CLINICAL MICROBIOLOGY REVIEWS, Apr. 2003, p. 265–272 Vol. 16, No.

2
0893-8512/03/$08.00⫹0 DOI: 10.1128/CMR.16.2.265–272.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Toxocariasis: Clinical Aspects, Epidemiology, Medical Ecology,

and Molecular Aspects
Dickson Despommier*
Department of Environmental Health Sciences and Department of Microbiology, Mailman School
of Public Health, Columbia University, New York, New York 10032

INTRODUCTION .......................................................................................................................................................265
HISTORY OF DISCOVERY .....................................................................................................................................265
LIFE CYCLE ...............................................................................................................................................................266
CLINICAL ASPECTS.................................................................................................................................................267
CLINICAL SIGNS AND SYMPTOMS ....................................................................................................................268
VLM ..........................................................................................................................................................................268
OLM .........................................................................................................................................................................269
DIAGNOSIS ................................................................................................................................................................269
TREATMENT..............................................................................................................................................................269
EPIDEMIOLOGY .......................................................................................................................................................269
MEDICAL ECOLOGY...............................................................................................................................................270
MOLECULAR ASPECTS ..........................................................................................................................................270
CONCLUDING REMARKS ......................................................................................................................................271
REFERENCES ............................................................................................................................................................271

INTRODUCTION ocular larva migrans (OLM), in which toxocariasis pathological

effects on the host are restricted to the eye and the optic nerve.
Toxocariasis is the clinical term applied to infection in the
T. canis and T. cati are distributed worldwide, due to human
human host with either Toxocara canis or Toxocara cati. Both
settlement of nearly all land masses. Our penchant (almost a
of these are ascarid nematodes in the order Ascaridida, super-
genetic imperative) for surrounding ourselves with various do-
family Ascaridiodea, family Toxocaridae. Their definitive hosts
mestic animals, particularly cats and dogs, has ensured a world-
are the domestic dog and cat, in which they live as adults within
wide distribution for toxocariasis. In addition, many places that
the lumen of the small intestine. Infection can occur by the
remain permanently uninhabited also have robust populations
host ingesting viable, embryonated eggs from contaminated
of feral dogs and cats, introduced there during the 17th
sources (e.g., soil and earthworms, etc.), or they can acquire
through the 19th centuries by sea-faring nations, thus facilitat-
the infection in utero (i.e., transplacentally) from the infected
ing the maintenance of these two ascarid infections on numer-
mother when she ingests more infective eggs. In contrast, the
ous islands throughout the Pacific Ocean basin, including the
human host is aberrant with respect to the completion of the
Galapagos Islands.
life cycle. Infective larvae hatch after ingestion of eggs, but the
Several species of Toxocara infecting domestic cats and
juvenile stages fail to develop to mature adult worms. Instead,
other felids have been recently identified. Toxocara malaya-
they wander throughout the body for months or up to several
siensis n. sp. (18) infects domestic cats, while Toxocara lyncus
years, causing damage to whatever tissue they happen to enter.
infects the caracal (30). It is not known whether either of these
The ability of a eukaryotic parasite to survive in any mammal
newly described entities cause human infection resulting in
for that length of time is unusual. Only a few others have
clinical disease, but given the epidemiological pattern estab-
evolved long-term survival strategies; namely, the adult stage
lished by T. canis and T. cati, it is likely that at least a portion
of schistosomes live for 10 to 25 years, the first-stage larva of
of the total number of aberrant infections in humans have
Trichinella spiralis lives for the life span of the host, some
resulted from exposure to their migrating larvae. This review
species of adult filarial nematodes live 10 to 15 years, and the
concentrates on the most prevalent of Toxocara species, name-
juvenile stage of most species of tapeworms survive for 5 to 10
ly, T. canis and T. cati.
years. To accomplish this daunting feat, all of these parasites
have acquired unique mechanisms for evading the host’s im-
mune system. Toxocara spp. are no exception. HISTORY OF DISCOVERY
The dominant clinical manifestations associated with toxo-
cariasis are classified according to the organs affected. There Human infection with Toxocara spp. was first described by
are two main syndromes; visceral larva migrans (VLM), which Wilder (61) in 1950. He identified a nematode larva of un-
encompasses diseases associated with the majors organs, and known species within a retinal granuloma of a child. In 1952,
Beaver and colleagues (4) reported on a similar series of chil-
dren who presented with high circulating eosinophilia, and
* Mailing address: Department of Environmental Health Sciences,
Mailman School of Public Health, Columbia University, 722 W. 168th
suffered from severe, long-term, multisystem disease. From
St., New York, NY 10032. Phone: (212) 781-6670. Fax: (212) 781-1830. this group of patients, they described most of the clinical fea-
E-mail: ddd1@columbia.edu. tures of VLM and, in histopathological sections of tissues ob-

