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Morphological and immunohistochemical responses of lambs following oral infection with 10,000 infective Toxocara canis (T. canis) eggs were studied up to 28 days post-infection (pi). The small intestine, liver, lungs and brain of both infected and control lambs were examined using the routine histological methods for paraffin sections and immunohistochemical techniques for frozen tissue sections. Eosinophil-rich hepatic granulomas and diffuse T. canis-induced pulmonary inflammation were the most prominent pathological features. CD2+, CD4+, CD8+, IgM bearing cells, and macrophages were demonstrated in the liver granulomas. The observed histomorphologic changes were similar to other paratenic hosts. It was concluded that larval toxocarosis followed the classical migratory path in the infected lambs.

The authors report a case of Löffler's fibroblastic endocarditis complicating a toxocarosis infection. Parasitic infestation with toxocara canis is usually asymptomatic, but this was a very rare observation of cerebral involvement associated with symptomatic Löffler's endocarditis. This is an unusual form of restrictive cardiac disease constantly accompanied by prolonged hypereosinophilia. In addition to the classical signs of cardiac failure, an acute febrile illness imitating a connective tissue disease may be observed. Echocardiography helps diagnosis by showing endomyocardial fibrosis and adherent thrombosis at one or both ventricular apices. The management of cardiac failure should include, whenever possible, radical treatment of the hypereosinophilia. At an advanced stage, surgical endocardial decortication is the only means of improving symptoms and the prognosis of these patients.

To elucidate the pathogenic potential of Toxocara cari, we observed the ophthalmologic changes of the fundi in Mongolian gerbils, Meriones unguiculatus, after oral inoculation of 17 embryonated eggs/g body weight. Ophthalmic conditions in 8 T. cati-infected gerbils were monitored using an ophthalmoscope from day 0 to day 156 and were compared with those of 57 T. canis-infected gerbils. The results showed that T. cati larvae migrated into the eye of the gerbil and then elicited ophthalmic changes, including retinal (25%) and vitreous (50%) hemorrhaging, vasculitis (37.5%), and exudative lesions (25%). Lesions were less prevalent, however, in T. cati-infected than in T. canis-infected gerbils. Unlike in T. canis-infected gerbils, the hemorrhagic lesions did not reappear in T. cati-infected gerbils after they were absorbed. These findings suggested that T. cati larvae are a potentially hazardous pathogen for ocular toxocariasis and that Mongolian gerbils infected with T. cati may be a useful model for the study of human ocular toxocariasis caused by T. cati. This is the first study to report that T. cati larvae can induce ophthalmic lesions in the retina of gerbils.

Male gerbils were inoculated intragastrically with embryonated Toxocara canis eggs. They were euthanised, and their eyes were excised at different days p.i. to identify the number of larvae as well as lesions resulting in these organs. In most animals, larvae were detected from day 5 to day 60 p.i. (end of the study). From days 10 to 20 p.i., larvae and haemorrhage were observed in the choroid and in the ciliary process. At days 30 and 40 p.i., some eyes had larvae surrounded by an infiltrate of neutrophils, oedema, haemorrhages and tissue damage in the retina or the ciliary process. On day 60 p.i., there were granulomatous lesions in the retina. This study provides a model for the study of ocular toxocariasis.

Progressive lameness and leg pain were the predominant clinical signs in a 17-week-old male border collie presented for examination. On clinical investigation, extrahepatic cholestasis in association with rickets due to inadequate vitamin D resorption was diagnosed. The dog was treated parenterally with vitamin D and a cholecystoduodenostomy was performed. At 25 days postsurgery the lameness had resolved and bone structure was radiographically normal. However, at six weeks postsurgery, the dog's condition deteriorated rapidly and euthanasia was finally performed at eight weeks postsurgery. At postmortem examination, Toxocara canis nematodes were found to have invaded the biliary system via the anastomosis between the gallbladder and duodenum, causing biliary and hepatic toxocariasis. The cause of the primary extrahepatic cholestasis was atresia of the common bile duct at the hepatic end. The liver tissue showed microscopic lesions of chronic extrahepatic cholestasis as well as acute inflammation associated with the nematode invasion. There was no postmortem evidence of bone lesions. Extrahepatic biliary atresia is extremely rare in animals and has not been described before in dogs. In contrast, it represents the most common cause of congenital cholestasis in children, occurring in approximately one per 10,000 to 15,000 live births.

