Is it canine DUSN?: Another view of retinopathies, some acquired, and others possibly "inherited": Another view of retinopathies, some acquired, and others possibly "inherited".

The term retinopathy has been used to group several heterogeneous retinal abnormalities that are clearly acquired or are suspected/proposed to be inherited. Some share characteristic focal/multifocal hyperreflective tapetal lesions with a dark center, and areas of non-tapetal depigmentation suggestive of patchy or diffuse outer retinal atrophy. Progression is variable, and some develop unilateral or bilateral fundus changes resembling the clearly inherited form of retinal degeneration referred to as PRA. In this Commentary and Review, we discuss the role of ocular larva migrans resulting in the entity we refer to as canine DUSN and suggest that it may be responsible for some of the retinal findings grouped under the retinopathy rubric that share this characteristic fundus lesion.

SEROLOGICAL DIAGNOSIS OF BAYLISASCARIS PROCYONIS IN PRIMATES USING A HUMAN ELISA TEST.

The usefulness of a human enzyme-linked immunosorbent assay (ELISA) for serological diagnosis of Baylisascaris procyonis larva migrans was assessed in nonhuman primates (NHP). The test was originally developed as an assay performed on human samples at Purdue University. Six participating zoos submitted 258 NHP serum samples, spanning these major phylogenetic groups: 1) great apes (n = 84), 2) lesser apes (n = 17), 3) Old World monkeys (n = 84), 4) New World monkeys (n = 20), and 5) prosimians (n = 53). Sera were tested in duplicate using a microtiter-well ELISA with B. procyonis larval excretory-secretory proteins as antigen, and serum from an experimentally infected baboon (Papio anubis) served as positive control. The ELISA clearly identified seropositive animals in all zoos. With putative cutoffs of optical density (OD) measured at 405 nm (OD405) of <0.150 = negative, 0.150-0.250 = indeterminate, and >0.250 = positive, 149 of 258 (57.8%) were clearly negative (mean OD 0.046), and 78 of 258 (30.2%) were clearly positive (mean OD 0.657, range 0.253-1.773), the rest being indeterminate. Of these, 15 were high positive with OD 1.095-1.773 (mean 1.314). Positive animals were seen from all zoos; 76 (97.4%) were great apes, lesser apes, or Old World monkeys. The four highest ODs were in a siamang (Symphalangus syndactylus), lion-tailed macaque (Macaca silenus), Sumatran orangutan (Pongo abelii), and western lowland gorilla (Gorilla gorilla gorilla), all from different zoos. Prosimians had a mean OD of 0.039 and New World monkeys 0.021, indicating that human reagents either did not work for these groups or few infected animals were represented. These results indicate that the human ELISA for B. procyonis works well for at least higher phylogeny NHP and that serologic evidence of infection is surprisingly common, correlating with what is known for exposure to this parasite in zoos.

Baylisascaris procyonis-Associated Meningoencephalitis in a Previously Healthy Adult, California, USA.

After severe neurocognitive decline developed in an otherwise healthy 63-year-old man, brain magnetic resonance imaging showed eosinophilic meningoencephalitis and enhancing lesions. The patient tested positive for antibodies to Baylisascaris spp. roundworms, was treated with albendazole and dexamethasone, and showed improvement after 3 months. Baylisascariasis should be considered for all patients with eosinophilic meningitis.

Update on Baylisascariasis, a Highly Pathogenic Zoonotic Infection.

Baylisascaris procyonis, the raccoon roundworm, infects a wide range of vertebrate animals, including humans, in which it causes a particularly severe type of larva migrans. It is an important cause of severe neurologic disease (neural larva migrans [NLM]) but also causes ocular disease (OLM; diffuse unilateral subacute neuroretinitis [DUSN]), visceral larva migrans (VLM), and covert/asymptomatic infections. B. procyonis is common and widespread in raccoons, and there is increasing recognition of human disease, making a clinical consideration of baylisascariasis important. This review provides an update for this disease, especially its clinical relevance and diagnosis, and summarizes the clinical cases of human NLM and VLM known to date. Most diagnosed patients have been young children less than 2 years of age, although the number of older patients diagnosed in recent years has been increasing. The recent development of recombinant antigen-based serodiagnostic assays has aided greatly in the early diagnosis of this infection. Patients recovering with fewer severe sequelae have been reported in recent years, reinforcing the current recommendation that early treatment with albendazole and corticosteroids should be initiated at the earliest suspicion of baylisascariasis. Considering the seriousness of this zoonotic infection, greater public and medical awareness is critical for the prevention and early treatment of human cases.

