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PubMed2006

Comparison between two amplification sets for molecular diagnosis of toxoplasmosis by real-time PCR.

PCR is now commonly applied to the diagnosis of toxoplasmosis. Although several methods are available, comparative studies are few, making it difficult to compare the performance of each technique. We compared the sensitivities of two real-time PCR assays through a prospective study on fetuses, neonates, and immunocompromised patients and on the ocular diagnosis of toxoplasmosis. The first system targeted the widely used B1 gene (GenBank accession number AF179871) while the second (RE) targeted a more recently described sequence repeated roughly 200 to 300 times (GenBank accession number AF146527). We demonstrated that molecular diagnosis requires the duplication of PCR assays, especially with the B1 system, as only one PCR was positive in 33.3% of cases. Our study showed that the RE target was more sensitive for all biological samples (amniotic fluid, placenta, aqueous humor, whole blood, and cerebrospinal and bronchoalveolar fluids) and significantly improved the performance of the diagnosis of toxoplasmosis. Taking into consideration all clinical samples, the mean gain in the crossing point value was 4.2 +/- 1.7 cycles and was even more significant for amniotic fluid (5.8 +/- 1.7 cycles).

Amniotic Fluid↗
PubMed1997

Retinal findings and characteristics in AIDS patients with systemic Mycobacterium avium-intracellulare complex and toxoplasmic encephalitis.

BACKGROUND AND OBJECTIVE: The purpose of this study was to evaluate the incidence and characteristics of retinal and choroidal manifestations of toxoplasmosis and/or Mycobacterium avium-intracellulare complex (MAC) in patients with acquired immunodeficiency syndrome (AIDS). PATIENTS AND METHODS: The authors analyzed their prospectively collected data and found 120 patients with new retinal lesions (group A) that were diagnosed 3 months or longer following the diagnosis of MAC and/or toxoplasmic encephalitis. The authors also performed a point prevalence study of retinal/choroidal findings in 25 consecutive AIDS patients (group B) without known eye disease who had been recently treated for toxoplasmic encephalitis and/or disseminated MAC infections. In addition, the characteristics of retinochoroidal toxoplasmosis scars in 5 AIDS patients were studied and compared with the characteristics of scars in 18 immunocompetent patients. RESULTS: In this study the incidence of ocular manifestations of MAC was zero (95% confidence interval [CI] 0.0% to 3.8%). Two of 25 patients (8%) (95% CI 1% to 26%) in group A and 2 of 11 patients (18.1%) (95% CI 3.3% to 51.8%) in group B had toxoplasmic retinochoroiditis. CONCLUSION: In AIDS patients, ocular manifestations of toxoplasmosis are more common than ocular MAC. In addition, when compared with immunocompetent patients, AIDS patients tend to have retinochoroidal scars with less retinal pigment epithelium hyperplasia (1.8+ vs 3+) (P = .03).

AIDS-Related Opportunistic Infections↗
PubMed2004

Performance of the immunoglobulin G avidity and enzyme immunoassay IgG/IgM screening tests for differentiation of the clinical spectrum of toxoplasmosis.

Toxoplasmosis has been well known as an important human infection to consider especially in pregnant women. Although many serologic methods are available, the diagnosis of toxoplasmosis can be extremely difficult. The presence of increased levels of Toxoplasma-specific IgG antibodies indicates an infection, but it does not differentiate between a recent and past infection. The purpose of our study was to compare the performance of the ELISA T. gondii IgG/IgM test, a widely used enzyme-linked immunosorbent assay, to the ELISA IgG avidity method. One hundred and four serum samples (from 38 males and 66 females) were tested and evaluated from symptomatic patients (chorioretinitis, lymphadenopathy), and from women in their first trimester of pregnancy who were suspected of having toxoplasmosis. The high IgG avidity and ELISA IgG antibody levels were in agreement for 51 of the specimens (49.0%). Thirty-eight discrepant (borderline) results from the IgG avidity method were positive for IgM (3 specimens) and IgG (37 specimens). Interestingly, out of the eight serum samples that were positive for both IgG and IgM antibodies, two samples were low IgG avidity, and three samples were borderline. There was no statistically significant relation observed between the results of the IgG avidity method and the ELISA IgG test, and the IgG avidity method and ELISA IgM test (chi2 = 1.987; p = 0.370 and chi2 = 2.152; p = 0.341, respectively). The IgG avidity method was considered easy to perform and an acceptable approach for the differentiation of discrepant results (recent/chronic) and for the current detection of T. gondii antibodies. We concluded that the determination of IgG avidity is a helpful tool for the diagnosis of the ocular form of toxoplasmosis and it is a safe method for screening this disease in the first trimester of pregnancy.

