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[Results of therapy in ocular toxoplasmosis. Comparison of various forms of therapy].

We performed a retrospective non-random study to evaluate the effectiveness of different therapeutical concepts in the treatment of retinal toxoplasmosis. Visual acuity after therapy and at the end of the observation period as well as the recurrence frequency were used to determine the success of treatment. The protocols of 75 patients treated for retinal toxoplasmosis at the University of Hamburg were evaluated for this study. The mean observation period was 220 weeks with a standard deviation of 110 weeks. Concerning the visual outcome, a therapeutic effect was statistically shown for monotherapy with antibiotics and for their combination with corticosteroids. Steroid therapy was demonstrated to be helpful, especially in cases of extramacular localization of fundus lesions. This was probably caused by steroid-induced improvement of vitreous infiltration. As for the different antibiotics used, the combination of clindamycin with sulfmethoxydiazine and/or pyrimethamine showed the best results. Monotherapy with clindamycine alone had statistically no effect on the final visual outcome. The relapse frequency was not influenced by any therapeutic concept used. According to these results, a combination of clindamycine and pyrimethamine should be the therapy of choice for treatment of retinal toxoplasmosis.

Coccidiostats↗

[Toxoplasmosis and cytomegalovirus serology in patients infected with HIV in Congo].

Cerebral toxoplasmosis and cytomegalovirus (CMV) infection are very frequent in AIDS. Biological markers of toxoplasmosis and CMV were studied in blood and cerebrospinal fluid (CSF) of 121 HIV-positive and 35 HIV-negative patients in the Central Hospital of the Congolese Army in Brazzaville. In the case of clinically suspected cerebral toxoplasmosis, the simultaneous presence of specific IgG antibodies in the blood and in the CSF can be considered as having complementary diagnostic value (PPV = 63.3%, NPV = 89.9%). The symptomatology of AIDS is very polymorphous and includes various etiological factors; as a result it is very difficult to estimate the responsibility of cytomegalovirus in the absence of positive viral culture, even with the simultaneous presence of specific IgG antibodies in the blood and CSF (PPV = 75.7%, NPV = 54.6%).

AIDS-Related Opportunistic Infections↗

Unilocular toxoplasmosis simulating intracerebral tumor.

Toxoplasmosis is a common infection with increased incidence in patients suffering from AIDS. In this paper we report a rare case of toxoplasmosis without evidence of AIDS: The patient had a singular tumor-like lesion in the right parietal lobe in CT and MRI. In neurosurgical intervention no tumor was found. Finally, different histopathological examinations led to the diagnosis of toxoplasmosis. Diagnostic and therapeutic regimes in patients with suspect tumor-like lesions should be discussed.

Aged↗

Neonatal toxoplasmosis in littermate cats.

Toxoplasmosis was diagnosed histologically in 9 kittens and 1 queen from 5 liters. In litter 1, four 3-month-old Siamese kittens and the queen were affected. The queen died of generalized toxoplasmosis, and her kittens died or were euthanatized 20, 22, or 28 days later. In litter 2, two of 3 Abyssinian 4- and 4.5-month-old kittens died of toxoplasmosis. In litter 3, an Abyssinian, delivered by cesarean section, became ill 17 days after delivery, and died 2 days later because of toxoplasmic hepatitis and pneumonia. In litter 4, three kittens, approximately 1 month old, were shedding Toxoplasma gondii-like oocysts, and the organism was identified histologically in tissues of 1 of them. In litter 5, one 3-week-old kitten out of 4 became ill. Toxoplasma gondii-like oocysts were found in feces and T gondii organisms were found in histologic sections of tissues.

Animals↗

[Toxoplasmosis in pregnancy. Diagnosis and new therapeutic possibilities].

Congenital toxoplasmosis results from contamination of the foetus by Toxoplasma gondii during pregnancy. It is a frequent and severe condition calling for close surveillance of mothers at risk. During the last few years, numerous advances have been made in the diagnosis and treatment of toxoplasmosis. Its diagnosis in the mother is now more reliable due to improvements in serological techniques, while in the foetus the use of foetal vascular techniques has made it possible to detect those who are infected. Owing to a new and effective therapeutic method certain foetuses can now be treated successfully in utero, so that induced abortion is reserved to cases with severe and early toxoplasmosis. The contribution of new molecular biology techniques to advances in this ever moving field is explained.

