was complicated by renal failure and the need for acute hemodialysis and transfusions. He subsequently regained renal function and returned to his normal routine. Three months later he noted decreased visual acuity in his right eye (OD), followed a week later in the left eye (OS). He had cells in the anterior chamber and in the vitreous. There were deep retinal or subretinal whitish-yellow lesions in both eyes. Findings of a workup for a blood-borne infectious agent were negative, as were results of a CT scan of the head and a lumbar puncture. The clinical diagnosis was intraocular lymphoma. An OD vitrectomy showed no malignant cells. However, suspicion remained high and an OS vitrectomy and retinal biopsy were performed. Results of both were negative for a malignant process, and results of a CT scan of the abdomen and chest, as well as bone marrow biopsy, were all normal. The retinal biopsy showed a large number of mature plasma cells.

The patient was sent to the National Institutes of Health for further evaluation. Results of his physical examination were normal. A magnetic resonance image showed a few small areas of ischemia consistent with involutional change. The erythrocyte sedimentation rate was 34 mm/h, there were no antibodies to hepatitis B, and liver and thyroid test results were normal. Chest

References

X-rays showed no active disease. A repeat OS vitrectomy showed T cells and macrophages but no malignant cells; viral cultures for zoster, varicella, and CMV were negative but showed herpes simplex 1 and 2 antibodies that were higher in the cerebrospinal fluid. The patient’s toxoplasmosis titer (IgG) was elevated at 1 : 1000. Analysis for Lyme disease and Leptospira organisms revealed seronegativity. Oral prednisone therapy was begun, and within 1 week new lesions developed in the fundus.

After the patient was seen by infectious disease specialists, an empirical regimen of pyrimethamine, sulfadiazine, and ganciclovir was begun. Rhegmatogenous retinal detachment developed, and during surgery the subretinal fluid was sent for toxoplasmosis titers and for culture. The C quotient for both vitreous and subretinal fluid was 300 compared to that for the serum. The ganciclovir was stopped, and the patient’s inflammation resolved with the anti-Toxoplasma medication.

Comment 14-4.  Although we evaluated the patient for toxoplasmosis, we did not consider this diagnosis as a high possibility. We would assume that the patient was infected via one of the transfusions he received after his coronary surgery. The C coefficient was the most helpful finding in this case.

1.Krick J, Remington J. Current concepts in parasitology. Toxoplasmosis in the adult – an overview. N Engl J Med 1978; 298: 550–553.

2.Lum F, Jones JL, Holland GN, et al. Survey of ophthalmologists about ocular toxoplasmosis. Am J Ophthalmol 2005; 140(4): 724–726.

3.Gilbert RE, Dunn DT, Lightman S, et al. Incidence of symptomatic

toxoplasma eye disease: aetiology and public health implications. Epidemiol Infect 1999; 123: 283–289.

4.Rai SK, Upadhyay MP, Shrestha HG. Toxoplasma infection in selected patients in Kathmandu, Nepal. Nepal Med Coll J 2003; 5(2): 89– 91.

5.Nicolle C, Manceaux L. Sur une infection a corps de Leishman (ou organismes voisins) du gondi. Compt Rend Acad Sci 1908; 147: 763–766.

6.Splendore A. Un nouvo protozoa parassita dei conigli: incontrato nell lesoni anatomiche d’une malattia che ricorda in molti punti il Kala-azar dell’uomo. Rev Soc Sci São Paulo 1908; 3: 109–112.

7.Janku J. Pathogenesis and pathologic anatomy of coloboma of macula lutea in eye of normal dimensions, and in microphthalmic eye, with parasites in retina. Cas Lek Cesk 1923; 62: 1021–1027, 154–1059, 1111–1115, 1138–1143.

8.Wolf A, Cowen D, Paige B. Human toxoplasmosis: Occurence in infants as an encephalomyelitis: Verification by transmission to animals. Science 1939; 89: 226–227.

9.Holland GN, Lewis KG, O’Connor GR. Ocular toxoplasmosis: a 50th anniversary tribute to the contribution of Helenor Campbell Wilder Foerster. Arch Ophthalmol 2002; 120: 1081– 1084.

10.O’Connor, G. The mucosae as possible sites of entrance for Toxoplasma gondii. In: O’Connor G, ed. Immunologic Diseases of the Mucous Membranes, 1989, New York: Masson Publishing USA Inc. 71–78.

11.Joiner K. Cell entry by Toxoplasma gondii: All paths do not lead to success. Res Immunol 1993; 144(1): 34–38.

