Toxoplasmosis : A common but neglected infectious disease

Toxoplasmosis is an infectious disease caused by the parasite, Toxoplasma gondii. Ocular involvement is the biggest clinical problem, characterised by recurrent attacks of retinitis that may extend to involve tissues abutting the retina — the choroid and the vitreous. Toxoplasmosis cannot be cured, but it is preventable and controllable.

There has been limited recognition of the substantial health burden of toxoplasmosis. We recently led an international call-to-action, highlighting that toxoplasmosis meets the World Health Organization criteria for a neglected tropical disease, although it has not been formally recognised. Recognition would identify toxoplasmosis for attention by the health sector and government, and open up funding streams for research on vaccines, better diagnostics, and curative drugs, plus support from the WHO to implement public health and One Health programs. 

Common in Australia

Approximately 1 in 150 Australians have ocular toxoplasmosis. The disease often presents in healthy adults and can be vision-threatening: approximately 50% of patients treated for ocular toxoplasmosis suffer permanent vision impairment in the affected eye, and 1 in 5 are blinded in that eye. Ocular toxoplasmosis can be more aggressive when it occurs in people who have immunodeficiencies or are immunocompromised. Congenital toxoplasmosis is a rare, but devastating form that can be disseminated and even result in loss of a pregnancy.

Mechanisms of infection

T. gondii is a single-celled parasite and a close relative of the Plasmodium species that cause malaria. It can infect any mammal or bird, and an estimated one-third of the global human population carries it. 

The parasite replicates sexually in the gut of the cat, its primary host. It is passed in cat faeces as highly infective sporozoites, packaged as hardy oocysts. Thus, T. gondii may contaminate the grazing areas of livestock. It lodges in the muscles of infected livestock as dormant encysted bradyzoites, and when the animals are slaughtered for meat, cuts may contain the parasite.

Humans can become infected with T. gondii by several routes. Many of us are infected by eating meat raw or undercooked. Contamination of Aussie lamb was documented in a study that involved testing mince purchased at a supermarket 3-weekly for six months: conservatively measured, 43% of mince purchases contained parasite DNA by polymerase chain reaction (PCR). Some health advisories state that red meat is safely eaten after searing the surface, but cooking to an internal temperature of 66°C is required to kill T. gondii.

T. gondii is also contracted by eating unwashed produce harvested from cat-soiled gardens. Congenital infections may occur if a woman is infected for the first time during pregnancy, when she lacks secondary immunity. 

The parasite converts to actively replicating tachyzoites in the intestine and moves into the blood stream, often taxiing in leukocytes. It crosses from the blood into the tissues, with a particular affinity for the retina that is likely related to specific molecular interactions with the local vascular endothelium. 

Within the retina, T. gondii replicates within and lyses retinal cells, and triggers a robust immune response. But, under threat from the immune system, tachyzoites soon convert to bradyzoites, which are invisible to leucocytes. Conversion back to tachyzoites at some later date triggers a recurrent attack of retinitis. In essence, the activity cycle of ocular toxoplasmosis is akin to that of herpetic stomatitis. 

Making the diagnosis

The initial infection with T. gondii is often asymptomatic or it passes as a mild influenza. There is no gender predilection. Common symptoms of a new attack of ocular toxoplasmosis are sudden onset of floaters and altered vision in one eye. 

In over 90% of patients, making the diagnosis of ocular toxoplasmosis is straightforward because of the characteristic lesion: a single focus of fluffy white retinitis adjacent to a pigmented scar (Figure 1), often associated with substantial inflammation in the vitreous. Ophthalmologists call this presentation ‘headlight in the fog’. Generally, T. gondii serology is not needed, although it may be ordered as a reassurance of the diagnosis. 

In a small percentage of patients, the presentation is atypical, for example, multiple active retinal lesions, no retinal scar, and neuroretinitis. In these situations, aqueous may be sampled by anterior chamber paracentesis for testing by PCR for T. gondii DNA. 

Treating ocular toxoplasmosis

Although toxoplasmic retinitis resolves spontaneously over approximately two months, ophthalmologists usually recommend treatment. This is particularly the case when the retinitis is located near the macula, as even a small area of retinal necrosis may irreversibly decrease the visual acuity. Moreover, the patient’s own inflammatory response may cause complications that also can impact the vision, such as glaucoma, macular epiretinal membrane, and retinal detachment. 

A combination of anti-microbial and anti-inflammatory drugs is commonly prescribed for healthy adults, often an extended course of trimethoprim-sulphamethoxazole and a limited course of prednisolone. Locally delivered treatment is occasionally used, involving intravitreal injections of clindamycin and dexamethasone. For those cases in which another flare could result in progressive vision loss, low-dose trimethoprim-sulphamethoxazole may be given. Treatment of immunocompromised or congenitally infected persons requires intensive anti-microbial drug regimens. 

Prevention

Toxoplasmosis is not an unavoidable consequence of our interactions with animals. Globally, various community-based measures can prevent or control T. gondii infections, including water treatment, management of stray cats, farming practices to protect livestock areas, pregnancy screening programs, and health systems that give access to drugs and low vision support. Additionally, there are simple precautions any individual can take to protect themselves against infection (Table 1).

Professor Justine Smith is an ophthalmologist-scientist at Flinders University and Flinders Medical Centre in Adelaide, Australia. Her clinical specialty is uveitis. 

Associate Professor João Furtado is an ophthalmologist at the Ribeirão Preto Medical School of the University of São Paulo, in Ribeirão Preto, Brazil. He also works on contract at the World Health Organization.