Animals↗
PubMed2003

Prognostic factors for the long-term development of ocular lesions in 327 children with congenital toxoplasmosis.

The aim of this study was to identify the high-risk factors associated with the development of ocular lesions in a large cohort of children with congenital toxoplasmosis (CT), irrespective of their gestational age at the time of maternal infection. Children were managed according to a standardized protocol and monitored for up to 14 years at the Croix-Rousse Hospital, Lyon, France. Cox model and a flexible regression, spline-based method were used for the analysis. During a median follow-up time of 6 years, 79 of the 327 children (24%) had at least one retinochoroidal lesion. No bilateral impairment of visual acuity was observed. The risk of a child developing ocular disease was higher not only when mothers were infected early during pregnancy, which was expected, but also when CT was diagnosed prior to or at the time of birth, when non-ocular manifestations were present at baseline and when birth was premature.

Adolescent↗
PubMed2003

[Diagnosis of toxoplasmosis and toxocariasis using fluid from the anterior ocular chamber].

The authors discuss methods of improvement of the etiologic diagnosis of the toxoplasma and toxocara associated posterior uveititis, by examining specific antibodies in the aqueous humor. Paired samples of aqueous humor and serum were analyzed in 23 patients. Chorioretinitis of infectious etiology was suspected in 15 patients, 3 patients were treated for panuveitis, 4 patients for intermediate uveitis, and in 1 patient the sample was obtained to rule out malignant melanoma. The local ocular antibody production was calculated according to Desmonts. Toxoplasma etiology was confirmed by local antibody production analysis in 1 patient, toxocara etiology in 5 patients. In 20 patients in the control group local specific antibody production was not demonstrated.

Adolescent↗
PubMed1983

Retinal manifestations of the acquired immune deficiency syndrome (AIDS): cytomegalovirus, candida albicans, cryptococcus, toxoplasmosis and Pneumocystis carinii.

The ocular manifestations of 34 patients with the Acquired Immune Deficiency Syndrome (AIDS), are reviewed. Cytomegalovirus retinitis was seen in 18 patients, cotton wool spots were observed in 11 patients with Pneumocystis carinii pneumonia; Fungal retinitis and Toxoplasmosis retinochoroiditis were each seen in 2 patients. A review of literature regarding AIDS is included.

Acquired Immunodeficiency Syndrome↗
PubMed1991

[Prevalence, morphology and therapy of toxoplasmosis chorioretinitis in AIDS].

Toxoplasmosis-retinochorioiditis is the second most frequent opportunistic infection of the eye among our series of AIDS patients. Between 1985 and 1990 we diagnosed 7 cases in 261 AIDS patients (Walter Reed classification 6); prevalence = 2.7%). The incidence has been increasing over the years. In four cases, toxoplasmosis was restricted to the eye, in three cases, ocular disease occurred combined with toxoplasmosis of the central nervous system. Since serological findings are not very reliable in AIDS-patients, the most important element in the differential diagnosis against retinitis of different etiology is ophthalmoscopy. There are a number of findings which allow differentiation of toxoplasmosis from other forms of retinitis, especially cytomegalovirus retinitis. Toxoplasmosis-retinitis was stopped in all cases by administering a specific therapy of pyrimethamine combined with clindamycin, a sulfonamide or spiramycin. Stable scar formation was achieved after 2-3 weeks therapy. Subsequent maintenance therapy with Fansidar (pyrimethamine + sulfadoxine) protected 4/4 patients from a relapse, while maintenance therapy with pyrimethamine alone allowed a relapse in 1/2 patients.

Acquired Immunodeficiency Syndrome↗
PubMedDate not supplied

[Observations of children with chorioretinitis in congenital toxoplasmosis].

