Animal models in ocular toxocariasis

Ocular toxocariasis is a clearly defined disease. However, much remains to be learned concerning the migratory route, ocular changes, diagnosis and treatment. Studies in paratenic hosts have contributed to our understanding and will yield more information. Various experimental animals have been used, such as mice, rabbits, guinea pigs, primates, hamsters and gerbils. Of these, the last appear to be the most appropriate model due to their high susceptibility to ocular infection. Results obtained from different animal models are often not comparable due to the fact that dose and routes of inoculation are diverse. Early stages in the pathogenesis of ocular toxocariasis are manifested by haemorrhages in the anterior chamber and iris, replaced in time by accumulations of white cells. Ocular migration produces an early cell reaction, formed by an infiltration of neutrophils accompanied by vasculitis and retinal microinfarcts. Over a period of time, an increase of macrophages and the distribution of the infiltrates is observed. Later, granulomatous lesions are formed. These do not necessarily contain a larva and their appearance varies in different animal models. Local production of IgE and the presence of specific IgG have been described.     

Histopathological investigation of experimental ocular toxocariasis in 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.     

Five cases of ocular toxocariasis confirmed by serology

We report 5 cases of ocular toxocariasis in Korean adults complaining of visual impairment along with floating or bubbling sensation. Fundoscopic examination revealed a retinal detachment along with exudate in 4 cases. They all showed typical reaction by ELISA and immunoblot against Toxocra excretory-secretory antigen. One case showed high level of anti-Toxocara IgE antibodies (34,000 Toxocara units/L) as well as increased level of serum total IgE antibodies and the specific IgE antibodies for 3 inhalant antigens, suggesting that high level of anti-Toxocara IgE antibodies was associated with an atopic status. Clinical manifestations were improved after the sequential use of steroids then mebendazole. We also suggest that ocular toxocariasis should be thoroughly investigated even when an evocative uniocular inflammatory lesion is encountered in peripheral retina without a systematic disease.     

The epidemiology and public health importance of toxocariasis: A zoonosis of global importance

Toxocariasis, caused by infection with larvae of Toxocara canis, and to a lesser extent by Toxocara cati and other ascaridoid species, manifests in humans in a range of clinical syndromes. These include visceral and ocular larva migrans, neurotoxocariasis and covert or common toxocariasis. Toxocara canis is one of the most widespread public health and economically important zoonotic parasitic infections humans share with dogs, cats and wild canids, particularly foxes. This neglected disease has been shown through seroprevalence studies to be especially prevalent among children from socio-economically disadvantaged populations both in the tropics and sub-tropics and in industrialised nations. Human infection occurs by the accidental ingestion of embryonated eggs or larvae from a range of wild and domestic paratenic hosts. Most infections remain asymptomatic. Clinically overt infections may go undiagnosed, as diagnostic tests are expensive and can require serological, molecular and/or imaging tests, which may not be affordable or available. Treatment in humans varies according to symptoms and location of the larvae. Anthelmintics, including albendazole, thiabendazole and mebendazole may be given together with anti-inflammatory corticosteroids. The development of molecular tools should lead to new and improved strategies for the treatment, diagnosis and control of toxocariasis and the role of other ascaridoid species in the epidemiology of Toxocara spp. Molecular technologies may also help to reveal the public health importance of T. canis, providing new evidence to support the implementation of national control initiatives which have yet to be developed for Toxocara spp. A number of countries have implemented reproductive control programs in owned and stray dogs to reduce the number of young dogs in the population. These programs would positively impact upon T. canis transmission since the parasite is most fecund and prevalent in puppies. Other control measures for T. canis include the regular and frequent anthelmintic treatment of dogs and cats, starting at an early age, education and enforcement of laws for the disposal of canine faeces, dog legislation and personal hygiene. The existence of wild definitive and paratenic hosts complicates the control of T. canis. Increasing human and dog populations, population movements and climate change will all serve to increase the importance of this zoonosis. This review examines the transmission, diagnosis and clinical syndromes of toxocariasis, its public health importance, epidemiology, control and current research needs.     

