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PubMed1991

An overview of the problem of toxoplasmosis and pneumocystosis in AIDS in the USA: implication for future therapeutic trials.

By the end of 1989, 18,518 cases of Pneumocystis carinii infection and 5,614 cases of Toxoplasma gondii infection were reported to the Centers for Disease Control as the AIDS indicator disease. Pneumocystosis did not vary according to gender, race or risk factors; whereas toxoplasmosis was more common in black males with no known risk factors. Immigrants to the USA from Africa, Latin America and Haiti are three to four times more likely to develop toxoplasmic encephalitis than American-born patients with AIDS. The implications of this epidemiologic data for the predictive value of serology and clinical trials are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Treatment of acute toxoplasmosis with oral clindamycin.

The combination of pyrimethamine and clindamycin, both administered orally, was evaluated for initial and maintenance therapy of toxoplasmosis in eight AIDS patients who were either allergic to sulfonamides or unresponsive to standard therapy. Symptomatic and neuroradiographic improvement occurred in the majority of patients. The regimen was well tolerated and associated with minimal toxicity, and appeared to be an effective alternative to standard therapy.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Role of clindamycin in the treatment of acute toxoplasmosis of the central nervous system.

Cerebral toxoplasmosis related to AIDS was treated with a combination regimen of pyrimethamine, clindamycin, and spiramycin, and in a second trial with a combination of pyrimethamine and clindamycin. Both regimens proved to be equally effective. The experience with the second trial shows that spiramycin does not provide additional benefit. Myelosuppressive side-effects due to pyrimethamine were prevented in most cases by addition of folinic acid to the regimen at the start of the antitoxoplasmic therapy. These data suggest that the combination of pyrimethamine and clindamycin is an effective alternative to the commonly used regimen consisting of pyrimethamine and sulfonamides.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Activity of gamma interferon in combination with pyrimethamine or clindamycin in treatment of murine toxoplasmosis.

The activity of recombinant gamma interferon (rIFN-gamma) in combination with either pyrimethamine or clindamycin was examined in a murine model of acute toxoplasmosis. Mice received either pyrimethamine or clindamycin alone or in combination with rIFN-gamma. Significantly increased survival and/or time to death was observed in animals treated with pyrimethamine or clindamycin in combination with rIFN-gamma compared to those that received treatment with any of the agents alone.

Animals↗
PubMed1982

Congenital toxoplasmosis: histological and ultrastructural study.

A case of congenital toxoplasmosis is reported in which the patient died at 32 days following seizures, coma and respiratory disturbances. Neuropathological examination showed numerous foci of softening throughout the brain. Histological examination disclosed widespread areas of inflammatory necrosis. Circumscribed areas of granulomatous inflammation were also found. Cysts containing a variable number of microorganisms and toxoplasmas free in the damaged areas were frequently observed. Small calcifications were scattered in the cerebral cortex and basal ganglia. Electron microscopy of postmortem brain specimens demonstrated toxoplasmas at various stages of development. The microorganism is enveloped by a two-layered membrane, the pellicle. Replication occurs in a vacuole inside the host cell. Following replication the newly formed parasites, the trophozoites, are released. Several replications without release may also occur with consequent cyst formation. The motile form of the toxoplasma, the tachyzoite, is fusiform with truncated cone shape of the anterior ending which is the presenting surface modified for host cell penetration. The modality of transplacental transmission and the clinical syndromes associated with toxoplasma infection are discussed. EM even of post mortem material contributes to knowledge of the structure of the parasite and of its life cycles.

Brain↗
PubMed1992

No interference of rheumatoid factor(s) with toxoplasmosis IgM determination in infancy.

Sera from 263 newborns and infants suspected of congenital toxoplasmosis were tested for the presence of rheumatoid factor (RF) by the latex agglutination test, of which 40 were also tested by the enzyme-linked immunosorbent assay (ELISA). RF was detected in only one serum sample (0.38%), suggesting that false-positive results of the IgM-indirect fluorescent antibody test and the IgM-ELISA due to RF is most unusual in infancy.

Enzyme-Linked Immunosorbent Assay↗
PubMed1995

Congenital toxoplasmosis: 10-year follow up.