THE STRUCTURE AND SEASONALITY OF BAYLISASCARIS PROCYONIS POPULATIONS IN RACCOONS (PROCYON LOTOR).

Baylisascaris procyonis , the raccoon ( Procyon lotor ) ascarid, is a common roundworm parasite of raccoons that is also a well-recognized zoonotic pathogen, and a cause for conservation concern. The transmission dynamics of B. procyonis differ with host population attributes, season, and landscape. We examined how the parasite's population attributes change with season, parasite population structure, and host demographics. We examined 1,050 raccoon gastrointestinal tracts collected from 1996 to 2012. Of the 1,050 raccoons necropsied, 382 (36%) were infected with at least one B. procyonis (x¯=15.8 [95% confidence interval=13.39-18.26]; median=7; range 1-199 worms/host), and populations were overdispersed. There was a seasonal change in prevalence with a peak in October/November. Worm burdens decreased approximately 28% per month from January to June and increased approximately 31% per month from June to December. The sex structure of B. procyonis populations was female-biased (56% female). Host demographics did not impact parasite population attributes. This study provides evidence that B. procyonis populations exhibit a yearly cycle of loss and recruitment that may impact the transmission dynamics of the parasite.

Identification of Heterobilharzia americana infection in a dog residing in Indiana with no history of travel.

CASE DESCRIPTION: A 1-year-old castrated male dog residing in Indiana was examined because of intermittent vomiting of 4 months' duration. CLINICAL FINDINGS: The dog's condition did not resolve with medication. Diagnostic imaging revealed a possible partial obstruction at the ileocecal junction. An exploratory laparotomy was performed. The jejunum contained diffusely distributed, nodular, intramural lesions; 2 biopsy specimens were collected from representative lesions. The pancreas was grossly swollen, and pancreatitis was presumed present. No other abnormalities were observed in the abdomen. Histologic examination of the submitted biopsy specimens revealed infection with Heterobilharzia americana. TREATMENT AND OUTCOME: After diagnosis, the dog was treated with fenbendazole suspension (48 mg/kg [21.8 mg/lb], PO, q 24 h) for 10 days. This treatment was subsequently repeated 11 and 80 days later. One week after the end of the last fenbendazole treatment, several H americana eggs were detected in a fecal sample via saline sedimentation, and the dog was given praziquantel (25 mg/kg [11.4 mg/lb], PO, q 8 h) for 2 days. No gastrointestinal signs were evident 4 months after that treatment. CLINICAL RELEVANCE: The dog described in this report was the first autochthonous canine case of H americana infection in Indiana, to the authors' knowledge; this case has confirmed that the distribution of this parasite in the Midwestern United States is broader than previously known. Increased awareness of the distribution of H americana should aid veterinarians in early, noninvasive diagnosis and appropriate treatment of affected animals. Repeated treatments and recheck fecal examinations may be necessary when managing these cases.

Baylisascaris procyonis and Herpes Simplex Virus 2 Coinfection Presenting as Ocular Larva Migrans with Granuloma Formation in a Child.

Ocular Baylisascaris procyonis infection results from ingestion of infective eggs of B. procyonis, the raccoon ascarid. Herpes simplex virus type 2 (HSV-2) infection of the retina is the result of either primary infection or reactivated disease. Herein, we report a case of a 12-year-old female resident of the Bronx in New York City, who presented with pan-uveitis and vision loss. Initial evaluation for etiologic causes was nondiagnostic. Serology for anti-Baylisascaris procyonis antibodies in serum and vitreous fluid were both positive. Polymerase chain reaction (PCR) of vitreous fluid was positive for HSV-2. Treatment with vitrectomy, albendazole, and acyclovir resulted in mild improvement of visual acuity. The atypical presentation of B. procyonis in this case, as ocular larva migrans with a peripheral granuloma and retinal detachment, underscores the importance of maintaining a high degree of suspicion for this pathogen even in non-diffuse unilateral subacute neuroretinitis (DUSN) patients in urban areas. This case further illustrates that it is possible to have coexisting infections in cases of posterior uveitis.