Purpose: To study the results of modern vitrectomy in traction and combined traction-rhegmatogenous retinal detachment involving the macula in cases of ocular toxocariasis., Methods: This was a cohort study of patients seen in different institutions in the United States. Ten eyes of 10 patients were studied. Vitrectomy was performed in all eyes, combined with membrane removal, scleral buckle, fluid-gas exchange, silicone oil, or lensectomy in certain cases. The anatomic and visual results of surgery were reviewed., Results: Ten eyes from 10 patients ranging in age from 2 to 33 years (median, 6 years) were reviewed. Follow-up ranged from 3 months to 8 years (median, 2 years). All eyes achieved macular attachment following surgery; vision improved in 5 (50%) eyes, and was unchanged in 5 (50%). Histologic specimens from six eyes were reviewed, and revealed combinations of fibrous tissue, eosinophils, plasma cells, lymphocytes, and giant cells. One specimen revealed an encysted Toxocara canis organism., Conclusion: Inflammation created in response to Toxocara larvae may lead to traction retinal detachment of the macula. Vitreoretinal surgery has a good chance of reattaching the macula and improving vision.

Objective: To review the cytologic findings of vitreous specimens and propose a simplified approach to them., Study Design: Seventy-four vitreous specimens from 60 patients obtained either during a pars plana vitrectomy or by vitreous aspiration were reviewed. Clinical correlation was obtained on all patients., Results: Findings suggestive of a specific disorder were present in 30 specimens (41%); cytologic examination of the remaining 44 showed nonspecific changes. A lymphoproliferative disorder, the intraocular malignancy suspected most often in this series, was identified in eight specimens (11%). Large cell lymphomas were evident in 5 specimens, 2 specimens were suspicious for lymphoma, and 1 specimen was consistent with plasmacytoma. Twelve specimens (16%) contained hemorrhage. In rare instances, specific infectious agents, such as parasites (5%), bacteria (1%) and fungi (3%), could be identified. The diagnosis of viral infections required ancillary studies. Lens fragments were identified in four cases (5%), and a diagnosis of lens-induced endophthalmitis could be rendered in one case (1%). Changes consistent with sarcoidosis were present in 3% of cases., Conclusion: Based on this experience with vitreous specimens submitted for clinical reasons, we found that they could be divided into three broad diagnostic categories: inflammation/infection (54 specimens/41 patients), hemorrhage (12 specimens/12 patients) and malignancy (8 specimens/7 patients).

In this study, interleukin-5 (IL-5) transgenic mice with lifelong eosinophilia were assessed for resistance to primary infections with two tissue-invading nematodes, Nippostrongylus brasiliensis and Toxocara canis. Relative to nontransgenic littermates, three lines of IL-5 transgenic mice with varying degrees of eosinophilia all displayed enhanced resistance to N. brasiliensis. Although the timing of final worm expulsion was similar in transgenic and nontransgenic hosts, intestinal worms in transgenic mice were fewer in number throughout infection, failed to increase in size over the course of the infection, and were much less fecund. In contrast, T. canis larvae were recovered in similar numbers from tissues of transgenic mice with "low" or "high" eosinophilia and from nontransgenic mice. These results and other data suggest that eosinophils can contribute to host resistance to some parasite species. Parasite transit time through the host may correlate with relative sensitivity to eosinophils.