12.Santoro F, Afchain D, Pierce R, et al. Serodiagnosis of toxoplasma infection using a purified parasite protein. Clin Exp Immunol 1985; (62): 262–269.

13.Kasper L, Khan I. Role of p30 in host immunity and pathogenesis of T. gondii infection. Res Immunol 1993; 144(1): 45–48.

14.Burg J, Perelman D, Kasper LH, et al. Molecular analysis of the gene coding tha major surface antigen of

Toxoplasmosis gondii. J Immunol 1988; (141): 3584–3591.

15.Kasper L, Crabb J, Pfefferkor E. Isolation and characterization of a monoclonal antibody-resistant antigenic mutant of Toxoplasma gondii. J Immunol 1982; 129: 1694–1699.

16.Sibley L, Krahenbuhl JL, Adams GM, et al. Toxoplasma modifies macrophage phagosomes by secretion of a vesicular network rich in surface proteins. J Cell Biol 1986; (103): 867–874.

17.Sharma S, Araujo F, Remington J. Toxoplasma antigen isolated by affinity chromatography with monoclonal antibody protects mice against lethal infection with Toxoplasm gondii. J Immunol 1984; 133: 2818–2820.

18.Cesbron-Delauw M, Capron A. Excreted/secreted antigens of

Toxoplasmosis gondii – their origin and role in the host – parasite interaction. Res Immunol, 1993; 144(1): 41–44.

19.Hughes H, Van Knapen F. Characterization of a secretory antigen from Toxoplasma gondii and its role in circulating antigen production. Int J Parasit 1982; 12: 433–437.

20.Howe DK, Sibley LD. Toxoplasma gondii comprises three clonal lineages: correlation of parasite genotype with human disease. J Infect Dis 1995; 172: 1561–1566.

21.Switaj K, Master A, Borkowski PK, et al. Association of ocular

toxoplasmosis with type I Toxoplasma gondii strains: direct genotyping from peripheral blood samples. J Clin Microbiol 2006; 44(11): 4262–4264.

22.Vallochi AL, Muccioli C, Martins MC, et al. The genotype of Toxoplasma gondii strains causing ocular toxoplasmosis in humans in Brazil. Am J Ophthalmol 2005; 139(2): 350–351.

23.Grigg ME, Ganatra J, Boothroyd JC, et al. Unusual abundance of atypical strains associated with human ocular toxoplasmosis. J Infect Dis 2001; 184: 633–639.

24.Howe DK, Honore S, Derouin F,

et al. Determination of genotypes of

ocular toxoplasmosis. Arch Ophthamol 1992; (110): 806–811.

60.Saraux H, Laroche L, Le Hoang P. Secondary Fuch’s heterochromic cyclitis: a new approach to an old disease. Ophthalmologica 1985; 190: 193–198.

61.Schwab I. The epidemiologic association of Fuch’s heterochromic iridocyclitis and ocular toxoplasmosis. Am J Ophthalmol 1991; 1: 356–362.

62.Moorthy R, Smith R, Rao N. Progressive ocular toxoplasmosis in patients with acquired immunodeficiency syndrome. Am J Ophthalmol 1993; 115: 742–747.

63.Gagliuso D, Teich SA, Friedman AH, et al. Ocular toxoplasmosis in AIDS patients. Trans Am Ophthalmol Soc 1990; (88): 63–86.

64.Yeo J, Jakobiec F, Iwamoto T. Opportunistic toxoplasmic retinochoroiditis following chemotherapy for systemic lymphoma. A light and electron microscopic study. Ophthalmology 1983; 90: 885–898.

65.Singer M, Hagler W, Grossniklaus H. Toxoplasma gondii retinochoroiditis after liver transplantation. Retina 1993; 13: 40–45.

66.Blanc-Jouvan M, Boibieux A, Fleury J, et al. Chorioretinitis following liver transplantation: Detection of

Toxoplasma gondii in aqueous humor. Clin Infect Dis 1996; 22(1): 184–185.

67.Sendi P, Sachers F, Drechsler H, et al. Immune recovery vitritis in an HIV patient with isolated toxoplasmic retinochoroiditis. AIDS 2006; 20(17): 2237–2238.

68.Brezin AP, Thulliez P, Cisneros B, et al. Lymphocytic choriomeningitis

virus chorioretinitis mimicking ocular toxoplasmosis in two otherwise normal children. Am J Ophthalmol 2000; 130: 245–247.

69.Auer C, Bornasconi O, Herbort CP. Indocyanine green angiography features in toxoplasmic retinochoroiditis. Retina 1999; 19(1): 22–29.

