baylisascariasis - clinical microbiology reviews

CLINICAL MICROBIOLOGY REVIEWS, Oct. 2005, p. 703–718 Vol. 18, No. 40893-8512/05/$08.00�0 doi:10.1128/CMR.18.4.703–718.2005Copyright © 2005, American Society for Microbiology. All Rights Reserved.

BaylisascariasisPatrick J. Gavin,1* Kevin R. Kazacos,2 and Stanford T. Shulman3

Microbiology and Infectious Diseases Research, Department of Pathology and Laboratory Medicine, Evanston NorthwesternHealthcare, Evanston,1 and Department of Veterinary Pathobiology, Purdue University School of Veterinary Medicine,

West Lafayette,2 Indiana, and Division of Infectious Diseases, Department of Pediatrics, Children’s Memorial Hospital, andNorthwestern University Feinberg School of Medicine, Chicago, Illinois3

INTRODUCTION .......................................................................................................................................................703HISTORICAL ASPECTS...........................................................................................................................................704LIFE CYCLE ...............................................................................................................................................................704EPIDEMIOLOGY.......................................................................................................................................................707

Baylisascaris in Raccoons .......................................................................................................................................707Baylisascariasis in Humans ..................................................................................................................................709

CLINICAL DISEASE .................................................................................................................................................710Visceral Larva Migrans .........................................................................................................................................710Neural Larva Migrans ...........................................................................................................................................710Ocular Larva Migrans ...........................................................................................................................................711

PATHOLOGY..............................................................................................................................................................711PATHOGENESIS........................................................................................................................................................712

Parasite Factors ......................................................................................................................................................712Host Factors ............................................................................................................................................................713

DIAGNOSIS ................................................................................................................................................................713Serology ....................................................................................................................................................................713Brain Biopsy ............................................................................................................................................................714Laboratory Tests .....................................................................................................................................................714Neuroimaging ..........................................................................................................................................................714Electroencephalography .........................................................................................................................................714Epidemiologic Field Studies ..................................................................................................................................714Differential Diagnoses ............................................................................................................................................714

TREATMENT..............................................................................................................................................................716Visceral and Neural Larva Migrans ....................................................................................................................716

Anthelmintic drugs .............................................................................................................................................716Corticosteroids ....................................................................................................................................................716

Ocular Larva Migrans ...........................................................................................................................................716Photocoagulation.................................................................................................................................................716

PREVENTION AND CONTROL..............................................................................................................................717CONCLUSIONS .........................................................................................................................................................717ACKNOWLEDGMENT..............................................................................................................................................717REFERENCES ............................................................................................................................................................717

INTRODUCTION

Baylisascariasis in humans is caused by infection with thenematode parasite Baylisascaris procyonis. Baylisascaris procyo-nis and related species are large nematodes of the order As-caridida. Other, more familiar ascarids are Ascaris lumbri-coides, Toxocara canis, and Toxocara cati, nematode parasitesof humans, dogs, and cats, respectively. Baylisascaris speciesare primarily parasites of lower carnivores. The North Amer-ican raccoon (Procyon lotor) is the definitive host for B. pro-cyonis. Baylisascaris procyonis is considered the most commoncause of clinical larva migrans in animals, in which it is usuallyassociated with fatal or severe neurological disease. It is dis-

tinguished from other causes of larval migrans by its propensityfor aggressive somatic migration, larval invasion of the centralnervous system (CNS), and the capability for continued larvalgrowth within intermediate hosts. More recently, the zoonoticpotential of B. procyonis has become evident. In its most severeform, B. procyonis is a rare cause of fatal or neurologically dev-astating neural larva migrans (NLM) in infants and young chil-dren. Characteristically, B. procyonis NLM presents as acute eo-sinophilic meningoencephalitis. Epidemiologic studies suggestthat pica or geophagia and exposure to infected raccoons orenvironments contaminated with their feces are the most impor-tant risk factors for infection. To date, despite treatment, neuro-logical outcome is dismal in the overwhelming majority of docu-mented cases. However, most cases of B. procyonis infection arepreventable by relatively simple measures. This review examinesthe epidemiologic, pathogenetic, clinical, and diagnostic featuresof baylisascariasis in humans and emphasizes the importance ofincreasing public awareness and ongoing preventive efforts.

* Corresponding author. Mailing address: Division of Microbiology,Department of Pathology and Laboratory Medicine, Evanston North-western Healthcare, 2650 Ridge Avenue, Rm. 1936, Evanston, IL60201. Phone: (847) 570-2744. Fax: (847) 733-5314. E-mail: [email protected].

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HISTORICAL ASPECTS

Baylisascaris procyonis was first isolated (as Ascaris colum-naris) from raccoons in the New York Zoological Park in 1931(38). It was later recognized as a distinct species (Ascaris pro-cyonis) in raccoons in Europe (61). The genus Baylisascaris wasdefined by Sprent in 1968 as including eight recognized andtwo provisional species previously classified as members of theAscaris or Toxascaris genus (60). The new genus was namedafter H. A. Baylis, formerly of the British Museum of NaturalHistory, London, United Kingdom.

The propensity of B. procyonis larvae to produce fatal NLMin various experimentally infected and wild rodents was recog-nized by Tiner from an early stage (62). More recently, B.procyonis was recognized as the most common and widespreadcause of clinical larva migrans in animals, being capable ofproducing severe or fatal NLM in over 100 species of birds andmammals (28, 29, 44).

The possibility of human infection was anticipated by Beaver(4) and later by Kazacos and colleagues (32). The markedzoonotic potential of B. procyonis has become apparent only inthe last 2 decades. The first confirmed cases of NLM in hu-mans were described to have occurred in two young boys, in1984 and 1985 (16, 25). Since that time, another 11 confirmedhuman cases have been documented (Table 1) (8, 10, 18, 41,44, 47, 51). An earlier (1975) unconfirmed case of NLM in-volved an 18-month-old girl with geophagia from Missouri,who presented with acute hemiplegia, cerebrospinal fluid(CSF) and peripheral eosinophilia, and elevated isohemagglu-

tinins (1). Serological testing, which was not available for Bay-lisascaris at that time, was positive for Ascaris and negative forToxocara in serum and CSF. Because Ascaris infection is notcharacterized by somatic or CNS migration, those authors as-tutely suggested that another animal ascarid species moreclosely related to A. lumbricoides than to T. canis was the mostlikely cause. Baylisascaris procyonis fits this description well.The closely related species B. columnaris and Baylisascaris me-lis, parasites of skunks and badgers, respectively, are rarecauses of clinical larva migrans in animals and, potentially, inhumans (29).

LIFE CYCLE

Baylisascaris procyonis infection in raccoons is usually sub-clinical; adult nematodes are confined to the small intestine(Fig. 1) (29). Adult B. procyonis organisms are large, tan-colored roundworms; the female is larger (20 to 22 cm long)than the male (9 to 11 cm) (Fig. 2). In the raccoon intestine,adult female worms produce prodigious numbers of eggs, withestimates of between 115,000 and 179,000 eggs/worm/day (29).In nature, infected raccoons shed an average of 20,000 to26,000 eggs per gram of feces and can shed in excess of 250,000eggs per gram of feces (29). Thus, infected raccoons can shedmillions of B. procyonis eggs daily, leading to widespread andheavy environmental contamination.