C57Bl/6 mice genetically deficient in interleukin (IL)-5 (IL-5-/-) and mice with the normal IL-5 gene (IL-5+/+) were infected with embryonated eggs of Toxocara canis. IL-5+/+ mice developed a marked eosinophilia in their peripheral bloods and bone marrows after infection. In contrast, the number of eosinophils at these sites actually decreased during the acute phase of infection in IL-5-/- mice. A smaller number of eosinophils infiltrated the lung, liver, heart and skeletal muscle of infected IL-5-/- mice than those of infected IL-5+/+ mice. Eosinophils were not produced in cultures of bone marrow cells from either IL-5+/+ or IL-5-/- mice which were stimulated with excretory secretory antigen of T. canis larvae. The capacity of cells from the bone marrow to differentiate into eosinophils when stimulated in vitro with recombinant murine IL-5 was the same whether the cells were from IL-5+/+ or IL-5-/- mice. Taken together, these results show that an IL-5-like molecule is not produced by the T. canis larvae and that IL-5 produced by host cells is solely responsible for the eosinophilia in mice infected with this nematode. The number and location of T. canis larvae were not altered in the absence of IL-5. In contrast, lung damage in infected IL-5-/- mice was less extensive than that in infected IL-5+/+ mice, although structures resembling Charcot-Leyden crystals were seen in the lungs of both IL-5+/+ and IL-5-/- mice. These results suggest that eosinophils play a role in the pathology in mice infected with T. canis.

The surface of T. canis is now recognized as a dynamic structure which turns over quite rapidly and serves as a renewable source of large quantities of antigen(s). The major host responses to these antigens include a marked eosinophilia and hyperglobulinemia. Both of these responses are apparently ineffective at ridding the body of infective larvae. Both eosinphils and IgE antibodies are manifestations of the Th2 subset of T helper cells and the cytokines that they secrete. Further, there is reason to believe that the antigens released from T. canis larvae favor the induction of this cellular population. Finally, there is mounting evidence that the chronic production of parasite antigen and its continued stimulation of the host immune system with a concomitant production of eosinophils can lead to a permanent alteration of the normal organization of the cardiopulmonary system. In the absence of any well-documented drugs capable of killing infective larvae, it would seem that immunological intervention may offer the only way to minimize or neutralize this 'gift from man's best friend'. This chapter was not intended to be an exhaustive review of the literature pertaining to toxocariasis. Several other recent publications will hopefully fulfill the need for more detailed information on the biology of this organism and the clinical spectrum of the disease it produces [16, 138-140]. Finally, a MEDLARS search of the current medical literature should bring anyone up to speed in a very short time.

Skin tests were done using larval extract and excretory-secretory (ES) antigens injected intradermally in the neck area of 30, 11- to 200-day-old buffalo calves and nine 27- to 100-day postparturition buffalo cows. The skin of the buffaloes infected with Toxocara vitulorum, mainly calves, demonstrated a hypersensitive response to antigens, especially to the larval extract antigens. Skin hypersensitivity responses were characterized by the presence of dermal nodules with progressive induration and an increase of up to four times the size of the original area at 30 min (immediate type) and at 72 h (delayed type) after injection. Histological preparations of skin reactions at 72 h showed a typical mononuclear cell infiltration, with eosinophils and perivascular cuffing in most of the animals. Fecal examination of 75 animals showed that 65 (86.7%) buffalo calves (9-115 days old) were parasitized with T. vitulorum. The peak of egg output from these animals occurred when they were approximately 45 days old.

In the second segment of this three-part review of parasitic infections of the central nervous system in children, we consider parasitic infections which typically involve various tissues and organs in addition to the brain and spinal cord. Parasites capable of dissemination in immunocompetent hosts are discussed first, and, as in Part I, organisms are grouped according to their predominant geographic location. This is followed by a discussion of the unique aspects of toxoplasmosis, strongyloidiasis and infection with microsporidia in immunocompromised patients, with an emphasis on the central nervous system.

The liver seems to be very attractive for many parasites which may either inhabit the organ or pass through during their normal development or may be carried to the liver leading to destruction there. Malaria parasites have a short developmental stage in the hepatocytes, but they do not damage the organ. For the leishmanias (Leishmania donovani complex) are the Kupffer cells are the target cells causing visceral leishmaniasis or kala azar. Nematodes of the ascarid group have a special affinity for the liver. The larvae of the human Ascaris have to pass through the parenchyma once during their developmental cycle, the larvae of animal ascarids on the contrary migrate within the liver for longer periods of time. Eggs of the schistosomes are carried via the portal system into the liver and trapped there in the tissue. An inflammatory granuloma develops around them. If the egg load is high, fibrosis of the liver may finally develop leading to portal hypertension. While small liver flukes (Clonorchis, Opisthorchis) living in the bile ducts do little harm to the liver in most cases, the larger liver fluke Fasciola hepatica destroys liver tissue during an early migratory phase of several weeks duration. Larval cestodes of the genus Echinococcus are usually found in the liver as closed cysts growing by expansion (E. granulosus) or as more solid structures growing by infiltration and destruction (E. multilocularis). Destruction results also if ameba (Entamoeba histolytica) invade the liver. Large areas of necrosis, liver abcesses are formed.

