**7. Efficient treatments are available but there is no real mean of prevention**

There is no real consensus on the treatment of retinochoroiditis [72-75]. Some experts will treat only patients in which the lesions are near the macula or the optic nerve and when there is an important hyalitis with an impairment of the optical acuity. The non-treated patient will be regularly checked. Other experts will treat all the lesions whatever their localizations and this is now possible because the recommended association pyrimethamine/azythromycine is better tolerated and has a better compliance than pyrimethamine associated to sulfadiazine [76, 77]. Corticosteroids (prednisone at 0.5 to 1mg/kg/d) are constantly administered for several weeks, except for immunocompromised patients [73, 78]. Pyrimethamine in adults is used at 100mg/d for several days then decreased at 50mg/d. It should be associated with sulfadiazine at 75mg/kg/d divided in 4 doses or better with azythromycine 250 mg/d. The total length of the treatment will be of 3 to 6 weeks, sometimes more, depending on the initial size of the lesion. In patients intolerant to treatment, clindamycine at 450-600 mg/d should be associated [79]. The treatment of congenital retinochoroiditis in newborns is based on sulfadiazine (50mg/kg/d in 2 doses) associated with pyrimethamine at 1mg/kg/d for 6 to 12 months. Fifteen mg folinic acid is given every 3 days. The prophylaxis of congenitally acquired OT is based on national programs of prevention of CT (e.g. France, Austria) but their efficiency is discussed [80-82] and depends on the local epidemiology and virulence of strains [83]. Peyron et al. [84] stated that "treating CT has little effect on the quality of life and visual function of the affected individuals". However, Kieffer et al. [10] showed that a period exceeding 8 weeks between maternal infection and the beginning of treatment was a risk factor for retinochoroiditis; therefore emphasizing the need to prevent and treat CT. Evidence for the effectiveness of prenatal or postnatal treatment for CT is still needed. Randomised controlled trials and cohort studies are in progress to provide information on prognosis, especially disability [85]. There is no radical prevention of acquired toxoplasmosis besides hygienic rules in preparing meals. Eating well done or deeply frozen meat should be particularly recommended in regions where highly pathogenic isolates are prevalent. In HIV patients, drug prevention of toxoplasmosis has been successfully used for years and is now less needed since the use of efficient HAART.

#### **8. Conclusions**

136 Toxoplasmosis – Recent Advances

PCR)

**prevention** 

more than 30 days after symptom onset.

techniques increases the sensitivity and the specificity but sometimes the volume size of the sample is so small that it is not possible to perform all three. On the basis of the presented results, we propose an algorithm for choosing the test with the best sensitivity according to ophthalmologic findings and delay after onset of the disease (figure 3). When paracentesis is performed during the 10 days following symptom onset, real-time PCR is most suitable, especially if the patient is immunocompromised or if the total size of the foci is large (> 2 optic disc diameters). Beyond 10 days, the best choice is the GWC if old scars are present and/or if the reaction in the anterior chamber is mild to severe, or PCR if the total size of foci is large (>2 optic disc diameters); IB should be preferred when paracentesis is performed

**Figure 3.** Algorithm for the biological diagnosis of ocular toxoplasmosis (in severely

**7. Efficient treatments are available but there is no real mean of** 

immunosuppressed patients a negative serology does not exclude OT which can be then confirmed by

There is no real consensus on the treatment of retinochoroiditis [72-75]. Some experts will treat only patients in which the lesions are near the macula or the optic nerve and when there is an important hyalitis with an impairment of the optical acuity. The non-treated patient will be regularly checked. Other experts will treat all the lesions whatever their Acquired or CT can be complicated by OT. The diagnosis relies on clinical aspects, responses to specific treatment and results of biological assays. The incidence and the prevalence of this complication are both difficult to establish precisely and depend on the parasite prevalence in the general population, and are affected by different factors such as type of exposure to the parasite, genetic background of the different parasites and the host, and the type of immune response elicited by the parasite. Prevention of CT (though still discussed), and a rapid specific treatment of acquired cases could be the key measures to avoid severe visual impairment but evaluation of these procedures is urgently needed.

#### **Author details**

Jean Dupouy-Camet\* , Hana Talabani, Florence Leslé and Hélène Yera *Service de Parasitologie-Mycologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France* 

<sup>\*</sup> Corresponding Author

Emmanuelle Delair and Antoine P. Brézin *Service d'Ophtalmologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, Université Paris Descartes, Paris, France* 

### **Acknowledgement**

Parts of this chapter were already published in Factors of occurrence of ocular toxoplasmosis. A review. Talabani H, Mergey T, Yera H, Delair E, Brézin AP, Langsley G, Dupouy-Camet J. Parasite. 2010 Sep;17(3):177-82. This chapter is published with the help of ADERMEPT.