70.Holland GN. Ocular toxoplasmosis: a global reassessment. Part I: epidemiology and course of disease. Am J Ophthalmol 2003; 136(6): 973–988.

71.Holland GN. Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and management. Am J Ophthalmol 2004; 137(1): 1–17.

72.Dutton G, Hay J, Hair DM, et al. Clinicopathological features of a congenital murine model of ocular toxoplasmosis. Graefes Arch Clin Exp Ophthalmol 1986; (224): 256–264.

73.Dutton G, McMenamin PG, Hay J, et al. The ultrastructural pathology of congenital murine toxoplasmic retinochoroiditis. Part II: The morphology of the inflamatory changes. Exp Eye Res 1986; (43): 545–560.

74.Roberts F, Mets MB, Ferguson DJ, et al. Histopathological features of

ocular toxoplasmosis in the fetus and infant. Arch Ophthalmol 2001; 119(1): 51–58.

75.Nussenblatt R, Mittal KK, Fuhrman S, et al. Lymphocyte proliferative responses of patients with ocular toxoplasmosis to parasite and retinal antigens. Am J Ophthamol 1989; (107): 632–641.

76.Fatoohi F, Cozon GJ, Wallon M, et al. Systemic T cell response to Toxoplasma gondii antigen in patients with ocular toxoplasmosis. Jpn J Ophthalmol 2006; 50(2): 103–110.

77.McLeod R, Skamene E, Brown C, et al. Genetic regulation of early survival and cyst number after peroral

Toxoplasma gondii infection of AXB/ BXA recombinant inbred and B10 congenis mice. J Immunol 1989; (142): 3247–3255.

78.McLeod R, Brown C, Mack D. Immunogentics influence outcome of Toxoplasma gondii infection. Res Immunol 1993; 144(1): 61–65.

79.Brown C, McLeod R, Class I MHC genes and CD8+ T cells determine cyst number in toxoplasma infection. J Immunol 1990; 145: 3438–3441.

80.Jamieson SE, de Roubaix LA, Cortina-Borja M, et al. Genetic and epigenetic factors at COL2A1 and ABCA4 influence clinical outcome in congenital toxoplasmosis. PLoS ONE 2008; 3(6): e2285.

81.Chan C, Hu S, Gekker G, et al. Effects of cytokines on multiplication of Toxoplasma gondii in microglial cells.

J Immunol 1993; (150): 3404–3410.

82.Nagineni CN, Pardhasaradhi K, Martins MC, et al. Mechanisms of interferon-induced inhibition of

Toxoplasma gondii replication in human retinal pigment epithelial cells. Infect Immun 1996; 64(10): 4188–4196.

83.Gazzinelli R, Eltoum I, Wynn TA,

et al. Acute cerebral toxoplasmosis is induced by in vivo neutralization of TNF-alpha and correlates with the down-regulated expression of inducible nitric oxide synthase and other markers of macrophage activation. J Immunol 1993; (151): 3672–3681.

84.Shen DF, Matteson DM, Tuaillon N, et al. Involvement of apoptosis and interferon-gamma in murine toxoplasmosis. Invest Ophthalmol Vis Sci 2001; 42: 2031–2036.

85.Beamon M, Hunter C, Remington J. Enhancement of intracellular replication of Toxoplasma gondii by IL-6. J Immunol 1994 153: 4583–4587.

86.Lyons RE, Anthony JP, Ferguson DJ, et al. Immunological studies of chronic ocular toxoplasmosis: up-regulation of major

histocompatibility complex Class I and transforming growth factor β and a protective role for interleukin-6. Infect Immun 2001; 69(4): 2589–2595.

87.Zamora DO, Rosenbaum JT, Smith JR. Invasion of human retinal vascular endothelial cells by Toxoplasma gondii tachyzoites. Br J Ophthalmol 2008; 92(6): 852–855.

88.Feron EJ, Klaren VNA, Wierenga EA, et al. Characterization of Toxoplasma gondii-specific T cells recovered from vitreous fluid of patients with ocular toxoplasmosis. Invest Ophthalmol Vis Sci 2001; 42: 3228–3232.

89.Herion P, Saavedra R. human T-cell clones as tools for the characterization of the cell-mediated immune response to Toxoplasma gondii. Res Immunol 1993; 144(1): 48–51.

90.Denkers E, Caspar P, Sher A.

Toxoplasma gondii possesses a superantigen activity that selectively expands murine T cell receptors Vbeta5-bearing CD8+ lymphocytes. J Exp Med 1994; 180: 985–994.