A 36-year-old female presented wit unilateral papillitis, followed by the development of a posterior pole granuloma. A positive ELISA-test for toxocara canis with a titer of 1/200 established the diagnosis. The patient was consecutively treated by pars plana vitrectomy and oral corticosteroids.

Leukokoria is an abnormal pupillary light reflection that usually results from an intraocular abnormality and is seen most often in children. One-half of the cases of childhood leukokoria are caused by retinoblastoma, a malignant tumor of immature retinoblasts that manifests in a normal-sized eye as a calcified mass, is often partially necrotic, and grows into the vitreous and through the choroid. Retinoblastoma enhances with contrast material and, unlike most tumors, may be darker than vitreous on T2-weighted images. When leukokoria is associated with microphthalmia, persistent hyperplastic primary vitreous (PHPV) (28% of cases) or retinopathy of prematurity (ROP) (5% of cases) should be considered. PHPV is a congenital, usually unilateral lesion that appears as a dense tubular mass extending from the lens to the retina along the course of the hyaloid canal. Hemorrhage from PHPV produces a subhyaloid (or subretinal) fluid collection, often with characteristic blood-fluid levels. ROP is bilateral and usually manifests in premature infants who received supplemental oxygen therapy. Coats disease (16% of leukokoria) is a sporadic unilateral idiopathic retinal telangiectasia that produces a lipoproteinaceous subretinal exudate leading to complete retinal detachment. The globe has normal size but increased attenuation and signal intensity from hemorrhage without calcification or enhancement. Toxocaral endophthalmitis (16% of leukokoria) is a granulomatous reaction to the parasite in the vitreous and uveoretinal coat. Retinal astrocytoma (3% of leukokoria), which manifests in a normal-sized globe, is an indolent benign neoplasm commonly associated with phakomatoses (usually tuberous sclerosis).

Histopathological examination of kidney of swiss albino mice, 2 1/2 months after infection with Toxocara canis eggs revealed various pictures of pathological affection. There was diffuse mesangioproliferative glomerulonephritis with mesangeal expansion of most of glomeruli. Some glomeruli showed severe hyalinosis with marked adhesions to the bowman's capsule. The lumina of glomerular capillaries were markedly obliterated. There was also cystic dilatation of tubules with proteinaceous casts. The intersitial tissue showed mild inflammatory oedema. Chronic inflammatory cellular infiltration to form granulomatous inflammation was noticed. Transplacental transmission of Toxocara larvae was assessed in embryo of pregnant female swiss albino mice which were infected with Toxocara eggs in the 1st week of pregnancy. The larvae were detected in the liver of embryo. Ultrastructural study of the egg shell revealed its formation of 4 layers; a thin uterine membrane with occassional small bulges, vitelline layer, thick homogenous layer, and fibrous lamellar and lipid layer.

Two hundred Toxocara canis larvae derived from Japanese quail liver were given orally to each of 50 8-week-old ddY mice and parasitism of the larvae was examined during 6 hr and 120 days after inoculation. Although there were no clinical signs in infected mice, larvae were recovered from the liver (21.5 +/- 16.3 larvae), lung (5.1 +/- 6.0 larvae), kidney (0.7 +/- 1.1 larvae), small intestine (1.0 +/- 2.0 larvae), mesentery (1.6 +/- 3.1 larvae), and brain (7.8 +/- 6.8 larvae).