Risk Factors, Pathogenesis and Diagnosis of Ocular Toxoplasmosis 139

[12] Freeman K, Tan HK, Prusa A, Petersen E, Buffolano W, Malm G, Cortina-Borja M, Gilbert R; European Multicentre Study on Congenital Toxoplasmosis. Predictors of retinochoroiditis in children with congenital toxoplasmosis: European, prospective

[13] Holland GN, Engstrom RE Jr, Glasgow BJ, Berger BB, Daniels SA, Sidikaro Y, Harmon JA, Fischer DH, Boyer DS, Rao NA, et al. Ocular toxoplasmosis in patients with the

[14] Ronday MJ, Ongkosuwito JV, Rothova A, Kijlstra A. Intraocular anti-*Toxoplasma gondii* IgA antibody production in patients with ocular toxoplasmosis. Am J Ophthalmol 1999;

[15] Holland G. Ocular toxoplasmosis: the influence of patient age. Mem Inst Oswaldo Cruz

[16] Johnson MW, Greven GM, Jaffe GJ, Sudhalkar H, Vine AK. Atypical, severe toxoplasmic retinochoroiditis in elderly patients. Ophthalmology1997; 104: 48-57. [17] Labalette P, Delhaes L, Margaron F, Fortier B, Rouland JF. Ocular toxoplasmosis after

[18] Portela RW, Bethony J, Costa MI, Gazzinelli A, Vitor RW, Hermeto FM, Correa-Oliveira R, Gazzinelli RT. A multihousehold study reveals a positive correlation between age, severity of ocular toxoplasmosis, and levels of glycoinositolphospholipid-specific

[19] Bosch-Driessen LH, Berendscho TT, Ongkosuwito JV, Rothova A. Ocular toxoplasmosis: clinical features and prognosis of 154 patients. Ophthalmology 2002;

[20] Garweg JG, Scherrer JN, Halberstadt M. Recurrence Characteristics in European

[21] Holland GN, Crespi CM, ten Dam-van Loon N, Charonis AC, Yu F, Bosch-Driessen LH, Rothova A. Analysis of recurrence patterns associated with toxoplasmic

[22] Norose K, Mun HS, Aosai F, Chen M, Piao LX, Kobayashi M, Iwakura Y, Yano A. IFNgamma-regulated Toxoplasma gondii distribution and load in the murine eye. Invest

[23] Meenken C, Rothova A, de Waal LP, van der Horst AR, Mesman BJ, Kijlstra A. HLA

[24] Jamieson SE, Cordell H, Petersen E, McLeod R, Gilbert RE, Blackwell JM. Host genetic and epigenetic factors in toxoplasmosis. Mem Inst Oswaldo Cruz 2009;104:162-9. [25] Saeij J., Boyle JP, Boothroyd JC. Differences among the three major strains of *Toxoplasma gondii* and their specific interactions with the infected host. Trends Parasitol 2005; 21:

[26] Su C, Khan A, Zhou P, Majumdar D, Ajzenberg D, Dardé ML, Zhu XQ, Ajioka JW, Rosenthal BM, Dubey JP, Sibley LD. Globally diverse *Toxoplasma gondii* isolates comprise six major clades originating from a small number of distinct ancestral

Patients with Ocular Toxoplasmosis. Br J Ophthalmol. 2008;92:1253-6.

typing in congenital toxoplasmosis. Br J Ophthalmol1995; 79: 494-7.

retinochoroiditis. Am J Ophthalmol, 2008;145:1007-1013.

lineages. Proc Natl Acad Sci U S A. 2012;109:5844-9.

Ophthalmol Vis Sci 2003; 44: 4375-81.

acquired immunodeficiency syndrome. Am J Ophthalmol 1988; 106: 653-67.

cohort study. Pediatrics 2008; 121, 1215-22.

the fifth decade. Am J Ophthalmol 2002; 133: 506-15.

immunoglobulin A. J Infect Dis 2004; 190: 175-83.

127: 294-300.

109, 869-78.

476-81.

2009; 104: 351-7.

#### **9. References**


[12] Freeman K, Tan HK, Prusa A, Petersen E, Buffolano W, Malm G, Cortina-Borja M, Gilbert R; European Multicentre Study on Congenital Toxoplasmosis. Predictors of retinochoroiditis in children with congenital toxoplasmosis: European, prospective cohort study. Pediatrics 2008; 121, 1215-22.

138 Toxoplasmosis – Recent Advances

**Acknowledgement** 

ADERMEPT.

**9. References** 

Emmanuelle Delair and Antoine P. Brézin

*Université Paris Descartes, Paris, France* 

*Service d'Ophtalmologie, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris,* 

Bulletin Epidémiologique Hebdomadaire 1995; 95(2):7 http://archives.invs.sante.fr/beh/1995/02/beh\_02\_1995.pdf

1916 patients. J Rheumatol 2009; 36: 127-36.