Central nervous system manifestations of Angiostrongylus cantonensis infection.

Over 20 species of Angiostrongylus have been described from around the world, but only Angiostrongylus cantonensis has been confirmed to cause central nervous system disease in humans. A neurotropic parasite that matures in the pulmonary arteries of rats, A. cantonensis is the most common cause of eosinophilic meningitis in southern Asia and the Pacific and Caribbean islands. The parasite can also cause encephalitis/encephalomyelitis and rarely ocular angiostrongyliasis. The present paper reviews the life cycle, epidemiology, pathogenesis, clinical features, diagnosis, treatment, prevention and prognosis of A. cantonesis infection. Emphasis is given on the spectrum of central nervous system manifestations and disease pathogenesis.

In vitro culture of Parascaris equorum larvae and initial investigation of parasite excretory-secretory products.

Currently, diagnosis of Parascaris equorum infection in equids is limited to patent infections. The goals of this study were to culture P. equorum larvae in vitro and identify excretory-secretory (ES) products for prepatent diagnostic testing. Parascaris equorum L2/L3 larvae were hatched and cultured for up to 3 weeks for ES product collection. Fifth stage (L5) P. equorum were also cultured for ES product collection. Examination of ES fractions by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and silver stain revealed L2/L3 products ranging from 12-94 kDa and L5 products ranging from 12-189 kDa. Western blot analyses were conducted using polyclonal antibodies produced against P. equorum or Baylisascaris procyonis L2/L3 ES products, sera from rabbits inoculated with B. procyonis or Toxocara canis eggs, and sera from animals naturally infected with P. equorum or T. canis. Western blot results indicated parasite antigens migrating at 19 and 34 kDa may be useful for specifically detecting P. equorum infections.

Surveillance for Baylisascaris procyonis in raccoons (Procyon lotor) from Wyoming, USA.

Baylisascaris procyonis is a common roundworm of raccoons that causes severe clinical disease in many vertebrates, including humans. The distribution of B. procyonis in the US is poorly documented in portions of its range and has not been reported from Wyoming. Our objectives were to determine the statewide distribution and prevalence of this parasite in raccoons in Wyoming, using intestinal and fecal examinations. We examined 363 raccoons from 23 Wyoming counties in 2009-11, testing the reliability of two methods (intestinal extrusion and incision) to determine worm burdens. We found 163 raccoons (45%) positive for B. procyonis. The two methods of examination did not differ, although extrusion missed some infections. Neither age nor sex affected apparent prevalence or worm burdens. Prevalence did not differ with land use, yet burden was highest among rural raccoons. Fecal examination revealed that juvenile raccoons had a higher proportion of patent infections than adults, but neither sex nor location were indicators of prevalence. Egg density (eggs per gram of feces) did not differ by sex or age; however, rural raccoons had higher egg densities than urban/suburban animals. Understanding the distribution and prevalence of B. procyonis in Wyoming, especially in and around highly populated areas, is an important step in educating the general public and medical community on the potential risks of raccoon roundworm infection.

Interlaboratory optimization and evaluation of a serological assay for diagnosis of human baylisascariasis.

A Western blot assay using a recombinant protein, recombinant Baylisascaris procyonis RAG1 protein (rBpRAG1), was developed for the diagnosis of human baylisascariasis concurrently by the Centers for Disease Control and Prevention (CDC) in Atlanta, Georgia, and the National Reference Centre for Parasitology (NRCP) in Montreal, Canada. Assay performance was assessed by testing 275 specimens at the CDC and 405 specimens at the NRCP. Twenty specimens from 16 cases of baylisascariasis were evaluated. Eighteen were positive, with the assay correctly identifying 14 of 16 patients. The rBpRAG1 Western blot assay showed no cross-reactivity with Toxocara-positive serum and had an overall sensitivity of 88% and a specificity of 98%.

Baylisascaris larva migrans.