Adult↗

[Pulmonary toxoplasmosis. Study of 4 cases and review of the literature].

BACKGROUND: Description of four cases of pulmonary toxoplasmosis and review of the literature. METHODS: A retrospective analysis (October 1990-December 1992) was carried out of the patients with samples of tracheal aspirate, bronchoalveolar lavage (BAL) and lung biopsy positive for T. gondii by immunofluorescence with anti-P30 monoclonal antibodies and cell cultures. RESULTS: Four patients were diagnosed of pulmonary toxoplasmosis, three being immunosuppressed (one renal transplant, one with chronic lymphoid leukemia and one intravenous drug user HIV seronegative) and the remaining one healthy. All the patients developed progressive dyspnea and a radiologic pattern of interstitial pneumonitis (3) or alveolar condensation (1). Three of the patients were cured with pyrimethamine and sulphadiazine. One patient had coinfection by CMV and died. Another 52 cases of this rare condition have been reported in the literature. CONCLUSIONS: In the authors experience, bronchoalveolar lavage material and lung biopsy for T. gondii culture should be performed in immunosuppressed patients with an unclear interstitial radiologic pattern to rule out pulmonary toxoplasmosis.

Adult↗

Incidence proportion of and risk factors for AIDS patients diagnosed with HIV dementia, central nervous system toxoplasmosis, and cryptococcal meningitis.

We undertook this study to determine the incidence proportion of and risk factors for AIDS patients diagnosed with human immunodeficiency virus (HIV) dementia, central nervous system (CNS) toxoplasmosis, and cryptococcal meningitis. A historical cohort of 487 consecutive inpatients with AIDS treated by San Francisco General Hospital inpatient and outpatient services entered the study. We abstracted all available records for demographic information, diagnoses, and dates of death and estimated the incidence proportion of AIDS patients diagnosed with major CNS complications using the Kaplan-Meier method. We used the Cox proportional hazards model to analyze the effect of demographic factors on the hazard (risk per unit time) of diagnosis with these CNS conditions. The estimated incidence proportion of patients diagnosed with HIV dementia within 1 and 2 years of AIDS diagnosis increased from 0.10 to 0.18. Corresponding proportions were 0.10 and 0.19 for CNS toxoplasmosis and 0.10 and 0.14 for cryptococcal meningitis. Only HIV dementia was independently associated with increasing age at AIDS diagnosis (relative hazard [RH] of 2.75 for ages 41-50 [95% confidence interval, 1.08-6.98]; RH of 4.73 for ages > 50 [95% confidence interval, 1.41-15.87]) and with injection drug use (RH of 2.03; 95% confidence interval, 1.19-3.47). HIV dementia, CNS toxoplasmosis, and cryptococcal meningitis are about equally common complications in patients with AIDS, but only HIV dementia is associated with increasing age at AIDS diagnosis and injection drug use.

AIDS Dementia Complex↗

[Prenatal and perinatal infections--problems for the practicing pediatrician: group B streptococci, varicella, toxoplasmosis].

A practical approach is reported for the care of the neonate born to a mother infected/colonized during pregnancy by group B streptococcus, varicella-zoster virus or Toxoplasma gondii. Starting from clinical situations, an attempt is made to work out evidence based recommendations using an overview of the current literature. GROUP B STREPTOCOCCI: Relevant factors for the treatment of infants born to colonized mothers are clinical symptoms, gestational age, additional risk factors (such as premature rupture of membranes or maternal fever) and intrapartum antibiotics. Postnatal antibiotic prophylaxis and laboratory screens failed the test of controlled trials. Transfer to a neonatology unit is recommended for symptomatic term and all preterm infants. Asymptomatic term infants should be carefully monitored during the first 48 hours for signs of respiratory, circulatory or thermoregulatory compromise. VARICELLA: In the case of maternal varicella near term, delaying delivery for one week will lower the risk of severe neonatal varicella. The postnatal administration of varicella-zoster-immunoglobulin to the neonate is supported by some (if limited) evidence from the literature in the case of maternal eruption between 7 days before and 2 days after delivery. In newborns of mothers with eruption appearing later immunoglobulin is often recommended, though no supporting clinical evidence is available. There are no data to justify the use of immunoglobulin after exposure during pregnancy in order to prevent pneumonia in the pregnant patient, but there are preliminary indications that its application could lower the risk of congenital varicella syndrome (2% between 13 and 20 weeks). The use of immunoglobulin in very low birth weight infants after nosocomial exposure is generally recommended but efficacy data are lacking. TOXOPLASMOSIS: The practical approach depends on clinical findings in the newborn and laboratory results during pregnancy and after birth. Examination of the newborn should include fundoscopy, cranial sonography and, in cases of documented infection, lumbar puncture. Serology from cord blood comprises assays for IgG, IgM and if possible IgA/IgE. If available, demonstration of the parasite by culture or PCR can be helpful. All infants with documented congenital toxoplasmosis should be treated for a minimum of 12 months. In the case of suspected toxoplasmosis the child should be treated as long as the suspicion persists. The prognosis after consequential therapy is less bleak than previously reported for untreated children even in seriously symptomatic patients.