Individual raccoons may have a heavy parasite burden(mean burden, 43 to 52 worms). Juveniles have a significantly

TABLE 1. Summary of published cases of human Baylisascaris procyonis neural larva migrans

Yra Ageb Location Risk factor(s) Treatment Outcome(s) Reference

1980 10 mo Pennsylvania Pica None Died 251984 18 mo Illinois Down syndrome and pica Thiabendazole Died 161986 21 yr Oregon Developmental delay,

pica/geophagiaNot recorded Persistent residual deficits Cited in

reference10

1990 13 mo New York Pica Thiabendazole, ivermectin,and prednisone

Severe residual deficitsand cortical blindness

10

1993 9 mo Michigan Pica Not recorded Severe residual deficitsand cortical blindness

Cited inreference44

1993 13 mo California Pica/geophagia Solumedrol and prednisolone Severe residual deficits,visual impairment, andepilepsy

51

1996 6 yr Illinois Developmental delay,pica/geophagia

Albendazole and prednisone Severe residual deficitsand epilepsy

18

1996 13 mo Minnesota Unknown Methylprednisolone,vincristine, andthioguanine

Died 41

1997 19 mo Minnesota Klinefelter syndrome Prednisone, vincristine, andthioguanine

Died 41

1998 11 mo California Pica Albendazole andmethylprednisolone

Severe residual deficits,visual impairment andepilepsy

47

2000 17 yr California Developmental delay andgeophagia

Albendazole and anti-inflammatories

Died 8

2000 2.5 yr Illinois Pica/geophagia Albendazole and solumedrol Severe residual deficitsand visual impairment

8, 18

2002 11 mo California Pica/geophagia Albendazole andantiinflammatories

Severe residual deficits,cortical blindness, andepilepsy

Cited inreferences44 and 53

a Year patient first presented.b All patients were male.

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higher prevalence of infection (93.5%) than adults (55.3%),the highest rate of egg shedding, and consequently a greaterpotential for environmental contamination (58). The higherparasite burden of juvenile raccoons (mean burden, 48 to 62

worms) than in adults (mean burden, 12 to 22 worms) likelyreflects differences in mechanisms of infection (13, 43, 58).Young raccoons are infected in the first few months of life byingestion of infective eggs (containing second-stage larvae),

FIG. 1. Life cycle of Baylisascaris procyonis. (Adapted from http://www.dpd.cdc.gov/DPDx/HTML/Baylisascariasis.htm. Accessed 14 July2005.)

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which stick to their mother’s fur or contaminate the den and itssurroundings (29, 43). Adult raccoons, in contrast, ingest third-stage larvae during predation or scavenging of infected inter-mediate hosts.

Baylisascaris procyonis eggs are ellipsoidal and dark brownand measure from 63 to 88 �m by 50 to 70 �m in size (Fig. 3)(29). The eggs contain a large single-celled embryo surroundedby a thick shell with a finely granular surface. Eggs of theclosely related Toxocara species are lighter in color, have acoarsely pitted shell, and are slightly larger in size (85 by 75�m). Baylisascaris procyonis eggs are not immediately infectiveafter shedding. With suitable environmental temperature andhumidity, B. procyonis eggs usually develop into infective sec-ond-stage larvae in 2 to 4 weeks and, occasionally, as early as11 to 14 days (29, 52). In nature, B. procyonis eggs resistdecontamination and environmental degradation and remainviable in moist soil for years (29).

After ingestion by young raccoons, second-stage larvae

hatch from infective eggs in the small intestine. Larvae thenmigrate to the intestinal mucosa, where they develop beforethey reemerge into the lumen and undergo final developmentinto adult worms (mean interval, 63 days) (29). After ingestionby adult raccoons, third-stage larvae encysted in tissues ofintermediate host prey also hatch in the small intestine, wherethey remain within the lumen and mature into adult worms(mean interval, 35days) (29).

In nature, intermediate hosts, usually small birds and mam-mals (particularly rodents) are infected by ingesting infectiveB. procyonis eggs while foraging for food at preferred sites ofraccoon defecation, termed latrines. After ingestion by inter-mediate hosts, infective eggs hatch in the small intestine, larvaerapidly penetrate the intestinal mucosa, migrate via the portalcirculation through the liver to the lungs, gain access to the leftside of the heart via the pulmonary veins, and are distributedto the tissues by the systemic circulation (29, 33, 59, 63).

A small but potentially devastating number of larvae (typi-

FIG. 2. Adult B. procyonis nematodes. The female, on the left, is 24 cm long; the male, on the right, is 12 cm long. (Reprinted from reference43 with permission from Elsevier.)


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cally 5 to 7%) then enter the CNS (33). Aggressive migrationand growth of larvae, particularly within the CNS, leads to thedebilitation or death of the intermediate host. Rodents, rab-bits, primates, and birds appear most susceptible to NLM fol-lowing ingestion of infective B. procyonis eggs (29). Larvaeeventually become encapsulated within eosinophilic granulo-mas, where they remain viable until they are ingested by rac-coons or for the lifetime of the host (33). Raccoons are om-nivorous and opportunistic carnivores, preying on debilitatedintermediate hosts and consuming larvae encysted in theirtissues. Humans are accidental intermediate hosts. Infectiontypically occurs in young children with pica or geophagia afteringestion of infective B. procyonis eggs from environments orarticles contaminated with raccoon feces (30).

A number of reports have documented infection of domesticdogs and puppies with egg-laying adult B. procyonis worms (2,22, 29). Because of their close contact with humans, particu-larly children, B. procyonis infection of domestic dogs and petsrepresents a greater potential risk of infection and is a worri-some development. In addition, because dogs defecate indis-criminately, the potential exists for even more extensive con-tamination of the domestic environment. At present,descriptions of infection of domestic pets by adult B. procyonisare limited to experimental studies and isolated case reports(40). The prevalence of infection of domestic dogs is unknownbut may be more widespread than is appreciated. Unless eggsor worms shed in dog feces are examined closely, B. procyonismay be misidentified as the closely related Toxocara or Toxas-caris species.

EPIDEMIOLOGY

Baylisascaris in Raccoons

To fully understand baylisascariasis in humans, it is neces-sary to consider the key epidemiologic role played by the rac-coon. Raccoons are common free-ranging mammals, native tothe Americas from Canada to Panama (27, 37). Baylisascarisprocyonis is indigenous in North American raccoons and hasbeen demonstrated to occur in raccoons introduced around theworld. The prevalence of B. procyonis infection is high in wildraccoons in Germany and those kept in zoos or as pets in Japan(3, 29, 40, 54). Raccoons were formerly introduced into Eu-rope (France, Germany, and The Netherlands), the SovietUnion, and Asia for the commercial fur trade and into Japanas pets (27, 29).