A long-term follow up was begun in 1982 on offspring of mothers who acquired toxoplasmosis during gestation. The 114 newborns were subdivided into 3 groups: (1) 26 born to mothers with certain infection; (2) 51 born to mothers with probable infection, and (3) 37 born to mothers with doubtful infection. There were five infections in the first group (19.2%), three in the second (5.8%) and none in the third. For purposes of data elaboration we considered only the 77 offspring of mothers with certain or probable infection. Of these, 2 infected cases out of 52 (3.8%) were born to mothers with infection in the first trimester of pregnancy, 4 out of 21 (19%) in the second trimester, and two out of four in the third. There were a total of 8 congenital infections (10.4%). Specific IgM antibodies were revealed in five out of eight infected children (62.5%). Infection was symptomatic in two children (2.6% of newborns at risk, 25% of infected cases), both born to mothers with infection in the second trimester. In the other six cases diagnosis was reached by evaluating trends in antibody levels: the percentage of infected newborns was higher in the group of maternal infections untreated (50%) or improperly treated (15.4%), compared to those receiving adequate treatment (6.9%). We suggest considering as infected children presenting specific IgM antibodies and/or antibody titres which do not become negative, even when symptoms are absent. Therapy with spiramycin should be started in all newborns at risk, while the use of sulphamides and pyrimethamine is justified only after the presence of infection is confirmed.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Protozoan↗
PubMed1975

[Antibody differentiation in human toxoplasmosis experiments on model cases (author's transl)].

Human sera with antibodies against Toxoplasma gondii were investigated-before and after gel filtration (Sephadex G 200)-by IgM-and IgG-specific immunofluorescent reactions as well as well by complement fixation tests.-In sera from patients with "latent" infections IgM-antibodies could not be demonstrated neither by the IgM-IFT-nor the CFT technique, although IgG antibodies with IFT titres between 1:50 qnd 1:200 were present.-In sera from patients in the "acute" stage of infection both IgM and IgG antibodies were always found. In some cases the IgG fraction had complement fixing properties only, although IgM antibodies were present as demonstrable by the IFT technique. -These observations leed to the possibility of immunologic differentiation between IgM-IFT and CF-antibodies. The role of the different antibodies in the serodiagnosis of human toxoplasmosis is discussed.

Adolescent↗
PubMed1989

Prevention of congenital toxoplasmosis; experience in The Netherlands.

Prevention is the pre-eminent strategy to control congenital toxoplasmosis. In a trial study in the province South-Holland a program of both primary and secondary prevention during pregnancy was applied. 28000 women were enrolled. 55% of them were seronegative, and only 55 primary infections were traced amongst them. Although a conclusive evaluation of the results of the study has not yet been accomplished, this low figure will be discussed within the scope of certain logistic and organizational obstacles incurred in the so-called TIP (Toxoplasma Infection Prevention)-study in the Netherlands.

Antibodies, Protozoan↗
PubMed1989

Therapy of ocular toxoplasmosis.

We performed a prospective multicentre study to evaluate the efficacy of therapeutic strategies currently used for ocular toxoplasmosis in a large number of patients (n = 106). Treatment was given for at least four weeks and consisted of three triple drug combinations: group 1, pyrimethamine, sulphadiazine and corticosteroids (n = 29); group 2. clindamycin, sulphadiazine and corticosteroids (n = 37); and group 3. cotrimoxazole (trimethoprim and sulphamethoxazole) and corticosteroids (n = 8). Patients with peripheral retinal lesions remained without systemic therapy (group 4, n = 32). Patients from group 1 received leucovorin 5 mg twice a week. No difference in the duration of inflammatory activity was observed between the treated and untreated patients or between the separate groups of patients. The most important factor predicting the duration of inflammatory activity was the size of the retinal focus itself, independently of the therapy given (P less than 0.05). We showed a reduction in size of the retinal inflammatory focus in 52% of the pyrimethamine patients as compared to 25% of untreated cases. However the most frequent side effects were also associated with pyrimethamine medication and included hematologic complications as thrombocytopenia and leucopenia despite leucovorin medication.

Chorioretinitis↗
PubMed1988

Cerebral toxoplasmosis in AIDS. Case report.

In a patient with AIDS presenting partial epilepsy cerebral toxoplasmosis was diagnosed on the serological and CT evidence. The diagnosis was confirmed by the immediate response to sulfonamide therapy.

Acquired Immunodeficiency Syndrome↗
PubMed2003

Cerebral toxoplasmosis following etanercept treatment for idiophatic pneumonia syndrome after autologous peripheral blood progenitor cell transplantation (PBPCT).

