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A retrospective study of treatment of cerebral toxoplasmosis in AIDS patients with trimethoprim-sulphamethoxazole.

AIMS OF THE STUDY: a retrospective study was designed to evaluate efficacy and tolerance of trimethoprim-sulphamethoxazole (TMP-SMZ) in AIDS patients with cerebral toxoplasmosis (TE). PATIENTS AND METHODS: we reviewed 471 patients with AIDS, and we analysed 71 AIDS patients with TE, who received intravenous therapy with TMP-SMZ (TMP: 10 mg/kg/day, SMZ: 50 mg/kg/day) for 4 weeks. RESULTS: 35 patients (49.2%) had a complete regression of clinical signs, and a complete resolution of radiological lesions was noted in 41 patients (57.7%). Improvement of clinical signs and radiological lesions were observed in 27 patients (38%), and in nine patients (12.6%), respectively. In contrast, nine patients (12.6%) did not show any clinical change, or worsened. Twenty-two patients (30.9%) suffered from adverse cutaneous reactions, whereas many patients had haematological toxicity. CONCLUSIONS: TMP-SMZ seems to be an efficient therapy for TE in AIDS patients, although further prospective, randomized therapeutic trials are required to confirm these results.

AIDS-Related Opportunistic Infections↗

Flow cytometric application of the Sabin and Feldman dye test in the diagnosis of toxoplasmosis.

Although time-consuming and requiring live parasites, the Sabin and Feldman dye test (DT) is still considered the 'gold standard' among the serological tests for toxoplasmosis diagnosis. The present study was initiated to compare detection of dead parasites using optical microscopy with flow cytometry and a fluorescent nonvital dye, propidium iodide. After incubation with sera (N = 150) and a complement source, tachyzoites were washed, then stained using a fluorescein-conjugated Toxoplasma-specific antiserum. Dead tachyzoites were detected by flow cytometry after addition of propidium iodide. Intra- and inter-assay reproducibilities of percentages of dead parasites varied between 7 and 14%, and 8 and 21%, respectively. When comparing flow cytometry with the classical DT, no discrepancy was noted for positive (N = 118) and negative sera (N = 32). Correlation was good (r = 0.85) for positive sera. In conclusion, when easily available, flow cytometry is a very sensitive, specific and time-sparing method to detect specific antibodies to Toxoplasma gondii.

Animals↗

Cutaneous toxoplasmosis.

A case of epidermotropic cutaneous toxoplasmosis is reported. The patient, a 53-year-old man with chronic myelogenous leukemia in blast crisis, received a bone marrow allograft but continued to have severe pancytopenia. Numerous diffuse, palpable, purpuric nodules appeared 21 days after the transplant. Organisms were found within the epidermal keratinocytes--both singularly and in cysts. Dermal and neural infiltration was also present. Toxoplasma gondii was identified on the basis of the ultrastructural features of the parasite. Possible sources of infection include reactivation of a previous latent infection, transmission through a bone marrow allograft, or nosocomial acquisition.

Bone Marrow Transplantation↗

Intention-to-treat vs. on-treatment analyses of clinical trial data: experience from a study of pyrimethamine in the primary prophylaxis of toxoplasmosis in HIV-infected patients. ANRS 005/ACTG 154 Trial Group.

Randomized clinical trials analyzed by the intent-to-treat approach provide unbiased comparisons among treatment groups. To avoid dilution of treatment effect, many people also perform an analysis by treatment actually received, although this method may introduce bias into the results. This paper presents several approaches used for analyzing data of a recent trial and the difficulties encountered in interpreting the results of each approach. The ANRS 005/ACTG 154 Study was a double-blind, placebo-controlled, randomized, international (French, U.S., and Spanish) multicenter trial designed to assess the effectiveness of pyrimethamine for the primary prophylaxis of cerebral toxoplasmosis (CT) in HIV-infected patients with advanced immunodeficiency. In the intention-to-treat analysis, the cumulative probability of CT at 1 year did not differ significantly between the pyrimethamine arm (11.9%) and the placebo arm (13.1%), Hazard Ratio (HR) = 0.94 (95% Confidence Interval (CI) = 0.62-1.42), whereas an on-treatment analysis resulted in a significant difference: 4.2% in the pyrimethamine arm and 12.4% in the placebo arm, HR = 0.44 (95% CI = 0.24-0.80). The data showed a significant interaction between compliance and treatment outcome; and side effects were more frequently cited as reasons for compliance violations in the pyrimethamine group. Several different analytic approaches (censoring data at the time patients discontinued the study medication only for selected reasons) failed to explain the disparity between the estimation of effect of pyrimethamine by the intention-to-treat and on-treatment analyses. This experience led us to believe that comparing the results of both analyses was the best method to convince clinicians that intention-to-treat was the only interpretable analysis. We were concerned that even if pyrimethamine had a beneficial effect, it was very difficult (1) to quantify and (2) to apply to clinical practice unless one could predict the occurrence of study drug discontinuation for each patient at the time of treatment assignment. Although exploratory analyses may yield clinically relevant information and useful clarifications in the evaluation of treatments, intention-to-treat remains the only interpretable analysis of clinical trials.

