Symptomatic ocular infection with T. gondii is seen in immunocompetent persons who acquired infection after birth (Wilder, 1952; Holland, 2003). It was unclear for many years whether the burden of T. gondii ocular eye disease in adults was due to reactivation of congenital infection or to infection acquired after birth (Hogan, 1961). Initially, congenital infections were considered to be responsible for the majority of ocular disease in adults (Hogan et al., 1964), but more recent studies have shown that acquired T. gondii infections in adults are responsible for the majority of ocular T. gondii disease in adults (Gilbert et al., 1999; Gilbert and Stanford, 2000). A lifetime risk of 18 cases per 100 000 persons has been found in the United Kingdom (Gilbert et al., 1995). A study from Finland found an annual incidence of 0.4 cases per 100 000 persons with a cumulative prevalence of T. gondii ocular disease of 3 per 100 000 (Paivonsalo-Hietanen et al., 2000).
In the United States a study in 1972 found that 0.6% of the adult population had retinal scars compatible with previous T. gondii infection (Smith and Ganley, 1972), and the same prevalence was found in another study from Alabama 15 years later (Maetz et al., 1987). It is estimated that approximately 2% of the adult population in the United States has retinal findings compatible with T. gondii infections, but the majority do not experience reduced vision (Holland, 2003).
An outbreak of waterborne T. gondii at Vancouver Island (British Columbia, Canada) was associated with symptomatic retinochoroiditis (Bowie et al., 1997; Burnett et al., 1998). It is not precisely known how many people were infected, but 20 patients with retinochorioditis and 51 with adenopathy were reported. It was estimated that 0.5% of infected individuals developed retinochorioditis within a year (Burnett et al., 1998).
Retinal changes due to T. gondii appear to be much more common in southern Brazil than other parts of the world. One study found that 21.3% of persons above 13 years of age had retinochorioditis (Glasner et al., 1992). A follow-up study of 131 patients over 6 years found that 11 (8.3%) had developed typical T. gondii ocular lesions and the authors concluded that acquired T. gondii ocular lesions are common in immunocompetent adults in Brazil (Silveira et al., 2001).
One report from Sierra Leone found that 43% of adults with uveitis had T. gondii infections, indicating that eye disease due to T. gondii may also be common in Africa (Ronday et al., 1996).
It has been suggested that infection with T. gondii is associated with bipolar disease (Torrey and Yolken, 2003), but it is possible that people with bipolar disease place themselves at risk of infection through behavioral practices such as improper preparation of food.
Immunocompromised Patients
The majority of T. gondii infections in immunocompromised hosts are reactivations of previous infections (Mele et al., 2002).
HIV-Infected Patients
The high rate of toxoplasma encephalitis in patients with AIDS was reported soon after the start of the HIV epidemic (Luft et al., 1983; Roue et al., 1984; Enzensberger et al., 1985; Suzuki et al., 1988) and toxoplasma encephalitis was an important cause of death in HIV-infected patients before the introduction of highly active antiretroviral therapy (HAART) in 1996. In the pre-HAART era up to 30% of T. gondii, seropositive, HIV-infected patients developed T. gondii encephalitis when the immunosuppression progressed (McCabe and Remington, 1988), depending on the prevalence of T. gondii infection in the community. Trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis jarovecii also reduced the risk of T. gondii encephalitis in HIV-infected patients (Schurmann et al., 2002).
Cardiac And Kidney Transplants
In one study of patients receiving a cardiac transplant, prophylaxis for 6 weeks with pyrimethamine reduced infection from 57% (4 out of 7) to 14% (5 out of 37) (Wreghitt et al., 1992). A review of 257 heart transplants 1985–93 and 33 heart–lung transplants found that 4.5% (n ¼ 13) donors were toxoplasma-positive/ recipient-negative in 4.5% (n ¼ 13) of cases; of these 9 were followed up and only one patient seroconverted. All patients received trimethoprim/sulfamethoxazole prophylaxis for P. jarovecii (Orr et al., 1994). A later study clearly showed the risk of infection in T. gondii-naive recipients receiving a cardiac transplant from a T. gondii -positive donor; 78% of recipients seroconverted (14 out of 16). In contrast, only 10% (6 out of 59) of donor-negative/ recipient-positive cases developed serological evidence of toxoplasma infection (Gallino et al., 1996). Toxoplasma infection has also been described after kidney transplants (Renoult et al., 1997; Aubert et al., 2000; Giordano et al., 2002; Wulf et al., 2005).