Med Hyg 2010; 82: 464-5.

Ophthalmol 2008;146:851–855.

toxoplasmosis. Clin Infect Dis1996; 23: 277-82.

toxoplasmosis. Pediatr Infect Dis J 2008; 27: 27-32.

Parts of this chapter were already published in Factors of occurrence of ocular toxoplasmosis. A review. Talabani H, Mergey T, Yera H, Delair E, Brézin AP, Langsley G, Dupouy-Camet J. Parasite. 2010 Sep;17(3):177-82. This chapter is published with the help of

[1] Dupouy-Camet J, Lahmi T., Vidal-Trecan G, Ancelle T, Mondon H. Prévalence des choriorétinites toxoplasmiques chez 4019 consultants d'un service d'ophtalmologie.

[2] Jakob E, Reuland MS, Mackensen F, Harsch N, Fleckenstein M, Lorenz HM, Max R, Becker MD. Uveitis subtypes in a german interdisciplinary uveitis center-analysis of

[3] Jones JL, Holland GN. Annual burden of ocular toxoplasmosis in the US. Am J Trop

[4] Bowie WR, King AS, Werker DH, Isaac-Renton JL, Bell A, Eng SB, Marion SA. Outbreak of toxoplasmosis associated with municipal drinking water. Lancet 1997; 350:173-7. [5] Glasner PD, Silveira C, Kruszon-Moran D, Martins MC, Burnier Júnior M, Silveira S, Camargo ME, Nussenblatt RB, Kaslow RA, Belfort Júnior R. An unusually high prevalence

[6] Balasundaram MB, Andavar R, Palaniswamy M, Venkatapathy N. Outbreak of acquired

[7] Delair E, Monnet D, Grabar S, Dupouy-Camet J, Yera H, Brezin AP. Respective roles of acquired and congenital infections in presumed ocular toxoplasmosis. Am J

[8] Stanford MR, Tan HK, Gilbert RE. Toxoplasmic retinochoroiditis presenting in childhood: clinical findings in a UK survey. Br J Ophthalmol 2006; 90: 1464-7. [9] Montoya JG, Remington JS. Toxoplasmic chorioretinitis in the setting of acute acquired

[10] Kieffer F, Wallon M., Garcia P, Thulliez P, Peyron F, Franck J. Risk factors for retinochoroiditis during the first 2 years of life in infants with treated congenital

[11] Binquet C, Wallon M, Quantin C, Kodjikian L, Garweg J, Fleury J, Peyron F, Abrahamowicz M. Prognostic factors for the long-term development of ocular lesions in

327 children with congenital toxoplasmosis. Epidemiol Infect 2003; 131: 1157-68.

of ocular toxoplasmosis in southern Brazil. Am J Ophthalmol 1992; 114: 136-44.

ocular toxoplasmosis involving 248 patients. Arch Ophthalmol 2010; 128: 28-32.


[27] Howe DK, Honoré S, Derouin F, Sibley LD. Determination of genotypes of *Toxoplasma gondii* strains isolated from patients with toxoplasmosis. J Clin Microbiol 1997; 35:1411-4.

Risk Factors, Pathogenesis and Diagnosis of Ocular Toxoplasmosis 141

[42] Denkers EY, Gazzinelli RT. Regulation and function of T-cell-mediated immunity

[43] Jones LA, Alexander J, Roberts CW. Ocular toxoplasmosis: in the storm of the eye.

[44] Nagineni CN, Pardhasaradhi K, Martins MC, Detrick B, Hooks JJ. Mechanisms of interferon-induced inhibition of *Toxoplasma gondii* replication in human retinal pigment

[45] Gazzinelli RT, Brezin A, Li Q, Nussenblatt RB, Chan CC. *Toxoplasma gondii*: acquired ocular toxoplasmosis in the murine model, protective role of TNF-alpha and IFN-

[46] Gaddi PJ, Yap GS. Cytokine regulation of immunopathology in toxoplasmosis.

[47] Delair E, Creuzet C, Dupouy-Camet J, Roisin MP. In vitro effect of TNF-alpha and IFNgamma in retinal cell infection with *Toxoplasma gondii*. Invest Ophthalmol Vis Sci.