Chickenpox↗

Restricted applicability of the polymerase chain reaction for the diagnosis of ocular toxoplasmosis.

The laboratory confirmation of ocular toxoplasmosis has been reported to be facilitated by the polymerase chain reaction (PCR) technique in anterior chamber taps. We utilized PCR specific for a sequence of the Toxoplasma gondii B 1 gene with a length of 194 bp. The sensitivity was adjusted to ten genomic copies per sample in stained gel and two copies after DNA hybridization using a digoxygenin-labeled probe. We amplified DNA from 43 aqueous, 14 serum, and 32 white blood cell (WBC) samples obtained from 31 consecutive otherwise healthy patients with the clinical diagnosis of ocular toxoplasmosis. In the series investigated, 1/43 aqueous samples and 2/32 WBC samples were found to contain detectable amounts of target DNA. An inhibition of the PCR by the aqueous humor as a reason for the low detection rates was excluded. Thus, we conclude that either the sensitivity of aqueous humor PCR is not sufficient for use in the routine diagnosis of ocular toxoplasmosis in immuno-competent individuals or the anterior chamber is not the proper compartment for investigation of this protozoal disease using this approach.

Adult↗

[Acute myocarditis caused by toxoplasmosis simulating infarction. Apropos of a case].

Acute myocarditis due to toxoplasmosis infection has been previously reported, usually in patients suffering from immuno-depression. Cardiac involvement by toxoplasmosis is rare in subjects with a normal immunological status. The authors report the case of a 16-year-old patient without immuno-depression with acute myocarditis caused by toxoplasmosis simulating myocardial infarction.

Acute Disease↗

Interferon-gamma receptor-deficiency renders mice highly susceptible to toxoplasmosis by decreased macrophage activation.

Toxoplasma gondii may cause severe infections in immunocompromised patients including fetuses and those with AIDS. Among the factors mediating protection against T. gondii, IFN-gamma has gained special attention. To analyze the role of IFN-gamma in the early phase of toxoplasmosis, IFN-gamma receptor-deficient (IFN-gamma R0/0) mice were orally infected with low-virulent toxoplasms. IFN-gamma R0/0 mice died of the disease up to day 10 postinfection, whereas immunocompetent wild-type (WT) mice developed a chronic toxoplasmosis. Histopathology revealed that in IFN-gamma R0/0 mice, the parasite multiplied unrestrictedly in the small intestine, the intestinal lymphatic tissue, the liver, and the spleen. Ultimately, animals died of a necrotizing hepatitis. In WT mice, the same organs were effected, but multiplication of the parasite was effectively limited. Compared with WT mice, immunohistochemistry and flow cytometry demonstrated that in IFN-gamma R0/0 mice, macrophages were only marginally activated in response to the infection, as evidenced by a reduced expression of major histocompatability complex class II antigens. In addition, immunohistochemistry and RT-PCR showed a reduced production of the macrophage-derived cytokines tumor necrosis factor-alpha, inducible nitric oxide synthase, and IL-1 beta in the liver of IFN-gamma R0/0 mice. In contrast, activation of T cells, recruitment of immune cells to inflammatory foci, and anti-T. gondii IgM antibody production were unaffected by the mutation of the IFN-gamma R. Moreover, induction of IL-2, IL-4, and IL-10 mRNA transcripts in the liver was normal in IFN-gamma R0/0 mice. Adoptive transfer experiments revealed that the immune T cells of WT animals did not protect IFN-gamma R0/0 mice from lethal infection with highly virulent toxoplasms, whereas WT mice were significantly protected by the adoptive transfer. Based on these studies, we conclude that IFN-gamma is absolutely required for an efficient activation of macrophages. Macrophages are of critical importance in toxoplasmosis, and insufficient macrophage activation cannot be compensated by other immune mechanisms.

