mean age of 20.3 years were included. Of the 21 patients, five (24%) had bilateral involvement with active or inactive toxoplasmic lesion. There were active lesions in 12 (46%) eyes and inactive lesions in 14 (54%) eyes. Indocyanine green angiograpy showed hypofluorescence of the active and inactive retinochoroiditis lesions at all phases. Hypofluorescent multiple satellite dark dots were observed in 11 (92%) eyes with active retinochoroiditis and in two (14%) eyes with inactive lesions. In two patients with unilateral active toxoplasmic retinochoroiditis, hyperfluorescent plaques were observed in the fellow eyes on indocyanine green angiograpy. The fundus examination and fluorescein angiography of the fellow eyes were normal and had a visual acuity of 10/10. Choroidal neovascularization was observed in two (8%) eyes. In eyes with active inflammation, fluorescein angiography revealed early hypo-fluorescence and late intense hyper-fluorescence with fuzzy margins of the retinochoroiditis lesion (12 eyes), hyperfluorescence of the optic nerve head (four eyes) and leakage from the vessels and/or vascular sheathing (four eyes) and neuroretinitis (one eye). CONCLUSION: Toxoplasmic retinochoroiditis is a more widespread inflammation than visible fundus lesions. Indocyanine green angiography is a useful method for evaluating the amount of inflammatory activity and late complications in patients with ocular toxoplasmosis.

Adolescent↗
PubMed2003

Congenital toxoplasmosis: assessment of risk to newborns in confirmed and uncertain maternal infection.

UNLABELLED: We identified 205 newborns at risk of congenital infection based on their mothers' immunological status during pregnancy, using the criteria established by the European Research Network on Congenital Toxoplasmosis to define the likelihood of infection in pregnant women. Of the 205 newborns, 60 (29.2%) were born to mothers with documented seroconversion, 49 (23.9%) to mothers with probable infection, 60 (29.2%) to mothers with possible infection, and 36 (17.6%) to mothers who were unlikely to be infected. Infection was transmitted to the child in 13 out of 60 cases (21.6%) of seroconversion, in 2 out of 49 (4.1%) cases of probable infections and in none of the possible and unlikely cases. The results were further analysed considering only the 109 newborns of mothers with confirmed and probable infection; in this group, toxoplasmosis was not transmitted to any of the 45 newborns of mothers infected in the first trimester of pregnancy, whereas it was transmitted to 5 out of 29 (17.2%) cases of seroconversion and 2 out of 12 (16.6%) with probable infection in the second trimester, and to 8 out of 23 (34.8%) with confirmed infection in the third trimester (no probable infections were dated in the third trimester). Among the newborns of mothers with seroconversion, the risk of symptomatic infection was 10.4% in the second trimester and 8.7% in the third trimester. CONCLUSION: the authors have quantified the risk of transmission of toxoplasmosis infection, not only in cases of seroconversion, as reported by others, but also in infections defined as probable or possible based on presence of IgM and/or IgA and with medium-high IgG levels. Probable infections in the second trimester of pregnancy carries the same risk of transmission as seroconversions and pregnant women and their newborns in these cases should undergo the same diagnostic and therapeutic approach. It is suggested that newborns of mothers with certain and probable infection must be carefully observed and undergo clinical and serological testing to identify and treat the infection as soon as possible. In the case of possible or unlikely maternal infection, serological testing at longer intervals is nevertheless advisable without the need for treatment.

Adult↗
PubMed1999

Diagnosis of congenital toxoplasmosis at birth: what is the value of testing for IgM and IgA?

UNLABELLED: Recommendations vary on the best combination of tests to use for the diagnosis of subclinical congenital toxoplasmosis at birth. The diagnostic accuracy of IgM and IgA tests was assessed in the context of routine clinical practice on 233 newborns with congenital toxoplasmosis and 661 healthy controls. IgM/IgA sensibility and specificity were compared in cord and postnatal samples. Both tests were considerably more specific in neonatal blood (IgM: 98%; IgA: 100%) than in cordblood (IgM: 85%; IgA: 88%). Sensitivity for IgM and IgA was not significantly different in neonatal blood (61% and 60%, respectively) and cord blood (67% and 54%, respectively). Combining IgM and IgA increased the overall sensitivity to 73% without any significant loss in specificity (98%). The influence of the date of maternal infection on the sensitivity and negative predictive value was also clearly demonstrated. CONCLUSION: Because of their relatively low cost compared to more sophisticated methods, IgM and IgA tests should remain the main method for the routine diagnosis of congenital toxoplasmosis although follow up is essential to identify the Ca. 25% of infected children who are missed at birth on the basis of these tests.