The distribution of T. canis larvae and pathological changes of the liver caused by them were studied in chickens inoculated orally with 1,500 embryonated eggs during 1 and 50 days after inoculation. The number of larvae recovered varied from 40 to 192 in the liver, 8 to 166 in the muscles, 0 to 4 in the heart, 0 to 2 in the spleen, 0 to 1 in the brain, respectively. Small white foci were observed on the surface of the liver since 6 days after inoculation. Histopathological examination of the liver revealed infiltrations of leukocytes and acidophilic cells, thickening of blood vessel and bile duct wall, and granulomatous nodules. The pathological changes become more remarkable in the later stage of inoculation.

The influence of T. canis larvae migration on the lung tissue of paratenic host (inbred mice, strain C57BL6/J) was evaluated. First macroscopic manifestation was already observed on day 2 in the time of the highest larval recovery. Larvae entering the lung tissue caused numerous small extravasations. Their migration from the lungs was manifested from day 6 with an increase in the number and extent of extravasations. The lungs assumed tiger spot appearance (Fig. 1). The larval recovery was decreasing. From day 14 the expressiveness of macroscopic changes was declining. Areas of emphysema and atelectasis were observed on the lungs. The genesis and the process of elimination of extravasations were studied histologically. In the first period, the primary extravasations, caused by larvae migrating to the lung tissue (Fig. 2), were eliminated by monocytes and eosinophilic granulocytes in increasing numbers (Fig. 3). Immunohistochemically macrophages and dendritic cells were already observed in the lungs on day 1 (Fig. 4). Acid phosphatase activity was increasing from day 1 and its highest level was observed on day 84. Alkaline phosphatase activity on days 2-4 was not observed in the areas of extravasations although within the larvae themselves it was high. The extravasations of the second period (caused by larval migration from the lungs) from day 5-6 were eliminated with humoral monocytes and cells of perivascular and peribronchial tissue. Eosinophils were not active in this process. Strong exudation was observed here. The humoral part of extravasations was eliminated primarily. The cytoplasmic volume of activated cells was enlarging. Multinuclear symplasms were originated (Fig. 5). The activities of alkaline phosphatase and nonspecific esterase were increased. Macrophages and dendritic cells were still present in high numbers and from day 14 aggregations of T and B lymphocytes were observed (Fig. 6). Reparative processes were frequently observed on the blood vessels altered by the leaving larvae (Fig. 7). Changes on the lungs caused by migration of larvae always ended in functional regeneration of the lung tissue. On the other hand dead larvae stimulated proliferative forms of inflammatory reactions which led to induration (Fig. 8).

Mice previously sensitized by infective-stage larvae of the canine nematode, Toxocara canis, trap large numbers of challenge larvae within the liver; trapped larvae are found within eosinophilic granulomas. To investigate the role of eosinophils in this phenomenon we examined larval trapping in mice depleted of blood and tissue eosinophils by treatment with a monoclonal antibody (MoAb) (TRFK-5) produced against recombinant murine interleukin 5 (rmIL-5). Control mice received either an isotype-matched control MoAb or PBS. On day 0 test mice were given a sensitization dose of 125 infective T. canis eggs. Test and challenge control mice received 500 infective eggs on day 28. All mice were killed on day 42 and larval numbers within the liver were determined. Liver samples were also collected for histopathological and morphometric examination. When compared to test mice treated with PBS or the isotype control, the level of circulating eosinophils in anti-IL-5-treated test mice was reduced by 94-96% on days 14 and 27, 99% on day 35, and 100% on day 42; the level of tissue eosinophils within liver granulomas on day 42 was reduced by 92-95%. The total area of inflammation within the liver was similar among all test groups. However, the highly eosinophilic infiltrates, present in control sections, were replaced in anti-IL-5-treated mice by lymphocytes, macrophages, and foreign-body giant cells. No difference was found in larval trapping between antibody-treated groups. These findings suggest that the eosinophil is not necessary for liver trapping in murine larval toxocariasis.

Histological examination of kidneys from mice experimentally infected with Toxocara canis embryonated eggs demonstrated the presence of a segmental or diffuse mesangioproliferative glomerulonephritis. Immunohistochemical studies established that renal alterations were associated with glomerular deposits of IgG, IgM and third component of complement (C3). These findings suggest that an immunomediated mechanism might possibly be involved in the genesis of kidney damage observed in mice infected with T. canis embryonated eggs.

