2. • Toxoplasmosis is caused by Toxoplasma gondii
• an obligate intracellular protozoan.
• It infests 10% of adults in northern temperate countries
and 50% of adults in Mediterranean and tropical
countries.
LIFE CYCLE
• definitive host - cat
• intermediate hosts -mice, livestock, birds& humans.
• Oocysts are excreted in cat faeces and then ingested by
intermediate hosts via contaminated water
3. Bradyzoite:
• is an inactive stage lying dormant within cysts in tissues
such as the eye, brain and skeletal muscle
• consumption of undercooked meat (or eggs) from an
intermediate host can lead to infestation.
Tachyzoites:
• Released from rupture of Bradyzoite cysts
• Are the proliferating active form
• stimulate an inflammatory reaction.
4. The principal modes of transmission include
• ingestion of undercooked, infected meat containing tissue
cysts
• ingestion of contaminated water, fruit, or vegetables with
oocysts
• inadvertent contact with cat feaces, cat litter, or soil
containing oocysts
• transplacental transmission with primary infection during
pregnancy
• blood transfusion
• organ transplantation
7. Systemic features
Congenital toxoplasmosis :
• 40% of primary maternal infections result in congenital infection;
• Transplacental transmission is highest during the third trimester.
• The risk of severe disease developing in the fetus is inversely
proportional to gestational age
Disease acquired in
• early pregnancy - result in spontaneous abortion, stillbirth, or
severe congenital disease
• late pregnancy - asymptomatic, normal-appearing infant with
latent infection.
8. • Chronic or recurrent maternal infection during pregnancy is not
thought to confer a significant risk of congenital toxoplasmosis
because maternal immunity protects against fetal transmission.
Clinical features
The classic presentation (Sabin’s tetrad) includes
• retinochoroiditis,
• hydrocephalus or microcephaly,
• intracranial calcifications, and
• cognitive impairment, occurring in less than 10% of infected
children.
• fetal death occurs in 10% of all congenital toxoplasmosis.
• Neurological and visceral involvement may be subclinical
• Retinochoroiditis occur in over 75%, leaving scars that are commonly
a later incidental finding
• 25% of these become blind in 1 or both eyes.
9. Pregnant women without serologic evidence of T gondii infection
should be advised to take the following precautions:
• Avoid ingestion of raw/undercooked meat (freezing at –20°C/–
4°F overnight also destroys tissue cysts).
• Drink only well-filtered or boiled water.
• Carefully wash vegetables and fruits before consumption.
• Use gloves and wash hands and kitchen utensils well after
handling meat or soil.
• Avoid contact with cats and their feces (including in soil or litter
boxes)
11. Retinochoroidal scars in congenital
toxoplasmosis :
(B) multiple peripheral scars on wide-feld
imaging;
(C) wide-feld autofluorescence
image of the eye in (B)
12. Postnatal childhood acquisition
• accounts for 50% of cases of childhood toxoplasmosis;
• Ocular lesions are common, but may not develop
for years after the initial infection
Acquired toxoplasmosis in immunocompetent adults
• subclinical in 80–90%
• Cervical lymphadenopathy, fever, malaise and pharyngitis
are common features in symptomatic patients
• Early retinitis may occur in about 20%.
13. Toxoplasmosis in immunocompromised patients
• may be acquired or result from reactivation of pre-existing
disease.
• As well as the constitutional symptoms occurring in the
immunocompetent like meningoencephalitis, pneumonitis,
retinochoroiditis can occur.
14. Ocular features
• The most common cause of ocular toxoplasmosis is from
intrauterine infection
• Toxoplasmosis constitutes 20–60% of all posterior uveitis.
• Retinochoroiditis is the most common manifestation of
ocular toxoplasmosis, but it is often accompanied by a
granulomatous anterior uveitis
• Reactivation at previously inactive cyst-containing scars is the rule
in the immunocompetent
• Recurrent episodes of inflammation are common and occur when
the cysts rupture and release hundreds of tachyzoites into normal
retinal cells
15. • Average age of 1st symptomatic presentation 29 years,
perhaps due to decreasing specific immunity.
• Ocular involvement from congenital infection may only be
detected later in life with the incidental discovery of typical
retinochoroidal scars, though occasionally macular or optic
nerve
damage may impair vision in childhood.
• Pregnancy may provoke the recurrence of ocular
toxoplasmosis in the mother, during which it may be
resistant to treatment
16. Symptoms
• Unilateral acute or subacute onset of floaters,
• blurring and photophobia.
‘Spill-over’ anterior uveitis is common
• It may be granulomatous or resemble Fuchs uveitis
syndrome
• IOP may be elevated
Satellite lesion
• A single inflammatory focus of fluffy white retinitis or
retinochoroiditis associated with a pigmented scar
(‘satellite
lesion’) is typical.
• Lesions tend to involve the posterior pole.
18. • De novo foci not associated with an old scar
• Vitritis may be severe and impair fundus visualization.
