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Neuroimaging of AIDS. I. Central nervous system toxoplasmosis.

Toxoplasmosis is the most common cerebral mass lesion encountered in HIV-positive patients. Previously uncommon, this disease has increased markedly since the AIDS epidemic. There are occasionally unusual appearances of central nervous system toxoplasmosis that make diagnosis by standard imaging techniques difficult or impossible. More recently, MR spectroscopy has increased the ability to differentiate between various central nervous system lesions.

AIDS-Related Opportunistic Infections↗

[Ocular toxoplasmosis. Utilization of immunohistochemical reaction for diagnosis].

The diagnosis of ocular toxoplasmosis is based primarily on clinical presentation and laboratory tests described else where. Eventually, unusual clinical presentation, as well unusual pathologic findings occur, mainly in immunosuppressed individuals. The authors report a case of a female patient from Paraná with a progressive ocular disease, for at least three years, without definite diagnosis. After an exhaustive clinical and laboratory investigation, as well empiric medical treatment, without success, it was decided to enucleate the atrofic organ and to proceed to a histologic examination. It revealed a cronic and inspecific inflammatory process without any specific agent. However the immunohistochemical technique was able to detect Toxoplasma gondii antigens in the ocular tissue. This technique provides an alternative method for the diagnosis of unusual forms of toxoplasmosis.

Female↗

[Miller-Fisher syndrome associated with toxoplasmosis].

We report on an immunocompetent patient who developed acquired toxoplasmosis and Miller-Fisher syndrome with central and peripheral neural involvement. We suggest the possible relationship between acquired toxoplasmosis and Miller-Fisher syndrome, even though we cannot exclude a mere coincidence. To our knowledge such an association has not been reported.

Adult↗

[Value of clindamycin in the treatment of ocular toxoplasmosis].

PURPOSE: Chorioretinal toxoplasmosis can threaten visual function when located in the posterior pole. The aim of this study was to compare the advantages and disadvantage of combination of malocid-sulfadiazine and clindamycin subconjunctivally. METHODS: Two groups of patients affected by unilateral chorioretinal toxoplasmosis were studied. The diagnosis was performed in 77% of cases on acqueous humor analysis. The first group of twenty-six patients was treated with a combination of malocid-sulfadiazine while the second group (seventeen patients) was treated with clindamycin subconjunctivally. Local and general corticosteroids were associated in all cases. Mean follow-up was 19 months in the first group and 16.5 months in the second. RESULTS: Visual acuity was increased in 88.5% of cases in the first group and in 94% of cases in the second group. Cicatrization obtained in both groups was comparably delayed 1.68 months for the first and 1.26 months for the second. Recurrences were rarely observed in the two groups: respectively 8% and 6% of cases. No local and general complication was noted. CONCLUSION: These findings suggest the advantages of subconjunctival clindamycin treatment due to the absence of general hematological toxicity.

Adolescent↗

Lack of therapeutic effect of colchicine on murine toxoplasmosis.

In a previous report, we showed that addition of colchicine to cultures of glial cells infected with Toxoplasma gondii decreased the number of parasites by up to 80%. To provide support for potential therapeutic use of colchicine in toxoplasmosis, a murine model of T. gondii infection was used. Mice infected with pure RH T. gondii tachyzoites (from 2,233 to 25,000 parasites) were treated daily with either pyrimethamine (80 or 51 mg/kg), colchicine (10 mg/kg), pyrimethamine-colchicine, or vehicle (controls). Survival rates were lower in animals treated with colchicine (from 40% to 27%) and pyrimethamine-colchicine (from 73% to 41%) than in animals treated with pyrimethamine alone (from 100% to 73%). There was no extension of mean survival time in animals treated with colchicine compared to controls. These results demonstrate that colchicine does not improve the course of acute toxoplasmosis in mice, and it is detrimental rather than beneficial at the regimen tested.

Administration, Oral↗

Fatal acute toxoplasmosis in three golden lion tamarins (Leontopithecus rosalia).