265
266 DESPOMMIER
FIG. 1. Life cycle of T. canis and T. cati.
tained at biopsy, correctly classified the causative agents as the
larva of either T. canis or T. cati. Since that time, the juveniles
of these two parasite species have been detected in a variety of
lesions of the eye and throughout the body (31, 59) in patients
from all corners of the world. Today, the public health com-
munity at-large acknowledges that toxocariasis in all its clinical
forms constitutes a major health risk, especially among chil-
dren exhibiting pica.
LIFE CYCLE
Ingestion of the embryonated eggs of Toxocara (Fig. 1) ini-
tiates infection in both the definitive and aberrant host. Chil-
dren accidentally come into contact with them when they play
in sandboxes and on playgrounds contaminated with Toxocara
CLIN. MICROBIOL. REV.
eggs. This situation arises from indiscriminate defecation on
these sites by cats and dogs that harbor the adult worms. After
ingestion, the eggs hatch to release larvae (juveniles) that pen-
etrate the small intestine, enter the circulation, and then are
free to wander throughout the body, with the possibility of
invading all organs. There is controversy as to whether these
are second- or third-stage larvae. In the definitive host, the
juvenile parasites go on to complete the life cycle, which, in
many ways, resembles that of Ascaris lumbricoides, the ascarid
infecting humans. Transplacental infection is common in both
dogs and cats. In addition, the definitive host can become
infected by ingesting embryonated eggs carried by paratenic
hosts, such as earthworms, ants, and other soil-dwelling inver-
tebrates. Humans can develop aberrant infections by ingesting
these same animals.
VOL. 16, 2003 TOXOCARIASIS 267

FIG. 2. Portion of dog small intestine with adult T. canis. Male worms have a curled tail; females have a straight tail.

Worms develop to the adult stage (Fig. 2) in the small
intestine about 60 to 90 days after the larvae hatch. Mating
then ensues, giving rise to nonembryonated eggs (Fig. 3), which
become excreted with the fecal mass. Embryonation occurs in
the soil within a week or so after deposition (Fig. 4). Incuba-
tion periods of longer duration are due to lower temperatures.
In northern latitudes, eggs can lie dormant until the tempera-
ture rises in spring, triggering embryonation.
CLINICAL ASPECTS
retina, inducing granulomatous reactions (Fig. 7; Fig. 8) lead-
ing to impaired sight. In severe cases, the granuloma was re-
sponsible for the loss of sight. These pathological manifesta-
tions have, in the past, occasionally been misdiagnosed as
retinoblastoma (28, 62). Today, with reliable immunodiagnos-
tic reagents and methods, OLM is almost never mistaken for
other clinical entities. Epidemiologic evidence suggests that
ocular disease tends to occur in the absence of systemic in-
volvement and vice versa, which has led to the proposal that
the two manifestations of this infection be reclassified as OLM