• ‘Headlight in the fog’ is the classic description of a white
retinal inflammatory nidus viewed through vitritis
• Retinal vessels in the vicinity of an active lesion may
show perivasculitis with diffuse venous sheathing and
segmental arterial plaques (Kyrieleis arteriolitis)
21. Toxoplasmic retinochoroiditis: fundus photograph showing
intense focal retinitis with dense overlying vitritis,
producing a
“headlight in the fog” appearance.
22. • Optic disc oedema is common.
• Extensive and fulminant retinal involvement is
generally confined to the immunocompromised, in
whom
it may be b/l and diffcult to distinguish from viral
retinitis.
• Retinochoroiditis absent in acute phase of acquired
disease, with activity consisting of anterior uveitis,vitritis
and retinal vasculitis; typical retinal scars may form later.
• Neuroretinitis is rare, marker of acutely acquired rather
than reactivated infection.
23. • Punctate outer retinal toxoplasmosis is an atypical
manifestation featuring clusters of small (25–75 µm
diameter) grey–white lesions.
• Visual loss
Causes of permanently reduced vision (around 25% of
eyes) include
• macular inflammatory lesions and oedema,
• optic nerve involvement,
• vascular occlusion
• serous, rhegmatogenous and tractional RD
• late secondary choroidal neovascularization
24. immunocompetent immunocompromised
isolated
often u/l lesion
Multifocal
b/l lesions
white, fluffy focus of necrotizing
retinitis is seen with associated
retinal edema, retinal vasculitis,
and vitritis
less vitritis, and the lesions may
simulate the appearance of
viral retinitis, such as acute retinal
necrosis or CMV retinitis
secondary nongranulomatous
inflammation of the adjacent
choroid and sclera.
• toxoplasmosis in
25. • Histologically, necrosis of the retina and retinal pigment
epithelium is seen
• Intact cysts containing viable organisms may be present
next to areas of scarring or necrosis
26. • On an average, the inflammation lasts for ~4 months.
• About one-third of the patients have recurrent
attacks.
There are three main morphologic variants.
1st variant :
• lesions are larger than 1DD dense, and elevated.
• largely destructive lesions and associated with
significant vitritis and anterior chamber reaction.
• Prompt therapy is usually necessary regardless of the
location of the lesion.
27. Second variant :
• punctate lesions of the inner retina
• The inflammation is mild, and no therapy is necessary
unless the lesion is close to the macula and threatens
vision.
Third variant :
• chr by punctate lesions on outer retina & mild vitritis.
• Lesions slowly resolve spontaneously but also tend to
recur in adjacent areas.
28. Atypical presentations of ocular toxoplasmosis include
• neuroretinitis,
• papillitis, and
• intraocular inflammation without retinochoroiditis
29. • Healing , in immunocompetent hosts usually occurs
spontaneously within 6–8 weeks, although vitreous
opacities
take longer to clear.
• The inflammatory focus is replaced by a sharply
demarcated atrophic scar that develops a pigmented
border
Recurrence:
• average number of recurrent attacks per patient is 2.7;
• within five years more than half of patients may
experience a further episode.
30. Complications of toxoplasmosis retinochoroiditis include
• posterior synechiae
• macular edema,
• dragging of the macula secondary to a peripheral lesion,
• retinal detachment,
• chorioretinal vascular anastomosis,
• choroidal neovascularization,
• branch retinal artery or vein occlusions,
• optic nerve atrophy
• cataract, and
• Glaucoma
• Unilateral pigmentary retinopathy simulating retinitis pigmentosa (as a
late sequela of recurrent ocular toxoplasmosis )
31. Common complications of Toxoplasma retinitis.
(A) Macular involvement, at presentation and (B) following treatment;
32. Common complications of Toxoplasma retinitis.
(C) juxtapapillary lesion involving the optic nerve head
33. Uncommon complications of Toxoplasma retinitis. (A) Periarteritis resulting in
branch retinal artery occlusion; (B) FA shows extensive non-perfusion at the
posterior pole;
34. Uncommon complications of Toxoplasma retinitis.(C) serous macular
detachment; (D) FA of (C) shows hyperfluorescence d/t pooling of
dye;
35. Uncommon complications of Toxoplasma retinitis. (E) choroidal
neovascularization adjacent to an old scar; (F) FA of (E) shows
corresponding hyperfluorescence
36. Progression of Toxoplasma retinitis. (A) Moderate activity;
(B) 3 months later, following antibiotic treatment
37. Investigations:
• Diagnosis is usually based on clinical examination findings.
Serology
• Serologic evaluation using indirect fluorescent antibody
and ELISA tests to detect specific anti–T gondii antibodies
is commonly used to confirm exposure to the parasite.
• IgG antibodies appear after the first 2 weeks of infection,
typically remain detectable for life at variable levels, and
cross the placenta.
• IgM antibodies increase in number early during the acute
phase of the infection, typically remain detectable for less
than 1 year, and do not cross the placenta.
38. • The presence of IgM in newborns confirms congenital infection and
is indicative of acquired disease when present in adults.
