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Severe sulfadiazine hypersensitivity in a child with reactivated congenital toxoplasmic chorioretinitis.

A 7-year-old with congenital toxoplasmosis who took pyrimethamine and sulfadiazine for reactivated chorioretinitis developed fever, severe cutaneous involvement, swelling, abdominal pain and transaminitis, persisting weeks after withholding medicines. Symptoms resolved when systemic corticosteroids were administered. This case underscores problems in clinical management with sulfadiazine hypersensitivity, potential immunosuppression from corticosteroids and selection of medications for recurrences of toxoplasmic chorioretinitis.

Animals↗

Ophthalmic findings among one thousand inhabitants of Rarotonga, Cook Islands.

A survey of 986 Polynesians was conducted in Rarotonga, Cook Islands, for the complications of diabetes. The ophthalmologists in the team made a general assessment of eye health. Trauma was a major cause of blindness. Diabetic retinopathy, trachoma, cataract and macular degeneration were not common findings. The initial criteria of nuclear cataract were pigmentation or opacification with loss of fetal suture detail. This was invalidated by the finding in young adults of enhanced pigmentation may augment the intrinsic filter of near ultraviolet light. Of the 118 people with chorioretinal scars, 25 shared features with cases reported from the Pacific region attributed to filariasis. The majority, however, were typical of toxoplasmosis. Cases of pseudoexfoliation were rare. This is surprising in view of the high prevalence reported among Australian Aborigines at a comparable latitude.

Adult↗

Ultrastructural findings in feline corneal sequestra.

OBJECTIVES: (1) To describe the ultrastructural features of corneal sequestra in cats; and (2) to enhance our understanding regarding the pathogenesis of feline corneal sequestration. METHODS: Nine corneal sequestra were harvested via keratectomy from globes of nine cats. The sequestra were routinely fixed then postfixed for high resolution light and transmission electron microscopy (HR-LM and TEM, respectively). The tissues were embedded in Epon/Araldite. Sections of 0.5-microm thickness were cut and stained with 1% toluidine blue in 1% sodium tetraborate solution for HR-LM. Ultrathin sections were collected on copper grids and stained with uranyl acetate and Sato's lead stain for TEM. Ultrathin sections were examined and the images were captured on an Advantage HR CCD camera using a Hitachi 7500 electron microscope operated at 80 kV. Two healthy corneas from two cats were harvested immediately following euthanasia. These corneal tissues (control samples) were processed in the same manner as the corneal sequestra for HR-LM and TEM. A portion of each sequestrum was also submitted for polymerase chain reaction (PCR) testing for infectious agents including feline herpesvirus-1 (FHV-1), Toxoplasma gondii, Chlamydophila felis and Mycoplasma spp. RESULTS: Ultrastructure of healthy corneal tissues revealed basal corneal epithelial cells aligned adjacent to a thin acellular layer similar to Bowman's layer with underlying tightly packed, regularly arranged, collagen fibrils oriented in different planes. Keratocytes were elongated and had long and irregularly shaped nuclei, and cytoplasm contained rough endoplasmic reticulum and abundant membrane-bound vesicles. In contrast, corneal sequestra contained varying amounts of an amorphous, electron-dense substance, continuous with intact basal epithelial basement membranes peripherally, and overlying corneal ulceration and loosely packed collagen fibrils. Remnants of necrotic keratocytes were seen in spaces between disarranged collagen layers. In all samples, occasional keratocytes exhibited morphology indicative of apoptosis including clumping and margination of chromatin, and shrunken cytoplasm. Varying degrees of inflammation were noted on HR-LM and TEM of affected corneas including peri- and intralesional neutrophils, lymphocytes, plasma cells, and macrophages. Corneal sequestra were FHV-1-positive (n = 3), FHV-1- and T. gondii-positive (n = 1), T. gondii-positive (n = 3), or negative for DNA of these infectious agents (n = 2) using PCR. All corneal sequestra were negative for DNA of Chlamydophila felis and Mycoplasma spp. using PCR. CONCLUSIONS: Apoptosis may play a role in the pathogenesis of feline corneal sequestration independent of the presence of DNA of these infectious organisms. Prospective clinical studies are warranted to further understand the significance of T. gondii in relation to feline corneal sequestration.