Agglutination Tests↗
PubMed2001

Serological rebound in congenital toxoplasmosis: long-term follow-up of 133 children.

UNLABELLED: Although serological rebound is common in infants with congenital toxoplasmosis, clinical recommendations for management, in particular the need for additional treatment, vary. The goals of our retrospective cohort study in 133 consecutive children with congenital toxoplasmosis were to estimate the incidence and duration of the rebounds, identify predictive factors, assess the long-term risk of eye lesions and the need for treatment. We first estimated the incidence and duration of rebounds and identified predictive factors using an univariate analysis and a Cox model modified to include time-dependent variables. Two cohort studies were then conducted to compare the incidence density of secondary eye lesions in children who had a rebound versus no rebound, and among children who had a rebound after initial therapy, in those who received an additional course of treatment and in those who did not. Of the 133 children, 93 (70%) had at least one rebound during a mean follow-up of 95 months. Of those with one rebound diagnosed after initial treatment, 33 received an additional 3-month course of pyrimethamine/sulphadoxine and 48 were not treated. Intracranial calcification at birth was associated with an increased relative risk (RR) of rebound (RR = 2.601; P = 0.03), and treatment with pyrimethamine/sulphadoxine between 2 and 12 months of age with a decreased risk (RR = 0.3; P = 0.0845), whereas age of pregnancy at maternal infection, type of treatment during pregnancy and sex were not found to be predictive factors. There was no difference in incidence densities of secondary eye lesions in children without rebound (7/3,367 child-months) compared to those with at least one rebound (22/9,609 child-months) (RR = 1.10; 95% CI: 0.47-2.58), and, among the 81 children who had one rebound diagnosed after initial treatment, in those who received an additional course of treatment and in those who did not (RR = 0.72; 95% CI: 0.30-1.72). CONCLUSION: serological rebound is common in children with congenital toxoplasmosis but, due to the risk and constraints, an additional course of treatment and more ophthalmological surveillance than currently practiced do not seem warranted.

Animals↗
PubMed1998

Serodiagnosis of acute toxoplasmosis using a recombinant form of the dense granule antigen GRA6 in an enzyme-linked immunosorbent assay.

We developed an indirect enzyme-linked immunosorbent assay (ELISA) for the serological diagnosis of acute toxoplasmosis that used the recombinant granule antigen GRA6-GST as diagnostic antigen for the detection of IgG antibodies to Toxoplasma gondii in human sera. A total of 431 sera obtained from 336 patients with acute and chronic toxoplasmosis and from patients who were not infected with T. gondii were tested. Sera from patients with acute T. gondii infection, chronic infection, and no infection showed different absorbance values. For discrimination between the presence and the absence of acute toxoplasmosis the assay reached a specificity of 99.6%. Only one of the sera without significant anti-T. gondii. IgM antibodies showed a positive reaction to rGRA6-GST. The assay showed good intra- and interassay reproducibility (CV 6%/14%). We included a glutathione S-transferase (GST)-IgG enzyme immunoassay as a control assay in this study. Only 7 (4%) of 159 random sample sera reacted positively with GST.

Acute Disease↗
PubMed2001

Obsessive-compulsive disorder and acquired toxoplasmosis in two children.