Bone Marrow Transplants (BMT)
An early review of 55 patients with allogeneic BMT complicated by T. gondii infection found that only 4% survived (Chandrasekar et al., 1997). The European Group for Blood and Bone Marrow Transplantation reported on 106 allogeneic, stem-cell transplants of which 55% of the donors were toxoplasma IgG-positive. All recipients received prophylaxis with trimethoprim and sulfamethoxazole for 6 months and 15% (16 out of 106; 95% CI: 8–21%) had at least one T. gondii, PCR-positive blood sample, and 6% (6 out of 106; 95% CI: 1–10%) experienced clinical disease due to T. gondii (Martino et al., 2005).
Treatment Of T. Gondii Infections
Drugs Effective Against T. Gondii
The effectiveness of sulfonamides was demonstrated in 1942 by Sabin and Warren and confirmed in later studies (Eyles, 1953). Later, pyrimethamine was found effective against T. gondii (Eyles and Coleman, 1952) and synergy between sulfadiazine and pyrimethamine was demonstrated soon after (Eyles and Coleman, 1953). Spiramycin was shown to be effective against T. gondii in 1958 (Beverly, 1958; Garin and Eyles, 1958). These three drugs have ever since been the main treatment for T. gondii infections in pregnancy, congenital toxoplasmosis, and ocular toxoplasmosis. However, in 1976, it was shown that sulfadoxine combined with pyrimethamine was also highly effective against T. gondii (Garin et al., 1976), and some centers advocate postnatal treatment with sulfadoxine/ pyrimethamine for up to 2 years in infants with congenital toxoplasmosis (Villena et al., 1998). It should be emphasized that there are no comparative studies of treatment versus no treatment of T. gondii infections in pregnant women or newborns. The different drugs available have recently been reviewed (Daveluy et al., 2006a, b; Derouin, 2006).
Treatment Of T. Gondii Eye Disease
Perkins et al. (1956) randomized 164 persons with acute uveitis to treatment for 4 weeks with pyrimethamine or placebo and found a significant improvement of lesions among the recipients of pyrimethamine. A randomized, open-labeled clinical trial comparing the recurrence of retinochorioditis in 61 patients treated by sulfamethoxazole and trimethroprim (cotrimoxazole) every 3 days for up to 20 months (duration of the study) and 63 patients without treatment, found a significantly lower rate of recurrence in the treatment group ( p = 0.054; 6 out of 61 vs. 15 out of 63) (Silveira et al., 2002). In a prospective multicenter study of 149 consecutive patients with active toxoplasmic retinochorioditis who were randomly assigned to a treatment with pyrimethamine and sulfadiazine, clindamycin plus sulfadiazine or cotrimoxazole, found no difference in resolving of the eye lesion or recurrence over 2 years follow-up between the treated groups. The untreated group had only peripheral lesions so the only valid comparison is between treated groups (Rothova et al., 1993). A descriptive study with historical controls of the effect of an additional course of pyrimethamine and sulfadiazine compared to historical controls did not report a reduced rate of recurrence after additional treatment (Wallon et al., 2001). A study comparing pyrimethamine and sulfadiazine with pyrimethamine and azithromycin in adult patients with retinochorioditis found no difference in the clinical outcome (Bosch-Driessen et al., 2002). A recent systematic review found a lack of evidence to support routine antibiotic treatment for acute toxoplasmic retinochoroiditis (Stanford et al., 2003). Placebocontrolled randomized trials of antibiotic treatment in patients presenting with acute or chronic toxoplasmic retinochoroiditis arising in any part of the retina are required (Stanford et al., 2003).
A review of observational studies in the EUROTOXO collaboration on the effectiveness of postnatal treatment did not find evidence of a benefit of treatment of infants with congenital toxoplasmosis. However, without randomized, controlled trials the findings are difficult to interpret (Thie´baut et al., 2006a, b). Observational data from a cohort of severely infected children found improvement over time, which was interpreted as an effect of treatment (McLeod et al., 2006).