Fatal acute toxoplasmosis was diagnosed in three golden lion tamarins (Leontopithecus rosalia), a breeding pair and their male offspring, by histology and immunohistochemistry. The distribution and severity of lesions differed among the animals, but the small intestine and the pancreaticoduodenal lymph nodes were especially affected. Protozoal organisms consistent with Toxoplasma gondii tachyzoites, often clustered, were seen in all lesions and were specifically immunostained with a T. gondii polyclonal antibody. The infection was probably acquired orally. Several breeding groups of golden lion tamarins have succumbed to toxoplasmosis both in North American and European zoos, so this disease should be considered an important problem in this endangered species. Toxoplasma gondii can cause latent infections in New World primates and therefore could potentially induce abortions or congenital infections in wild golden lion tamarins born from latently infected reintroduced females.

Acute Disease↗

Diagnosis of cerebral toxoplasmosis by a nested polymerase chain reaction: a case report.

A 24-year-old man infected with human immunodeficiency virus type I rapidly progressed to acquired immune deficiency syndrome. His clinical picture was compatible with a presumptive diagnosis of cerebral toxoplasmosis. Application of a nested polymerase chain reaction (PCR) succeeded in detecting Toxoplasma gondii DNA in both the venous blood and cerebrospinal fluid specimens. This result indicates that PCR is a convenient tool for making a rapid and accurate diagnosis of cerebral toxoplasmosis, especially in developing countries.

Adult↗

[Toxoplasmosis in Dakar. Seroepidemiologic sampling of 353 women of reproductive age].

Thanks to a serological survey carried out in Dakar from January to November 1993 among 353 procreative women, immune cover regarding toxoplasmosis was assessed using ELISA methodology: 40.2% of the surveyed population had antibodies of toxoplasmosis. No evidence of age, pregnancy, number of previous pregnancies was noted in antitoxoplasmosis antibodies prevalence. The seroconversion risk seems to be low even when it has existed during pregnancy. Contamination occurred during childhood. Some sanitary education should be provided to the procreative population in order to achieve a better compliance with basic hygiene regulations during pregnancy.

Adolescent↗

[A case of congenital toxoplasmosis confirmed by detection of Toxoplasma gondii in placenta].

We report a case of congenital toxoplasmosis with a prenatal diagnosis of fetal hydrocephalus. A CT scan performed at birth revealed ventricular dilation with calcification. The serum and CSF Toxoplasma specific IgM were elevated. The diagnosis was confirmed by the presence of Toxoplasma cysts in the placenta, and detection of the Toxoplasma SAG1 gene by a polymerase chain reaction (PCR) (placenta, positive; CSF, negative). Signs of active central nervous system infection, such as the decreased CSF glucose, and elevated CSF protein, neuron specific enolase and LDH, resolved after initiation of treatment with pyrimethamine and sulfazoxine. A PCR test using the placental tissue may be useful for the rapid diagnosis of congenital toxoplasmosis.

Adult↗

Toxoplasmosis.

QUESTION: A 28-year-old patient is 3 months pregnant with her first child. She has heard about toxoplasmosis from her friends and asks if it is safe to keep her cat. How should I reply? ANSWER: Your patient does not have to give up her cat. She should be encouraged to take primary preventive measures. If toxoplasmosis serology is performed, a baseline should be done as early as possible with serial follow up in the second and third trimesters.

Adult↗

Nifurtimox plus pyrimethamine for treatment of murine toxoplasmosis.

In the search for novel antitoxoplasmic agents, we evaluated the efficacy of nifurtimox (3-methyl-4[5'-nitrofurfurylidene-amino]-tetrahydroe-4H-1,4- thiazine-1,1-dioxide), an antiprotozoal drug effective against trypanosomiasis, in an experimental model of acute toxoplasmosis in mice. One hundred NIH mice were inoculated intraperitoneally, each with 2,614 RH tachyzoites of Toxoplasma gondii, and randomly allocated into 5 groups (n = 19-21). Animals from each group were orally treated for 10 days either with nifurtimox 25 mg/kg/day (NF1), nifurtimox 50 mg/kg/day (NF2), pyrimethamine 60 mg/kg/day (P), the combination nifurtimox 50 mg/kg/day plus pyrimethamine 60 mg/kg/day (NF2-P), or with corn oil (controls). Survival of mice was recorded daily for 1 mo after the experimental infection. Comparisons of cumulative mortality between groups were made applying the chi2 test. Mean survival time was longer in animals from P and NF2-P groups than those from NF1, NF2, and control groups. Cumulative mortality was less in mice from the NF2-P group (25%), than that in mice from the P (65%), the NF1 (100%), the NF2 (89%), or the control (95%) groups (P < 0.01). The doses of nifurtimox used in the present study were not significantly effective against murine toxoplasmosis. However, when combined with pyrimethamine, a strong anti-toxoplasma effect was obtained in comparison with survival rates associated with pyrimethamine or nifurtimox alone. It seems feasible that nifurtimox inhibits the replication of T. gondii tachyzoites similar to that of other protozoans, e.g., Trypanosoma and Leishmania. It will be important to determine if the reduction of mortality in mice treated with the nifurtimox-pyrimethamine combination results from summation or from synergism. Further studies on the toxic mechanisms exerted by nifurtimox on T. gondii seem warranted.