91.Curiel T, Krug ED, Purner MB, et al. Cloned Human CD4+ cytotoxic T lymphocytes specific for Toxoplasma gondii lysetachyzoite-infected target cells. J Immunol 1993; (151): 2024–2031.

92.Goncalves RM, Rodrigues DH, Camargos da Costa AM, et al. Increased serum levels of CXCL8 chemokine in acute toxoplasmic retinochoroiditis. Acta Ophthalmol Scand 2007; 85(8): 871–876.

93.Hafizi A, Modabber F. Effect of cyclophosphamide on Toxoplasma gondii infection: reversal of the effect by passive immunization. Clin Exp Immunol 1978; 33: 389–394.

94.Wilson C, Haas J. Cellular defense against Toxoplasma gondii in newborns. J Clin Invest 1984; 73: 1606–1616.

95.Roberts F, Roberts CW, Ferguson DJ, et al. Inhibition of nitric oxide production exacerbates chronic ocular toxoplasmosis. Parasite Immunol 2000; 22: 1–5.

96.Wyler D, Blackman J, Lunde M. Cellular hypersensitivity to toxoplasmal and retinal antigens in patients with toxoplasmal retinochoroiditis. Am J Trop Med Hyg 1980; 29: 1181–1186.

97.Abrahams IW, Gregerson DS. Longitudinal study of serum antibody responses to retinal antigens in acute ocular toxoplasmosis. Am J Ophthalmol 1982; 93(2): 224–231.

98.Whittle RM, Roberts CW, Ferguson DJ, et al. Human antiretinal antibodies in toxoplasma retinochoroiditis. Br J Ophthalmol 1998; 82: 1017–1021.

99.Vallochi AL, da Silva Rios L, Nakamura MV, et al. The involvement of autoimmunity against retinal antigens in determining disease severity in toxoplasmosis. J Autoimmun 2005; 24(1): 25–32.

100.Rollins D, Tabbara K, O’Connor G. Detection of toxoplasmal antigen and antibody in ocular fluids in experimental ocular toxoplasmosis. Arch Ophthalmol 1983; 101: 455.

101.Davidson MG, Lappin MR, English

References

KV, et al. A feline model of ocular toxoplasmosis. Invest Ophthalmol Vis Sci 1993; (34): 3653–3660.

102.Rehder JR, Burnier MB Jr, Pavesio CE, et al. Acute unilateral toxoplasmic iridocyclitis in an AIDS patient. Am J Ophthalmol 1988; 106(6): 740–741.

103.Greven C, Teot L. Cytologic Identification of Toxoplasma gondii from Vitreous Fluid. Arch Ophthalmol 1994; 112: 1086–1088.

104.Klaren VNA, van Doornik CE, Ongkosuwito JV, et al. Differences between intraocular and serum antibody responses in patients with ocular toxoplasmosis. Am J Ophthalmol 1998; 126: 698–706.

105.Klaren VNA, Peek R. Evidence for a compartmentalized B cell response as a characterized by IgG epitope specifity in human ocular toxoplasmosis. J Immunol 2001; 167: 6263–6269.

106.Weiss M, Velazquez N, Hofeldt A. Serologic tests in the diagnosis of presumed toxoplasmic retinochoroiditis. Am J Ophthalmol 1990; 109: 407–411.

107.Brezin A, Egwuagu CE, Burnier M Jr, et al. Identification of Toxoplasma gondii in paraffin-embedded sections by the polymerase chain reaction. Am J Ophthalmol 1990; (110): 599–604.

108.Ongkosuwito JV, Bosch-Driessen EH, Kijlstra A, et al. Serologic evaluation of patients with primary and recurrent ocular toxoplasmosis for evidence of recent infection. Am J Ophthalmol 1999; 128: 407–412.

109.Rothova A, van Knapen F, Baarsma GS, et al. Usefulness of aqueous humor analysis for the diagnosis of posterior uveitis. Ophthalmology 2008; 115(2): 306–311.

110.Rothova A, van Knapen F, Baarsma G. Serology in ocular toxoplasmosis. Br J Ophthalmol 1986; 70: 615–622.

111.Phaik C, Seah S, Guan OS, et al. Anti-toxoplasma serotitres in ocular toxoplasmosis. Eye 1991; 5(5): 636–639.

112.Desmonts G. Definitive serological diagnosis of ocular toxoplasmosis. Arch Ophthalmol 1966; 76: 839–853.

113.Goichot E, Bloch-Michel E. Interet de l’etude detaillee de la serologie quantitative de l’humeur aqueuse pour le diagnostic de la toxoplasmose oculaire. A propos de 180 cas. J Fr Ophthalmol 1980; 3: 21–26.

