Eosinophil-Associated Inflammation and Elaboration of Eosinophil-Derived Proteins in 2 Children With Raccoon Roundworm (Baylisascaris procyonis)Encephalitis

Abstract

ABSTRACT. Objective. Eosinophil-associated proteins, especially eosinophil-derived neurotoxin, may be important contributors to the neurologic pathology and symptoms caused by Baylisascaris procyonis infection.Methods. Two cases of severe B procyonis encephalitis with evidence of marked eosinophil degranulation in the central nervous system are presented. Serial cerebrospinal fluid (CSF) specimens were collected from each patient during the course of their illness. Antibodies against B procyonis were measured in the patients' serum and CSF. Levels of the eosinophilopoietin interleukin-5 (IL-5) and 2 important eosinophil proteins, eosinophilderived neurotoxin and major basic protein, were assayed in the CSF.Results. Both patients had rapidly progressive central nervous system disease with evidence of eosinophilic meningoencephalitis. Both tested positive for antibodies to B procyonis in serum and CSF and had progressively worsening deep white matter changes on magnetic resonance images of the brain. CSF levels of IL-5, eosinophilderived neurotoxin, and major basic protein were markedly elevated over controls.Conclusions. This is the first report of the measurement of IL-5, eosinophil-derived neurotoxin, and major basic protein in human CSF. In addition to traumatic damage and necrosis caused by migrating larvae, eosinophil-derived neurotoxin from associated eosinophilic inflammation may be an important contributory factor in the pathogenesis of B procyonis encephalitis. Pediatrics 2001;108(5). URL: http://www.pediatrics.org/cgi/content/ full/108/5/e93; parasite, eosinophil-derived-neurotoxin, major basic protein, eosinophilia, hypereosinophilia, interleukin-5, encephalitis, child.ABBREVIATIONS. CSF, cerebrospinal fluid; CNS, central nervous system; MRI, magnetic resonance imaging; IL-5, interleukin-5; PBS, phosphate-buffered saline.B aylisascaris procyonis, the common raccoon ascarid, is a well-known cause of severe neurologic disease (neural larva migrans) in animals, with cases identified in Ͼ90 species of mammals and birds in North America. 1,2 Neural larva migrans and eosinophilic meningoencephalitis attributable to B procyonis have now been identified in 7 young children, including the 2 reported here. [3][4][5][6][7] We specifically note a novel correlation with elevated cerebrospinal fluid (CSF) levels of major basic protein and the neurotoxic protein eosinophil-derived neurotoxin associated with eosinophilic inflammation in these 2 cases. We hypothesize that the severe neurologic consequences of Baylisascaris encephalitis are attributable, in part, to marked eosinophil degranulation and release of these toxic eosinophil proteins in the central nervous system (CNS) of patients with this disease. CASE REPORTS Case 1A 13-month-old boy became irritable 3 weeks before hospital admission, then became progressively irritable, ataxic, and weak. Three days before admission, he was unable to cruise, sit up, or walk, and exhibited dysmetria. He then had an episode of limb twitching followed by rigidity and decreased...

Baylisascariasis

“…Immunofluorescence studies suggest that eosinophilic material surrounding migration tracks, larvae, and perivascular areas consists of eosinophil major basic protein arising from eosinophil degranulation (23). Moertel et al and others demonstrated markedly increased CSF levels of eosinophil major basic protein, eosinophil-derived neurotoxin, and interleukin 5, a critical cytokine involved in eosinophilia and the eosinophilic response to helminth parasites, in two fatal cases of B. procyonis NLM (35,41,49). At autopsy, larvae have been identified in cerebrum, cerebellum, and spinal cord, with and without surrounding inflammatory reaction.…”

“…The first confirmed cases of NLM in humans were described to have occurred in two young boys, in 1984 and 1985 (16,25). Since that time, another 11 confirmed human cases have been documented (Table 1) (8,10,18,41,44,47,51). An earlier (1975) unconfirmed case of NLM involved an 18-month-old girl with geophagia from Missouri, who presented with acute hemiplegia, cerebrospinal fluid (CSF) and peripheral eosinophilia, and elevated isohemagglutinins (1).…”

“…Both presented with rapidly progressive and ultimately fatal eosinophilic meningoencephalitis. Other reports followed, namely, of severe nonfatal NLM in young boys from upstate New York (n ϭ 1), California (n ϭ 3), Illinois (n ϭ 2), and Michigan (n ϭ 1) and in a young adult with developmental delay from Oregon (n ϭ 1) and of additional fatal disease in toddlers from Minnesota (n ϭ 2) and a teenager with developmental delay from California (n ϭ 1) (Table 1) (8,10,18,41,44,47,51). Notably, raccoon populations in these areas have the highest prevalence of B. procyonis infection (29).…”

Zoonosis Caused by Baylisascaris procyonis

“…Protein epitopes of 33-kDa to 45-kDa antigens appear to be recognized selectively by antibodies from B. procyonis-infected humans and animals but not by normal human or T. canis antibody-positive sera . In addition, children with clinical B. procyonis NLM are strongly positive for anti-Baylisascaris antibodies in CSF and serum and have consistently been negative for anti-Toxocara antibodies (Cunningham et al, 1994;Fox et al, 1985;Gavin et al, 2002;Kazacos, 2001;Moertel et al, 2001;Murray, 2002;Park et al, 2000;Rowley et al, 2000). In several of these cases, positive B. procyonis serology was confirmed by brain biopsy or at autopsy (CDC, 2002;Fox et al, 1985;Huff et al, 1984;Rowley et al, 2000).…”

“…In several of these cases, positive B. procyonis serology was confirmed by brain biopsy or at autopsy (CDC, 2002;Fox et al, 1985;Huff et al, 1984;Rowley et al, 2000). Acute and convalescent-phase titers characteristically demonstrate several fold increases in both serum and CSF anti-Baylisascaris antibody levels (Gavin et al, 2002;Moertel et al, 2001). …”