Ocular involvement in toxoplasmosis.

Toxoplasmosis is a major and preventable cause of severe visual handicap and blindness in young people. Congenital toxoplasmosis, as well as toxoplasmosis in immunocompromised patients, is a serious, sometimes fatal disease. 2 Toxoplasmic encephalitis has gained importance as a leading cause ofAIDS related mortality. Toxoplasma gondii, the aetiological agent of human and animal toxoplasmosis, is ubiquitous in nature. The organism is an obligate intracellular parasite and its definitive host is the cat. Oocysts, which are excreted in cat faeces, are highly resistant and may remain infective for more than 1 year. Usually only young cats are infected for a short period of time. The infected cat is not the primary source of infection for humans but is a very important cause of contamination of the environment (soil, fruit, and vegetables and thus other infected animals which become intermediate hosts). Toxoplasma gondii is the most important protozoan cause of intraocular inflammation owing to its widespread distribution throughout the world, the frequency of ocular involvement, and the seriousness of the symptoms it may cause. Toxoplasmosis was first recognised in patients with congenital disease: in 1923 Janku' in Prague presented the first report on a boy who became blind at the age of 3 months and died ofhydrocephalus; a granulomatous inflammation of the eye with protozoa in the retina was found.3 Wolf subsequently verified the aetiology by recovering the Toxoplasma and transmitting the infection to animals.4 Retrospective analysis of specimens has demonstrated the disease in a large number of patients with neonatal encephalitis, thus emphasising the possibility of toxoplasmosis in such cases.5 The major problem in diagnosing ocular toxoplasmosis in adults was the difficulty of establishing the presence of the parasite in ocular lesions. Helenor Wilder provided proof by demonstrating organisms with the morphological characteristics of Toxoplasma gondii in the eyes of patients with chorioretinitis, who had undergone enucleation because of blindness and pain.6 Human infection may occur by either the congenital or the acquired route. Acquired disease usually develops after ingestion of oocysts or tissue cysts and almost all cases (in immunocompetent individuals) are asymptomatic. The prevalence of seropositivity due to a previous Toxoplasma infection varies among different populations, depending on eating habits, climate, etc. In the Netherlands the majority of the population has already been infected by the age of 40 years.7 Congenital infection can occur when a pregnant woman becomes infected; during the parasitaemia, Toxoplasma crosses the placenta and invades the tissues of the developing fetus. The risk and severity of infection in the child depend on the time of gestation in which the mother acquires the infection.8 The severity of congenital infection is greatest when the disease is acquired during the early stages of pregnancy. The frequency of transmission to the fetus is highest during the third trimester, when contact between the maternal and fetal circulations is more likely to occur.8 Overall, about 40% of children of infected mothers will also become infected. Of these infected children only a small proportion will exhibit clinical symptoms directly after birth. However, long term follow up has shown that about 80% of these infected children will eventually develop neurological and/or ocular sequelae.111 Once maternal immunity has developed, it is believed that all subsequent fetuses will be protected against congenital toxoplasmosis. However, a case of repeated fetal infections acquired from the same mother with presumed chronic toxoplasmic endometritis has been reported. '2 Toxoplasmic scars present in multiple siblings have also been documented, but whether these scars were caused by acquired or congenital disease remains unclear. '3 Ocular recurrence during pregnancy in three patients did not cause an infection of the fetus. 14 Until recently it has been assumed that ocular toxoplasmosis represents a (frequently late) manifestation of congenital disease. '5 In 1973 Perkins, who performed a retrospective review of patients with acquired toxoplasmosis, showed that only 3% had associated ocular disease. Furthermore, an epidemiological study on a South Pacific island, where 90% of the population over 22 years of age had already been infected by Toxoplasma, revealed virtually no cases of either congenital or ocular disease. '6 Population surveys showed that the number of acquired infections increased with age, while the ocular disease affected mainly young individuals the age ofonset lying between 10 and 20 years of age. In contrast, recent reports support the view that acquired infection may lead to ocular disease and may even be amore important cause ofocular involvement than previously thought. '4 17-21 Although absence of retinal lesions was noted in patients with an acute stage of acquired toxoplasmosis, ocular involvement may not become manifest until several years after initial seroconversion. '8 In a largepopulation based household study in southern Brazil, the incidence of ocular toxoplasmosis was 18%, which is extremely high.2' The authors argued that ocular toxoplasmosis in the affected area was not of congenital origin, since systemic congenital toxoplasmosis is uncommon there. Furthermore, in the same area, IgM antibodies were found in fewer than 1% of cord blood specimens and the ocular lesions were also documented in multiple siblings. 14 21 The epidemiological pattern revealed a paucity of ocular lesions in young children and an increase in the prevalence of ocular lesions during adolescence, a phenomenon which has also been noted in congenital disease.9'0 Several hypotheses have been presented on the role of acquired toxoplasmosis in ocular disease, addressing the importance of infection at an early age, long term antigen exposure and the role of reinfections, strain differences between parasites, as well as genetic differences between hosts. Immunocompromised patients may develop lethal disseminated toxoplasmosis and/or toxoplasmic encephalitis. 371