The risk of animal and human exposure to B. procyonis isrelated to numbers and the prevalence of infected raccoonsand latrine density in a given locale. In North America, rac-coons are extremely common in rural, suburban, and urbansettings, where they have become well adapted to living along-side people. Raccoons thrive in areas with a permanent watersupply, a readily available source of food, and suitable sites fordens (24, 27). Some of the highest raccoon population densi-ties are described to be in and around suburban and urbanparks and residences (24, 47, 48). The abundance of supple-mental food (from gardens, garbage, bird feeders, and petfood) and den sites and reduced predation and hunting inthese areas further contribute to increasingly high raccoon

FIG. 3. Infective B. procyonis egg (diameter, 70 �m) containing a coiled second-stage larva. Recovered from soil and debris at a raccoon latrine.Magnification, �40.


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population densities (48). Stomach contents of wild raccoonsare frequently found to contain (43%) pet food, suggestingthat such food is made accessible to raccoons, either intention-ally or inadvertently (42). The predominantly nocturnal habitsof raccoons may conceal the presence of these large popula-tions (Fig. 4). Thus, in many parts of the United States, largepopulations of raccoons with a high prevalence of B. procyonisinfection now live in close proximity to humans (18, 42, 47, 50).According to the Department of Natural Resources, in 1999,raccoons in the United States were responsible for in excess ofan estimated $41 million in damage (15). In the absence ofhunting and trapping, it is projected that raccoon populationsin the northeastern United States will double over the nextdecade (34).

In North America, the prevalence of B. procyonis is high inthe Midwest, northeast, and West Coast raccoon populations,where prevalences of 68% to 82% are reported (highest inIllinois) (14, 29, 47). However, over time, the local prevalenceof B. procyonis in raccoons varies and is subject to changebecause of natural migration, translocation to restock huntingareas, or accidental transport by garbage trucks (29, 67). Thus,veterinarians, physicians, and public health officials need to bealert to the possibility of zoonotic Baylisascaris infection out-side of traditional high-risk areas. Specifically, B. procyonis isan emerging infection in raccoons in the southeastern UnitedStates, an area traditionally considered as being low risk (12).It seems likely that B. procyonis infection is a possibility wher-ever raccoons are found.

Although generally solitary animals, raccoons defecate inpreferred communal sites, termed latrines (19, 27). Raccoonlatrines play a central role in the transmission dynamics of B.procyonis (44). Individual latrines are visited by many raccoonsand may contain substantial quantities of feces; a single latrine

may contain between 370 and 750 g of feces (46, 50). Activeraccoon latrines are characterized by the constant addition offresh feces to older decomposing feces, such that eggs found atraccoon latrines are at various stages of development (46).Latrines are routinely visited by a variety of small mammalsand birds, which forage for undigested seeds and grain (46). Innature, most transmission of B. procyonis to intermediate hostsoccurs by ingestion of infective eggs from raccoon latrines (46).Similarly, contact with raccoons or their feces is the mostimportant risk factor for infection in cases of B. procyonis NLMin humans (18, 29).

In forested and rural areas, raccoon latrines are character-istically found on raised flat surfaces, such as stumps and limbsof trees, large logs, downed timber and rocks, and at the basesor in the crotches of trees (Fig. 5) (18, 24, 46, 50). In suburbanand urban settings, raccoon latrines are also found in lofts,attics and chimneys, and on flat roofs, wooden decks, wood-piles, and patios (Fig. 5) (24, 29, 43, 46, 50). In addition, soilnear latrines is frequently heavily contaminated with infectiveeggs and constitutes a potential long-standing source of infec-tion for foraging animals and children with geophagia or pica.Over 3,300 infective B. procyonis eggs were recovered from asingle 20-g soil sample collected adjacent to an active raccoonlatrine (18). Typically, eggs in soil surrounding raccoon latrinesoriginate from older degraded feces and commonly containinfective second-stage larvae. Human cases have also resultedfrom egg-laden raccoon feces in roof latrines being washeddown gutters by rainfall and contaminating the surroundingground below (44, 50, 53).

Raccoon feces are typically dark, tubular, and 7 to 15 cmlong by 2 cm in diameter, have a pungent odor, and maycontain a variety of foodstuffs, such as corn fragments, undi-gested seeds, bones of small mammals and fish, shells of crus-

FIG. 4. Large group of raccoons living in a suburban Chicago cemetery and feeding on bread left by well meaning but misguided wildlifeenthusiasts. (Photograph courtesy of Jon Randolph, Chicago, Ill., reproduced with permission.)


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taceans, and remnants of garbage (24, 44). Old feces mayresemble leaves or debris. Just as raccoon latrines are an at-tractive and important source of food for many animal and birdspecies, they conceivably may represent attractive play areasfor young children (30, 46). Because B. procyonis eggs mayremain infective for years, long after surrounding raccoon fe-ces has degraded, contaminated areas can serve as long-termsources of infection for susceptible animals and humans (29).

Baylisascariasis in Humans

The first confirmed cases of human B. procyonis NLM weredescribed in 1984 and 1985 in 10- and 18-month-old boys fromPennsylvania and central Illinois, respectively (16, 25). Both

presented with rapidly progressive and ultimately fatal eosin-ophilic meningoencephalitis. Other reports followed, namely,of severe nonfatal NLM in young boys from upstate New York(n � 1), California (n � 3), Illinois (n � 2), and Michigan(n � 1) and in a young adult with developmental delay fromOregon (n � 1) and of additional fatal disease in toddlers fromMinnesota (n � 2) and a teenager with developmental delayfrom California (n � 1) (Table 1) (8, 10, 18, 41, 44, 47, 51).Notably, raccoon populations in these areas have the highestprevalence of B. procyonis infection (29). Within these regions,cases have occurred in rural, urban, and suburban areas.

In epidemiologic studies, two factors placed these patients atrisk for severe infection: (i) contact with infected raccoons,their feces, or a contaminated environment and (ii) geophagia

FIG. 5. Typical raccoon latrines, found at the base of a group of trees (A), on logs (B), and on the roof of a home in suburban California (C).(Reprinted from reference 43 with permission from Elsevier.)


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or pica. Specific risk factors included exposure to baby or petraccoons; indoor storage of contaminated downed timber,wood chips, or bark for firewood; indoor contamination byraccoon dens in chimneys and fireplaces; or outdoor contam-ination of children’s play areas by raccoon feces. In field stud-ies, infective B. procyonis eggs have been isolated from barkand wood chips, soil from play areas, and surrounding latrines.All patients were observed eating dirt or debris or suckingwood chips from contaminated areas or were known to exhibitpica or geophagia. Pica or geophagia is common in infantsunder 2 years of age (7). In addition, young infants and olderdevelopmentally delayed patients have relatively poor hygiene.Presumably, if exposed to a contaminated environment, suchindividuals are more likely to ingest large quantities of B.procyonis eggs and are predisposed to severe NLM.

Of the documented cases of NLM, all were males, and 11 ofthe 13 cases occurred in toddlers or young children. The malepredominance is probably related more to play habits ratherthan an inherent increased susceptibility to infection. Conceiv-ably, raccoon latrines may make particularly attractive playareas for inquisitive infants and children (30). Several of thecases had an antecedent diagnosis of developmental delay ormental handicap. The only documented cases in older patientsoccurred in 17- and 21-year-old males with developmentaldelay and geophagia living in areas of Los Angeles and Ore-gon, respectively, with high raccoon populations (8, 10).