The degree of host damage, and the concomitant elicitation

of signs and symptoms, varies with regard to which tissue has
been invaded; the liver (20), lungs (27), and central nervous
system (CNS) (32), including the eyes (49), appear to be most
sensitive. In addition, the number of migrating juveniles and
the age of the host are two additional factors important as to
whether a given individual’s condition will become elevated
above the clinical horizon. Pathological consequences are
largely dependent upon the death of the juveniles. Their death
heralds the onset of marked delayed-type and immediate-type
hypersensitivity responses. Inflammation manifests as eosino-
philic granulomas. The immediate hypersensitivity responses
to dying and dead larvae in the viscera, including the lungs,
liver (Fig. 5), and brain (Fig. 6), produce symptoms character-
istic of VLM.
In the eye, migrating third stage larvae can damage the FIG. 3. Unembryonated egg of T. canis (90 by 75 ␮m).
268 DESPOMMIER
FIG. 4. Embryonated egg of T. canis (90 by 75 ␮m).
and VLM (19). It is possible that there are strains of T. canis
with specific tropisms. Alternatively, VLM may reflect the con-
sequences of a host inflammatory response to repeated waves
of migrating larvae through the viscera, whereas OLM occurs
in individuals who have not been previously sensitized (24).
CLINICAL SIGNS AND SYMPTOMS
VLM
VLM is mainly a disease of young children (⬍5 years old)
(63). It presents with fever; enlargement and necrosis of the
liver (46); enlargement of the spleen; lower respiratory symp-
toms (particularly bronchospasm, resembling asthma); eo-
sinophilia sometimes approaching 70% (1); and hypergam-
maglobulinemia of immunoglobulin M (IgM), IgG, and IgE
classes. In the last of these instances, symptoms are more
pronounced, with increased levels of IgE/anti-IgE immune
complexes (39). Myocarditis (44), nephritis (53), and involve-
ment of the CNS have been described. CNS involvement can
lead to seizures, neuropsychiatric symptoms, or encephalopa-
thy.
There is an increasing appreciation that more subtle clinical
manifestations might also arise as a result of long-term expo-
sure to the migrating juveniles. So-called covert toxocariasis
FIG. 5. Juvenile T. canis from impression smear of brain tissue
from an experimentally infected mouse (390 by 30 ␮m).
CLIN. MICROBIOL. REV.
FIG. 6. Juvenile T. canis in liver of an experimentally infected
mouse.
ranges in spectrum from asymptomatic infection to larvae mi-
grating in specific target organs (38, 52, 57). In the lungs, larval
migrations may result in asthma (6, 56). T. canis has been
suggested as an environmental risk factor for asthma among
some inner-city populations (42). Similarly, in the brain, T.
canis has been implicated as one of the causes of so-called
idiopathic seizure disorders (9), as well as a cause of functional
intestinal disorders (25). One study implicated Toxocara as a
contributing factor in skin disorders of at least two varieties
(prurigo and urticaria) (22), while another presented indirect
evidence linking Toxocara infection with a form of eosinophilic
arthritis (45). In experimental infections in mice, learning be-
havior and memory are affected, and both appear to be dose
and time dependent (8). It is therefore reasonable to speculate
that similar phenomena are likely to be at work in long-term
infections in humans, as well.
Experimental infections in mice have also shed some light as
to the effects of VLM on the overall pattern of immune re-
sponses. Inbred C3H/HeN mice infected with T. canis juveniles
had altered patterns of cytokine responses that were presumed
FIG. 7. Portion of retina from a child suffering from OLM.
VOL. 16, 2003
to favor the survival of the parasite. Both IL-12 and tumor
necrosis factor alpha were significantly lowered in the infected
group compared to controls (26). IL-5 was associated with re-
sistance to Nippostrongylus braziliensis but had no effect against
the migrating larvae of T. canis (11).
Protective immunity is slow to develop, if it develops at all.
This is primarily due to factors most likely related to the ability
of the juvenile to periodically change its antigenic signal. Data
supporting this speculation will be given more attention below.
OLM
OLM usually occurs in children 5 to 10 years old and typi-
cally presents as unilateral vision impairment that is sometimes
accompanied by strabismus (12). The most serious conse-
quence of the infection is invasion of the retina, leading to
granuloma formation, which occurs typically peripherally or in
the posterior pole. These granulomas drag the retina and cre-
ate a distortion, heteropia, or detachment of the macula (54).
The degree of visual acuity impairment depends on the specific
area involved, and blindness is common. OLM can also cause
diffuse endophthalmitis or papillitis; secondary glaucoma can
follow. In at least one rare instance following long-term infec-
tion with Toxocara, a choroidal neovascular membrane formed
after presenting earlier as chorioretinitis (37).
DIAGNOSIS
Any pediatric patient with an unexplained febrile illness
and eosinophilia should be suspected of having VLM. Hepa-
tosplenomegaly and evidence of multisystem disease and his-