AIDS-Related Opportunistic Infections↗

[Risk factors of cerebral toxoplasmosis in patients with HIV infection: data of a primary prevention trial].

To identify risk factors for cerebral toxoplasmosis (CT) in HIV patients (pts) with positive serology for Toxoplasma gondii and CD4 < 200/mm3, data from the placebo group (N = 280) of a primary prophylaxis trial, were analyzed. The probability of onset of CT (n = 46) was, at one year, 13.1%. Three baseline variables were independently associated with a higher risk of CT: group IV non AIDS, AIDS stage and CD4 < 50/mm3. Initial titer of antibodies to Toxoplasma gondii was not.

Double-Blind Method↗

[Primary prevention of cerebral toxoplasmosis in patients with HIV infection: results of a double-blind randomized trial, pyrimethamine versus placebo].

To assess the efficacy of pyrimethamine (Pyr) for primary prophylaxis of cerebral toxoplasmosis (CT) in HIV patients (pts), 554 pts were randomized in a double-blind, placebo-controlled trial (mean follow-up: 14 months). The intent-to-treat analysis found no significant difference in the incidence of ct at 1 year: 12% (Pyr) versus 13% (Pcb) nor in survival. Side-effects leading to stop the study drug were more frequent in Pyr group, especially cutaneous rashes: 8% (Pyr) versus 2% (Pcb).

Double-Blind Method↗

Pregnancy as a risk factor for acute toxoplasmosis seroconversion.

OBJECTIVE: To test the hypothesis that pregnancy is a risk factor for toxoplasmosis seroconversion. MATERIALS AND METHODS: A prospective observational study of women at child-bearing age vulnerable to Toxoplasma gondii. Serological reactions with indirect immunofluorescent antibody and immunoenzyme tests were used. The risk estimate used limits of reliability at 95%, and the results were validated by chi(2) and RR tests. RESULTS: Acute infection among pregnant women was 8.6% (45/522), and pregnancy was confirmed to be a risk factor for seroconversion (P=0.001). Living in close contact with host animals and vehicles of oocyst transmission proved to be a statistical risk for pregnant women to seroconvert, which was aggravated in adolescents. CONCLUSION: Gestation, potentiating susceptibility to this infection, points to the need of primary and secondary prevention for all pregnant women at risk.

Adolescent↗

Discordant prenatal diagnosis of congenital toxoplasmosis in a dizygotic pregnancy.

Prenatal diagnosis of toxoplasmosis gondii in twin pregnancies has been described twice. In both cases they were accomplished by prenatal blood sampling of the foetuses. We report the first prenatal diagnosis with a discordant result in a dizygotic pregnancy. One of the foetuses died in utero and the other was born unaffected at term.

Adult↗

Toxoplasma gondii recombinant antigens H4 and H11: use in ELISAs for detection of toxoplasmosis in swine.

Toxoplasma gondii recombinant antigens H4 and H11 were assessed for their potential for use in ELISA for diagnosis of toxoplasmosis in swine. The antigens were evaluated with sera from young pigs experimentally infected with T. gondii. Results were compared with ELISAs based on a native T. gondii antigen extract. Although recombinant antigen ELISAs showed a sharp rise in response with some sera very early after infection, they were relatively non-reactive with late (chronic) infection sera.

Animals↗

The incidence and economic significance of ovine toxoplasmosis in Uruguay.

Antibodies to Toxoplasma gondii were measured before and after pregnancy in a 1:64 dilution of sera with the direct agglutination test in 1613 ewes from 18 farms in 8 different counties of Uruguay from 1992 to 1994. The overall seroprevalence increased from 28.7% before mating to 38.5% after lambing in 2.5 yr and thus, the incidence was 9.8%. Losses due to toxoplasmosis during pregnancy were estimated to be 1.4 to 3.9% of the total number of ewes investigated, amounting to approximately US$1.4-4.7 million for the whole country.

Abortion, Veterinary↗

Toxoplasmosis of rats: a review, with considerations of their value as an animal model and their possible role in epidemiology.