Baylisascaris procyonis is also increasingly recognized as acause of ocular disease in humans. In contrast to NLM, whichis almost exclusively restricted to infants and young children,isolated ocular larva migrans (OLM) usually occurs in other-wise healthy adults (21, 31). Most commonly, in such casesthere is no obvious or only incidental exposure to raccoons ortheir feces and no history of pica. This suggests that isolatedOLM follows the ingestion of relatively few B. procyonis eggsand the chance migration of a single B. procyonis larva into theeye.

The apparent increase in cases of NLM and OLM in humansparallels the increase of cases in animals and of raccoon pop-ulations and the contamination of domestic environments inthe same areas. The contributions of increased awareness ofthe condition and of the availability of a diagnostic test to thisobserved “emergence” are unclear.

CLINICAL DISEASE

The full clinical spectrum of human baylisascariasis is un-known but includes visceral larva migrans (VLM), NLM, andOLM. In addition, preliminary evidence suggests that asymp-tomatic infection also occurs. As in animals, it is likely that theclinical presentation of B. procyonis infection in humans isdetermined primarily by the number of eggs ingested, which inturn determines the number of larvae entering the CNS. Ad-ditional determining factors likely include the site and extentof larval migration in the CNS and size of the host brain (29).Thus, severe NLM is almost exclusively described to occur inyoung infants with geophagia or pica who are most likely toingest large numbers of eggs. In addition, their relatively smallbrain size increases the likelihood that larval migration willcause severe clinical disease. In contrast, in adults with OLM,contact with raccoons or their feces is incidental or not appar-

ent, the number of eggs ingested is presumably smaller, andthe brain size is larger. The absence of eosinophilia or positiveantibaylisascaris serology in OLM supports this hypothesis (21,31).

The finding of antibaylisascaris antibodies in healthy asymp-tomatic adults, presumably reflecting exposure to small inoculaof eggs and the presence of isolated VLM or a small number oflarvae in silent areas of the larger adult brain, suggests thatlow-level infection may be more common than is appreciated(9, 10).

Visceral Larva Migrans

Larva migrans is defined as the prolonged migration andpersistence of helminth larvae in the organs and tissues ofhumans or animals (4, 29). In severe infections of infants andyoung children, as in intermediate animal hosts, B. procyonislarvae undergo widespread somatic migration. Numerousgranulomata have been demonstrated histologically in theheart, mediastinal soft tissues, pleura and lungs, small andlarge bowel walls, and mesentery and mesenteric lymph nodes(16, 25). Nonspecific clinical manifestations of this migrationinclude macular rash (predominantly on the face and trunk),pneumonitis, and hepatomegaly (10, 16, 18, 25, 51). It is pre-sumed that the development of dyspnea and tachypnea, whichis seen in primates 3 to 5 days after experimental infection, issecondary to early pulmonary migration (32, 33). Baylisascarisprocyonis is also considered the likely but unproved cause ofthe sudden unexpected death of a mildly mentally handicapped10-year-old boy from Massachusetts who presented with aninflammatory polypoid mass in the left ventricular myocardiumand marked peripheral eosinophilia (5). At autopsy, the intra-cardiac mass consisted of several large (60 to 70 �m in diam-eter) degenerating ascarid larvae surrounded by eosinophilicgranules and granulomata. Additional visceral or CNS involve-ment was not apparent, and confirmatory serologic testing wasnot performed.

Neural Larva Migrans

The incubation period of baylisascariasis in humans is un-known; however, if the inoculum of eggs is large enough, ful-minant NLM can develop within 2 to 4 weeks. Although arelatively low percentage of ingested larvae enter the CNS (5%to 7% in mice), widespread migration and continued growthwithin host tissues leads to extensive damage (29).

The majority of human patients with B. procyonis NLMpresent with an acute fulminant eosinophilic meningoenceph-alitis. Common early features include low-grade fever, ataxia,increasing lethargy, somnolence, and periods of increased ir-ritability. Over time there is regression and loss of develop-mental milestones, progression to extensor posturing, increas-ing spasticity with hemi- or quadriparesis, and ocular or cranialnerve involvement. Seizures occur commonly and may be dif-ficult to control. Neurologic status may deteriorate rapidly tostupor, coma, and death. To date, all survivors have been leftin a persistent vegetative state or with severe residual deficits.Blindness and visual impairment are common sequelae, andmost patients require total nursing care.

A more subacute, indolent encephalopathy has occasionally


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been described to occur in older patients with developmentaldelay and geophagia. This presumably reflects the accumula-tion over time of a sufficient number of larvae to produceclinical disease within a larger-size brain (10, 18).

Ocular Larva Migrans

Ocular disease in baylisascariasis occurs in association withsevere NLM or as an isolated finding. Most infants and chil-dren with clinical VLM and NLM also have evidence of oculardisease. Here, visual impairment or blindness results fromwidespread larval migration, with destruction of the visual cor-tex, or from larval migration within the eye itself. Ophthalmo-scopic exam demonstrates choroidioretinitis, optic neuritis, oratrophy and occasionally may reveal motile larvae migratingwithin the retina (21, 31, 39). Morphometric measurement ofretinal larvae allows differentiation of the larger B. procyonislarvae (1,500 to 2,000 by 60 to 70 �m) from those of relatedToxocara spp. (350 to 445 by 20 �m), which are a somewhatmore common cause of isolated OLM (21).

Baylisascaris is now considered the most common cause ofthe large nematode variant of diffuse unilateral subacute neu-roretinitis (DUSN), a form of OLM associated with progres-sive monocular visual loss and changes in retinal pigmentationand optic nerve anatomy (21, 39). Severe localized ocular dam-age results from inflammation of the retina, retinal vascula-ture, and optic nerve in response to the local presence of B.procyonis larvae (21, 31).

PATHOLOGY

Although well characterized for animals, the pathology ofhuman baylisascariasis is based on autopsies of the first twofatal human cases (16, 25). In these cases, the brain was themost severely affected organ. Massive larval invasion of theCNS is characteristic, with estimates of more than 3,200 larvaebeing isolated from the brain of a single case (3 larvae/g oftissue) (16). Acute, macroscopic findings included markedswelling and softening of the brain, leptomeningeal congestionand thickening, and evidence of cerebellar herniation (Fig. 6)(16). Necrosis was most marked in the inner third of theperiventricular white matter, with numerous “track-like”spaces being visible to the naked eye. In contrast, generalizedatrophy, with thickening of the basal and spinal meninges, wasevident in a child who died 14 months after acute infection(25). Severe generalized atrophy was evident in the cerebralhemispheres, corpus callosum, basal ganglia, thalami, cerebel-lum, brain stem, and spinal cord, in association with a loss ofgray-white matter demarcation and ventricular enlargement.