Hundred eleven children with congenital toxoplasmosis were followed up in the Department of Infectious and Parasitic Diseases in Childhood, Medical Academy in Warsaw, within 1979-1988. Ocular changes found in 91 children including chorioretinitis in 86 microphthalmia in 7, ophthalmic nerve atrophy in 15, vitreous body inflammation in 5, and cataract in 4. Only in 16 children the diagnosis was performed in the first year of life. In 15 children the recurrence of inflammatory process, most frequently in the time of puberty, was noted; twice in 5 of them. It was independent on the treatment which was previously administrated. Serological tests in ocular form of congenital toxoplasmosis do not indicate the dynamic changes in the inflammatory process. It is very important that small children are examined early and the treatment is started in the first year of life.

Adolescent↗
PubMed1977

The ocular manifestations of congenital infections produced by toxoplasma and cytomegalovirus.

Chorioretinitis is the most common ocular manifestation of congenital toxoplasmosis occurring in both symptomatic and the more freqeunt subclinical form of the disease. Chorioretinitis also occurs in symptomatic congenital cytomegalovirus (CMV) but not in the subclinical form of this congenital congenital infection. Diagnosis cannot be made from ocular signs alone. Knowledge of the epidemiology of both congenital infections along with information about the postnatal history will assist in the differentiation.

Adult↗
PubMed2001

Involvement of apoptosis and interferon-gamma in murine toxoplasmosis.

PURPOSE: A murine toxoplasmosis model has been developed that results in central nervous system (CNS) and ocular inflammation characterized by encephalitis with numerous brain tissue cysts and milder inflammation with rare tissue cysts in the eye after 4 weeks of Toxoplasma gondii infection. In this model IFN gamma and inducible nitric oxide (iNO) are protective against T. gondii infection. In this study, the role of apoptosis in the pathogenesis of toxoplasmosis was investigated. METHODS: C57BL/6 (wild-type mice), B6MRL/lpr, and B6MRL/gld (defective Fas or FasL expression, respectively) mice were infected intraperitoneally with 20 to 30 tissue cysts of the ME-49 strain of T. gondii. Mice were killed at days 0, 14, or 28 after infection. The eyes and brains were harvested for histologic, immunohistochemical, and molecular studies. Analysis included immunostaining for Fas, FasL, Bcl-2, and Bax; in situ apoptosis detection (TUNEL assay); RT-PCR amplification for IFN gamma; and measurement of ocular nitrite levels. The control mice were naïve mice of each strain that received no inoculation or injection. RESULTS: Wild-type mice appeared to constitutively express apoptotic molecules at higher levels in the eye than in the brain. Consequently, during T. gondii infection, apoptosis was greater in the eyes than in the brain. Untreated naïve lpr and gld mice showed no expression of Fas and FasL, respectively. After infection, a slightly higher number of tissue cysts (lpr, 11.8 +/- 2.4; gld, 10.3 +/- 3.4) were found in the brains of the mutants than in the control animals (8.8 +/- 2.9). However, no significant differences between the number of apoptotic cells, inflammatory scores, or number of tissue cysts were noted in the eyes. IFN gamma mRNA in control mice was detected at day 28 after infection, whereas in both mutants, mRNA production occurred earlier, at day 14. Ocular nitrite levels were higher in lpr and gld mice than in wild-type mice. CONCLUSIONS: No significant difference in the degree of ocular inflammation and apoptosis was detected between the wild-type and Fas or FasL mutant mice. However, there was an earlier and subjectively greater expression of IFN gamma in the brain and eye and a higher level of nitrite in the ocular tissue of mutant strains than in the wild type. Multiple factors are likely to be involved in the pathogenesis of ocular toxoplasmosis.

Animals↗
PubMed1977

Immunosuppression and eye disease. First Vail lecture.

Several viral, fungal, and protozoal diseases of the eye are significantly associated with immunologic deficiencies. Of the viral agents, cytomegaly and herpes simplex and zoster cause a discrete necrotizing retinopathy that has the characteristics of vascular occlusion. Measles may result in a delayed retinopathy that is predominantly macular and associated with subacute progressive encephalopathy. Of the fungal agents, Candida and Aspergillus are apt to involve the eye, beginning as choroidal lesions with extension forward to involve the pigment epithelium and retina secondarily. Mucor and Cryptococcus are less common. Toxoplasmosis is the one ocular protozoal disease whose incidence is increased by immunosuppression, and, like the viral diseases, is characterized by a discrete necrotizing retinopathy and probably results from activation of dormant organisms in the retina. Autoimmunity undoubtedly plays an important role in eye disease but its ocular pathogenesis is obscure.