[48] Yamamoto JH, Vallochi AL, Silveira C, Filho JK, Nussenblatt RB, Cunha-Neto E, Gazzinelli RT, Belfort R Jr, Rizzo LV. Discrimination between patients with acquired toxoplasmosis and congenital toxoplasmosis on the basis of the immune response to

[49] Ongkosuwito JV, Feron EJ, van Doornik CE, Van der Lelij A, Hoyng CB, La Heij EC, Kijlstra A. Analysis of immunoregulatory cytokines in ocular fluid samples from

[50] Yoshimura T, Sonoda KH, Ohguro N, Ohsugi Y, Ishibashi T, Cua DJ, Kobayashi T, Yoshida H, Yoshimura A.. Involvement of Th17 cells and the effect of anti-IL-6 therapy

[51] Lahmar I, Abou-Bacar A, Abdelrahman T, Guinard M, Babba H, Ben Yahia S, Kairallah M, Speeg-Schatz C, Bourcier T, Sauer A, Villard O, Pfaff AW, Mousli M, Garweg JG, Candolfi E. Cytokine profiles in toxoplasmic and viral uveitis. J Infect Dis 2009; 199:

[52] Garweg JG , Candolfi E. Immunopathology in ocular toxoplasmosis: facts and clues.

[53] Cordeiro CA, Moreira PR, Costa GC, Dutra WO, Campos WR, Oréfice F, Teixeira AL Interleukin-1 gene polymorphisms and toxoplasmic retinochoroiditis. Mol Vis 2008; 14:

[54] Cordeiro CA, Moreira PR, Costa GC, Dutra WO, Campos WR, Oréfice F, Teixeira AL.. TNF-alpha gene polymorphism (-308G/A) and toxoplasmic retinochoroiditis. Br J

[55] Cordeiro CA, Moreira PR, Andrade MS, Dutra WO, Campos WR, Oréfice F, Teixeira AL. Interleukin-10 gene polymorphism (-1082G/A) is associated with toxoplasmic

[56] Albuquerque MC, Aleixo AL, Benchimol EI, Leandro AC, das Neves LB, Vicente RT, Bonecini-Almeida Mda G, Amendoeira MR. The IFN-gamma +874T/A gene

patients with uveitis. Invest Ophthalmol Vis Sci 1998; 39: 2659-65.

in autoimmune uveitis. Rheumatology (Oxford) 2009; 48:347-54.

retinochoroiditis. Invest Ophthalmol Vis Sci 2008; 49: 1979-82.

during *Toxoplasma gondii* infection. Clin Microbiol Rev 1998 ;11: 569-588.

Parasite Immunol 2006; 28: 635-42.

epithelial cells. Infect Immun 1996; 64: 4188-96.

parasite antigens. J Infect Dis 2000; 181: 2018-22.

Mem Inst Oswaldo Cruz 2009; 104: 211-20.

Ophthalmol 2008; 92: 986-8.

gamma. Exp Parasitol, 1994; 78: 217-29.

Immunol Cell Biol 2007; 85:155-9.

2009;50:1754-60.

1239-49.

1845-9.


[42] Denkers EY, Gazzinelli RT. Regulation and function of T-cell-mediated immunity during *Toxoplasma gondii* infection. Clin Microbiol Rev 1998 ;11: 569-588.

140 Toxoplasmosis – Recent Advances

Ophthalmol 2005; 139: 350-1.

birth. BMJ 1995; 310: 1037-40.

Microbiol. 2011;49:1513-7

(Lond) 2009; 23: 756-766.

1993; 34(13): 3579-3584.

154.

3560-3566.

function. J Immunol 2011;186: 305-311.

1032-7.

[27] Howe DK, Honoré S, Derouin F, Sibley LD. Determination of genotypes of *Toxoplasma gondii* strains isolated from patients with toxoplasmosis. J Clin Microbiol 1997; 35:1411-4. [28] Grigg ME, Ganatra J, Boothroyd JC, Margolis TP. Unusual abundance of atypical strains

[29] Vallochi AL, Muccioli C, Martins MC, Silveira C, Belfort Jr R, Rizzo LV. The genotype of *Toxoplasma gondii* strains causing ocular toxoplasmosis in humans in Brazil. Am J

[30] Khan A, Jordan C, Muccioli C, Vallochi AL, Rizzo LV, Belfort R Jr, Vitor RW, Silveira C, Sibley LD. Genetic divergence of *Toxoplasma gondii* strains associated with ocular

[31] Gilbert RE, Stanford MR, Jackson H, Holliman RE, Sanders MD. Incidence of acute symptomatic toxoplasma retinochoroiditis in south London according to country of

[32] Burnett AJ, Shortt SG, Isaac-Renton J, King A, Werker D, Bowie WR. Multiple cases of acquired toxoplasmosis retinitis presenting in an outbreak. Ophthalmology 1998; 105:

[33] Fekkar A, Ajzenberg D, Bodaghi B, Touafek F, Le Hoang P, Delmas J, Robert PY, Dardé ML, Mazier D, Paris L. Direct genotyping of *Toxoplasma gondii* in ocular fluid samples from 20 patients with ocular toxoplasmosis: predominance of type II in France. J Clin