Histologic findings for acute fatal cases demonstrate necro-sis and inflammation with numerous macrophages, eosino-phils, lymphocytes, and occasional plasma cells concentrated incerebral periventricular white matter and leptomeninges.Characteristically, large numbers of eosinophils and eosino-philic granules and deposits of extracellular eosinophilic ma-terial (the Splendore-Hoeppli phenomenon) are presentaround necrotic migration tracks and cerebral blood vessels(23). Immunofluorescence studies suggest that eosinophilicmaterial surrounding migration tracks, larvae, and perivascularareas consists of eosinophil major basic protein arising from

eosinophil degranulation (23). Moertel et al. and others dem-onstrated markedly increased CSF levels of eosinophil majorbasic protein, eosinophil-derived neurotoxin, and interleukin5, a critical cytokine involved in eosinophilia and the eosino-philic response to helminth parasites, in two fatal cases of B.procyonis NLM (35, 41, 49). At autopsy, larvae have beenidentified in cerebrum, cerebellum, and spinal cord, with andwithout surrounding inflammatory reaction. In one of the firstfatal cases, 185 live motile larvae were recovered postmortemfrom one 60-g sample of cerebrum (16).

Subacute cases of NLM demonstrate well-defined granulo-mata, composed of relatively few intact eosinophils surroundedby a chronic fibrotic reaction, and the absence of major basicprotein deposition, consistent with subsidence of the acuteinflammatory reaction (25). Microscopically, CNS granulo-mata containing larvae surrounded by a chronic fibrotic reac-tion were concentrated in the deep periventricular white mat-ter.

In fatal human cases, NLM is accompanied by widespreadvisceral involvement. Somatic larval migration causes mechan-ical tissue damage and necrosis and provokes an intense eo-sinophilic and granulomatous inflammatory reaction. Macro-scopically, VLM manifests as multiple small whitish nodules 1to 1.5 mm in diameter on pleural surfaces, soft tissues sur-rounding the laryngo-tracheo-bronchial tree, lung hila, epicar-dium and myocardium, the wall of the colon and ileocecalregions, small bowel mesentery, and mesenteric lymph nodes(16, 25). Microscopically, the nodules consist of granulomatacontaining coiled B. procyonis larvae surrounded by macro-phages, eosinophils, plasma cells, and dense fibrous collage-nous tissue (16, 25).

Histologically, B. procyonis larvae are 60 to 80 �m in greatestdiameter and have a characteristic appearance, best seen intransverse section through the midbody/midintestinal region(29). Characteristic diagnostic features include a large, cen-trally located, and laterally compressed intestine; paired trian-gular lateral excretory columns flanking the intestine, and

FIG. 6. Coronal section of the brain of an 18-month-old boy whodied of acute B. procyonis NLM. The leptomeninges are congested.There is marked swelling and softening of the brain parenchyma.Necrosis is evident in the deep periventricular white matter, and thereare numerous track-like spaces visible to the naked eye.


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prominent single lateral cuticular alae on either side of thebody (Fig. 7).

Although OLM is described in conjunction with NLM, de-scriptions of ocular pathology are lacking (25, 39, 47, 51). Innaturally and experimentally infected animals, B. procyonisOLM is characterized histopathologically by the presence oflarval migration tracks in the retina, progressing to necrosisand intense eosinophilic inflammation of the retina, choroid,and vitreous (29, 31). The clinical description of intra- andsubretinal motile larvae of the size of B. procyonis in cases ofNLM or OLM suggests that acute pathology in humans issimilar (21, 31). Histologic findings in the late stages of DUSNdemonstrate retinitis, retinal and optic nerve perivasculitis andatrophy, peripheral retinal degeneration and depigmentation,and low-grade choroiditis (17).

PATHOGENESIS

Humans are accidental intermediate hosts for B. procyonis.Infection follows the ingestion of B. procyonis eggs containinginfective second-stage larva. In humans, as in natural interme-diate hosts, B. procyonis larvae undergo aggressive tissue mi-gration that includes the CNS and eyes. Although clinicalNLM is a common sequela of infection, B. procyonis larvae arenot inherently neurotropic. Experimental and wild animal dataand human autopsies suggest that CNS involvement resultsfrom extensive somatic larval migration. Continued larvalgrowth and migration following entry of even a few B. procyo-nis larvae into the CNS may have potentially severe conse-quences. In marked contrast, the related nematode Toxocara,a much more common cause of VLM and OLM, is a veryunusual cause of NLM (55, 64).

Animal and limited human autopsy data suggest that B.procyonis larvae hatch in the small intestine, penetrate thebowel mucosa, and pass, presumably via the portal circulation,through the liver and along vascular channels to the lungs (16,25, 29). Although hepatomegaly is described for baylisascari-asis, hepatitis and hepatic larvae or granulomata are not prom-inent. In contrast, Toxocara larvae commonly affect the liver, aslarvae are trapped once the host becomes sensitized (55). Inthe lungs, B. procyonis larvae rupture pulmonary capillaries,enter pulmonary veins, return to the left side of the heart, andgain access to the systemic circulation. From the systemic cir-culation, larvae may be distributed throughout the body, in-cluding the CNS. Larvae most likely access the brain by pen-etrating cerebral blood vessels. After hatching in the intestine,a small number of larvae migrate locally in the intestinal wall,mesentery, and lymphatics and move from the lungs to thepleura, hilar tissues, mediastinum, and heart.

Parasite and host factors contribute to the success of B.procyonis as a parasite and to the pathogenesis of baylisascari-asis in humans. Parasite factors include the fecundity of adultworms, the longevity and durability of the ova, the broad hostrange, the ability of the larvae to continue to grow to a largesize within the intermediate host, and the toxicity of larvalexcretory and secretory products. Host factors include the sizeof the host brain and the host eosinophilic inflammatory re-sponse.

Parasite Factors

The long persistence and resistance of B. procyonis eggs toenvironmental degradation or efforts at decontamination arethe principal reasons for the success of B. procyonis as a par-asite. The eggs are extremely hardy, and given adequate mois-ture they can remain viable and potentially infective in soil formany years, long after latrines have ceased to be active andsurrounding raccoon feces has degraded (29). Larvae evenremain viable in eggs stored for months in 10% formalin (44).In addition, B. procyonis eggs tend to be sticky and adhere toanimal fur, surfaces, and objects, including children’s toys andpresumably the fingers of infants. The combination of prolificegg laying by adult B. procyonis worms and the persistent via-bility of eggs further increase the potential for larval transmis-sion.

Like most other ascarids, B. procyonis has no obligatory

FIG. 7. (A) Baylisascaris procyonis larva recovered from the brainof a pet New World parrot with fatal NLM; (B) cross-section (atmidbody level) (diameter, 60 �m) recovered from the cerebrum of arabbit with NLM. Characteristic features of the larva include a cen-trally located (slightly compressed) intestine, flanked on either side bylarge triangular excretory columns. Prominent lateral cuticular alae arevisible on opposite sides of the body. Hematoxylin and eosin stain.