Adult↗
PubMedDate not supplied

Toxoplasmosis.

Toxoplasmosis is the most common cause of posterior uveitis in immunocompetent subjects. The infection can be congenital or acquired. Ocular symptoms are variable according to the age of the subject. For instance, young children present with reduced visual acuity, strabismus, nystagmus, and leucocoria, while teenagers and adults complain of decreased vision, floaters, photophobia, pain, and hyperemia. Toxoplasmic retinochoroiditis typically affects the posterior pole, and the lesions can be solitary, multiple or satellite to a pigmented retinal scar. Active lesions present as grey-white focus of retinal necrosis with adjacent choroiditis, vasculitis, hemorrhage and vitreitis. Cicatrization occurs from the periphery towards the center, with variable pigmentary hyperplasia. Anterior uveitis is a common finding, with mutton-fat keratic precipitates, fibrine, cells and flare, iris nodules and posterior synechiae. Atypical presentations include punctate outer retinitis, neuroretinitis, papillitis, pseudo-multiple retinochoroiditis, intraocular inflammation without retinochoroiditis, unilateral pigmentary retinopathy, Fuchs'-like anterior uveitis, scleritis and multifocal or diffuse necrotizing retinitis. The laboratory diagnosis of toxoplasmosis is based on detection of antibodies and T. gondii DNA using polymerase chain reaction (PCR). Toxoplasmosis therapy includes specific medication and corticosteroids. There are several regimens, with different drug combinations. Medications include pirimetamine, sulfadiazine, clindamycin, trimethoprime-sulphamethoxazol, spiramycin, azithromycin, atovaquone, tetracycline and minocycline. The prognosis of ocular toxoplasmosis is usually good in immunocompetent individuals, as long as the central macula is not directly involved.

Animals↗
PubMedDate not supplied

[Fuchs' cyclitis: etiologic and clinical aspects].

45 patients with Fuchs' heterochromic cyclitis were examined. The clinical signs and their chronological order are summarized. A possible etiological role for ocular injuries and toxoplasmosis is discussed.

Adolescent↗
PubMed2004

[Necrotic herpetic retinitis].

The diagnosis of necrotic herpetic retinitis is suggested on clinical grounds, prompting urgent appropriate intravenous and intravitreal treatment. PCR on ocular samples is most often successful in identifying the herpetic agent. Classic acute retinal necrosis syndrome caused by herpes simplex or zoster virus and the different clinical forms present in immunocompetent or immunodepressed patients are described. The differential diagnosis includes atypical presentation of retinal necrosis caused by toxoplasmosis, syphilis, or ocular lymphoma; the ocular samples are useful in establishing the etiological diagnosis. We describe the different therapeutic strategies in the acute phase and as secondary prophylactic treatment. The clinical outcome appears to be influenced by rapid, appropriate treatment, limiting the extension of the retinal necrosis.

Diagnosis, Differential↗
PubMed2002

Causes of uveitis at The Eye Center in Saudi Arabia: a retrospective review.

AIMS AND BACKGROUND: The main objective of this study was to determine the causes of uveitis at a referral center in Riyadh, Saudi Arabia. METHODS: We carried out a retrospective review of clinical records of 200 uveitis cases referred to The Eye Center, a referral center in Riyadh, Saudi Arabia. There were 120 (60%) males and 80 (40%) females with an age range of 7 to 91 years and a mean age of 35 (SD +/- 17). Patients had complete ophthalmic and medical examinations. Laboratory studies were requested whenever indicated. Patients were followed up for a minimum of 12 months. RESULTS: In the period 1995-2000, we encountered 200 cases of uveitis among a total of 20,191 consecutive new cases, yielding a prevalence of 1%. Acute anterior uveitis of undetermined origin was found in 58 (29%) of 200 patients. There were 13 (6.5%) cases of Behçet's disease, 7 (3.5%) of Fuchs' heterochromic iridocyclitis, 6 (3%) of sarcoidosis, and 5 (2.5%) patients had Vogt-Koyanagi-Harada syndrome (VKH). Among the infectious causes, herpetic uveitis was found in 32 (16%) patients, tuberculosis in 21 (10.5%), and toxoplasmosis in 13 (6.5%) cases. Seventeen (8.5%) cases were of miscellaneous origin and in 28 (14%) cases the etiologic diagnosis was undetermined. CONCLUSION: Acute anterior uveitis of undetermined origin was the most common cause of uveitis, followed by Behçet's disease. Herpetic uveitis was the most common infectious cause of uveitis. Ocular tuberculosis and toxoplasmosis were found to be common causes of infectious uveitis at this referral center in Saudi Arabia.

