Cerebral Toxocariasis: Silent Progression to Neurodegenerative Disorders? Chia-Kwung Fan, a,b * Celia V. Holland, c Karen Loxton, c Ursula Barghouth d Department of Molecular Parasitology and Tropical Diseases, School of Medicine, Taipei Medical University, Taipei, Taiwan a ; Master Program in Global Health and Development, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan b ; Department of Zoology, School of Natural Sciences, Trinity College, Dublin, Ireland c ; A. T. Still University School of Osteopathic Medicine in Arizona, Mesa, Arizona, USA d SUMMARY ..................................................................................................................................................663 INTRODUCTION ............................................................................................................................................663 IMMUNODIAGNOSTICS IN INVESTIGATIVE CLINICAL PRACTICE ..........................................................................................664 SEROPREVALENCE AND ASSOCIATED RISK FACTORS IN GENERAL POPULATIONS .....................................................................664 A Brief Review of Global Seroprevalence .................................................................................................................664 Risk Factors ...............................................................................................................................................665 TYPES OF HUMAN TOXOCARIASIS AND IMMUNOPATHOGENESIS .......................................................................................665 Visceral Larva Migrans ....................................................................................................................................666 Ocular Toxocariasis .......................................................................................................................................666 Covert or Common Toxocariasis .........................................................................................................................668 Neurotoxocariasis ........................................................................................................................................668 GLOBAL CASES OF HUMAN CEREBRAL TOXOCARIASIS WITH VARIOUS NEUROLOGICAL DISORDERS FROM 1985 TO 2014...........................669 Eosinophilic Meningoencephalitis, Meningitis, and Encephalitis .........................................................................................669 Cerebral Vasculitis ........................................................................................................................................672 Myelitis ...................................................................................................................................................672 Seizure....................................................................................................................................................673 Schizophrenia ............................................................................................................................................673 Cognitive Deficits.........................................................................................................................................674 Idiopathic Parkinson’s Disease............................................................................................................................675 Dementia .................................................................................................................................................675 MURINE MODELS OF NEUROLOGICAL INFLAMMATION, UBIQUITIN-PROTEASOME IMPAIRMENT, AND COGNITIVE DEFECTS IN CEREBRAL TOXOCARIASIS ........................................................................................................................................675 CEREBRAL TOXOCARIASIS VERSUS ALZHEIMER’S DISEASE: A SILENT PROGRESSION....................................................................677 CONCLUSIONS .............................................................................................................................................679 APPENDIX ..................................................................................................................................................679 ACKNOWLEDGMENT .......................................................................................................................................679 REFERENCES ................................................................................................................................................679 AUTHOR BIOS ..............................................................................................................................................686 SUMMARY Toxocara canis and T. cati are highly prevalent nematode infec- tions of the intestines of dogs and cats. In paratenic hosts, larvae do not mature in the intestine but instead migrate through the somatic tissues and organs of the body. The pres- ence of these migrating larvae can contribute to pathology. Toxocara larvae can invade the brains of humans, and while case descriptions of cerebral toxocariasis are historically rare, im- proved diagnosis and greater awareness have contributed to in- creased detection. Despite this, cerebral or neurological toxocaria- sis (NT) remains a poorly understood phenomenon. Furthermore, our understanding of cognitive deficits due to toxocariasis in human populations remains particularly deficient. Recent data de- scribe an enhanced expression of biomarkers associated with brain injury, such as GFAP, APP, transforming growth factor 1 (TGF-1), NF-L, S100B, tTG, and p-tau, in mice receiving even low doses of Toxocara ova. Finally, this review outlines a hypothesis to explore the relationship between the presence of T. canis larvae in the brain and the progression of Alzheimer’s disease (AD) due to enhanced AD-associated neurodegenerative bio- marker expression. INTRODUCTION H elminths of the genus Toxocara belong to the class Nematoda, order Ascaroidea, and superfamily Ascaridoidea. Among a total of 21 species within the Toxocara genus, 2 are of significant public health concern, namely, Toxocara canis and T. cati, for which dogs and cats, respectively, are the definitive hosts. After ingestion of food or water contaminated by infective Toxocara eggs, larvae hatch in the small intestine, penetrate the gut wall, and are transported to the liver and lungs via the blood circulation. Subsequently, the larvae undergo a further migration by the tra- Published 10 June 2015 Citation Fan C-K, Holland CV, Loxton K, Barghouth U. 10 June 2015. Cerebral toxocariasis: silent progression to neurodegenerative disorders? Clin Microbiol Rev doi:10.1128/CMR.00106-14. Address correspondence to Chia-Kwung Fan, tedfan@tmu.edu.tw. * Present address: Chia-Kwung Fan, Department of Molecular Parasitology and Tropical Diseases, School of Medicine, Taipei Medical University, Taipei, Taiwan. Copyright © 2015, American Society for Microbiology. All Rights Reserved. doi:10.1128/CMR.00106-14 crossmark July 2015 Volume 28 Number 3 cmr.asm.org 663 Clinical Microbiology Reviews on June 16, 2015 by NATIONAL TAIWAN UNIVERSITY http://cmr.asm.org/ Downloaded from