Seroprevalence of Toxocara antibodies among patients suspected of ocular toxocariasis in Slovenia

Ocular toxocariasis named also ocular larva migrans is caused by larvae of the roundworm Toxocara spp. The purpose of this study was to find out the seroprevalence of Toxocara antibodies in patients suspected of ocular toxocariasis. Between January 2001 and December 2003, sera from 239 ocular patients, aged 3 to 80 years, were examined by ELISA and confirmed by Western blot test. Out of the 239 patients, 172 (72%) were seronegative and 67 (28%) were Toxocara seropositive; 95% CI (22-34%). The median age of Toxocara seropositive patients was 37.6 years. There was no significant difference in the number of Toxocara positive sera between the younger age group (< or = 14 years) and the older age group (> 14 years), p > 0.05. A high rate of Toxocara seropositivity in ocular patients should alert the ophthalmologists in Slovenia to include toxocariasis in the differential diagnosis of eye diseases more frequently.     

Highlights of human toxocariasis

Human toxocariasis is a helminthozoonosis due to the migration of Toxocara species larvae through human organism. Humans become infected by ingesting either embryonated eggs from soil (geophagia, pica), dirty hands or raw vegetables, or larvae from undercooked giblets. The diagnosis relies upon sensitive immunological methods (ELISA or western-blot) which use Toxocara excretory-secretory antigens. Seroprevalence is high in developed countries, especially in rural areas, and also in some tropical islands. The clinical spectrum of the disease comprises four syndromes, namely visceral larva migrans, ocular larva migrans, and the more recently recognized "common" (in adults) and "covert" (in children) pictures. Therapy of ocular toxocariasis is primarily based upon corticosteroids use, when visceral larva migrans and few cases of common or covert toxocariasis can be treated by anthelmintics whose the most efficient appeared to be diethylcarbamazine. When diagnosed, all of these syndromes require thorough prevention of recontamination (especially by deworming pets) and sanitary education.     

Evidence for the involvement of the optic nerve as a migration route for larvae in ocular toxocariasis of Mongolian gerbils

Although Toxocara canis, an important pathogen of ocular disease, tends to migrate to the eye, the precise migratory route has yet to be determined experimentally. Mongolian gerbils, Meriones unguiculatus, known as a useful animal model for human toxocariasis, were used to investigate the migration route toward the eyes. Infective larvae of T. canis were directly inoculated into the intracranial region. Haemorrhagic lesions or larvae were observed in 56.3% of cases. Histopathologically, a larva was observed in the optic nerve of gerbils 6 days after inoculation, and two larvae were found in the optic chiasma in the gerbils having a haemorrhage in the retina 9 days after inoculation. These results indicate that T. canis migrates from the brain to the eye through the optic nerve. Considering these data and previous studies showing that the ocular changes appear as early as 3 days of infection in the oral-administrated gerbils, there are two phases in the migration to the retina: a haematogenous early phase and an optic nerve route late phase.     

Immunodiagnosis of ocular toxocariasis using Western-blot for the detection of specific anti-Toxocara IgG and CAP for the measurement of specific anti-Toxocara IgE

A prospective multicentric study was carried out to assess both the performance of Western-blot (WB) detecting specific anti-Toxocara IgG and that of CAP measuring specific IgE titre for the immunodiagnosis of ocular toxocariasis. For 14 outpatients presenting ophthalmic symptoms (choroiditis, chorioretinitis, papillar oedema, hyalitis, retinal detachment and/or uveitis), samples of serum and aqueous fluid (AF) were sent to the Department of Parasitology, University Hospitals, Toulouse, France. All patients but two tested positive with WB on the serum; 13 WB tests were performed on the AF, 12 of which were positive. The two patients who had a negative WB serum result tested positive for the AF. Specific IgE detection was considered as a complementary test of WB. Two patients showed a greater specific IgE titre in the AF than in the serum, and one had a positive result in the AF, but not in the serum. These six patients were considered as clear cases of ocular toxocariasis. Western-blot coupled with specific anti-Toxocara IgE detection appeared therefore to be an accurate procedure for the immunodiagnosis of ocular toxocariasis, provided the testing was simultaneously performed on the serum and AF.     