Baylisascaris procyonis is a roundworm of the raccoon found primarily in North America but also known to occur in other parts of the world including South America, Europe, and Japan. Migration of the larvae of this parasite is recognized as a cause of clinical neural larva migrans (NLM) in humans, primarily children. It is manifested as meningoencephalitis associated with marked eosinophilia of the cerebrospinal fluid and peripheral blood. Diagnosis is made by recovering and identifying larvae in or from the tissues, epidemiological history, serology, and imaging of the central nervous system. Treatment is with albendazole and steroids, although the prognosis is generally poor. This parasite can also cause ocular larva migrans (OLM) which usually presents as diffuse unilateral subacute neuroretinitis (DUSN). The ocular diagnosis can be made by visualizing the larva in the eye and by serology. Intraocular larvae can be destroyed by photocoagulation although albendazole and steroids may also be used. However, once visual disturbance is established the prognosis for improved vision is poor. Related Baylisascaris species occur in skunks, badgers, and certain other carnivores, although most cases of NLM are caused by B. procyonis. Baylisascaris procyonis has also been found in kinkajous in the USA and South America and may also occur in related procyonids (coatis, olingos, etc.).

Prevalence of Baylisascaris procyonis in habitat associated with Allegheny woodrat (Neotoma magister) populations in Indiana.

Allegheny woodrat (Neotoma magister) populations have been in decline across their range since the late 1970s. Hypotheses proposed to explain these declines include habitat fragmentation and loss, decreased food availability, and increased mortality from infection with Baylisascaris procyonis. We investigated the prevalence of B. procyonis at raccoon (Procyon lotor) latrines in woodrat cliff habitats (n = 18) along the Ohio River in southern Indiana in 1995. We located 275 latrines (mean = 15.3/site; range, 6-34) and found B. procyonis in 13 (4.7%) latrines across all sites. When present at a site, B. procyonis occurred, on average, at 11.1%of latrines (range, 3-36%). Woodrat abundance, determined through a concurrent live-trapping program, was significantly higher (χ(2) = 5.12, df = 1, P = 0.024) at sites where B. procyonis was not found (9.5 ± 2.52) than at sites with B. procyonis (3.7 ± 2.2). Our analyses support the hypothesis that this parasite could contribute to declines in woodrat abundance. Because woodrats cache nonfood items, including raccoon feces, and are highly susceptible to the parasite, they are at increased risk for B. procyonis infection, which could be deleterious, especially to small populations.

Good outcome with early empiric treatment of neural larva migrans due to Baylisascaris procyonis.

We report a remarkably good outcome in a 14-month-old boy with early clinical diagnosis and aggressive empirical treatment of neural larva migrans caused by the raccoon roundworm Baylisascaris procyonis. He presented with fever, meningismus, lethargy, irritability and asymmetric spastic extremity weakness. Early findings of marked blood and cerebrospinal fluid eosinophilia and of diffuse white matter signal abnormality in the brain and spinal cord on MRI suggested a parasitic encephalomyelitis. Rapid presumptive treatment with albendazole and high-dose steroids halted progression of clinical signs. The diagnosis was confirmed by 2 sequential enzyme-linked immunosorbent assay studies positive for B procyonis serum immunoglobulin G and by Western blot. Field examination with soil sampling yielded infective Baylisascaris eggs. Repeat MRI 3 months later showed atrophy and diffuse, chronic white matter abnormalities, discordant with the marked clinical improvement in this interval. At 10 months, residual neurologic deficits included subtle paraparesis and moderate language delay. This case is the first in which spinal involvement in human Baylisascaris infection was clinically suspected and confirmed by neuroimaging. Importantly, early diagnosis and aggressive treatment of Baylisascaris meningo-encephalitis and myelitis with albendazole and high-dose steroids likely contributed to the good outcome in this patient, in contrast with previous reports.

Echinococcus multilocularis identified in Michigan with additional records from Ohio.

Echinococcus multilocularis was identified in a coyote in Indiana in January 1990, prompting an investigation of the distribution and prevalence of the parasite in wild canids in Indiana and surrounding states. In 1990-1991, the parasite was found throughout northern and central Indiana, in northwestern Ohio, and in east-central Illinois. In 1993-1994, 162 wild canids (97 red foxes, 54 coyotes, 11 gray foxes) were collected from Michigan, and an additional 75 (55 red foxes, 7 coyotes, 13 gray foxes) from Ohio, and examined for this parasite. Of these, 15 wild canids (6.3%) were found to be infected with E. multilocularis , including 4 of 97 (4.1%) red foxes from Michigan and 9 of 55 (16.4%) red foxes and 2 of 7 (28.6%) coyotes from Ohio. In Michigan, all infected animals were from the central and southwestern parts of the state. No infected animals were found in northern Michigan, including the Upper Peninsula. In Ohio, infected animals were limited to the northwestern and west-central portions of the state. These findings constitute new state and distribution records for E. multilocularis in the midwestern United States and indicate that the parasite continues to spread eastward and into Michigan from the south.

