Overview
- Definition
A protozoal disease caused by Toxoplasma gondii, contracted from cat feces, consumption of unfiltered water, or undercooked meat (especially pork, lamb, and venison). Infection can also be acquired via vertical transmission (from mother to fetus) and via receipt of an organ transplanted from an infected donor
Up to a third of the world’s population is infected, but only a very small percentage manifest symptomatically
Ocular toxoplasmosis is the number one cause of infectious posterior uveitis in the world (>80% in some regions)
While chorioretinitis is common in all hosts, systemic disease is exceedingly rare in immunocompetent hosts
- Symptoms
Blurry vision
Floaters
Pain (from anterior uveitis and/or scleral involvement of retinochoroiditis)
Redness
Photophobia
Photopsia
- Laterality
Unilateral or bilateral (but simultaneous bilateral inflammation is extremely rare)
- Course
Retinochoroiditis is self-limited over 2–4 weeks in immunocompetent hosts but can recur in two-thirds of patients
Visual prognosis is favorable unless lesion affects macula or optic nerve; surprisingly, congenital macular scar may be associated with relatively good vision
Much more aggressive in immunocompromised hosts
- Age of onset
All ages affected, but more severe in older patients
Seroconversion increases with age: 5–30% of 10–19 years old are seropositive for T. gondii, and this goes up to 70% in those older than 50
- Gender/race
No gender or racial predilection
Higher prevalence in tropical areas close to sea level
- Systemic association
- Congenital toxoplasmosis
- Incidence of primary infection during pregnancy is <1%; among these, transplacental transmission risk increases with gestational age at the time of maternal infection, up to ~70% at 36 weeks
More severe clinical sequelae for the fetus when contracted early on in pregnancy (may lead to spontaneous abortion)
No risk of congenital infection from reactivation of latent toxoplasmosis during pregnancy in immunocompetent hosts; very small to no risk in immunocompromised hosts
Retinochoroiditis is the most common manifestation: often bilateral with macular involvement (15–40%)
Cerebrospinal fluid pleocytosis and elevated proteins (20%)
Intracranial calcifications (10%)
Anemia, thrombocytopenia, and jaundice at birth
Mental retardation, seizures, spasticity, sensorineural hearing loss are some severe neurologic sequelae
- Acquired toxoplasmosis
- Immunocompetent patients: only 10–20% ever develop symptoms, which are usually mild and nonspecific, and self-limited over 2–4 weeks
Lymphadenopathy, with mono-like illness: headache, malaise, sore throat, fatigue, fever, and night sweats
More severe (but unusual) symptoms: meningismus, meningoencephalitis, myalgias, arthralgias, abdominal pain, and maculopapular rash sparing palms and soles
Potentially lethal (but very rare) complications: encephalopathy, pneumonitis, myocarditis, polymyositis, hepatitis, and splenomegaly
- Immunocompromised patients: many develop rapidly fatal disease if untreated
CNS disease (50%): encephalopathy, meningoencephalitis, and mass lesions
Myocarditis
Pneumonitis
Disseminated disease with septic shock
Exam: Ocular
Anterior Segment
Mild to severe granulomatous or non-granulomatous uveitis
Elevated IOP (10–15%)
Posterior Segment
- Classic appearance (“headlight in the fog”): fluffy, focal necrotizing retinitis or retinochoroiditis adjacent to a variably pigmented chorioretinal scar, with significant overlying vitritis
Lesion size ranges from 1/10 disc diameters to large enough to span two quadrants of the fundus
Recurrent lesions are typically single and contiguous with old inactive scars, but can also recur at sites distant from the primary lesion or in the fellow eye
Vascular occlusion can occur if lesion involves vessels
Healed lesions are characterized by peripheral hyperpigmentation and central atrophy exposing the choroid and sclera; tractional bands may form between one scar to a neighboring scar or the optic disc; may be complicated by proliferative vitreoretinopathy and choroidal neovascularization
Vascular sheathing typically involving veins but sometimes arteries (Kyrieleis arteriolitis)
Optic atrophy
Tractional or exudative retinal detachment
Atypical Forms
Anterior uveitis without evidence of retinochoroiditis
Punctate outer retinal toxoplasmosis
Neuroretinitis
Isolated optic neuritis
Multifocal retinochoroiditis simulating acute retinal necrosis (ARN) (immunocompromised or recently acquired)