114.Turunen H, Leinikki P, Saari K. Demonstration of intraocular synthesis of immunoglobulin G toxoplasma antibodies for specific diagnosis of toxoplasmic chorioretinitis by enzyme immunoassay. J Clin Microbiol 1983; 17: 988–992.

115.Westeneng AC, Rothova A, de Boer JH, et al. Infectious uveitis in immunocompromised patients and the diagnostic value of polymerase chain reaction and Goldmann

– Witmer coefficient in aqueous analysis. Am J Ophthalmol 2007;

207

Ophthalmol 2002; 134(1): 102– 114.

146.Sabates R, Pruett R, Brockhurst R. Fulminary ocular toxoplasmosis. Am J Ophthalmol 1981; 92: 497–503.

147.Aggio FB, Muccioli C, Belfort R Jr. Intravitreal triamcinolone acetonide as an adjunct in the treatment of severe ocular toxoplasmosis. Eye 2008; 22(9): 1200–1201.

148.Tabbara K, O’Connor G. Treatment of Ocular toxoplasmosis with clindamycin and sulfadiazine. Ophthalmology 1980; 87: 129–134.

149.Lakhanpal V, Schocket S, Nirankari V. Clindamycin in the treatment of toxoplasmic retinochoroiditis. Am J Ophthalmol 1983; 95: 605–613.

150.Sobrin L, Kump LI, Foster CS. Intravitreal clindamycin for toxoplasmic retinochoroiditis. Retina 2007; 27(7): 952–957.

151.Thiermann E, Apt W, Atias A. Comparative study of some combined treatment regimens in acute toxoplasmosis in mice. Am J Trop Med Hyg 1978; 27: 747–750.

152.Mittelviefhaus, H. Clindamycin therapy of suspected toxoplasmosis retinochoroiditis. Klin Monatsbl Augenheilkd 1992; 200: 123–127.

153.Ferguson JJ. Clindamycin therapy for toxoplasmosis. Ann Ophthalmol 1981; 13: 95–100.

154.Kishore K, Conway MD, Peyman GA. Intravitreal clindamycin and dexamethasone for toxoplasmic retinochoroiditis. Ophthalmic Surg Lasers 2001; 32(3): 183–192.

155.Phan L, Kasza K, Jalbrzikowski J, et al. Longitudinal study of new eye lesions in children with toxoplasmosis who were not treated during the first year of life. Am J Ophthalmol 2008; 146(3): 375–384.

156.Phan L, Kasza K, Jalbrzikowski J, et al. Longitudinal study of new eye lesions in treated congenital toxoplasmosis.

Ophthalmology 2008; 115(3): 553–559 e8.

157.McLeod R, Boyer K, Karrison T, et al. Outcome of treatment for congenital toxoplasmosis, 1981–2004: the National Collaborative ChicagoBased, Congenital Toxoplasmosis Study. Clin Infect Dis 2006; 42(10): 1383–1394.

158.Opremcak EM, Scales, DK, Sharpe MR. Trimethoprim-sulfamethoxazole therapy for ocular toxoplasmosis. Ophthalmology 1992; 99: 920–925.

159.Silveira C, Belfort R Jr, Muccioli C, et al. The effect of long-term, intermittent trimethoprim/ sulfamethoxazole treatment on recurrencs of toxoplasmic retinochoroiditis. Am J Ophthalmol 2002; 134: 41–46.

160.Araujo F, Huskinson J, Remington J. Remarkable in vitro and in

vivo activities of the hydroxynaphthoquinone 566C80 against tachyzoites and tissue cysts of Toxoplasma gondii. Antimicrob Agents Chemother 1991; 35:

293–299.

161.Gormley PD, Pavesio CE, Minnasian D, et al. Effects of drug therapy on Toxoplasma cysts in an animal model of acute and chronic disease. Invest Ophthalmol Vis Sci 1998; 39: 1171–1175.

162.Lane H, Laughon Be, Falloon J, et al. NIH Conference: Recent advances in the management of AIDS-related opportunistic infections. Ann Intern Med 1994; (120): 945–955.

163.Lopez J, de Smet MD, Masur H, et al. Orally Administered 566C80 for treatment of ocular toxoplasmosis in a patient with the acquired immunodeficiency syndrone. Am J Ophthalmol 1992; (113): 331–333.

164.Baatz H, Mirshahi A, Puchta J, et al. Reactivation of toxoplasma retinochoroiditis under atovaquone therapy in an immunocompetent patient. Ocul Immunol Inflamm 2006; 14(3): 185–187.

165.Pearson PA, Piracha AR, Sen HA, et al.