Two children presenting symptoms of obsessive-compulsive disorder (OCD) and with acquired toxoplasmosis are described and the possibility of a previously rarely reported association between OCD and acquired toxoplasmosis is discussed. Case 1 is a 14-year-old boy with Tourette syndrome (TS), attention deficit hyperactivity disorder (ADHD) in partial remission and a three-year history of OCD referred to our department due to an acute deterioration of obsessive-compulsive (OC) symptoms. Case 2 is an 11-year-old boy referred to our department because of a two-year history of OCD. The OC symptoms were observed immediately following an infection. In both cases laboratory tests confirmed the diagnosis of acquired toxoplasmosis. The pharmacological therapy of T.gondi infection without any psychopharmacological treatment caused remission or significant improvement regarding OC symptoms.

Adolescent↗
PubMed2003

Evaluation of a commercial IgG/IgM Western blot assay for early postnatal diagnosis of congenital toxoplasmosis.

The aim of this study was to evaluate a commercial Western blot IgG/IgM assay for use in the early serological diagnosis of congenital toxoplasmosis. This assay compares the immunological profile of mother and infant and allows differentiation between passive transmitted maternal antibodies and newly synthesized antibodies of the infant within the first 3 months of life. Over a 6-year period (1995-2001), the sera from 169 mothers and their 175 offspring (6 had twins) were examined for specific anti- Toxoplasma gondii IgG, IgM and IgA antibodies with an enzyme-linked immunosorbent assay or an immunosorbent agglutination assay. All mothers had primary Toxoplasma infection during pregnancy. Serological and clinical follow-up of the infants during the first year of life confirmed 36 cases of congenital toxoplasmosis. In 139 cases, infection could be ruled out. Three hundred fifty-one paired samples from 175 mother-child pairs were tested retrospectively for IgG and IgM patterns by Toxoplasma Western blot IgG/IgM (LDBIO Diagnostics, France). The results of conventional serological analysis (immunosorbent agglutination assay or enzyme-linked immunosorbent assay) to detect IgM or IgA were compared with the results of the Toxoplasma Western blot IgG/IgM on samples obtained within the first 3 months of life. The performance of the combination of the two methods was also assessed. At birth, the sensitivity values of conventional serological analysis and the Toxoplasma Western blot were 52% and 67%, with specificity values being 99% and 96%, respectively. Combination of the Western blot and conventional serological analysis increased the sensitivity at birth to 78% and within the first 3 months of life to 85%. Overall, the combination of both methods detected 94% of congenital infections. Therefore, this commercial Western blot represents a useful tool for early postnatal diagnosis of congenital toxoplasmosis.

Animals↗
PubMed2004

Delayed maturation of IgG avidity in congenital toxoplasmosis.

The aim of this comparative study was to investigate the clinical usefulness of the measurement of Toxoplasma gondii IgG avidity in the postnatal diagnosis of congenital toxoplasmosis. IgG avidity values in serum samples from infants with congenital infection were compared with those in samples from uninfected infants, all born to mothers with toxoplasmosis acquired during gestation. This analysis revealed that IgG avidity values soon after birth reflected maternal values in the large majority of the samples. Low or borderline IgG avidity values were systematically found in the cohort of congenitally infected subjects. After birth, IgG avidity values slowly increased over time for up to 2 years in congenitally infected subjects. On the contrary, IgG avidity values in the uninfected infants remained stable over time. The presence of low IgG avidity in a newborn can be considered a marker of maternal seroconversion in the second or third trimester of gestation and, as a consequence, an indicator of risk for congenital toxoplasmosis. An IgG avidity assay can be easily carried out with antibodies eluted from dried blood spots (Guthrie cards), providing an opportunity to retrospectively evaluate the risk of congenital infection in special clinical circumstances, for example when suspicion of congenital infection arises during late infancy.

Aging↗
PubMed1983

Central nervous system toxoplasmosis in homosexual men.

Many opportunistic infections have been associated with an acquired immunodeficiency state in which cellular immune status has been altered. Two homosexual patients are described who presented with fever, peripheral eosinophilia, and a travel history to Haiti and were found to have central nervous system toxoplasmosis. Despite definitive diagnosis and appropriate therapy, both died. Techniques for diagnosis of central nervous system toxoplasmosis are discussed, and the importance of brain biopsy in this clinical situation is stressed. Eosinophilia may serve as an early diagnostic marker for disseminated toxoplasmosis in homosexual patients.

Adult↗