Toxoplasmosis
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TOXOPLASMOSIS
Toxoplasmosis represents the most common form of posterior uveitis worldwide, with
higher prevalence in tropical areas. It is caused by Toxoplasma gondii, an obligatory
intracellular parasite.
Transmission occurs by ingestion of any of these forms of the organism, which depends
on hygienic and alimentary habits. High levels of exposure to contaminated meat, such as
reported in Southern Brazil, has been identified as a possible explanation for high
prevalence of toxoplasmic scars in that population and to the occurrence of disease in
several siblings (not possible by congenital infection). More recently it has been found,
in another part of Brazil, that contamination of water supplies may play an even bigger
role in the transmission of the disease to the community. The disease can also be acquired
by transfusion of whole blood or leukocytes, organ transplant or accidentally, in
laboratory workers.
Ocular toxoplasmosis is commonly attributed to congenital infection, which only occurs
when the disease is acquired during pregnancy, but the role of acquired infection has
been confirmed as more important than previously thought.
Congenital transmission occurs only when the infection is acquired during pregnancy.
Primary ocular disease occurs more frequently during acute systemic infection, but may
also occur during the course of the chronic phase of systemic disease. Case reports show
that new lesions can appear for the first time as early as 2 months after onset of infection,
or as late as 5 years. Recurrences are typical of both the congenital form and of the
chronic phase of postnatally acquired disease. The risk of recurrence of lesions in cohorts
of prenatally infected children and case series of patients with postnatal disease appear to
be similar (8-40%), but are based on small numbers.
The classical ocular lesion is a focal necrotizing retinitis, with overlying vitreous
inflammatory haze. This lesion is most likely caused by actively replicating organisms
released form a ruptured cyst. The inflammation of the choroid and anterior segment are
secondary, and probably due to direct extension of the retinal inflammation or a
hypersensitivity reaction. Recurrent retinal lesions occur at the borders of retinochoroidal
scars (satellite lesion). A bilateral macular lesion is suggestive of congenital disease, and
unilateral lesions can be a consequence of both acquired and congenital disease. These
lesions lead to destruction of the retina and underlying choroid resulting in scars, which
will progressively show accumulation of pigment.
The symptoms from posterior disease include floaters and blurring of vision, while pain
and redness will occur as consequence of anterior segment involvement. Retinal vascular
involvement is frequently seen, with sheathing of vessels occurring even far from the
original lesion. Vascular occlusion is not common, but may occur when a vessel crosses
the main focus of inflammation.
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Toxoplasmosis
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Loss of vision may occur as a consequence of lesions affecting the macula, optic nerve,
or retinal detachment secondary to organisation of a heavily infiltrated vitreous. Other
complications involve subretinal neovascular membranes. Anterior segment
complications include cataract, posterior synechiae and glaucoma.
The disease is more severe and tends to have a very different clinical behaviour in
immunosuppressed individuals, such as in AIDS. Multifocal, bilateral or extensive areas
of necrosis can be seen.
Pathogenesis of ocular toxoplasmosis depends on the virulence of the Toxoplasma strain
and the host’s immune response. The reason for recurrences is not entirely clear with
many theories including rupture of tissue cysts, hypersensitivity reaction or autoimmune
mechanisms.
The diagnosis is mainly clinical, with serological tests used to confirm previous exposure
to the organism. The dye test is the gold standard, but involves the use of live tachyzoites,
which makes it less practical. The IFA has comparable sensitivity and specificity, but it is
easier, safer and less expensive. ELISA sensitivity and specificity depend on the
commercially available tests. Local production of specific antibodies can also be
determined by the Witmer-Desmont coefficient.
In atypical cases, such as seen in immunocompromised individuals, the need for
confirmation of etiological diagnosis becomes more important. Diagnosis can be
confirmed by isolation of T gondii from body fluids or tissue specimens, histological
demonstration of organisms in fluids or tissue specimens, and polymerase chain reaction
(PCR) techniques for detection of T gondii DNA.