Idiophatic pneumonia syndrome (IPS) is a term used to describe lung injury following hematopoietic stem cell transplantation (HSCT) without an infectious etiology. Diagnostic criteria include multilobar infiltrates on chest X-ray, clinical symptoms consistent with pneumonia and evidence of abnormal pulmonary physiology. The incidence after autologous transplantation is low (6%) but it has a high mortality (70-80%). Treatment with high-dose steroids has been used but the results are discouraging. Etanercept is a recombinant human soluble TNF receptor fusion protein that inhibits tumor necrosis factor alpha (TNFalpha) function. Recently, promising results have been obtained with etanercept for the treatment of acute and chronic GVHD after HSCT, but there is a little information regarding adverse effects. We report a case of IPS after autologous peripheral blood progenitor cell transplantation (PBPCT) successfully treated with etanercept. The patient developed cerebral toxoplasmosis immediately after etanercept treatment with a good outcome.

Adolescent↗
PubMed2006

The antibody response in experimental ocular toxoplasmosis.

BACKGROUND: The dynamics of the humoral immune response in ocular toxoplasmosis (OT) are poorly understood. We therefore investigated this process in a rabbit model of the disease. MATERIALS AND METHODS: Of 24 infection-naive adult rabbits, 12 were left untreated and 12 were systematically infected with 5,000 tachyzoites of the non-cystforming BK strain of Toxoplasma gondii. Three months later, all rabbits were inoculated transvitreally with 5,000 tachyzoites of Toxoplasma gondii. Paired samples of aqueous humor and serum were analyzed temporally for their total and specific IgG contents. RESULTS: In infection-naïve rabbits with primary OT, specific IgG reached detectable levels in the inoculated eyes between 5 and 15 days after inoculation. In infection-immunized rabbits with secondary OT, a significant increase in specific IgG was regularly detected after 5 days. The antibody ratio C was diagnostic (> or =3) from day 15 onward in primary OT and from day 21 onward in secondary OT. In the uninfected partner eyes, the antibody ratio C was found sporadically diagnostic from day 15 onward in primary OT, but at no time in secondary OT. Specific IgG persisted both locally and in the serum until the end of the monitoring period (100 days). CONCLUSION: Our findings relating to the rabbit model of OT reveal three features of clinical relevance: a diagnostic window precedes the establishment of a humoral immune response; specific antibodies persist long after the cessation of disease activity; and in primary OT, the antibody ratio C may also increase in the uninfected partner eye.

Animals↗
PubMed2005

Treatment of infants with congenital toxoplasmosis: tolerability and plasma concentrations of sulfadiazine and pyrimethamine.

The aim was to study the tolerability and plasma concentrations of pyrimethamine and sulfadiazine in children treated for congenital toxoplasmosis. Infants were diagnosed through the Danish Toxoplasma Neonatal Screening Programme, based on detection of toxoplasma-specific IgM- and/or IgA-antibodies on 3 mm blood spots collected from phenylketonuria [PKU cards (Guthrie cards)]. Toxoplasma-infected children received 3 months' continuous treatment with 50-100 mg/kg per day sulfadiazine in two separate administrations and 1 mg/kg per day pyrimethamine after a 1-day loading dose of 2 mg/kg, and folinic acid 7.5 mg was administered twice weekly. Blood cell counts and body weight were recorded during follow-up. The plasma concentrations of pyrimethamine and sulfadiazine were analysed in a subgroup of seven children, using high performance liquid chromatography with ultraviolet and mass spectrometric detection. Of 48 infants, 41 completed the treatment without change in schedule. Six infants had neutrophil counts below 0.5x10(9)/l, and one infant had an elevated bilirubin value. Twenty-nine children were tested by a series of neutrophil counts during treatment. The neutrophil count was <or=0.5x10(9)/l or lower in 4/29 (13.8%). None of the children had anaemia or thrombocytopenia. The drugs did not affect weight gain. Mean plasma drug concentrations varied between 1.3 microg/ml and 2.2 microg/ml for pyrimethamine and between 60 microg/ml and 86 microg/ml for sulfadiazine. Treatment efficacy is still a concern, since progression of eye lesions was observed in three eyes during the follow-up period. We concluded that the treatment was well tolerated in 86% (25/29) of the children. The drugs did not affect their weight gain. Drugs given in the recommended doses led to concentrations within expected therapeutic limits.

Antiprotozoal Agents↗
PubMed2004

Ocular toxoplasmosis: the role of retinal pigment epithelium migration in infection.

