Pathophysiology of ocular toxoplasmosis: Facts and open questions

Abstract

Infections with the protozoan parasite Toxoplasma gondii are frequent, but one of its main consequences, ocular toxoplasmosis (OT), remains poorly understood. While its clinical description has recently attracted more attention and publications, the underlying pathophysiological mechanisms are only sparsely elucidated, which is partly due to the inherent difficulties to establish relevant animal models. Furthermore, the particularities of the ocular environment explain why the abundant knowledge on systemic toxoplasmosis cannot be just transferred to the ocular situation. However, studies undertaken in mouse models have revealed a central role of interferon gamma (IFNγ) and, more surprisingly, interleukin 17 (IL17), in ocular pathology and parasite control. These studies also show the importance of the genetic background of the infective Toxoplasma strain. Indeed, infections due to exotic strains show a completely different pathophysiology, which translates in a different clinical outcome. These elements should lead to more individualized therapy. Furthermore, the recent advance in understanding the immune response during OT paved the way to new research leads, involving immune pathways poorly studied in this particular setting, such as type I and type III interferons. In any case, deeper knowledge of the mechanisms of this pathology is needed to establish new, more targeted treatment schemes.

Bicyclic azetidines target acute and chronic stages of Toxoplasma gondii by inhibiting parasite phenylalanyl t-RNA synthetase

“…Although effective in controlling acute infection, there are issues with allergic reactions to the sulfa component, bone marrow suppression that requires co-administration of leucovorin (folinic acid), and adverse reactions to pyrimethamine 31 . These issues are particularly problematic where long-term treatment is required to control disease such as in immunocompromised patients 8 or in cases of recurrent ocular infection, which is common in South America 32 . Additionally, this combination treatment, while synergistic in controlling tachyzoite proliferation, is unable to eradicate chronic infection, presumably because bradyzoites divide slowly and asynchronously and hence they are not susceptible to the inhibitory action of anti-folates 8 .…”

The pathogenicity and virulence of Toxoplasma gondii

“…There, they can cause self-limiting lesions, but might encyst and be able to subsequently reactivate if host immunity becomes impaired. Although this is for the moment poorly understood, recurrences may also occur in immunocompetent subjects, where T. gondii is a major cause of posterior uveitis worldwide [ 46 ]. Of note, higher severity and frequency of ocular toxoplasmosis in South America compared with Europe is probably due to exposure to more virulent strains [ 47 , 48 ].…”

Identification of Oocyst-Driven Toxoplasma gondii Infections in Humans and Animals through Stage-Specific Serology—Current Status and Future Perspectives

“…When using disability-adjusted life years as a measure of disease burden, congenital toxoplasmosis is ranked alongside hepatitis B and pneumococcal infection and ahead of tetanus in Europe [4]. Ocular toxoplasmosis is among the other manifestations contributing to the disease burden [5], and chronic T. gondii infections have been associated with mental disorders, although solid evidence for this is limited and requires further studies [6].…”

“…The consumption of oocyst-contaminated food products such as shellfish (whereby filter feeders act as mechanical vectors) as well as water have also been implicated in outbreaks or as risk factors for infection [42,43]. There are few documented T. gondii outbreaks in humans, and the acute infection can present with vague, unspecific clinical signs that can be overlooked [5]. Waterborne outbreaks have been easier to identify given the large number of people affected [33,40,44,45].…”