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intermediate host (43). However, the broad host range of B.procyonis larvae is most unusual and likely represents a distinctsurvival advantage for the parasite (29). Specifically, the abilityof larvae to infect over 100 species of animals and birds in-creases the number of potential intermediate hosts for theparasite. Aggressive somatic migration that includes the CNSand continued growth of larvae within the CNS also confer asurvival advantage and are likely to have been selected for overtime (29). Neural larva migrans that causes death or debilita-tion of intermediate hosts increases the probability that the lifecycle is perpetuated as larvae are transmitted back to preda-tory or scavenging raccoons (29, 62). Baylisascaris procyonislarvae demonstrate somatic tropism for the cranial rather thancaudal regions of intermediate hosts. Thus, B. procyonis VLMis characterized by preferential concentration of larvae in thehead, neck, and thoracic regions (32, 56, 63). Distribution oflarvae to these areas probably occurs by migration from the leftside of the heart via the first major arterial branches of thesystemic circulation arising from the aortic arch (32). Thispreferential somatic distribution may create a survival advan-tage for B. procyonis; raccoons appear to first eat the head,neck, and muscular regions of their prey and frequently discardthe rest of the carcass (56, 63). Again, concentration of larvaein these areas probably increases the chances of their beingingested by raccoons.

The relatively large size of B. procyonis larvae also contrib-utes to the pathogenicity of this organism. Baylisascaris procyo-nis larvae molt and continue to grow and develop as theymigrate, reaching comparatively large size (Fig. 7) (29). Spe-cifically, second-stage larvae measure approximately 300 �m inlength when they hatch from ingested eggs. During their so-matic migration in intermediate hosts, they grow and developinto third-stage larvae measuring 1,500 to 1,900 �m in lengthby 60 to 80 �m in maximal diameter (16, 21, 52). Migration ofsuch large larvae within the CNS is likely to exacerbate me-chanical tissue damage. Among helminths that cause VLM,such continued growth of larvae is unusual; e.g., larvae ofToxocara spp. measure 350 to 445 �m in length and do notgrow within intermediate or paratenic hosts (45, 55). Andfinally, migrating B. procyonis larvae also leave a trail of highlyantigenic and neurotoxic secretory and excretory products intheir wake (29). These larval products cause marked localtissue necrosis and recruit a characteristically strong eosino-philic host inflammatory response (23, 41). Eosinophil degran-ulation releases eosinophil proteins (including major basicprotein, eosinophil-cationic protein, and eosinophil-derivedneurotoxin), which are toxic to mammalian cells, in vitro and invivo (20, 35).

Host Factors

Unfortunately, the host inflammatory response to B. procyo-nis larvae is neither protective nor curative and is probablydamaging. Despite a vigorous serum and tissue eosinophilicresponse, encapsulation of larvae within eosinophilic granulo-mata is slow and cessation of migration is delayed, particularlywithin the CNS. The finding of larvae in normal-appearingbrain without surrounding inflammation and with only a fewintact eosinophils suggests that the inflammatory reaction lagsbehind actively migrating larvae (23). In addition, Baylisascaris

larvae remain viable while encapsulated in tissues of humanand intermediate animal hosts (16, 59). When the inflamma-tory reaction eventually develops, eosinophil degranulationcauses extensive necrosis of surrounding tissues and is itselfneurotoxic (23). Furthermore, survival of B. procyonis larvae ineosinophilic granulomata within animal and human tissuessuggests a role for additional mechanisms to evade the hostimmune response (16, 59).

Finally, epidemiologic and experimental animal data sup-port the hypotheses that infants and young children are atespecially high risk for development of severe NLM because oftheir propensity to ingest large numbers of infective B. procyo-nis eggs and because of their relatively small brain size.

DIAGNOSIS

The combination of encephalopathy with CSF and periph-eral eosinophilia and diffuse white matter disease on neuroim-aging, with or without eye disease, in a patient from NorthAmerica or Europe should strongly suggest the diagnosis ofBaylisascaris NLM, and a history of exposure to raccoons ortheir feces should be sought. At present, in the absence of abrain biopsy, the diagnosis of B. procyonis NLM is dependenton serology. Demonstration of anti-B. procyonis antibodies inserum and CSF, particularly in the setting of a compatibleclinical case and epidemiologic history, is the mainstay of di-agnosis. Although basic laboratory tests, neuroimaging, andencephalography are, by themselves, nondiagnostic, they doprovide important supportive evidence and may rule out otherconfounding diagnoses.

Serology

Anti-Baylisascaris antibodies can be demonstrated in CSFand serum by indirect immunofluorescence, enzyme-linked im-munosorbent assay, and Western blotting. Enzyme-linked im-munosorbent assay is the current test of choice. Serologic test-ing is currently available only from the Department ofVeterinary Pathobiology at Purdue University, West Lafayette,IN (K. Kazacos). Indirect immunofluorescence tests use frozensections of B. procyonis third-stage larvae as an antigen. Gen-erally, in documented cases of NLM, good differential stainingof larval sections is observed (41). Enzyme-linked immunosor-bent assay and Western blotting use excretory-secretory prod-ucts from in vitro cultures of B. procyonis larvae as the antigen(6). Larval excretory-secretory antigens have been character-ized as complex glycoproteins, with molecular masses of 10kDa to 200 kDa, that contain several different sugar residues(6). Protein epitopes of 33-kDa to 45-kDa antigens appear tobe recognized selectively by antibodies from B. procyonis-in-fected humans and animals but not by normal human or T.canis antibody-positive sera (6). In addition, children with clin-ical B. procyonis NLM are strongly positive for anti-Baylisas-caris antibodies in CSF and serum and have consistently beennegative for anti-Toxocara antibodies (10, 16, 18, 29, 41, 43, 47,51). In several of these cases, positive B. procyonis serology wasconfirmed by brain biopsy or at autopsy (8, 16, 25, 51). Acute-and convalescent-phase titers characteristically demonstrateseveralfold increases in both serum and CSF anti-Baylisascarisantibody levels (18, 41).


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In the absence of large population-based serologic studies,Baylisascaris seroprevalence is unknown. However, the findingof anti-Baylisascaris antibodies in asymptomatic family mem-bers of human cases and in individuals who have had contactwith raccoons and preliminary results of a seroprevalencestudy in Chicago area children suggest that low-level asymp-tomatic infection may occur (9, 10) (W. B. Brinkman, K. R.Kazacos, P. J. Gavin, H. J. Binns, J. D. Robichaud, M. O’Gor-man, and S. T. Shulman, Abstr. Pediatr. Acad. Soc. Ann. Mtg.,abstr. 1872, 2003).

Brain Biopsy

While a positive serologic test in a patient with compatibleclinical signs and epidemiological risk factors is highly sugges-tive of the diagnosis, demonstration of larvae in tissues isconfirmatory. Diagnosis of B. procyonis NLM has been madeantemortem by demonstration of characteristic B. procyonislarvae in brain biopsies (8, 51). Nevertheless, the chances ofisolating a portion of a larva in a small biopsy are low; Rowleyand colleagues considered themselves fortunate to have madethe diagnosis by biopsy in their case (51). If a diagnostic brainbiopsy is considered, a deep white matter site is recommended.In addition to the fact that the diagnostic yield from a biopsy ispotentially low, the availability of a serologic test has undoubt-edly contributed to the decrease in numbers of diagnostic brainbiopsies.