Animals↗

A murine model of congenital toxoplasmic retinochoroiditis.

A histopathological study of toxoplasmic retinochoroiditis in 39 eyes of mice infected in utero with Toxoplasma gondii and sacrificed at 16 weeks post-partum showed a wide variation in the pattern of tissue destruction. The changes in individual eyes were graded from mild to severe; Toxoplasma cysts were present in the retina and optic nerve in each grade. In the least affected eyes, Toxoplasma cysts were rarely seen and the disease was limited to a low grade uveitis and retinal lymphocytic perivasculitis. In the more severely affected eyes, there was focal, sectorial or total retinal destruction with secondary degeneration in the lens. In some eyes inflammatory destruction of the outer retina was associated either with a paucity of cells, or with lymphocytic infiltration or with plasma cell infiltration; giant cell granulomatous reactions were rare. In the most severely affected eyes the retina was necrotic and calcified. The findings illustrate the complexity of toxoplasmic retinochoroiditis and suggest that autoimmunity may play a part in the disease process.

Animals↗

Aggressive toxoplasma retinitis.

Toxoplasma infection is a common cause of infectious uveitis. It usually produces a characteristic fundal appearance, with evidence of previous inflammation. However, it may occur in an atypical and aggressive form. Steroids administered to salvage vision may then worsen the clinical course. Retinal biopsy may be diagnostic in cases where doubt exists. We illustrate these points with two cases.

Aged↗

Plate hemolysin test for the rapid screening of toxoplasma antibodies.

A plate hemolysin test was developed to screen serum specimens for the presence of toxoplasma antibodies. When we tested 130 sera by both this test and the standard toxoplasma dye test, we found the plate hemolysin test to be a rapid, sensitive, and economical method for detecting toxoplasma antibodies. In all but one instance it paralleled the dye test. A comparison of the results of testing six sera by the hemolysin, hemagglutination, and dye-test techniques suggested that the hemolytic antibodies were more closely related to hemagglutinating antibodies than to dye-test antibodies. We could not store sheep erythrocytes sensitized with toxoplasma lysate for more than 3 days without altering the sensitivity of the test. Concanavalin A proved to be an effective coupling agent for binding toxoplasma antigens to red-cell membranes, a quality attributed to its affinity for specific polysaccharide-combining sites.

Animals↗

Toxoplasma gondii infection induces gene expression and secretion of interleukin 1 (IL-1), IL-6, granulocyte-macrophage colony-stimulating factor, and intercellular adhesion molecule 1 by human retinal pigment epithelial cells.

We have used human retinal pigment epithelial (HRPE) cultures to investigate the primary cellular responses of retinal resident cells to intracellular Toxoplasma gondii replication. At 4 days postinoculation, when all of the cells were infected, the secretion of interleukin 1beta (IL-1beta), IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), and intercellular adhesion molecule 1 (ICAM-1) was augmented by 23-, 10-, 8-, and 5-fold, respectively, over the control. Northern and reverse transcriptase PCR analyses showed significant upregulation of steady-state levels of mRNA for IL-1beta, IL-6, GM-CSF, and ICAM-1. The secretion of these molecules by HRPE cells may play a critical immunoregulatory role in the pathophysiological processes associated with T. gondii-induced retinochoroiditis.

Animals↗

Detection of specific immunoglobulin E during maternal, fetal, and congenital toxoplasmosis.