Pars plana vitrectomy was performed in a 30-year-old patient who presented a posterior traction detachment due to an inflammatory granuloma. The granuloma removed in toto during surgery revealed characteristic features of toxocariasis lesion (first case described in the literature). An ELISA test performed on a vitreous sample was strongly positive. Retinotomy around the granuloma was necessary to re-attach the retina and silicone oil was used as a tamponade for 4 months. VA improved from HM to 15/200 after silicone removal.

The distribution of T. canis larvae and pathological changes caused by them were studied in Japanese quails orally inoculated with 1,500, 4,000 or 15,000 embryonated eggs. Larvae were distributed mainly in the liver and, to lesser extent, in the muscles, brain, eyes and other organs. The number of larvae varied from 7 to 3,346, and from 1 to 288 in the liver and muscles (breast and legs), respectively. A small number of larvae were also recovered from the heart, gizzard, brain and eyes. In the groups of quails inoculated with 4,000 or 15,000 eggs, small white foci were observed on the surface of the liver 6 or 12 hr after inoculation. Histopathological examinations revealed necrotic lesions, leukocytic infiltration, granuloma and nodular lesions. The pathological changes became more serious with the large size of inoculum and days after inoculation.

Small intestinal histopathology and absorption were examined in Beagle puppies infected with either a moderate or a low burden of Toxocara canis. Infection with T. canis significantly reduced absorption of xylose, but only slightly delayed absorption of para-aminobenzoic acid. Fat assimilation was reduced and faecal proteolytic activity was increased. A significant reduction in villous height occurred and was inversely related to the extent of the infection. Villous goblet cell numbers, particularly those in the luminal third of the villus, were lowest and crypt goblet cell numbers were highest in the most heavily infected of the puppies. Villous goblet cell numbers increased rapidly after treatment of the puppies with piperazine or after the spontaneous elimination of the T. canis infection while crypt goblet cell numbers were less affected by elimination of the parasites. Intra-epithelial lymphocyte numbers were lowest in 33- to 37-day-old puppies infected with greater than 127 T. canis and highest in 44- to 46-day-old puppies losing their infection. Infection with T. canis had no apparent effect on mast cell numbers or pyroninophilic cell numbers in the lamina propria.

The nature and dynamics of inflammatory changes have been studied in the liver and lungs of CBA/j mice infected with T. canis oocysts (Moscow and Irkutsk strains). It has been shown that in larval toxocariasis of mice two peaks of total leukocyte concentration are observed in the peripheral blood, on days 8 and 13-15 of invasion, which reflects terms of larvae migration via liver and lungs. The course of the inflammatory process in the parenchymatous organs of experimental animals is 7 days slower than in aseptic inflammation due to 2-4-fold inhibition of leukocyte chemotaxis and 3-fold decrease in bactericidal activity. Larval migration of Irkutsk T. canis strain from the liver to the lungs and to the brain is 7-10 days slower than in the Moscow strain.

Migrating larvae of the canine nematode Toxocara canis induce inflammatory responses in the lungs of infected mice. Histological examination of the lungs showed that mice, developed persistent multifocal inflammation in which eosinophils (eos), macrophages (M phi) and many lymphocytes were involved. Cuffing of blood vessels and bronchioles with mixed cell populations was also observed. Investigation into the response of isolated tracheae to cholinergic and beta-adrenergic receptor agonists demonstrated a significant decreased reactivity despite the pronounced involvement of eos and M phi. This hyporeactive state persisted for greater than or equal to 4 weeks p.i..

Male mice, strain C57 black, were infected with Toxocara canis by a single intragastric dose of 1500 infective eggs. The eyes were studied at sequential time periods after infection (6 to 63 days) by conventional microscopic techniques, and the histological characteristics of the inflammatory response were recorded. In the majority of animals the disease was unilateral. Twenty-six larvae were found in the retina, in the retinal vessels, and in the subretinal space in 20 eyes, while in 29 eyes there were inflammatory changes which were not related to the presence of intact or fragmented larval forms. The inflammatory reaction began as a polymorphonuclear response but after day 13 became a granulomatous reaction. This suggests that the inflammatory phenomenon may be propagated by the secreted surface antigens in the absence of the living or dead larvae.