Panophthalmitis (immunocompromised)
Exam: Systemic
Enlarged lymph nodes (cervical [symmetrical, nontender] > suboccipital > supraclavicular > axillary > inguinal > mediastinal)
Abdominal tenderness, hepatosplenomegaly
Maculopapular rash (sparing palms and soles)
Altered mental status, cerebellar signs, cranial nerve palsies, sensory abnormalities, weakness
Imaging
- OCT
Active lesion: hyperreflective retinal layers with posterior optical shadowing and overlying posterior hyaloid thickening
Healed lesion: atrophic retina with hyperreflectivity of the underlying choroid
- FA
Active lesion: early central hypofluorescence followed by late leakage from the margins; adjacent retinal vascular leakage
Healed lesion: variable early fluorescence depending on RPE proliferation or atrophy; late staining of margins
- ICG
Active lesion: early hyperfluorescence or hypofluorescence with late hyperfluorescence
Healed lesion: early and late hypofluorescence
Laboratory and Radiographic Testing
- Serum or ocular fluid anti–T. gondii IgG and IgM titers
In acute infection, IgM should be positive within a week of developing symptoms and persist for several weeks
IgG develops over the next 2–3 weeks and typically persists for life
Patients with positive IgM and negative IgG may have acute infection but may also have false-positive IgM results due to cross-reactivity with rheumatoid factor, antinuclear antibodies, or nonspecific binding in vitro. These patients should have repeat serologies checked 2–3 weeks later to assess for development of IgG, which confirms true acute infection
Patients with symptoms for more than 2 weeks who lack both toxoplasma IgG and IgM likely do not have toxoplasmosis
In reactivation disease, serum IgM antibodies are typically absent, while IgG antibodies are present
- Goldmann-Witmer coefficient
0.5–2: No anti-toxoplasma intraocular antibody (Ab) production
2–4: Possible intraocular Ab production
>4: Definitive intraocular Ab production
- Serum and ocular fluid T. gondii DNA PCR
Done in suspicious cases with negative serologic testing
MRI or CT of brain
Histopathology: tachyzoites or cysts may be seen in lymph nodes, brain tissue, or other infected organs
Differential Diagnosis
Congenital disease: TORCH infections
- Endogenous fungal endophthalmitis
Candidiasis
Aspergillosis
Blastomycosis
Subretinal abscess from endogenous bacterial endophthalmitis
Viral retinitis
Syphilis
Tuberculosis
Toxocariasis
Sarcoidosis
Lymphocytic choriomeningitis virus (LCMV)
Treatment
- “Classic” therapy (nonpregnant adults)
- Pyrimethamine: 100 mg on day 1, then 25–50 mg daily
Access to pyrimethamine in the United States is currently difficult— it must be obtained through a program administered by the manufacturer or from a compounding pharmacy (www.daraprimdirect.com/how-to-prescribe). If this cannot be done promptly, then trimethoprim–sulfamethoxazole should be used until pyrimethamine is obtained
Sulfadiazine: 2 g loading dose on day 1, then 500 mg–1 g QID
Folinic acid (leucovorin): 5–25 mg/d based on neutrophil count
Congenital toxoplasmosis in newborn is treated 6–24 months
- Prophylaxis in HIV
Pyrimethamine 25–75 mg daily
Sulfadiazine 0.5–1 g QID
Folinic acid 5–25 mg daily
- Trimethoprim/sulfamethoxazole
160/800 mg BID, then every other day for 1 year
May be less effective than classic therapy, but a good alternative when retinochoroiditis is not threatening posterior pole or optic nerve
Can be used in late second or third trimester for maternal and fetal infections
- Atovaquone, preferably with pyrimethamine but alone if unable to give pyrimethamine
1500 mg BID
Give with food to increase bioavailability
Excellent choice when patient has sulfa allergy
May need to treat for at least 3 months if giving without pyrimethamine
- Clindamycin
300 mg q6–8 h
Intravitreal 1 mg/0.1 ml can be used in conjunction with systemic therapy when vision is threatened
- Azithromycin
0.5–1 g daily
- Spiramycin
1 g TID
Drug of choice during early pregnancy (<18 weeks gestation) due to concerns about teratogenicity with pyrimethamine–sulfadiazine in early pregnancy
Significantly lowers vertical transmission rate
Licensed in Canada and Europe but available in the United States only via the Food and Drug Administration (FDA) using an IND
- Prednisone
Indicated if active chorioretinitis threatens posterior pole or optic nerve, or if there is visually significant vitritis
Start 24–72 hours after antiparasitic therapy
Referral/Co-management
Infectious Disease
Ob-Gyn
Neurology
Cardiology
Pulmonology