Administration, Oral↗

[Toxoplasmosis in families. I. Detection of T. gondii invasion and serological appraisal].

Toxoplasmosis was studied in 102 families, in which index-cases manifested the fully symptomatic course of the acquired lymphnodular toxoplasmosis, confirmed by presence of IgM and IgG class antibodies (ELISA, Vidas, BioMerieux). The index-cases (group A) provided a rational index of the acquired invasion or its late sequele in other families members. The studies were performed in 388 persons, originating from Wielkopolska region, including 102 patients of a group A and 286 of families members of group B (167 children and 221 adults). In group A patients (including 49 children and 53 adults) immunoserological studies detected IgM class antibodies in 68.7% of cases and IgG class antibodies in 94.1% patients. In 286 family members (group B), presence of IgM class antibodies was found in 12.2% and IgG class antibodies was found in 55.2% studied persons; clinical pathology was noted in 46 patients (16.3%) including 3 pregnant women. The obtained results point to the need of complex evaluation of family environments based on analysis of serological tests (including estimation of IgM and IgG class antibodies) and accompanied by clinical analysis of studied children and adults.

Adolescent↗

[Contribution of gene amplification in the biological diagnosis of toxoplasmosis].

Biological diagnosis of toxoplasmosis is generally based on indirect arguments (serology). In cases of immaturity or of immune depression, however, evidence of the parasite has to be obtained. This involves time-consuming or relatively insensitive culture techniques. Molecular biology, and more particularly the polymerase chain reaction gene amplification technique, makes it possible to identify an extremely small quantity of parasites in a complex biological fluid in a few hours. We summarized our experience with an original technique using toxoplasma ribosomal DNA as the target. Its use in the amniotic fluid provides a distinct improvement in antenatal diagnosis and is fast becoming the technique of reference. Difficult cases have been solved by its application in ophthalmology. Finally, in immunodepressed patients, especially in cases of acquired immunodeficiency syndrome, assessment is currently ongoing. The results obtained so far, especially in the analysis of the cerebral spinal fluid, are encouraging.

Adult↗

Cerebral Toxoplasmosis.

The choice of drugs for treating cerebral toxoplasmosis is limited. There are only three drugs available, and, of these, pyrimethamine and sulfonamide are invariably used in combination. Clindamycin is an alternative choice. Another drug, spiramycin, has poor central nervous system penetration, but achieves high concentrations in the placenta, and it is useful for treatment of toxoplasmosis during pregnancy. Because long-term maintenance therapy is often necessary, particularly in patients with AIDS, a wider choice of antibiotics is urgently necessary, because of potential problems with drug resistance and side effects. Treatment may be started empirically in any patient with HIV infection and multiple brain lesions. The drugs of choice are a combination of sulfadiazine and pyrimethamine. Folinic acid should be added to prevent pyrimethamine-induced bone marrow suppression. Repeated neuroimaging, 2 weeks after initiating therapy, is needed to assess efficacy of treatment. If CD4 cell counts remain below 100 cells per mm(3), lifelong therapy is needed. Tissue diagnosis should be established in patients who do not respond to treatment, who have solitary lesions, or in patients without AIDS. Recent breakthroughs in the understanding of the biology of Toxoplasma will result in the development of a range of new therapies in the near future.

Journal Article↗

Toxoplasmosis: the first commercial vaccine.

Infection with Toxoplasma gondii can have serious consequences in pregnant women and in immunocompromised individuals. For the farming industry it is a major cause of economic loss through neonatal mortality, particularly in sheep. In the following short review, David Buxton summarizes the main features of the complex immune response to the parasite and outlines how the first commercial vaccine was developed to control toxoplasmosis in pregnant sheep. Although the vaccine is inappropriate for use in human beings, the manner in which it induces immunity in sheep will prove vital to our understanding of the infection and the eventual development of a suitable vaccine to combat toxoplasmosis in people as well as in animals.