[34] Hori J, Vega JL, Masli S. Review of ocular immune privilege in the year 2010: modifying

[35] Streilein JW. Tissue barriers, immunosuppressive microenvironments, and privileged

[36] Forrester JV. Privilege revisited: an evaluation of the eye's defence mechanisms. Eye

[37] Bora NS, Gobleman CL, Atkinson JP, Pepose JS and Kaplan HJ. Differential expression of the complement regulatory proteins in the human eye. Invest Ophthalmol Vis Sci

[38] Denniston AK, Kottoor SH, Khan I, Oswal K, Williams GP, Abbott J, Wallace GR, Salmon M, Rauz S, Murray PI, Curnow SJ. Endogenous cortisol and TGF-beta in human aqueous humor contribute to ocular immune privilege by regulating dendritic cell

[39] Zhou R, Horai R, Mattapallil MJ,Caspi RR. A new look at immune privilege of the eye: dual role for the vision-related molecule retinoic acid. J Immunol 2011;187: 4170-4177. [40] Ferguson TA , Griffith TS. The role of Fas ligand and TNF-related apoptosis-inducing ligand (TRAIL) in the ocular immune response. Chem Immunol Allergy, 2007; 92: 140-

[41] Roychoudhury J, Herndon JM, Yin J, Apte RS and Ferguson TA. Targeting immune privilege to prevent pathogenic neovascularization. Invest Ophthalmol Vis Sci 2010; 51:

the immune privilege of the eye. Ocul Immunol Inflamm 2010;18: 325-333.

sites: the eye's point of view. Reg Immunol 1993; 5: 253-268.

associated with human ocular toxoplasmosis. J Infect Dis 2001; 184: 633-9.

toxoplasmosis, Brazil. Emerg Infect Dis 2006; 12: 942-9.


polymorphism is associated with retinochoroiditis toxoplasmosis susceptibility. Mem Inst Oswaldo Cruz, 2009, 104, 451-5.

Risk Factors, Pathogenesis and Diagnosis of Ocular Toxoplasmosis 143

[69] Garweg JG, Jacquier P, Boehnke M. Early aqueous humor analysis in patients with

[70] Garweg JG, Garweg SD, Flueckiger F, Jacquier P, Boehnke M. Aqueous humor and serum immunoblotting for immunoglobulin types G, A, M, and E in cases of human

[71] Cassaing S, Bessieres MH, Berry A, Berrebi A, Fabre R, Magnaval JF. Comparison between two amplification sets for molecular diagnosis of toxoplasmosis by real-time

[72] Rothova A, de Boer JH, Ten Dam-van Loon NH, Postma G, de Visser L, Zuurveen SJ, Schuller M, Weersink AJ,. M. van Loon A, de Groot-Mijnes JD. Usefulness of aqueous humor analysis for the diagnosis of posterior uveitis. Ophthalmology

[73] Stanford MR, Gilbert RE. Treating ocular toxoplasmosis: current evidence. Mem Inst

[74] de-la-Torre A, Stanford M, Curi A, Jaffe GJ and Gomez-Marin JE. Therapy for ocular

[75] Vance SK, Freund KB, Wenick AS, Nguyen QD, Holland GN and Kreiger AE.

[76] Wakefield D, Cunningham ET Jr., Pavesio C, Garweg JG, Zierhut M. Controversies in

[77] Bosch-Driessen LH, Verbraak FD, Suttorp-Schulten MS, van Ruyven RL, Klok AM, Hoyng CB and Rothova A. A prospective, randomized trial of pyrimethamine and azithromycin vs pyrimethamine and sulfadiazine for the treatment of ocular

[78] Yazici A, Ozdal PC, Taskintuna I, Kavuncu S and Koklu G. Trimethoprim/Sulfamethoxazole and azithromycin combination therapy for ocular

[79] Bosch-Driessen LH and Rothova A. Sense and nonsense of corticosteroid administration in the treatment of ocular toxoplasmosis. Br J Ophthalmol 1998; 82(8): 858-860. [80] Djurkovic-Djakovic O, Stanojevic-Paovic A, Bobic B, Bergam J, Nikolic A, Paovic J, Vukovic D. Short-term effects of the clindamycin-steroid regimen in the treatment of

[81] McLeod R, Kieffer F, Sautter M, Hosten T, Pelloux H. Why prevent, diagnose and treat

[82] Gilbert R. Treatment for congenital toxoplasmosis: finding out what works. Mem Inst

[83] Faucher B, Garcia-Meric P, Franck J, Minodier P, Francois P, Gonnet S, L'Ollivier C and Piarroux R. Long-term ocular outcome in congenital toxoplasmosis: A prospective

[84] Sauer A, de la Torre A, Gomez-Marin J, Bourcier T, Garweg J, Speeg-Schatz C, Candolfi E. Prevention of retinochoroiditis in congenital toxoplasmosis: Europe versus South

human ocular toxoplasmosis. J Clin Microbiol 2000, 38:996–1001

ocular toxoplasmosis. J Clin Microbiol 2004; 42:4593–4598.

toxoplasmosis. Ocul Immunol Inflamm 2011; 19: 314-320

ocular toxoplasmosis. Ocul Immunol Inflamm 2011;19: 2-9.

toxoplasmosis. Am J Ophthalmol 2002; 134(1): 34-40.

cohort of treated children. J Infect 2012; 64: 104-109.

