A power point presentation on toxoplasmosis

Toxoplasmosis

1. TOXOPLASMOSIS BY DR. ENYINNAYA DANIEL

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

5. Life cycle of Toxoplasma gondii 

6. Toxoplasma gondii tissue cysts containing bradyzoites 

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)

10. Retinochoroidal  scars in congenital toxoplasmosis Macular lesion

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 1 st 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.

17. Active Toxoplasma retinitis. (A) Typical ‘satellite’  lesion adjacent to an old scar

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 )

19. Active Toxoplasma retinitis (B) two small foci; 

20. Active Toxoplasma retinitis (C) severe vitreous haze and ‘headlight in the fog’  appearance of lesion

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. 1 st 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

41. wide-field  autofluorescence  image of the eye with toxoplasmosis

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 has been reported.

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.

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