Factors affecting disease manifestation of toxocarosis in humans: Genetics and environment

Abstract

Toxocara canis is regarded as the main cause of human toxocarosis but the relative contribution of T. cati is probably underestimated; serological and other diagnostic methods used in most studies of this zoonotic disease do not distinguish between the two parasites. The definitive hosts for T. canis are caniidae. Pups generally have higher infection rates than adult animals and are a major source of eggs in the environment. Humans usually acquire T. canis infection by accidental ingestion of embryonated eggs or encapsulated larvae from the environment or contaminated food, such infections may lead to visceral larva migrans (VLM), ocular larva migrans (OLM) or covert toxocarosis (CT). Although a mixed Th1- and Th2-mediated immunological response, particularly with high levels of IgE and eosinophilia is observed, the underlying mechanisms of molecular and immunopathogenesis for the development of the symptomatic syndromes of VLM, OLM, or of asymptomatic CT are largely unclear. Studies have indicated that immunological defences against various infectious diseases may be highly influenced by complex interactions of environmental and host genetic factors e.g. MHC class I and II, also known as human leucocyte antigen (HLA). Toxocara spp. infections are associated with a polarized CD4(+) Th2 response with high IgE levels and eosinophilia, mediated mainly by HLA class II molecules. Associations have been made between HLA class II and pathological severity and host genetic effects on exposure to infection. Recent research suggests Foxp3(+) CD4(+)CD25(+)-expressing T regulatory (Treg) cells play a role in regulation of the immunopathology of granulomas in experimental toxocaral granulomatous hepatitis and in enhanced expression of TGF-β1, which is an important factor for the local survival and function of Treg observed during T. canis invasion in the mouse small intestine, liver, muscle, and brain. Since the potential susceptibility loci HLA class II molecules, are considered involved in the regulation of a Th2-dominant immunity which is highly controlled by Foxp3(+) CD4(+)CD25(+) Treg cells by stimulation through TGF-β1, which thus provides a beneficial environment to T. canis larvae but severe injuries to local organs. However, TGF-β1 variant Leu10Pro known to be involved in disease severity warrants further elucidation as this too may have a role in the severity of human toxocarosis. Exploration of TGF-β1 polymorphism, Foxp3(+) CD4(+)CD25(+) Treg cells, and MHC polymorphisms may allow insight into the contribution made by environmental and genetic factors in influencing disease syndrome type and severity in humans with toxocarosis.

Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders?

“…In such paratenic hosts, T. canis L3 larvae neither molt, grow, nor replicate and will wander through a number of internal organs in humans so as to cause neurotoxocariasis (NT), ocular toxocariasis (OT), or visceral larva migrans (VLM) (19,20). Therefore, diagnosis in the context of investigative and clinical practice predominantly depends upon immunological techniques.…”

“…1) (20,41). Infections caused by ingesting encapsulated larvae in raw or undercooked infected organs or muscle tissues from paratenic hosts, such as chicken, lamb, or rabbit, have been reported from adults in northeastern Asian countries, e.g., Japan or South Korea, albeit rarely ( Fig.…”

“…Infections caused by ingesting encapsulated larvae in raw or undercooked infected organs or muscle tissues from paratenic hosts, such as chicken, lamb, or rabbit, have been reported from adults in northeastern Asian countries, e.g., Japan or South Korea, albeit rarely ( Fig. 1) (20,(42)(43)(44)(45)(46)(47)(48)(49). However, successful infection is influenced by a number of exposure-and susceptibility-related factors, including cultural and socioeconomic factors, environmental, geographic, and host immunity, genetics, age, gender, nutrition, coinfection, and the behavior of human and definitive hosts (20,50,51).…”

Seroprevalence of toxoplasmosis, toxocariasis and cysticercosis in a rural settlement, São Paulo State, Brazil

“…It is well known that T. solium metacestoda and T. canis are associated with a Th2 immune response with high levels of IgE and eosinophilia, mediated mainly by HLA class II molecules. 34 One possibile reason for the high levels of IgE and eosinophils found was the strong allergic environment stimulus suffered by this population as shown previously in rural settlement individuals living in the surrounding area of Dona Carmen. 14,15 Furthermore, in the studied population, an association between Th2 cytokines and T. gondii IgG infection was demonstrated.…”

Prevalence, risk factors, and geographical distribution of zoonotic pathogens carried by peri-urban wild dogs

“…Another possible source of infection in humans is through consumption of L3s in the raw or undercooked muscle tissues of a paratenic host. Infections in humans may occasionally go un-noticed due to the absence of clinical signs, however syndromes that are associated with the pathogen include visceral larva migrans (VLM), ocular larva migrans (OLM), neurological toxocarosis (NT) and covert toxocarosis (CT) (Fan et al, 2013;Rubinsky-Elefant et al, 2010). VLM is associated with higher intensity of worm burdens and migration of larvae, being more common in children below eight years of age.…”