The epidemiology of ocular toxocariasis

Ocular toxocariasis damages vision and may cause blindness. It is a relatively 'new' disease, the histological changes having been described in 1950 and the causative organism identified in 1956. Many aspects of the epidemiology of toxocariasis are unclear. It is generally accepted that the usual route of entry to the eye is via the blood stream. Once the eye is invaded characteristic changes are produced with comparative sparing of the anterior segment. Species differences in susceptibility can be very marked. In Mongolian gerbils 55% of infected animals exhibit ocular lesions. Humans are fortunate in that they are far less susceptible to ocular infection. While it has been established that ocular toxocariasis is caused by Toxocara canis, the role of T. cati in this condition is still unclear. It is perhaps surprising that the prevalence of such a disease in humans should remain in doubt. However, the wide variation in the few estimates of prevalence may well be a reflection of the wide variation in exposure as evidenced by the wide variation in seroprevalence. A further factor mitigating against an identification of prevalence rates is the fact that the condition is usually unilateral. Most surveys of blindness stipulate a vision of 6/60 or less in the better eye and so toxocariasis cases go unrecorded. There is a need for surveys which identify the level of vision in both eyes.     

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.     

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.     

A comparative study of toxocariasis and allergic asthma in murine models

Histopathology of the lung and total IgE in serum were compared in toxocariasis and allergic asthma murine models using BALB/c and C57BL/6 mice. Infection with Toxocara canis resulted in both strains of mice in marked histological changes and increased levels of total serum IgE. The ovalbumin (OVA) sensitization/challenge treatment for the induction of allergic asthma resulted in similar histological changes in BALB/c and, to a less extent, in C57BL/6 mice. Serum IgE levels of OVA-treated C57BL/6 mice were low. Histological changes observed included perivascular infiltration with eosinophils and mononuclear cells, peribronchiolitis, alveolitis and mucus production. Although these changes in addition to increased IgE production did occur in T. canis-infected C57BL/6 mice they were more pronounced in BALB/c mice. Thus, BALB/c mice appear to be the most appropriate strain of mice to perform studies on the possible connection between infection with T. canis and allergic asthma.     

Animal models of osteoarthritis

Animal models have proved to be of considerable importance in elucidating mechanisms underlying joint damage in osteoarthritis (OA) and providing proof of concept in the development of pharmacologic and biologic agents that may modify structural damage in the OA joint. The utility of animal models in predicting the response to an intervention with a drug or biologic agent in humans, however, can be established only after evidence is obtained of a positive effect of the agent in humans. To date, no agent has been shown unequivocally to have such an effect, although diacerhein and glucosamine have recently been reported to lower the rate of loss of articular cartilage in patients with hip OA and knee OA, respectively, based on measurements of the rate of joint space narrowing in plain radiographs. Furthermore, the predominant manifestation of OA - and the feature that leads people with radiographic changes of the disease to decide to seek medical attention and contributes to the enormous medicoeconomic and socioeconomic burden imposed by the disease - is joint pain. Notably, none of the animal models of OA is a good indicator of the analgesic effects of pharmacologic agents. Indeed, it should not be assumed a priori that reduction in the rate of progression of joint damage in OA will be associated with a reduction in joint pain.     

Animal models of pheochromocytoma

Pheochromocytomas are neuroendocrine tumors of adrenal chromaffin cells. They are rare in all species except rats but occur with increased frequency in several human familial tumor syndromes. Concurrence of pheochromocytoma with other tumors sometimes parallels these human syndromes in rats, bovines, horses and dogs but a shared genetic basis for human and spontaneously occurring animal pheochromocytomas has thus far not been established. Pheochromocytomas are inducible in rats by a variety of non-genotoxic substances that may act indirectly by stimulating chromaffin cell proliferation. They are not known to be similarly inducible in other species but arise with increased frequency in transgenic and knockout mice that to varying degrees recapitulate human tumor syndromes. Preliminary evidence suggests that homologous somatic genetic changes might contribute to pheochromocytoma development in humans and some mouse models. The nerve growth factor-responsive PC12 cell line, established from a rat pheochromocytoma, has for almost 30 years served as a research tool for many aspects of neurobiology involving normal and neoplastic conditions. Recently developed pheochromocytoma cell lines from neurofibromatosis knockout mice supplement the PC12 line and have generated additional applications. Advantages of the mouse lines include expression of substantial levels of the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase and expression of high levels of the receptor tyrosine kinase, Ret, which is characteristic of sporadic and familial human pheochromocytomas but not of PC12 cells. Disadvantages include an apparently less stable phenotype. It is difficult to establish pheochromocytoma cell lines from any species, although the tumor cells persist in culture for many months. Understanding of factors that permit pheochromocytoma cells to proliferate might itself provide important insights for tumor biology.     