America. Pediatr Infect Dis J. 2011; 30:601-3.

toxoplasmosis. Ocul Immunol Inflamm 2009;17: 289-291.

ocular toxoplasmosis. J Chemother. 1995 Nov;7 Suppl 4:199-201

congenital toxoplasmosis? Mem Inst Oswaldo Cruz. 2009;104:320-44.

Diagnostic and therapeutic challenges. Retina 2011;31: 1224-1230.

PCR. J. Clin. Microbiol 2006; 44:720–724.

Oswaldo Cruz 2009;104: 312-315.

Oswaldo Cruz 2009; 104: 305-311.

2008;115:306–311.


[69] Garweg JG, Jacquier P, Boehnke M. Early aqueous humor analysis in patients with human ocular toxoplasmosis. J Clin Microbiol 2000, 38:996–1001

142 Toxoplasmosis – Recent Advances

2012;26:723-8

1991; 324:699.

Ophthalmol 1996; 121:650–658.

Ophthalmol 2002;134:196–203.

2008; 46:1965–1967.

785.

47: 2131-5.

Am J Ophthalmol 2006;141:313–318.

38.

Inst Oswaldo Cruz, 2009, 104, 451-5.

polymorphism is associated with retinochoroiditis toxoplasmosis susceptibility. Mem

[57] Delair E, Latkany P, Noble AG, Rabiah P, McLeod R and Brezin AP. Clinical manifestations of ocular toxoplasmosis. Ocul Immunol Inflamm 2011; 19: 91-102. [58] Kovačević-Pavićević D, Radosavljević A, Ilić A, Kovačević I, Djurković-Djaković O. Clinical pattern of ocular toxoplasmosis treated in a referral centre in Serbia. Eye (Lond)

[59] Garweg JG, de Groot-Mijnes JD and Montoya JG. Diagnostic approach to ocular

[60] Robert-Gangneux F, Binisti P, Antonetti D, Brezin A, Yera H, Dupouy-Camet J. Usefulness of immunoblotting and Goldmann-Witmer coefficient for biological diagnosis of toxoplasmic retinochoroiditis. Eur J Clin Microbiol Infect Dis 2004; 23:34–

[61] Brezin AP, Eqwuagu CE, Silveira C, Thulliez P, Martins MC, Mahdi RM, Belfort Jr R, Nussenblatt RB. Analysis of aqueous humor in ocular toxoplasmosis. N Engl J Med

[62] de Boer JH, Verhagen C, Bruinenberg M, Rothova A, de Jong PT, Baarsma GS, Van der Lelij A, Ooyman FM, Bollemeijer JG, Derhaag PJ, Kijlstra A. Serologic and polymerase chain reaction analysis of intraocular fluids in the diagnosis of infectious uveitis. Am J

[63] De Groot-Mijnes JD, Rothova A, Van Loon AM, Schuller M, Ten Dam-Van Loon NH, De Boer JH, Schuurman R, Weersink AJ. Polymerase chain reaction and Goldmann-Witmer coefficient analysis are complimentary for the diagnosis of infectious uveitis.

[64] Fardeau C, Romand S, Rao NA, Cassoux N, Bettembourg O, Thulliez P, Lehoang P.Diagnosis of toxoplasmic retinochoroiditis with atypical clinical features. Am J

[65] Fekkar A , Bodaghi B, Touafek F, Le Hoang P, Mazier D, Paris L. Comparison of immunoblotting, calculation of the Goldmann-Witmer coefficient, and real-time PCR using aqueous humor samples for diagnosis of ocular toxoplasmosis. J Clin Microbiol

[66] Villard, O., D. Filisetti, F. Roch-Deries, J. Garweg, J. Flament, and E. Candolfi. Comparison of enzyme-linked immunosorbent assay, immunoblotting, and PCR for

[67] Westeneng AC, Rothova A, de Boer JH, de Groot-Mijnes J. Infectious uveitis in immunocompromised patients and the diagnostic value of polymerase chain reaction and Goldmann-Witmer coefficient in aqueous analysis. Am J Ophthalmol 2007;144:781–

[68] Talabani H, Asseraf M, Yera H, Delair E, Ancelle T, Thulliez P, Brézin AP, Dupouy-Camet J.Contributions of immunoblotting, real-time PCR, and the Goldmann-Witmer coefficient to diagnosis of atypical toxoplasmic retinochoroiditis. J Clin Microbiol 2009;

diagnosis of toxoplasmic chorioretinitis. J Clin Microbiol 2003; 41:3537–3541.

toxoplasmosis. Ocul Immunol Inflamm 2011; 19: 255-261.


