Part 4 • Infectious Uveitic Conditions

Chapter 16 Toxocara canis

Figure 16-4.  OCT of a Toxocara mass protruding into the vitreous.

(Reproduced with permission from Suzuki, T., et al., Following the migration of a Toxocara Iarva in the retina by optical coherence tomography and fluorescein angiography. Reprinted in part from Jpn J Ophthalmol 2005;49:159–161.)

Histopathology and immune factors

The immune reaction to the Toxocara organism is similar to that seen for other parasites of this type. A profound eosinophilic response is initially noted histologically. Later, the immune response will change to include macrophages, lymphocytes, and epithelioid cells. A large granulomatous response to the organism is not unusual (see Fig. 16-1). In late lesions scarring may be prominent. The inflammatory response may be quite profound and cause more destruction than the offending organism. Therefore, a careful search of the lesion may be needed to discover the parasite. In addition, in severe inflammatory reactions the organism may be essentially destroyed, and therefore the diagnosis can only be suspected on the basis of the massive inflammatory response. In vitro work by Del Prete and colleagues34 isolated clones of T cells from patients using the T. canis excretory/ secretory antigen. They found that these clones secreted interleukin (IL)-4 and IL-5 but no or only minimal amounts of IL-2 and interferon-γ, the reverse of what was seen from clones that were specific to the purified protein derivative of

Mycobacterium tuberculosis.

An eosinophilic amorphous material called the Splendore– Hoeppli phenomenon can be seen in the organs of children with VLM. Werner and colleagues35 reported on the histopathologic examination of subretinal material removed from an eye with T. canis infection: eosinophilic amorphous material, possibly representing a Splendore–Hoeppli phen­ omenon was noted. This reaction is not specific to the Toxocara organism but rather is seen for several parasites that probably initiate a similar type of eosinophilic response. Experimentally induced disease will produce a marked eosinophilic response and a histologic picture not unlike that seen in humans.36 Further, Rockey and colleagues37 have noted that eosinophils adhere firmly to the larval sheath. However, the parasite is able to partially evade eosinophils in culture by shedding its sheath. This in vitro observation supports the notion that the larval sheath could act as an antigenic stimulus without the presence of the parasite itself. Kayes38 has emphasized the important role of T cells in the host’s immune response to this parasite.

Carter39 used 35S-labeled T. canis to determine larval numbers in various tissues. It was found that although initially the larvae congregated in the liver, by day 14 after

infection the majority of the isotope was found in the brain. Cuellar and colleagues40 reported that measuring the level of immune complexes may be a good technique for monitoring treatment efficiency because they fell quickly and remained low with therapy. Various animal models have been used.41 Hamsters and gerbils seem most susceptible to Toxocara. Gerbils may develop ocular lesions 55% of the time. Ollero et al.42 studied the prevalence of eye disease in a mouse model of Toxocara. Eye disease occured after the larva reached the brain, but was not dependent on the inoculating dose.42 Another animal model using Swiss mice43 tested the administration of ciclosporin. Of interest was the fact that the medication increased the susceptibility of the mice to the Toxocara larvae, but the antiparasitic effect of the medication was great, leading to a diminution in the number of living larvae.

Laboratory tests can be important in the diagnosis of T. canis infection. Children with VLM will have an eosinophilia and hyperglobulinemia.29 No eggs will be found in the stool because their lifecycle in humans would not reach this stage. Children with this condition tend to be 2–4 years of age. Those with ocular toxocariasis are generally older (7 years and older), and they may or may not have a history of VLM. Further, because there is no acute systemic illness, elevated immune parameters are rarely present.

Enzyme-linked immunoabsorbent assay

Many of the older methods used to evaluate antibody responses to Toxocara were not specific, cross-reacting with other ascarids. The enzyme-linked immunoabsorbent assay (ELISA) is the most reliable and readily available test for the evaluation of antibodies directed against this organism. This test has used at least two Toxocara-derived antigens: one from the embryonated egg and the excretory-secretory antigen or exoantigen. One report44 suggested that the exoantigen may give more consistent findings. Gillespie and colleagues45 found that a two-site antigen-capture ELISA that detects a carbohydrate epitope on the excretory–secretory antigens of Toxocara was reasonably efficient (in 50% of patients) in detecting antibodies in patients with acute toxocariasis, but not effective in detecting antibodies in those with inactive or ocular disease. One ELISA kit evaluated46 had a calculated diagnostic sensitivity of 91%, but 14% of serum samples showed false-positive results because of cross-reactions with other protozoan or helminthic infections. This is why many feel that a negative serum test warrants testing ocular fluids if the clinical suspicion is high enough. De Visser and coworkers47 paired fluid samples with serum samples. In their study, which found no adults with the disorder, two children with the ocular disease had low serum titers but significantly high antibody titers in the their ocular fluids, permitting the diagnosis.

Looking more closely at this test, a serum titer of 1 : 8 is usually taken as evidence of a positive test for ocular toxocariasis (Table 16-3). As with all tests, the ELISA is not foolproof. Albert and Marcus48 reported a case of a 4-year- old boy with a serum ELISA titer of 1 : 4; examination of the enucleated eye revealed a second-stage larva of Toxocara. Kieler49 reported the case of a 5-year-old with an ELISA titer of 1 : 2 in whom the Toxocara parasite was present in an eosinophilic granuloma in the vitreous cavity, whereas