Journal Article↗

Hemophagocytic syndrome associated with extracerebral toxoplasmosis in an HIV-infected patient.

Hemophagocytic syndrome (HPS) is a clinical entity that combines non-specific clinical and biological features. The diagnosis is usually confirmed by a bone marrow examination. HPS may be primary or secondary to a malignancy or to an infectious or autoimmune disease. Since it was first described, various agents have been implicated, including viruses, bacteria, and parasites. In HIV patients, many cases occur with lymphoma or with a variety of opportunistic infections due to CMV, HHV8, Pneumocystis carinii, Mycobacterium tuberculosis, MAC, toxoplasmosis, and even pneumococcus. We report here a case of an AIDS patient presenting a HPS secondary to an extracerebral form of systemic toxoplasmosis that was only revealed by specific PCR in tissue other than the CNS.

Journal Article↗

Effect of clindamycin in a model of acute murine toxoplasmosis.

OBJECTIVE: To characterize the antitoxoplasma activity of clindamycin in a murine model of acute toxoplasmosis. METHODS: Rates of survival and mean survival times of Swiss Webster mice infected intraperitoneally with 106-102 tachyzoites of the RH strain of Toxoplasma gondii treated with clindamycin or sulfamethoxazole (positive control) or untreated (negative control) were compared. Survivors were submitted to examination of untreated brain tissue preparations, intraperitoneal and peroral subinoculations of brain tissue homogenates into fresh mice, and to pathohistology, including immunohistochemistry, of brain and lungs. RESULTS: The effect of clindamycin treatment (400 mg/kg/day) on infected Swiss Webster mice was inoculum size dependent, ranging from no survivals in animals infected with 106 parasites, to 100% survivals with an inoculum of 102. Treatment initiated 24 h before and at time of infection prolonged mean survival times comparably to sulfamethoxazole, and significantly when compared to untreated controls. In contrast, treatment initiated 48 h postinfection with an inoculum of 106 did not postpone death. In the clindamycin-treated survivors, there was no biological or histologic evidence for the persistence of toxoplasma. CONCLUSIONS: The results obtained show that at an appropriate parasite dose/drug dose ratio, clindamycin is strongly toxoplasmacidal in a murine model of acute toxoplasmosis.

Journal Article↗

[Chemotherapeutic efficacy of trimethoprim-sulfamethoxazole (Bactrim) in experimental murine toxoplasmosis]

The chemotherapeutic efficacy of trimethoprim-sulfamethoxazole (Bactrim) in mice experimentally infected with Toxoplasma gondii was evaluated. The average survival days and survival rate of mice infected intraperitoneally with 1 x 10(5) trophozoites and treated with Bactrim were compared with those of untreated group. The hematologic findings of blood samples of experimental mice were observed for comparison of side effects between Bactrim and pyrimethamine (Daraprim), the latter of which has been one of the favorable drugs for the treatment of toxoplasmosis. The results are summarized as follows: Bactrim showed a strong evidence of potent anti-Toxoplasma activity. The survival rate of mice administered with 24 mg of Bactrim per mouse per day for 7 days, was 83.3 percent, and the rate was increased to 100 percent in mice administered with two-fold concentrated dose of the drug. The average numbers of white blood cells (W.B.C.) in the mouse groups treated with Bactrim or Daraprim were more increased than those only infected with T. gondi. The mice treated with Daraprim, however, showed remarkably decreased numbers of W.B.C. as compared with those treated with Bactrim. The average numbers of red blood cells (R.B.C.) and platelets both in the drug-treated and untreated T. gondii-infected mice were decreased as compared with normal mice. The numbers of R.B.C. in Daraprim-treated mice, however, were more decreased than in Bactrim-treated mice. The average levels of hemoglobin both in the drug-treated and untreated T. gondii-infected mice were decreased, compared with normal mice. But there was no difference in the levels of hemoglobin between Bactrim- and Daraprim-treated groups. In conclusion, trimethoprim-sulfamethoxazole (Bactrim) was proven to be effective and safe for the treatment of murine toxoplasmosis. The efficacy was comparable with pyrimethamine (Daraprim), but bone marrow depression was less severe with Bactrim treatment.

Journal Article↗