[85] Peyron F, Garweg JG, Wallon M, Descloux E, Rolland M, Barth J. Long-term impact of treated congenital toxoplasmosis on quality of life and visual performance. Pediatr Infect Dis J 2011; 30:597-600.

**Chapter 8** 

© 2012 Bahia-Oliveira et al.,licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

© 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

**Immunological and Immunogenetic Parameters** 

**Evidence to Support Morphological Criteria to** 

**Classify Retinal/Retinochoroidal Scar Lesions in** 

Toxoplasmosis is highly prevalent in Brazil, where its prevalence ranks among the highest in the world. However, the prevalence of ocular toxoplasmosis may vary from one region to another within the country, even in the face of seroprevalence of the same magnitude. For over a decade we have been studying toxoplasmosis in Campos dos Goytacazes, which has amongst the highest prevalence of the condition already reported. Local social and environmental peculiarities influence the risk factors and impact the seroprevalence when analyses are performed in local populations stratified by socioeconomic status [1]. Campos dos Goytacazes, usually referred to as Campos, is located in the northern state of Rio de Janeiro in the most important oil-producing region of Brazil. The city is composed of an area equivalent to 4,027 km2, and with 463.731 inhabitants, it is the third most economically important city in the state of Rio de Janeiro. Some aspects related to the natural history of toxoplasmosis in Campos are connected to its historic past with respect to economic agricultural and rural activities that were linked to the Sugar Cane economy. Sugar production prevailed as the most important economic activity until the mid-80s, at which point it began gradually giving way to activities related to oil. The city still preserves its spatial organization and cultural points, which are characteristics of a city with strong rural

**on the Diversity of Ocular Toxoplasmosis:** 

Lílian M.G. Bahia-Oliveira, Alba L.P. Rangel, Marcela S.B. Boechat, Bianca M. Mangiavacchi, Livia M. Martins, Francielle B. Ferraz, Maycon B. Almeida, Elisa M. Waked Peixoto, Flavia P. Vieira

**Epidemiologic Surveys** 

Additional information is available at the end of the chapter

and Ricardo G. Peixe

http://dx.doi.org/10.5772/50086

**1. Introduction** 

features.

[86] Wallon M, Kieffer F, Binquet C, Thulliez P, Garcia-Méric P, Dureau P, Franck J, Peyron F, Bonnin A, Villena I, Bonithon-Kopp C, Gouyon JB, Masson S, Félin A, Cornu C. Congenital toxoplasmosis: randomised comparison of strategies for retinochoroiditis prevention. Therapie 2011; 66:473-80. French.

**Immunological and Immunogenetic Parameters on the Diversity of Ocular Toxoplasmosis: Evidence to Support Morphological Criteria to Classify Retinal/Retinochoroidal Scar Lesions in Epidemiologic Surveys** 

Lílian M.G. Bahia-Oliveira, Alba L.P. Rangel, Marcela S.B. Boechat, Bianca M. Mangiavacchi, Livia M. Martins, Francielle B. Ferraz, Maycon B. Almeida, Elisa M. Waked Peixoto, Flavia P. Vieira and Ricardo G. Peixe

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/50086

#### **1. Introduction**

144 Toxoplasmosis – Recent Advances

Infect Dis J 2011; 30:597-600.

prevention. Therapie 2011; 66:473-80. French.

[85] Peyron F, Garweg JG, Wallon M, Descloux E, Rolland M, Barth J. Long-term impact of treated congenital toxoplasmosis on quality of life and visual performance. Pediatr

[86] Wallon M, Kieffer F, Binquet C, Thulliez P, Garcia-Méric P, Dureau P, Franck J, Peyron F, Bonnin A, Villena I, Bonithon-Kopp C, Gouyon JB, Masson S, Félin A, Cornu C. Congenital toxoplasmosis: randomised comparison of strategies for retinochoroiditis

> Toxoplasmosis is highly prevalent in Brazil, where its prevalence ranks among the highest in the world. However, the prevalence of ocular toxoplasmosis may vary from one region to another within the country, even in the face of seroprevalence of the same magnitude. For over a decade we have been studying toxoplasmosis in Campos dos Goytacazes, which has amongst the highest prevalence of the condition already reported. Local social and environmental peculiarities influence the risk factors and impact the seroprevalence when analyses are performed in local populations stratified by socioeconomic status [1]. Campos dos Goytacazes, usually referred to as Campos, is located in the northern state of Rio de Janeiro in the most important oil-producing region of Brazil. The city is composed of an area equivalent to 4,027 km2, and with 463.731 inhabitants, it is the third most economically important city in the state of Rio de Janeiro. Some aspects related to the natural history of toxoplasmosis in Campos are connected to its historic past with respect to economic agricultural and rural activities that were linked to the Sugar Cane economy. Sugar production prevailed as the most important economic activity until the mid-80s, at which point it began gradually giving way to activities related to oil. The city still preserves its spatial organization and cultural points, which are characteristics of a city with strong rural features.

