Tachyzoite to bradyzoite conversion

Bradyzoite to tachyzoite conversion

Figure 14-14.  Factors that affect conversion from tachyzoite to bradyzoite.

(From Lyons RE, McLeod R, Roberts CW. Toxoplasma gondii tachyzoite-bradyzoite interconversion. Trends Parasitol 18: 198, 2002, with permission.)

The authors concluded that antiretinal activity can be accounted for by antibodies directed not only against S-anti- gen but also against other antigens. These observations raise the provocative argument that the inflammatory disease we see is at least partly, or at times, autoimmune driven. However, Vallochi et al.99 reported that the peripheral blood from ocular toxoplasmosis patients also recognized retinal antigens. But their data suggest that such autoimmune responses were associated with less severe disease. We know that the Toxoplasma cyst may include tissue from the host, and perhaps S-antigen is sequestered there until the cyst breaks open. Alternatively, the initial destruction caused by the proliferating organism releases immunogenic antigens to the general circulation, thereby causing sensitization. This then results in a secondary autoimmune response, which can prolong the initial response or become the center of a recurrent inflammatory episode some time in the future.

The mechanism for the anterior uveitis and the Fuchs’-like syndrome seen in conjunction with the retinitis of ocular toxoplasmosis still is a subject of conjecture. In a rabbit model of experimental ocular toxoplasmosis, toxoplasmic antigen has been found in the vitreous.100 In a feline model of ocular toxoplasmosis in which chorioretinal lesions form after injection of organisms into the carotid, an anterior uveitis can be seen in some of the animals.101 It may be that in the human situation the antigen is also found in the anterior chamber, producing an inflammatory response there; alternatively, immune complexes formed more posteriorly in the eye may fix to the tissue in the anterior chamber, including the iris, giving the clinical findings described. However, an intact Toxoplasma organism has been found in only one immunocompromised person with AIDS.102 Greven and Teot103 reported recovering encysted bradyzoites from the cytospin of a vitrectomy specimen obtained in the course of a retinal detachment repair, which helped confirm the clinical impression and led to the initiation of therapy.

Methods of diagnosis

Serologic evidence of the Toxoplasma organism is of immense importance in helping the clinician make the diagnosis.

Histopathology and immune factors

Research has suggested that there is a selective activation of a subset of B cells locally in nonlymphoid tissue, such as the eye.104 Indeed, research evaluating serum and intraocular antibody responses has shown differences.105 Antibody from the aqueous of patients with chronic toxoplasmosis stained more intensely to a 28-kDa antigen, believed to be the GRA-2 antigen, which is expressed in both tachyzoites and bradyzoites. We would accept seropositivity even in undiluted serum, although admittedly this can be problematic because the incidence of false-positive results is high. The presence of immunoglobulin (Ig) M titers to the organism suggests a recently acquired infection. Observations by Rubens Belfort Jr, MD, in Brazil (personal communication, 1993) suggested that at least in some cases the IgM peak may be highly ephemeral and thus easily missed. The type of serologic testing that is the most reliable is still being debated, although the ELISA technique has been recommended by many. Weiss and colleagues106 reported their experience comparing the immunofluorescence antibody test, the Sabin–Feldman dye test, and the ELISA. They found

that for three patients the immunofluorescence test result was negative (titer <1 : 16) whereas the Sabin–Feldman test

result was positive for these three patients, as was the ELISA in the one patient tested. These data suggest that the Sabin– Feldman test or ELISA antibody test be performed before one excludes the diagnosis of ocular toxoplasmosis on the basis of a negative antibody test result.106

The polymerase chain reaction (PCR) is being used increasingly for diagnostic purposes and has become one of the mainstays for diagnosis but it does have its drawbacks.107 Initial problems were raised about this methodology. In one early study comparing antibody determinations with the detection of T. gondii DNA,108 intraocular IgG was more commonly found in recurrent ocular toxoplasmosis than in recently acquired disease (81% versus 41% of patients). However, DNA from T. gondii was found intraocularly in recently acquired disease compared with recurrent ocular toxoplasmosis (37% versus 4% of patients). Using the aqueous to diagnose posterior segment disorders is well accepted today.109

The diagnosis of this disease by serologic means alone may not always be reliable.110 Rothova and coworkers noted that even though IgG antibody positivity was seen in 100% of their patients with clinically apparent ocular toxoplasmosis, 58% of the control subjects also showed positive results. Although seven of 25 patients (28%) with toxoplasmosis had detectable circulating immune complexes with IgG and Toxoplasma antigen, two of 12 control subjects (16%) did as well. In reviewing findings from normal control subjects and patients with suspected ocular toxoplasmosis, Phaik and

coworkers111 estimated that at least 77% of those with ocular toxoplasmosis had serotiters ≥1 : 256, somewhat higher than

those found in control subjects. Nonetheless, we believe that the diagnosis is very much a clinical one, with serologic findings being supportive but not definitive.

The serologic examination of the aqueous is a technique reported by Desmonts.112 In this classic paper, Desmonts postulated that in patients with purely an ocular recurrence of toxoplasmosis, local antibody formation against the organism will occur and therefore the local titer will be greater than that found in the circulation. His impressive demonstration of this phenomenon and the calculation of

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