Laboratory Tests

Although no routine laboratory test is considered diagnosticof B. procyonis NLM by itself, a number of studies provideadditional supportive evidence. Most importantly, the pres-ence of eosinophilia, particularly eosinophilic meningitis,should alert the physician to the possibility of a parasitic eti-ology (36, 49, 65). Eosinophilic meningitis, defined as the pres-ence of 10 or more eosinophils/�l or eosinophilia of at least10% in CSF, should never be ignored (36, 65). Eosinophils arenot normally present in CSF; their presence narrows the dif-ferential diagnosis of CNS disease and provides an early or theonly etiologic clue. In documented cases of NLM, the periph-eral white blood cell count is usually mildly elevated (median,17,400 cells/mm3; range 10,000 to 28,400 cells/mm3), but eo-sinophilia may be marked (median, 28%; range, 5% to 45%).Cerebrospinal fluid cell counts may be normal at presentationand generally demonstrate only mild leukocytosis (median,16.5 cells/mm3; range, 1 to 125 cells/mm3), again with eosino-philia (median, 32%; range, 4% to 68%). Notably, even in theabsence of pleocytosis, demonstrable CSF eosinophilia may beevident. Because eosinophils are easily missed in unstained orGram-stained CSF, it may be necessary to request Wright’s orGiemsa stain of cytocentrifuged CSF specimens. In docu-mented cases of NLM, CSF protein is generally normal or onlymildly elevated (median, 30 mg/dl; range, 18 to 69 mg/dl),while CSF glucose levels are normal (median 66 mg/dl; range,41 to 81 mg/dl).

Although the finding of elevated serum isohemagglutinins,caused by cross-reactions between larval glycoproteins and hu-man blood group antigens, is not specific for baylisascariasis, itdoes provide an additional clue to the diagnosis (6). Impor-

tantly, because B. procyonis does not complete its life cycle inhumans, eggs or larvae are not shed in the feces of infectedpatients.

Neuroimaging

In acute B. procyonis NLM, changes on neuroimaging lagbehind clinical disease and do not lead to earlier diagnosis.Initially, neuroimaging is frequently normal but eventuallydemonstrates only nonspecific diffuse white matter abnormal-ities, particularly of cerebral periventricular and deep cerebel-lar regions (Fig. 8) (10, 16, 18, 25, 41, 47, 51). This may beassociated with changes of hydrocephalus, cortical edema, andloss of gray-white matter differentiation, with little or no men-ingeal or parenchymal enhancement. Evolution of clinical dis-ease is manifest on neuroimaging as a progressive confluenceof white matter changes and resolution of acute inflammationending in residual global atrophy (18, 25, 41, 51).

Electroencephalography

In confirmed cases of NLM, electroencephalography oftendemonstrates nonspecific diffuse slow-wave activity consistentwith generalized encephalitis, but it may be normal (10, 16, 18,41, 47, 51).

Epidemiologic Field Studies

Field studies have played an important part in the diagnosticworkup of several of the documented cases of B. procyonisNLM, have contributed greatly to our understanding of theepidemiology and pathogenesis of the condition, and demon-strate targets for ongoing preventive efforts. In those cases inwhich formal field studies were carried out, unequivocal evi-dence of exposure to environments contaminated with raccoonfeces has been demonstrated, and raccoon latrine densitieshave invariably been high (8, 10, 16, 18, 25, 47, 50). In PacificGrove on the Monterey peninsula of California, Park andcolleagues demonstrated B. procyonis eggs in fecal samplesfrom 100% of latrines on a patient’s property (21/21) com-pared to 44% (12/27) of fecal samples from latrines elsewherein the city (47). Subsequently, a larger field study that includedtwo additional northern California residential communitiesdemonstrated a total of 244 latrines on 164 properties (50).Approximately half (44% to 53%) of the latrines contained B.procyonis eggs. Similarly, in southern California, a recent studyof 800 raccoon latrines demonstrated 100% prevalence for B.procyonis eggs (14).

Differential Diagnoses

While peripheral and CSF eosinophilia, the hallmarks of B.procyonis NLM, are rare clinical entities, they occur underother infectious and noninfectious conditions (35, 65). Amonghelminth infections worldwide, Angiostrongylus cantonensis andGnathostoma spinigerum are the most common causes of eo-sinophilic meningitis (36). Although angiostrongyliasis is en-demic in southeast Asia, China, Japan, and the Pacific andCaribbean Islands, international travel increases the likelihoodthat such infections may be encountered locally (57). An-


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FIG. 8. Neuroimaging of human brain with B. procyonis NLM. (A) In acute NLM, an axial-flair magnetic resonance (MR) image (at the levelof the posterior fossa) demonstrates an abnormal hyperintense signal of cerebellar white matter; (B) an axial T2-weighted MR image (at the levelof the lateral ventricles) demonstrates an abnormal patchy hyperintense signal of periventricular white matter and basal ganglia; (C) an axialT2-weighted MR image (at the level of the lateral ventricles) of a patient with subacute/chronic NLM demonstrates residual abnormal hyperintensesignal of the periventricular white matter, loss of white matter volume, and dilation of ventricles and sulci, consistent with generalized cerebralatrophy.


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giostrongyliasis, in contrast to baylisascariasis, is generally as-sociated with meningitis rather than meningoencephalitis, hasa relatively benign course, and usually, but not always, carriesa good prognosis. Gnathostomiasis, similar to baylisascariasis,may be associated with severe neurologic sequelae and a poorprognosis but is characterized by myeloencephalitis, focal ce-rebral hemorrhage (with xanthochromia), painful radiculopa-thy, and migrating cutaneous swellings. Neurocysticercosis, ce-rebral paragonimiasis, cerebral toxocariasis, neurotrichinosis,and CNS schistosomiasis are other, less common causes ofeosinophilic meningoencephalitis. Although Toxocara spp. area more common cause of VLM in humans, they are a veryuncommon cause of NLM (65). Rare cases of cerebral toxo-cariasis are usually associated with signs of VLM and thepresence of Toxocara antibodies in blood and CSF. Dissemi-nated Coccidioides immitis infection, which is perhaps the mostcommon cause of eosinophilic meningitis in the United States,is usually associated with intense basilar enhancement, hydro-cephalus, acute infarction on neuroimaging, and positive CSFserology. Acute disseminated encephalomyelitis, which pre-sents as an acute encephalopathy with cerebral white matterchanges on neuroimaging in a previously healthy child, may beconfused with B. procyonis NLM. However, acute disseminatedencephalomyelitis is typically a monophasic nonprogressive ill-ness, with more discrete multifocal gray and white matter ab-normalities on neuroimaging, and generally has a good prog-nosis (51).

TREATMENT

Visceral and Neural Larva Migrans

Anthelmintic drugs. The prognosis for B. procyonis NLM isgrave with or without treatment; among documented cases,there are no neurologically intact survivors. The majority ofcases have been treated with anthelmintics and corticosteroids.Empirical anthelmintic treatment with thiabendazole, fen-bendazole, tetramisole, or ivermectin has failed to preventdeath or unfavorable outcomes. Anthelmintics successfullyeradicate adult B. procyonis worms from the intestines of rac-coons and skunks but are much less effective against larvae intissues of intermediate hosts and humans (29). In one of thefirst-documented human cases, thiabendazole treatment failedto prevent the isolation of numerous live motile larvae fromthe child’s brain postmortem (16).