Our aim was to study the migration of retinal pigmented epithelium (RPE) into the retinal layer during infection of C57BL/6 mice with Toxoplasma gondii. Eyes from infected and non-infected animals were analyzed on the 60th day of infection by light and transmission electron microscopy. Non-infected eyes showed a normal morphology. In contrast, we observed free parasites in the retinal vasculature, the presence of mononuclear inflammatory infiltrate (MNII) and parasites in the vasculature of choroids in infected eyes. No inflammatory infiltrate was observed; RPE cells were identified near the MNII in nuclear and plexiforme layers. RPE cells were also found on the ganglion cell layer and in the outer segments of the photoreceptor. The morphology showed that RPE cells caused a discontinuity in the nuclear and plexiforme layers. Clusters of parasites were found surrounded by RPE cells and MNII in the inner plexiforme layers. Ultrastructural analysis showed that RPE cells migrated through the epithelium into the inner retinal layers. We did not observe Toxoplasma cysts in many eyes in which pathological changes were detected. Only 8.3% of the animals had Toxoplasma cysts in the inner nuclear layer in the absence of inflammatory cells. The migration of RPE cells can be triggered by a disruption of the RPE monolayer or injury to the neural retina, as in the case of toxoplasmosis.

Animals↗
PubMed1996

Effect of immunosuppressive drug regimens on acute and chronic murine toxoplasmosis.

To evaluate the potential risk of dissemination or reactivation of toxoplasmosis following the administration of immunosuppressive therapy we examined the effect of corticoids, azathioprine, and cyclosporine given alone or in combination on the course of murine acute and chronic toxoplasmic infection. Swiss Webster mice were infected perorally with a high-level inoculum of cysts of the C strain of Toxoplasma gondii. The evolution of the kinetics of parasite loads in the blood, brain, and lungs of infected and immunosuppressed mice was then sequentially followed. In mice with orally acquired infections initiated 2 days after the beginning of drug treatment, immunosuppression led to the persistence of parasites, especially in the lungs, which was most marked in mice treated with azathioprine and/or cortisol acetate. Administration of immunosuppressive therapy in mice previously infected with T. gondii resulted in a brief resurgence of parasite loads when treatment was started early after infection. Finally, under our experimental conditions we found that the immunosuppressive drugs that were given altered the natural course of infection with a prolonged persistence of parasites in the lungs but did not significantly affect parasite loads in the brain or lead to disseminated infection with detectable parasitemia.

Acute Disease↗
PubMed2006

Delayed maturation of immunoglobulin G avidity: implication for the diagnosis of toxoplasmosis in pregnant women.

The low avidity of immunoglobulin G has been reported to be a useful marker of recent infection with Toxoplasma. Several investigators, however, have published discrepant result on the maturation of avidity over time. The aim of this study was to analyse persistent low avidity of immunoglobulin G in immunocompetent individuals and in pregnant women and how it could interfere in the flowchart of antenatal diagnosis of toxoplasmosis in the latter group. An international literature search was conducted together with a retrospective study of a hospital database. Eleven publications that met the inclusion criteria reported delayed maturation of avidity at a frequency ranging from 0 to 66.6% of the patients. Examination of those publications demonstrated an important heterogeneity in the type of assay used, the calculation of avidity, the cutoff above which avidity was considered to be elevated, and the delay since infection after which indices are expected to be high. In the hospital database, persistent low avidity was found even after a median follow-up period of 6 years. Different factors could interfere with maturation of avidity, such as variations between individuals, the assay system used, and, possibly, the treatment administered. The results of this study clearly demonstrate that, in a pregnant woman, an acute infection cannot be reliably diagnosed solely on the basis of low avidity of immunoglobulin G. Further investigations and standardization of assays are urgently needed. Estimation of the time of infection remains difficult, especially in cases in which the samples are drawn late in pregnancy; the final estimate must be based on several tests repeated at intervals of weeks.

Animals↗
PubMed1976

Chronic lymphadenopathic toxoplasmosis. A case with marked hyperglobulinemia and impaired delayed hypersensitivity responses during active infection.

A patient with lymphadenopathic toxoplasmosis characterized by prolonged symptoms and repeated relapses with isolation of toxoplasma from lymph nodes is described. As the disease persisted and progressed, striking immunologic changes occurred that ultimately resulted in a state of extreme hyperglobulinemia associated with impaired delayed hypersensitivity responses. The case in question illustrates that progressive infection may occur in the face of high antibody levels of all immunoglobulin types whereas the only demonstrable immunologic impairment was of delayed hypersensitivity.

Adolescent↗