Human infection by toxocara larvae has been thought to be predominantly a disease of young children, but the percentage of the population with antibodies to this nematode worm has recently been shown to increase with age. Although a definite diagnosis of ocular toxocariasis can be made only by identifying the larva histologically, the evidence in three cases presenting with recent uniocular loss of vision strongly suggests that adults may also be affected. The lesions noted on ophthalmoscopy closely resembled toxocaral granulomata in children. Toxocaral fluorescent antibody tests were positive in each case.

The clinical and autopsy findings of a two and a half year-old infant with Toxocara sp. infection of the brain and granulomatous lesions in the liver are reported. The cause of death was non-accidental injury. The relationship between Toxocara infection and behavioural disorders is discussed.

The effects of thiabendazole on the survival and migration of Toxocara canis larvae in mice were studied. Although thiabendazole had a negligible larvicidal effect, it produced marked inhibition of the migration of the larvae in tissues. Larvae were arrested in the liver after oral inoculation and in the lungs after intravenous inoculation. Observations indicated that the drug may have a reversible, as well as a progressive, time-related metabolic effect on the larvae. Significant inhibition of migration required administration of the drug in medicated feed at a concentration of 0.25% or more. Periodic oral administration of a thiabendazole suspension was ineffective in inhibiting larval migration. It was concluded that the immobilizing effect of the drug on the larvae of T. canis may account for the clinical improvement observed after treatment with thiabendazole in cases of visceral larva migrans, the prevention of prenatal or mammary transmission of infection in dogs, and the suppression of tissue damage by nematode larvae in general.

Spontaneous release of a taut, fibrotic subretinal strand was observed in a patient with rhegmatogenous retinal detachment. This strand had been elevating the retina, and its release led to partial reattachment. Whereas spontaneous resolution of preretinal membrane contraction in retinal detachment has been reported, this is the first report of spontaneous release of such a subretinal fibrotic strand. The manner in which the strand released raised the question of whether efforts should be made to rupture such strands with transcleral pressure prior to considering retinotomy.

A primate model for the study of Toxocara canis infection was created by intravitreal, periocular, systemic, and intracarotid injection of viable larvae in cynomolgus monkeys. The results were as follows: (1) Intravitreal larvae caused retinal hemorrhages, perivasculitis, mild vitritis, and retinal nodules. (2) Apparently viable larvae without inflammatory reaction were found in the vitreous, retina, and optic nerves up to nine months after intravitreal inoculation. (3) Other larvae were surrounded by an acute inflammatory granuloma or a chronic fibrotic granuloma, but they did not appear to be necrotic. (4) Toxocara canis larvae apparently had the ability to move through ocular tissue, to leave the site of tissue reaction, and to exit via the optic nerve. Viable larvae were found in the retina up to 15 months after inoculation. (5) Culture fluid containing Toxocara proteins stimulated a severe retinal vasculitis. Dead larvae caused little reaction. (6) Positive aqueous and vitreous enzyme-linked immunosorbent assay titers were found in the most severely inflamed eyes, which often harbored live larvae.

The gross and histological findings of a case of disseminated granulomatous disease caused by larval nematode infection in a cat are presented. The larvae were identified as those of Toxocara canis and the lesions associated with infection of cats with various ascaridoid larvae are discussed.

A 4-year-old white female presented with leukocoria of the right eye. White punctate lesions were observed posterior to the retrolental membrane, which suggested retinoblastoma of some examiners. A full history, physical examination, ultrasonography, and CT scan failed to rule the diagnosis of retinoblastoma in or out. A serum ELISA titer was 1:4, which was considered nondiagnostic. Examination of the enucleated eye revealed a midsegment of the second stage larva of Toxocara canis. The strengths and weaknesses of various diagnostic modalities used to differentiate leukocoria caused by retinoblastoma and T canis are discussed.