Adoptive Transfer↗

Disseminated toxoplasmosis. Unusual presentations in the immunocompromised host.

OBJECTIVE: Owing to the increasing number of patients with acquired immunodeficiency syndrome and immunosuppressed transplant patients, disseminated Toxoplasma gondii has emerged as a potentially fatal pathogen. Common presentations include encephalitis, pneumonia, and myocarditis. The objective of this report is to describe the clinical course, histologic features, and outcome in two immunocompromised patients with disseminated toxoplasmosis presenting with parasitemia and panniculitis. MATERIALS AND METHODS: Two cases of disseminated toxoplasmosis presenting with parasitemia (patient 1) and panniculitis (patient 2) were retrieved from the clinical, surgical, and autopsy pathology archives of Vanderbilt University Medical Center, Nashville, Tenn. The histology and diagnostic approaches used are reported. Charts were reviewed for primary diagnosis, therapy protocols, clinical presentation of infection, and outcome. RESULTS: Patient 1 developed a clinically unexplained sepsis syndrome shortly after heart transplantation; T gondii parasitemia was diagnosed by examination of peripheral blood smears. The diagnosis was confirmed at autopsy. Patient 2 was a child undergoing induction chemotherapy for lymphoma who developed rapidly progressive neurologic deterioration accompanied by a maculopapular skin rash; T gondii panniculitis was diagnosed retrospectively when histologic examination was combined with immunohistochemistry. Autopsies performed in both cases confirmed widely disseminated infection. CONCLUSIONS: Disseminated toxoplasmosis should be considered in the differential diagnosis of immunocompromised patients with culture-negative sepsis syndrome, particularly if combined with neurologic, respiratory, or unexplained skin lesions. Examination of Wright's-stained peripheral blood smears or antitoxoplasma immunoperoxidase studies of skin biopsies may be diagnostic and allow rapid initiation of antibiotic therapy. Autopsy findings contributed to both of our cases by documenting the wide-spread heavy parasite burden and demonstrating numerous diagnostic T gondii cyst forms.

Animals↗

[Exploration of immune response in a murine model of congenital toxoplasmosis].

We used a model of acquired toxoplasmosis to study the immune response in pregnant BALB/c mice (IL4+/+) and in pregnant transgenic IL4-deficient BALB/c mice (IL4-/-) during acute toxoplasmosis. Female BALB/c mice were infected orally by 20 tissue cysts of the avirulent PRU strain of Toxoplasma gondii on day 11 of pregnancy. After infection, cultured spleen cells from pregnant mice produced more IFN gamma (a type 1 cytokine) and more NO than non pregnant mice, and the type 2 response (IL4 and IL10) was weak. Although this kind of immune response may be required for mice to recover from toxoplasmosis, pregnant mice were more susceptible to infection than non pregnant mice, as illustrated by a larger parasite load in lungs and brain. Pregnant IL4-/- mice showed lower susceptibility to T. gondii infection and a lower materno-fetal transmission rate (24% versus 53% infected fetus) without increased production of type 1 cytokines (IFN gamma and NO). These data indicate that type 2 response plays an important role in increasing mouse susceptibility to T. gondii infection during pregnancy and that IL4 and pregnancy-associated substances increase the transplacental passage of T. gondii. This is the first time that biased towards type 2 immune response induced by pregnancy was shown to increase susceptibility to T. gondii.

Animals↗

The role of psychological factors in questionnaire-based studies on routes of human toxoplasmosis transmission.

The paper studies impacts of particular toxoplasmosis risk factors (consumption of raw meat and contact with cats), their interactions, and their relationship with the personality of the subjects. Among 243 men and 343 women the frequency of subjects with antitoxoplasma immunity was 26.6% and 21.6%, respectively. The association of antitoxoplasma immunity (assessed by the toxoplasmin skin test) with the two risk factors was estimated by log-linear analysis. Reported contact with cats has no influence on the probability of having antitoxoplasma immunity (P = 0.23) while the consumption of raw meat increased this probability (P = 0.0008). Very strong positive association between the contact with cats and the raw meat consumption was found among subjects without toxoplasmosis (P = 0.0028), suggesting that among these persons some subjects either incorrectly assessed their exposition to the risk factors or provided false data during the interview. The results of logistic regression suggest that the contact with cat and the consumption of raw meat are associated with particular personality traits. However, these traits differ from those associated with antitoxoplasma immunity suggesting that the correlation between antitoxoplasma immunity and consumption of raw meat reflects epidemiological importance of the raw meat rather than a correlation of both factors (raw meat consumption and probability of acquiring toxoplasmosis) with the subjects personality.