We critically review and summarize information on the prevalence of Toxoplasma gondii infections in rats, mainly Rattus norvegicus, and their possible role as a source of infection for larger carnivores and omnivores. We also review information on immunology and natural resistance, contributing to the model value of rats in the analysis of human infection. Rats can be successfully infected with oocysts (sporozoites), tissue cysts (bradyzoites), and tachyzoites. Even adult rats, that are resistant to clinical toxoplasmosis, can be infected orally with a few oocysts or tissue cysts. Infections with tachyzoites of the RH strain are highly variable. Congenital transmission of T. gondii occurs at a high rate when rats are infected during pregnancy. Congenitally infected rats can harbor viable T. gondii in the absence of detectable antibodies to T. gondii and rats with low antibody titers may harbor few or no organisms. The isolation of viable T. gondii by bioassay is the only reliable means to determine persistence of chronic T. gondii infection in feral rats. No evidence was found for maintenance of T. gondii in rats by vertical transmission in the absence of cats.

Animals↗

The incidence and economic significance of ovine toxoplasmosis in Uruguay.

Antibodies to Toxoplasma gondii were measured before and after pregnancy in a 1:64 dilution of sera with the direct agglutination test in 1613 ewes from 18 farms in eight different counties of Uruguay from 1992 to 1994. The overall seroprevalence increased from 28.7% before mating to 38.5% after lambing in 2.5 years and thus the incidence was 9.8%. Losses due to toxoplasmosis during pregnancy were estimated to be 1.4-3.9% of the total number of ewes investigated, amounting to approximately US$1.4-4.7 million for the whole country.

Abortion, Veterinary↗

Imaging of an atypical case of congenital toxoplasmosis.

In this article we describe the cranial computerized tomography findings of an infant with congenital toxoplasmosis, which was performed because she showed an atypical clinical course consisting of meningitis and multiple cerebral abscesses. In this case the cranial computerized tomography allowed the diagnosis of hydrocephalus and multiple cerebral abscesses, and guided the therapeutic approach.

Brain Abscess↗

Ocular toxoplasmosis.

Toxoplasmosis is the most common infectious cause of posterior uveitis. Although the classic presentation including moderate to severe vitreous inflammation associated with a focal retinochoroiditis and an adjacent or nearby retinochoroidal scar offers little diagnostic difficulty, numerous atypical presentations have been recognized. Here, both serologic and PCR-based analyses can be used to support the diagnosis in clinically challenging cases. Treatment decisions can be complex and need to be individualized for each patient.

Humans↗

Treatment protocol determines the efficacy of clindamycin in acute murine toxoplasmosis.

To determine the contribution to the efficacy of clindamycin in acute murine toxoplasmosis of treatment protocol variables, groups of Swiss Webster mice inoculated intraperitoneally with 10(2) RH strain Toxoplasma gondii tachyzoites were treated with peroral clindamycin at 25, 50 and 400 mg/kgBM per day for 1, 2 and 3 weeks. While the lowest drug dose applied for a single week prolonged survival time as compared to untreated animals, not even the highest dose applied for 1 or 2 weeks completely prevented mortality. Conversely, 100% protection was achieved with 3-week treatment courses at both 50 and 400 mg/kg per day. While both survival rates and survival times increased in parallel with the drug dose and treatment duration, the latter was shown to be critical to the outcome, suggesting the use of clindamycin as an antitoxoplasmic agent should be as a prolonged course.

Acute Disease↗

Feline toxoplasmosis: interpretation of diagnostic test results.

Based on seroprevalence studies, approximately 30% of the cats in the United States have been infected by T gondii. Cats are the only species that pass the environmentally resistant oocyst in feces. Sporulated oocysts are infectious to humans and the organism can cause significant disease in immunocompromised people and transplacentally-infected babies. Clinical illness including liver disease, lung disease, central nervous system disease, fever, and uveitis occur in some infected cats. Veterinarians need to be able to identify T gondii infection in cats because of potential public health risks and during the workup of clinical diseased cats. Oocyst shedding by cats is of short duration, but can be detected by fecal examination. There are currently no serological tests that can accurately determine when a cat has shed oocysts in the past. The combination of serological test findings, clinical signs of disease, exclusion of other causes, and response to anti-Toxoplasma drugs is required to make the diagnosis of antemortem++ clinical toxoplasmosis in cats.

Animals↗

[Toxoplasmosis and pregnancy: current trends in serological follow-up].

Prevention of congenital toxoplasmosis is based on serological follow-up of pregnant patients. Routine serology includes search and titration of specific IgG and IgM. In presence of specific IgM, complementary tests should be carried out for a better dating of the contamination. Among them, the avidity test is the most currently used. It allows to exclude a recent infection in the majority of the cases. For difficult cases, it is useful to contact a specialized laboratory.

Adult↗

Toxoplasmosis: a persisting challenge.

The sixth biennial International Congress on Toxoplasmosis, organized by Uwe Gross (University of Göttingen, Germany), was held on 21-25 May 2001 in Freising, Germany. The first meeting of this kind in 1990 was attended by only 26 investigators and this year there were 115 participants covering various research topics including the immunology, epidemiology, cellular and molecular biology of Toxoplasma gondii.

Animals↗