Empirical treatment of suspected or proven NLM is extrap-olated from studies of experimentally infected animals andindividual case reports. Among currently available anthel-mintics, animal data suggest that albendazole and diethylcar-bazine have the best CSF penetration and larvicidal activity(29). Of the two, only albendazole has been used in childrenwith NLM. In addition, albendazole appears to have the morefavorable pharmacologic profile, with good absorption, highserum concentrations of the active metabolite, good penetra-tion across the blood-brain barrier, and minimal toxicity (11,26).

Experimental animal data and clinical observation of humancases emphasize the importance of the timing of treatmentrelative to larval invasion of the CNS. Anthelmintic treatmentof experimentally infected mice was successful only if it was

started before B. procyonis larvae entered the brain. Larvaeenter the brain of mice as early as 3 days after ingestion,leading to signs of clinical infection by day 9 or 10 (29). How-ever, laboratory mice fed B. procyonis eggs were protectedfrom clinical NLM by treatment with albendazole (100%),diethylcarbazine (100%), mebendazole (80%), or thiabenda-zole (80%), daily from days 1 to 10 after infection (40). Incontrast, when treatment started later, protection from clinicaldisease decreased with albendazole (75%) and diethylcarba-zine (45%) treatment daily from days 7 to 10 after infection(29). In addition, it appears that treatment must be continuedthroughout the period of CNS vulnerability to larval invasion.Rates of protection from CNS disease were much lower inmice treated with albendazole (40%), mebendazole (20%), orthiabendazole (20%) from days 1 to 3 after infection only (40).

The majority of documented human cases were treated withthiabendazole (50 mg/kg of body weight/day) or, more re-cently, albendazole (20 to 40 mg/kg/day) for 1 to 4 weeks afterpresentation. However, because the diagnosis of B. procyonisNLM is considered only at the onset of clinical signs andsymptoms, anthelmintic treatment has started late in thecourse of infection, at which stage larval invasion of the CNShas already occurred. Although ivermectin is effective in tissuenematode infections, such as lymphatic filariasis, its use shouldprobably be avoided. It was unsuccessful in zoonotic B. pro-cyonis NLM and did not appear to cross the blood-brain bar-rier (10, 29).

While treatment after the onset of symptoms has failed toprevent unfavorable outcomes, the role of prophylactic anthel-mintic treatment for asymptomatic children is unclear but isfelt to be potentially beneficial. Given the potentially devastat-ing sequelae of untreated infection or late treatment and theavailability of well-tolerated anthelmintics, prophylaxis ap-pears warranted in select cases with documented exposure toinfected raccoons, raccoon feces, or contaminated environ-ments. Prophylactic albendazole has been started in childrenafter exposure to raccoon latrines or cages, while results oftests to rule out contamination by B. procyonis are awaited (30,44). In this situation, treatment has been discontinued after afew days when results of environmental tests were negative.

Corticosteroids. Systemic corticosteroids have proved bene-ficial as adjunctive anti-inflammatory treatment in neurocystic-ercosis and as single agents in angiostrongyliasis and oculartoxocariasis and have been used in the majority of B. procyonisNLM cases. In theory, corticosteroids are used to decrease thepotentially deleterious eosinophilic inflammatory response andbecause of concerns that the larvicidal effect of anthelminticsmay stimulate additional eosinophilic degranulation.

Ocular Larva Migrans

Photocoagulation. Baylisascaris procyonis OLM and DUSNhave been treated successfully with the combination of laserphotocoagulation and systemic corticosteroids to kill intrareti-nal larvae and decrease any resulting intraocular inflammatoryresponse, respectively (21, 31). The role, if any, of anthel-mintics in the treatment of B. procyonis OLM has not beenestablished.


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PREVENTION AND CONTROL

In the absence of effective treatment and early diagnosis,prevention of B. procyonis infection remains the best medicine.Most cases of B. procyonis infection are preventable by rela-tively simple measures. Education of the public regarding thepotential dangers of contact with raccoons or their feces is themost important preventive step. Risk of infection is greatestwhen infants or toddlers with geophagia or pica come in con-tact with raccoon latrines or an environment contaminated byinfected raccoon feces. Young infants and toddlers, particu-larly those with pica or geophagia, should be kept away frompotentially contaminated areas. Parents should be observantfor and discourage pica, and they should stress the importanceof hand washing after outdoor play or contact with animals,including pet dogs. Raccoons should not be encouraged to visithomes or yards for food, and the keeping of raccoons as pets,particularly in households with young children, should bestrongly discouraged. Downed timber should not be storedindoors or in areas readily accessible to inquisitive infants.Raccoon latrines in and around homes and play areas shouldbe cleaned up and decontaminated. However, the longevity ofB. procyonis eggs and their resistance to disinfection or decon-tamination makes successful environmental cleanup difficult.Detailed guidelines are available for raccoon latrine cleanup(29, 53). Heat is by far the best method of killing B. procyoniseggs (29). Boiling water, steam-cleaning, flaming, or fire arehighly effective and practical methods for decontamination oflarge or small areas. The use of direct flames from a propaneflame-gun is a favored method (29). For heavily contaminatedareas a combination of removal and disposal of the top fewinches of surface soil with flaming is most effective. Ideally,personnel cleaning contaminated areas should wear disposableoveralls, gloves, and mask and eye protection. All potentiallycontaminated material removed from these sites, includingused protective clothing, should be incinerated. Contaminatedsurfaces can be adequately cleaned with a xylene-ethanol mix-ture, after solid waste has been removed. However, chemicaldisinfection, in general, is rarely effective and not practical forlarge outdoor areas. Eggs are resistant to most common dis-infectants; 20% bleach (1% sodium hypochlorite) will washaway sticky eggs but does not kill them (29).

While deworming wild raccoons may theoretically reducethe risk of infection in an area, interventions that combineraccoon depopulation and removal with cleanup and decon-tamination of latrines are likely to be more effective at reduc-ing new and existing sources of infection (29, 44). If raccoonsbecome a nuisance in residential areas, local authorities maybe approached to trap and relocate or euthanize nuisancewildlife. However, if conditions in an area remain favorable forraccoons, such measures are unlikely to be effective in the longterm. Simple and humane recommendations are available toprotect humans and property while promoting harmoniouscoexistence with raccoons (66). Essentially, if there is no foodor shelter to support them, most wild animals will go away.

CONCLUSIONS

Baylisascaris procyonis NLM is a potentially fatal, neurolog-ically devastating infection, primarily of infants or young chil-

dren. Although documented cases remain comparatively rare,the increase in populations of raccoons with B. procyonis in-fection living in close proximity to human residential popula-tions suggests that the likelihood of human exposure and in-fection are high. While much has been learned concerning theepidemiology and pathogenesis of B. procyonis NLM, moreremains to be elucidated. Large population-based seropreva-lence studies should help to define the full clinical spectrum ofinfection and to identify at-risk populations most likely tobenefit from targeted public health interventions. In the ab-sence of effective treatment, prevention of infection remainsparamount. Education of the public to the potential dangers isthe most important first step.

ACKNOWLEDGMENT

We thank Tess Anton for assistance with access to the literature.

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