Animal models of AIDS

Animal models of AIDS are essential for understanding the pathogenesis of retrovirus-induced immune deficiency and encephalopathy and for development and testing of new therapies and vaccines. AIDS and related disorders are etiologically linked to members of the lentivirus subfamily of retroviruses; these lymphocytopathic lentiviruses are designated human immuno-deficiency virus type 1 (HIV-1) and human immuno-deficiency virus type 2 (HIV-2). The only animals susceptible to experimental HIV-1 infection are the chimpanzee, gibbon ape, and rabbit but AIDS-like disease has not yet been reported in these species. Macaques can be persistently infected with some strains of HIV-2 but no AIDS-like disease has resulted. It is not yet clear how suitable HIV-infected SCID-hu mice will be as a model for AIDS. Several subfamilies of naturally occurring cytopathic retroviruses cause immune suppression, including fatal immunodeficiency syndromes in chickens, mice, cats, and monkeys. Domestic cats suffer immunosuppression from both an onco-virus, feline leukemia virus, and a member of the lentivirus subfamily, feline immunodeficiency virus (FIV). Asian macaques are susceptible to fatal simian AIDS from a type D retrovirus, indigenous in macaques, and from a lentivirus, simian immunodeficiency virus (SIV), which is indigenous to healthy African monkeys. SIV is the animal lentivirus most closely related to HIV. Of these animal models, the lentivirus infections of cats (FIV) and macaques (SIV) appear to bear the closest similarity in their pathogenesis to HIV infection and AIDS. This review will summarize these various animal model systems for AIDS and illustrate their usefulness for antiviral therapy and vaccinology.     

Animal models simulating anaerobic infections

Animal models simulating human disease have played an important role in our understanding of the pathogenesis and treatment of infections caused by obligately anaerobic bacteria. These models helped document the primary source of such infections as the host's own normal microflora. In addition, the polymicrobial nature of anaerobic infections was documented by using animal models for intraabdominal sepsis. Subsequent studies using animal models have led to an understanding of the nature of the host immune response to abscess causing agents and have been instrumental in defining the molecular basis for the virulence and protection provided by the polysaccharide capsule of Bacteroides fragilis. Animal models have also been important components for studies of toxigenic clostridial diseases, such as antibiotic associated colitis and ulcerative colitis. A discussion of some of these models is provided in this review.     

Animal models of drug-induced cardiomyopathy

Animal models of drug-induced cardiomyopathy relevant to clinical medicine have been difficult to produce. Animal species commonly used to study cardiomyopathies include the rabbit, rat, and mouse of which none are completely satisfactory. Recently, the turkey poult has been proposed as an attractive animal model for investigation of drug-induced cardiomyopathy.     

Animal models of human pneumonia

Pneumonia is a medical and public health priority, and advances against this disease will require improved knowledge of biological mechanisms. Human pneumonia is modeled with experimental infections of animals, most frequently mice. Mouse models are leading to important discoveries relevant to pneumonia, but their limitations must be carefully considered. Several approaches to establishing pneumonia in mice have been developed, and each has specific strengths and weaknesses. Similarly, procedures for characterizing microbial and host responses to infection have unique advantages and disadvantages. Mice are not small humans, and the applicability of results from murine models to human disease depends on understanding the similarities and differences between species. Additional considerations such as mouse strain, microbe strain, and prior mouse-microbe interactions also influence the design and interpretation of experiments. Results from studies of pneumonia in animals, combined with complementary basic and translational studies, are elucidating mechanisms responsible for susceptibility to and pathophysiology of lung infection.     

Animal models for breast cancer

Rodent mammary tumors induced by chemical carcinogens have proven to be very useful in the genetic analysis of initiation, promotion and progression of mammary carcinogenesis. We are studying rat mammary carcinomas induced by the chemical carcinogen, N-nitroso-N-methylurea. The earliest genetic event observed in the mammary gland is the activation of Ha-ras oncogenes, which is followed by promotion of the initiated cells by hormones involved in puberty. Preferential amplification of the mutated Ha-ras allele, of PRAD-1 and IGF2, loss of expression of the mitogenic growth factor gene, MK, and mutation in the tumor suppressor gene, p53, are seen in the mammary tumors during tumor progression.     

Animal models of gene therapy

Somatic gene therapies are based on the introduction of genes in somatic cells in an attempt to correct a gene defect, to induce a resistance or to add a particular activity. In their principle, they are not very different from organ grafts and do not set specific ethic problems. Their application to human therapy has to be subjected to a critical evaluation of their harmlessness and efficiency. For this purpose, animal models of somatic gene therapy are essential. Such therapy have been tried in bone marrow and endothelial cells, in fibroblasts, keratinocytes hepatocytes, but also by direct transfer of genes in the organism. These different approaches are briefly reviewed and compared in this article.