Adolescent↗

Crucial role of TNF receptor type 1 (p55), but not of TNF receptor type 2 (p75), in murine toxoplasmosis.

TNF-alpha exerts its biologic activity through two distinct receptors, TNF receptor type 1 (TNFR1, p55) and TNF receptor type 2 (TNFR2, p75). To analyze their function in toxoplasmosis, we orally infected mice genetically deficient for TNFR1 (TNFR1(0/0)), TNFR2 (TNFR2(0/0)), or both TNF receptors (TNFR1/2(0/0)), as well as wild-type (wt) mice with a low-virulent strain of Toxoplasma gondii. TNFR1/2(0/0) and TNFR1(0/0) mice succumbed to toxoplasmosis within 17 and 27 days, respectively, whereas TNFR2(0/0) and wt mice were equally resistant to acute toxoplasmosis. Histopathology attributed death of TNFR1/2(0/0) and TNFR1(0/0) mice to a fulminant necrotizing encephalitis. In addition, pneumonia contributed to the fatal outcome. The poor prognosis of TNFR1/2(0/0) and TNFR1(0/0) mice was reflected by a significantly increased parasitic load in the brain and lung as compared with TNFR2(0/0) and wt mice. Immunohistochemistry demonstrated a remarkable reduction of inducible nitric oxide synthase protein in brain and lung of TNFR1/2(0/0) and TNFR1(0/0) as compared with TNFR2(0/0) and wt mice. Reverse-transcribed PCR showed that in contrast to TNFR2(0/0) and wt mice, TNFR1(0/0) mice were unable to up-regulate inducible nitric oxide synthase mRNA transcripts in the course of infection, whereas intracerebral levels of IFN-gamma, TNF-alpha, and IL-1beta mRNA transcripts, recruitment of immune cells to the brain, and the amount of apoptotic cells in inflammatory foci did not differ significantly among the various experimental groups. These results illustrate that in Toxoplasma encephalitis, TNF-alpha-mediated immune responses are of crucial importance and that signaling through TNFR1, but not TNFR2, provides the stimulus required for the induction of protective nitric oxide.

Animals↗

Toxoplasmosis of the central nervous system in the acquired immunodeficiency syndrome.

Acute encephalitis caused by Toxoplasma gondi was diagnosed at autopsy in 10 (20.4%) of the 49 patients. All patients had under lying immunodeficiency due to AIDS and showed selective involvement of central nervous system at autopsy. Sexual promiscuity was the risk factor in nine cases while one case had a history of blood transfusion. Diagnosis of toxoplasmosis was hampered by a lack of suspicion that Toxoplasma could be the agent causing necrotising encephalitis. The large number of cases of CNS toxoplasmosis appearing in AIDs patients emphasize the necessity of including toxoplasmosis in the differential diagnosis of encephalitis of unknown aetiology.

AIDS-Related Opportunistic Infections↗

Post-transplant cerebral toxoplasmosis diagnosed by magnetic resonance imaging.

Cerebral toxoplasmosis is a rare late complication in allogeneic bone marrow transplanted patients. Neuroradiological findings may suggest the correct diagnosis. We report a patient in whom cerebral magnetic resonance imaging (MRI) showed a lesion characteristic of toxoplasmosis. Anti-toxoplasma treatment led to clinical and radiological improvement. MRI seems to be a valid tool for detection and follow-up of cerebral toxoplasmosis.

Adult↗

[Peripheral thrombopenic purpura associated with acquired toxoplasmosis].

Acquired Toxoplasma Gondii infection has a benign course in adults and children immunologically competent. Thrombocytopenia is much more common during congenital toxoplasma infection and the rare cases of purpura associated with acquired toxoplasmosis are usually not thrombocytopenic. We report a case of thrombocytopenic purpura in an immunocompetent child, associated with active acquired toxoplasmosis. In rare circumstances, acquired toxoplasmosis in an immunocompetent patient may be associated with severe thrombocytopenia. However, the low incidence of such cases makes a therapeutic consensus difficult.

Adult↗