© 2012 Bahia-Oliveira et al.,licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

In areas with a high prevalence of infectious and parasitic diseases, such as toxoplasmosis in Campos, several challenges are posed to the health authorities with regard to diagnoses, accurate assessment of incidence and prevalence, and clinical management of disease symptoms. Our studies in toxoplasmosis have focused on the natural history, epidemiology, immune response and immunogenetics of infected individuals in order to better understand the clinical presentation of the disease. In this chapter, we present in four sections, data related to 1) the diversity of presumable toxoplasmic retinal/retinochoroidal scar lesion presentations in comparison to other population-based studies of the same nature in Brazil; 2) the profile of the *in vitro* immune response of patients in the context of the clinical presentation of ocular toxoplasmosis; 3) evidence for candidate genes that are associated with susceptibility for or protection against the development of toxoplasmic retinal lesions; and 4) the association of ocular toxoplasmosis with other infectious diseases.

Immunological and Immunogenetic Parameters on the Diversity of Ocular Toxoplasmosis: Evidence to Support Morphological Criteria to Classify Retinal/Retinochoroidal Scar Lesions in Epidemiologic Surveys 147

development of new therapeutic approaches that may benefit patients who have more

In light of these considerations, subjective criteria certainly influence the clinical diagnosis of ocular toxoplasmosis in population-based studies, which are based on the appearance of inactive retinal/retinochoroidal scar lesions left by presumed toxoplasmic lesions that were previously active. In addition, the ophthalmologists' clinical experience on the resolution of active lesions is important for the recognition of retinal/retinochoroidal toxoplasmic scar

An important epidemiological study conducted in Brazil by Glasner and associates in 1992 reported a ranking of probability for the classification of retinal scar lesions that are presumably caused by *T. gondii* infection [4]. The system was established by the authors to try to estimate the actual prevalence of ocular toxoplasmosis in a highly endemic area for *T. gondii* infection located in a small village in southern Brazil called Erechim. According to the authors, on the basis of a conservative assessment of ophthalmic findings, 17.7% of the patients (184 out of 1042 examined) were considered to have ocular toxoplasmosis. They categorized the different types of lesions that were identified during the examination of 1042 individuals and organized them into five groups numbered 1 through 5 according to the probability that the lesion was caused by *T. gondii* infection. Those classified from grade one to grade three were considered to be definitively caused by *T. gondii* infection [4]. We found the authors' initiative very important, and with the same objective, we have proposed some descriptive criteria to classify the most commonly found retinal/retinochoroidal lesions from our population-based work in Campos dos Goytacazes [7, 10, 11]. However, as mentioned earlier, the nature of the toxoplasmic retinal/retinochoroidal scar lesions, or even active lesions described during the fundoscopic examination, is subjective. Thus, the decision as to whether a scar lesion was caused by *T. gondii* infection depends, to some extent, on subjective criteria. To minimize the intrinsic characteristic of this decisional process, in population-based studies, a group of ophthalmologists consensually decide which scar lesions have the greatest probability of being caused by toxoplasmic infection. During this process, the ophthalmologists are usually uninformed as to whether the patient serology is

There is a type of retinal/retinochoroidal scar lesion that is universally accepted as being healed from active retinal/retinochoroidal inflammation caused by *T. gondii* infection. These scars usually result from the active typically visible yellow-white focus with fluffy borders, which may or may not be accompanied by vitreous inflammation that limits the visualization of the posterior pole [12]. However, there exist other lesions that are equally recognized by specialists as toxoplasmic lesions, termed as "atypical" toxoplasmic lesions, and their active forms have been reviewed [3, 12]. The frequency of scar lesions healed from "atypical" active toxoplasmic lesions in population-based studies is not well known because in previous studies, with the intent of avoiding an over estimation of ocular toxoplasmosis, only scars healed from typical lesions, which are most likely equally typical in terms of toxoplasmic retinochoroidal scar lesion representativeness, have been usually used to infer the ocular prevalence of *T. gondii* infection in epidemiologic surveys. As a consequence,

severe forms of disease, especially recurrent forms of ocular toxoplasmosis.

lesions.

positive or negative for *T. gondii*.