Experimental toxocariasis and hyperactivity in mice

An observational study using videorecordings and computer-assisted data analysis was undertaken in order to investigate the behaviour of mice infected with larvae of Toxocara canis. The findings indicated that the infection had a marked effect on five readily and reliably differentiable categories of murine behaviour. A marked increase in the number of shorter bouts of each of the five behaviours was also associated with the infection. These results support previous findings and further suggest that T. canis infection affects the way in which mice respond to their environment. In particular the infection appears to be associated with hyperactivity in mice. Possible causes of such behavioural abnormalities as well as implications of these findings for clinical studies concerned with relationships between T. canis infection and hyperactivity in children are discussed.     

Serologic evidence of toxocariasis in northeast Brazil

Sera from 54 Brazilian children with a history of tropical eosinophilia syndrome were screened for toxocariasis. The enzyme-linked immunosorbent assay detected 21 positive sera (40%). Many of these cases (15 of 21) were positive for Dilofilaria immitis as well. Of the six Toxocara-positive children with hypereosinophilia, two were asthmatic. Their sera were further examined by the Toxocara species-specific Ouchterlony's diffusion-in-gel test and one Toxocara canis and one T. cati infections were identified. This is the first report of serologically diagnosed toxocariasis in Brazil.     

Epidemiology of human toxocariasis in northern Italy

Sera from both clinically healthy adults (2112) and adult patients (471) were tested to assess the main risk factors for Toxocara infection in humans in Northern Italy. The patient group included 257 adult epileptics, 76 Strongyloides stercoralis-infected adult patients and 142 institutionalized mentally retarded adult patients. The overall seroprevalence in healthy population was 3.98%. No significant differences in seroprevalence were observed for sex, residence (urban or rural) or dog ownership, while seroprevalence significantly increased with age (18- greater than 51 years). Highest seroprevalence values were found in outdoor or soil-related workers. The seroprevalence was 4.35% in adult epileptics, 9.21% in Strongyloides stercoralis-infected patients and 14.47%-10.61% among institutionalized mentally retarded patients. These findings suggest that the prevalent source of human toxocariasis is the environmental contamination by infectious eggs of the parasite.     

The epidemiology of Giardiasis

Giardiasis is now known to occur not only endemically, but also as an epidemic disease spread primarily via drinking water. Giardia from different animals, although morphologically indistinguishable, vary in host specificity. This raises the possibility that lower animals may harbour representatives of this genus which are transmissible to humans. In this article, Ernest Meyer discusses our present understanding of the epidemiology of Giardia, related to problems of speciation in this genus.     

Seroprevalence of toxocariasis among healthy people with eosinophilia

The aim of this study is to determine the Toxocara seropositive rate among healthy people with eosinophilia. A total of 97 people residing in Seoul who were healthy and whose blood eosinophilia was over 10%, as shown by regular health check-ups in 2004, were subjected to this study. Their sera were tested by immunoblotting and ELISA with the antigen of larval Toxocara canis excretory-secretory (ES) protein. Sixty-five sera were band-positive (67.0%). The seropositve control sera were positive to band sizes of 66 kDa, 56 kDa, 32 kDa, and 13 kDa. In ELISA, 63 sera (65.0%) were positive to T. canis ES protein. There was no significant correlation between the IgG ELISA titer and the level of eosinophilia (r = 0.156, P = 0.156). As there were insufficient data to determine whether there were cross-reactions with other helminthic infections, or whether atopy occurred, further studies are required to verify the cause of the seropositive reactions against T. canis ES antigen. Toxocariasis seropositivity is suggested to be the major cause of eosinophilia, since the Toxocara seroprevalence among Korean rural adults was shown to be approximately 5%.