The role of eosinophils in ocular ascarid infection is studied in an animal model. Primary intravitreal infection of guinea-pig eyes with ascarid (Toxocara canis, Ascaris suum) second-stage (L2) larvae resulted in an anterior chamber exudate containing 98% or more eosinophils. Anterior chamber aspirates were cultured in RPMI media 1640 with T. canis or A. suum L2 larvae at 37 degrees C for 1-96 hours. The in vitro interaction of eosinophils with L2 larvae was studied by light, and scanning and transmission electron microscopy. Eosinophil interaction with L2 larvae in vitro was dependent upon soluble factors present in the anterior chamber aspirates from the infected eyes. Eosinophils adhered firmly to the surface of the L2 larvae, to a larval sheath, or to attached eosinophils. Eosinophils interacting with larvae displayed a range of granular matrix changes, core duplication, and reversal of the relative electron densities of the core and matrix, suggestive of eosinophil activation. An eosinophil secretory granule was seen to empty its contents onto a T. canis L2 larval surface. Electron-dense material was observed in the interphase between eosinophils and the larval cuticle or sheath. Large lipid droplets within muscle cells and ballooned-out epidermal cells were seen within larvae immediately beneath adherent eosinophils. Parasites were able to partially evade interaction with eosinophils in culture by shedding their sheaths. A similar phenomenon in vivo may allow the parasite to migrate from a site of inflammation. It is possible that a discarded sheath or membrane serves as an antigenic stimulus for a local intraocular granulomatous reaction free of parasite.

The cellular evolution of the persisting, muscle-associated granuloma in murine toxocariasis (visceral larva migrans) was chronicled for 11 weeks by light and electron microscopy. The initial granuloma consisted primarily of eosinophils and appeared to develop from the acute inflammatory infiltrate. During the ensuing 48 hours, most of the eosinophils appeared to loose their granules and disintegrate. The resulting cellular debris was then taken up by newly arrived macrophages which become the predominant mononuclear cell in the lesion by 28 days of infection. By 11 weeks, the granuloma had become a fibrotically encapsulated epithelioid granuloma surrounding the inciting larva. This histologic reaction is compared with the liver granulomatous response to Toxocara and to the well-characterized schistosome egg granuloma. A possible delayed hypersensitive etiology for the Toxocara granuloma is suggested.

Toxocara canis, the parasitic roundworm of the dog may infect aberrant hosts including mice and humans. The present study examined the behavioral and pathological changes at each of three postintubation periods (Period 1: 8-10 days, 2: 49-51 days, and 3: 84-86 days postintubation, respectively) in independent groups of mice intubated with 1000 eggs of T. canis. Eight-ten days after intubation Toxocara infected animals typically showed depressed levels of activity relative to saline-intubated controls. The scope and severity of behavioral changes were attenuated when different mice were tested 49-51 days after infection, and then became more severe when the third set of animals was tested 84-86 days after intubation. While brain pathology increased over the three periods, visceral organs showed marked pathology 8-10 days after intubation followed by a decrease in severity. These data suggest that Toxocara associated pathological changes in visceral organs and in the brain have behavioral consequences in mice. Given the similarity in migratory pathways of this parasite in rodents and humans, and the findings of T. canis larvae in human brain tissue, the results of this animal study may have implications concerning the possible etiology of behavioral disorders for children who have a known history of pica for dirt.

Toxoplasma, nematodes, and cytomegalovirus are the most common causes of uveitis in children involving the posterior pole. Discussion of treatment and management is detailed. Rubella retinitis and subacute sclerosing panencephalitis are specific entities which are limited in their initial presentation in children. Panuveitis including sympathetic ophthalmia, Vogt-Koyanagi-Harada, and Behçet's syndromes, while relatively rare in their occurrence, demand early treatment intervention. Specific antimicrobial therapy and adrenocorticosteroids as well as therapeutic suggestions are also included. This is the last part of a three-part series of articles.

A five-year old boy had clinical findings consistent with ocular toxocariasis, blood eosinophilia, and repetitive negative (titer 1:2) ELISA. The eye was enucleated and larval fragments consistent with Toxocara were present within an eosinophilic granuloma in the vitreous cavity overlying a chorioretinal scar entrance site.