Therapy is indicated for lesions threatening central vision (macula and optic disc) or for
very exudative lesions leading to intense vitritis. There is no convincing data to support
the use of one anti-Toxoplasmic drug over the others, with the most commonly used
being the combination of Pyrimethamine and Sulfadiazine, Clindamycin, Spiramycin,
Tetracyclines, Azithromycin, Clarithromycin and Atovaquone.
In immunocompetent hosts systemic steroids are used in association with antimicrobial
agents, since the intense inflammatory reaction is probably the most important factor in
tissue damage. Treatment of anterior segment inflammation is done accordingly with
topical steroids and cycloplegic agents. Recently, studies have looked into the use of
intraocular therapy, combining clindamycin and dexamethasone as a way of avoiding
systemic therapy and its potential complications. Results have been encouraging.
In immunocompromised individuals systemic steroids are contraindicated, since the
damage is mainly caused by replicating organisms, with minimal inflammatory
component. In these patients maintenance therapy is necessary due to the high risk of
reactivation of the infection.
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Toxoplasmosis
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Prevention is aimed at breaking the transmission cycle. Better hygiene and proper
cooking of meat are important in this process. In immunosuppressed patients drug
prophylaxis becomes important for those who are seropositive and have reached a low
level of immunity. The use of prolonged use of low-dose sulfamethoxazole/trimethoprim
(Bactrin, Septrin) has also shown to lead to a reduction in the number of recurrences
when compared to a control group, and could represent a good option for those patients
with high risk of visual loss due to the central location of their scars.
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Recommended Reading :
Dubey JP, Beattie CP. Toxoplasmosis of Animals and Man. CRC Press. Boca Raton,
1988.
Silveira CM, Belfort Jr R, Burnier Jr MNN, Nussenblatt R. Acquired toxoplasmic
infection as the cause of toxoplasmic retinochoroiditis in families. Am J Ophthalmol
1988, 106:362-4.
Engstron BS, Holland GN, Nussenblatt RB, Jabs DA. Current practices in the
management of ocular toxoplasmosis. Am J Ophthalmol 1991, 111:601-10.
Rothova A. Ocular involvement in toxoplasmosis. Br J Ophthalmol 1993, 77:371-7.
Couvreur J, Thulliez P. acquired toxoplasmosis of ocular or neurologic site:49 cases.
Presse Med 1996;25:438-442.
Mets MA, Holfels E, Boyer KM, Swisher CN, Roizen N, Stein L, Stein M, Hopkins J,
Withers S, Mack D, Luciano R, Patel D, Remington J, Meier P, McLeod R. Eye
manifestations of congenital toxoplasmosis. Am J Ophthalmol 1996;122:309-324.
Holland GN, Muccioli C, Silveira C, Weisz JM, Belfort R Jr, O’Connor GR. Intraocular
inflammatory reactions without focal necrotizing retinochoroiditis in patients with
acquired systemic toxoplasmosis. Am J Ophthalmol 1999, 128(4):413-20.
Bosch-Driessen EH, Rothova A. Recurrent ocular disease in postnatally acquired
toxoplasmosis. Am J Ophthalmol 1999;128(4):421-5.
Gilbert R, Stanford M. Is ocular toxoplasmosis caused by prenatal or postnatal infection ?
Br J Ophthalmol 2000;84:224-226.
Silveira C, Belfort R Jr, Muccioli C, Abreu MT, Martins MC, Victora C, Nussenblatt RB,
Holland GN. A follow-up study of Toxoplasma gondii infection in southern Brazil. Am
J Ophthalmol 2001;131(3):351-4.
Bosch-Driessen LE, Berendschot TT, Ongkosuwito JV, Rothova A. Ocular
toxoplasmosis: clinical features and prognosis of 154 patients. Ophthalmology
2002;109(5):869-78.
Arevalo JF, et al. Ocular toxoplasmosis in the developing world. Int Ophthalmol Clin
2010;50:57-69.
London NJ, et al. Prevalence, clinical characteristics, and causes of vision loss in patients
with ocular toxoplasmosis. Eur J Ophthalmol 2011.
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Soheilian M, et al. Randomized trial of intravitreal clindamycin and dexamethasone
versus pyrimethamine, sulfadiazine, and prednisolone in treatment of ocularn
toxoplasmosis. Ophthalmology 2011;118:134-41.
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