Spinal cord involvement in a child with raccoon roundworm (Baylisascaris procyonis) meningoencephalitis.

A 14-month-old previously healthy boy developed progressively worsening neurological symptoms secondary to eosinophilic meningoencephalitis with myelitis caused by raccoon roundworm (Baylisascaris procyonis) infection. MRI demonstrated T2 hyperintensity and enhancement of the cerebral white matter, cerebellum and spinal cord. Prior case reports have described signal abnormality within the brains of patients with raccoon roundworm neural larva migrans (NLM). This is a unique case in which spinal cord involvement was established by imaging. Knowledge of this combination of imaging findings expands the known imaging phenotype of this noteworthy infection.

Recombinant antigen-based enzyme-linked immunosorbent assay for diagnosis of Baylisascaris procyonis larva migrans.

Baylisascaris larva migrans is an important zoonotic disease caused by Baylisascaris procyonis, the raccoon roundworm, and is being increasingly considered in the differential diagnosis of eosinophilic meningoencephalitis in children and young adults. Although a B. procyonis excretory-secretory (BPES) antigen-based enzyme-linked immunosorbent assay (ELISA) and a Western blot assay are useful in the immunodiagnosis of this infection, cross-reactivity remains a major problem. Recently, a recombinant B. procyonis antigen, BpRAG1, was reported for use in the development of improved serological assays for the diagnosis of Baylisascaris larva migrans. In this study, we tested a total of 384 human patient serum samples in a BpRAG1 ELISA, including samples from 20 patients with clinical Baylisascaris larva migrans, 137 patients with other parasitic infections (8 helminth and 4 protozoan), and 227 individuals with unknown/suspected parasitic infections. A sensitivity of 85% and a specificity of 86.9% were observed with the BpRAG1 ELISA, compared to only 39.4% specificity with the BPES ELISA. In addition, the BpRAG1 ELISA had a low degree of cross-reactivity with antibodies to Toxocara infection (25%), while the BPES antigen showed 90.6% cross-reactivity. Based on these results, the BpRAG1 antigen has a high degree of sensitivity and specificity and should be very useful and reliable in the diagnosis and seroepidemiology of Baylisascaris larva migrans by ELISA.

Molecular cloning of an immunogenic protein of Baylisascaris procyonis and expression in Escherichia coli for use in developing improved serodiagnostic assays.

Larva migrans caused by Baylisascaris procyonis is an important zoonotic disease. Current serological diagnostic assays for this disease depend on the use of the parasite's larval excretory-secretory (ES) antigens. In order to identify genes encoding ES antigens and to generate recombinant antigens for use in diagnostic assays, construction and immunoscreening of a B. procyonis third-stage larva cDNA expression library was performed and resulted in identification of a partial-length cDNA clone encoding an ES antigen, designated repeat antigen 1 (RAG1). The full-length rag1 cDNA contained a 753-bp open reading frame that encoded a protein of 250 amino acids with 12 tandem repeats of a 12-amino-acid long sequence. The rag1 genomic DNA revealed a single intron of 837 bp that separated the 753-bp coding sequence into two exons delimited by canonical splice sites. No nucleotide or amino acid sequences present in the GenBank databases had significant similarity with those of RAG1. We have cloned, expressed, and purified the recombinant RAG1 (rRAG1) and analyzed its diagnostic potential by enzyme-linked immunosorbent assay. Anti-Baylisascaris species-specific rabbit serum showed strong reactivity to rRAG1, while only minimal to no reactivity was observed with sera against the related ascarids Toxocara canis and Ascaris suum, strongly suggesting the specificity of rRAG1. On the basis of these results, the identified RAG1 appears to be a promising diagnostic antigen for the development of serological assays for specific detection of B. procyonis larva migrans.