Toxoplasma immunoglobulin E (IgE) antibodies in 664 serum samples were evaluated by using an immunocapture method with a suspension of tachyzoites prepared in the laboratory in order to evaluate its usefulness in the diagnosis of acute Toxoplasma gondii infection during pregnancy, congenital infection, and progressive toxoplasmosis. IgE antibodies were never detected in sera from seronegative women, from patients with chronic toxoplasma infection, or from infants without congenital toxoplasmosis. In contrast, they were detected in 86.6% of patients with toxoplasmic seroconversion, and compared with IgA and IgM, the short kinetics of IgE was useful to date the infection precisely. For the diagnosis of congenital toxoplasmosis, specific IgE detected was less frequently than IgM or IgA (25 versus 67.3%), but its detection during follow-up of children may be interesting, reflecting an immunological rebound. Finally, IgE was detected early and persisted longer in progressive toxoplasmosis with cervical adenopathies, so it was also a good marker of the evolution of toxoplasma infection.

Adolescent↗

Utility of tissue culture for detection of Toxoplasma gondii in vitreous humor of patients diagnosed with toxoplasmic retinochoroiditis.

Laboratory recovery and confirmation of the etiologic agent in necrotizing retinochoroiditis are problematic. Tissue culture and intraocular antibody titers were compared as adjuncts to clinical diagnosis for toxoplasmic retinochoroiditis: the correlations were 91 and 67%, respectively. Isolation of Toxoplasma gondii may establish a definitive diagnosis in patients with toxoplasmic retinochoroiditis.

Animals↗

Necrotising retinopathies simulating acute retinal necrosis syndrome.

AIM: To determine an aetiological diagnosis in patients presenting with necrotising retinopathies that simulate acute retinal necrosis (ARN). METHODS: Retrospective non-comparative case series. The charts of 16 patients presenting with a clinical impression of ARN at Pitie-Salpetriere Hospital, Paris, France, between 1994 and 1999, who required initial antiviral therapy were reviewed. All of the patients had extensive laboratory tests. Anterior chamber paracentesis was performed on 14 patients and evaluated by polymerase chain reaction (PCR) and/or the Witmer-Goldmann coefficient to determine the cause of retinitis. Three of the 14 cases also had diagnostic vitrectomy. Responses to specific treatment, initiated based on laboratory results, and the final outcome were evaluated. RESULTS: Seven of the 16 patients were female and nine were male. The retinitis was bilateral in five patients and unilateral in 11 patients. The average age of the patients at presentation was 53.6 years. 13 patients were immune deficient for various reasons. Upon initial presentation, the patients' visual acuities were less than 20/200 in 68% of the affected eyes. The final diagnoses, based on laboratory data and therapeutic response were toxoplasmic retinochoroiditis (62.5%), syphilitic retinitis (12.5%), aspergillus endophthalmitis (12.5%), Behcet's disease (6.2%), and intraocular lymphoma (6.2%). Visual acuity was stabilised or improved in 12 patients (75%). Two patients with aspergillosis died despite antifungal therapy. CONCLUSIONS: Toxoplasmic retinochoroiditis is the major cause of retinal necrosis that simulates ARN, and PCR analysis of the aqueous humour is helpful in establishing the diagnosis. Such atypical toxoplasma retinochoroiditis may be associated with poor visual outcome.

Acute Disease↗

The visual field in toxoplasmic retinochoroiditis.

AIMS: To document loss of central field in patients with scars from toxoplasmic retinochoroiditis close to the disc after resolution of disease. METHODS: Patients with a clinical diagnosis of toxoplasmic retinochoroiditis were enrolled from four centres. Automated central visual field testing was performed when their disease had settled and retinal photographs of the lesions were taken. The type of central field defect (whether absolute or relative) and whether it broke out to the periphery were correlated with the size of the retinochoroidal scar and its proximity to the optic nerve head. RESULTS: 69 eyes were enrolled; 16 (26%) were discarded because of poor field performance. Of the 53 remaining eyes, 31 showed absolute defects and 20 relative defects. Scars within one disc diameter of the disc were more likely to be associated with absolute defects breaking out to the periphery. CONCLUSION: The scarring induced by toxoplasmic retinochoroiditis is associated with considerable field loss when it occurs close to the optic nerve head. Current treatment is unlikely to ameliorate this situation. The degree of visual field loss should be an outcome measure for future trials of the efficacy of treatment trials for the disease.

Adolescent↗