Adolescent↗
PubMed1997

Recognition of tissue cyst-specific antigens in reactivating toxoplasmosis.

Current serological tests do not discriminate between asymptomatic latent Toxoplasma gondii infection and reactivating toxoplasmosis, but timely therapeutic intervention before the development of symptoms would lead to major reductions in morbidity and permanent disability. This study developed a new enzyme-linked immunosorbent assay (ELISA) for antibody to T. gondii tissue cyst antigens and screened tissue cyst antigens by Western blot analysis to test the hypothesis that antibody recognition of T. gondii tissue cyst-derived antigen is a good indicator of reactivation disease. A total of 187 sera was tested by Sabin-Feldman dye test and tissue cyst ELISA, AIDS patients and patients with ocular disease were considered separately, as the exposure to parasite antigens may be different in these two groups. The dye test did not discriminate between immunocompetent and immunocompromised T. gondii seropositive patients or between active and quiescent toxoplasmosis. Tissue cyst ELISA demonstrated a raised specific antibody response in immunocompetent T. gondii seropositive patients and in quiescent HIV positive sera. These data support th view that the tissue cyst population is in a state of dynamic equilibrium. It is proposed that, in the immunocompetent host, tissue cyst development and rupture are under some degree of immune control, but that in the immunocompromised host this equilibrium is disturbed and reactivation disease results. Data from patients with reactivating ocular toxoplasmosis demonstrate that tissue cyst-specific antibody levels are not different in active and quiescent disease and indeed they are not significantly different from immunocompetent T. gondii seronegative sera. In the Western blot analysis of 57 HIV positive patient sera, eight antigens (65, 57, 49, 47, 36, 28, 26 and 18 kDa) were consistently recognised by one third or more of the sera tested, but no single antigen was diagnostic of quiescent or active toxoplasmosis. It is concluded that tissue cyst-derived antigens are not a reliable serological marker of reactivating toxoplasmosis.

AIDS-Related Opportunistic Infections↗
PubMed1983

Toxoplasma gondii--an environmental contaminant.

Toxoplasma gondii, the causal agent of toxoplasmosis, is a ubiquitous protozoan parasite which has the potential to infect man and all warm-blooded animals. It has as its definitive host the cat. Infections acquired by the human adult are generally subclinical. However, if acquired for the first time during pregnancy, the parasite can invade the developing foetus. Under these circumstances infection can result in abortion, stillbirth or production of live-born offspring with severe multiple organ involvement. Alternatively, offspring can be symptomless at birth but may manifest neurological and ocular sequelae of toxoplasmosis in later life. The degree of clinical involvement is thought to be dependent upon the time of acquisition of infection by the pregnant female. Recent investigations have been concerned with behavioural aspects of predator-prey relationships between cats and rodents. Since these aspects affect the spread of toxoplasmosis in the environment, they have strong epidemiological and ecological implications. Toxoplasma infection in the environment, they have strong epidemiological and ecological implications. Toxoplasma infection in mice is associated with subtle alterations in exploratory behaviour which are almost certainly maladaptive, rendering infected mice more susceptible to predation by cats. Consequently the behavioural abnormalities in mice associated with Toxoplasma infection would be of major importance for the continuation of the life-cycle of the parasite. Ingestion of Toxoplasma-infected mice leads to oocyst production in cats and this opens up the well-known pathway whereby Toxoplasma infection reaches the human species.

Animals↗