• Measurement of IgA antibody titers may also be useful in a
diagnosis of congenital toxoplasmosis in a fetus or newborn;
• during this period, IgM production is often weak and the presence
of IgG antibodies may indicate passive transfer of maternal
antibodies in utero.
• IgA antibodies usually disappear by 7 months.
39. Ocular fluid antibody assessment
Goldmann–Witmer coefficient
• Calculating the ratio of specifc IgG in aqueous humour to
that in serum
• Intraocular production of specific anti-Toxoplasma
antibodies may be computed using the Goldmann–
Witmer coefficient
• A ratio of greater than 3 is considered diagnostic of local
antibody production.
PCR testing of intraocular fluid
• is variably sensitive but highly specific and can be
diagnostic in clinically uncertain cases
40. Imaging.
• Macular OCT will demonstrate any macular oedema if
vitritis is not preventative.
• B-scan ultrasonic imaging can be used to exclude retinal
detachment in the presence of severe vitritis.
• FAF may facilitate monitoring of inflammatory activity
• CT brain is done immunocompromised pt, as these
patients will have concomitant CNS involvement
42. Treatment
• eradication of the parasite has not been demonstrated but
parasite activity and multiplication may be reduced, with a
decrease in size of the eventual retinochoroidal scar.
• spontaneous resolution generally occurs, treatment is not
administered in every case.
Clear indications include
• a sight-threatening lesion involving the macula,
papillomacular bundle, optic nerve head or a major blood
vessel
• severe vitritis
• immunocompromised.
43. • Treatment of congenital toxoplasmosis in neonates with
antimicrobials for one year may reduce the frequency of
subsequent development of retinochoroidal scars.
44. Prednisolone (1 mg/kg)
• given initially and tapered according to clinical response
• should always be used in conjunction with a specific anti
Toxoplasma agent
• Most frequently pyrimethamine combined with
sulfadiazine
(‘classic’ or ‘triple’ therapy, sometimes supplemented with
clindamycin)
• Systemic steroids should be avoided in
immunocompromised patients
45. Pyrimethamine
• is a folic acid antagonist that is believed to be highly effective.
• Loading dose of 75–100 mg for 1–2 days
• Maintenaince dose 25–50 mg daily for 4 weeks
• Used in combination with oral folinic (not folic) acid 5 mg 3 times a
week to retard thrombocytopenia, leukopenia and folate defciency.
• Weekly blood counts should be performed.
• In acquired immunodefciency syndrome (AIDS) pyrimethamine is
avoided or used at a lower dosage because of possible pre-existing
bone marrow suppression and the antagonistic effect of zidovudine
when the drugs are combined.
46. Sulfadiazine
• 1 g 4 times daily for 3–4 weeks is usually given in combination
with pyrimethamine.
• Side effects -renal stones, allergic reactions and Stevens–
Johnson syn
Intravitreal therapy with clindamycin (1 mg) &dexamethasone
(400 µg)
• as effective as triple therapy in reactivated infection
• 2 to 3 injections (2-weekly intervals) may be required
• may be preferred in recurrent infection in pregnancy,
• generally not used in isolation in the immunocompromised.
• In newly acquired (IgM-positive) infection systemic therapy has
apparently superior efficacy.
• Depot steroid intra- and periocular preparations such as
triamcinolone should be avoided as uncontrolled progression
47. Azithromycin
• 250–500 mg daily shows evidence of reducing the rate of
recurrence of retinochoroiditis
• used in combination with pyrimethamine, folinic acid and
prednisolone is a newer regimen.
Co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800
mg)
• twice daily in combination with prednisolone is a lower-cost
, but not as effective as classic therapy.
Clindamycin
• 300 mg four times daily may be added to triple therapy (see
above) or used instead of pyrimethamine.
• Pseudomembranous colitis is a potential adverse effect
48. Atovaquone
• theoretically attacks encysted bradyzoites but does not seem
to prevent recurrence in vivo;
• 750 mg two to four times daily.
Topical steroid and mydriatic may be given for anterior uveitis.
Antimicrobial maintenance therapy is used in
immunocompromised patients.
49. Pregnancy.
• Treatment of recurrent ocular toxoplasmosis during pregnancy
should be chosen carefully and only started if clearly necessary
• management should be multidisciplinary.
• Several of the drugs discussed above have the potential to harm
the fetus.
• Intravitreal therapy for reactivated disease, or systemic treatment
with
azithromycin, clindamycin and possibly prednisolone may
be appropriate.
• Specifc treatment to prevent transmission to the fetus is not
generally given except in newly acquired infection.
50. • Spiramycin (treatment dose, 400 mg 3 times daily) reduces the
rate of tachyzoite transmission to the fetus and may be used
safely without undue risk of teratogenicity
• Newborns with congenital toxoplasmosis are commonly
treated with pyrimethamine and sulfonamides (plus folinic
acid) for 1 year
Vitrectomy may be performed in selected cases.
51. Ref :
• Kanski 8th ed
• AAO2016-17
• Jakobiecs Principles and
Practice of Ophthalmology 3rd ed