tory of pica make the diagnosis of VLM more likely. Similarly,
OLM should be suspected in any child with unilateral vision
loss and strabismus. Diagnostic tests for VLM are primarily
immunological (50). The precipitin test is subject to cross-
reactions with common antigens of the larvae and blood group
substance A. The enzyme-linked immunosorbent assay (ELISA),
which employs antigens secreted by the second-stage larva, has
sufficient specificity to be the best indirect test for diagnosing
this infection. Recombinant antigens have been produced from
the second-stage larvae of T. canis that promises to add even
greater specificity to an already-reliable test (approximately
92%) employing ELISA. The ELISA has a reasonably high
degree of sensitivity, as well (approximately 78%), at a titer
greater than 1:32 (51).
Other indicators of infection include hypergammaglobu-
linemia and an elevated isohemagglutinin titer. Thus, a con-
stellation of clinical disease described above, a history of
pica, eosinophilia, and positive serology, strongly point to the
diagnosis. Liver biopsy may reveal a granuloma surrounding a
larva, but a successful diagnosis using this approach is fortu-
itous at best and not recommended.
OLM is diagnosed primarily on the basis of clinical criteria
during an ophthalmologic examination. The immunodiagnostic
tests used for VLM are not as reliable for OLM. In one study,
only 45% of patients with clinically diagnosed OLM had titers
higher than 1:32 (51).
TOXOCARIASIS 269
FIG. 8. Portion of a retina from a child suffering from OLM. Note
eosinophilic granulomatous lesion due to reaction against a dead ju-
venile worm.
TREATMENT
Albendazole is the treatment of choice for toxocariasis. Pa-
tients receiving a 5-day treatment course of albendazole (10
mg/kg of body weight/day in two divided doses) improved rel-
ative to patients who received treatment with the older anthel-
minthic drug thiabendazole (55). A dose of 400 mg of al-
bendazole twice a day for 5 days is the currently recommended
therapy (21). Because the other commonly used benzimid-
azole, mebendazole, is poorly absorbed outside the gastroin-
testinal tract, this agent is a second-line treatment, although
some success has been reported in patients who ingest 1 g or
more for a 21-day course (21). Symptomatic treatment, includ-
ing administration of corticosteroids, has been helpful for sup-
pressing the intense allergic manifestations of the infection.
OLM is treated by surgery (vitrectomy), anthelminthic chemo-
therapy, and/or corticosteroids (12, 54).
EPIDEMIOLOGY
T. canis and T. cati, as alluded to, are unfortunately all too
common parasites of most domestic and peridomestic dogs
and cats, particularly young ones. Even those sold through re-
liable kennels and pet shops may harbor adult worms. This is
because, as stated in the section dealing with its life cycle,
puppies and kittens acquire Toxocara juveniles transplacentally
from the infected mother. Therefore, having a litter of puppies
in the home has been identified as a significant risk factor (35).
As expected, children with pica are at higher risk of ingesting
embryonated eggs from soil than those not exhibiting this be-
havior. Growing up in a poor neighborhood is associated with
a higher rate of seropositivity for toxocariasis than is being
raised in middle-income bracket housing.
Outdoor parks in urban and suburban settings are, in most
cases, highly contaminated with embryonated eggs of T. canis
and T. cati, since it is in this environment that people routinely
walk their pets (7, 17, 36, 41, 47). Burgeoning populations of
urban, semiwild cats and dogs represent a growing problem in
many tropical and subtropical regions and most likely contrib-
270 DESPOMMIER
ute in a major way to the maintenance of high levels of Toxo-
cara eggs in the environment (48). It should be added that an
increased incidence of rabies is also associated with urban and
suburban cohorts of abandoned dogs. Adult patients institu-
tionalized for mental retardation are also at high risk (23).
Preventing the indiscriminate deposition of dog and cat fe-
ces in play areas frequented by children appears to be the best
control strategy for limiting infection in adolescent populations
in large urban centers. In one study in Japan, placing clear
vinyl plastic covers over sandboxes at night seemed to effec-
tively discourage pets from using them as fecal dump zones. In
addition, during the summer months, temperatures within the
sand often rose above 45°C, a condition created by covering
them over at night. The authors speculated that this might
render the play area safe for use with respect to Toxocara (60).
Routine treatment of nonferal dogs and cats with ivermectin,
mebendazole, or other related benzimidazoles is another avail-
able measure which may prove effective in certain settings to
limit the spread of this resilient group of parasites. Some cities
have solved the dilemma associated with the use of sandboxes
by eliminating them from municipal parks and playgrounds.
Veterinarians continue to play an important role in combat-
ing the spread of Toxocara infection in situations where they
see large numbers of dogs and cats that are brought to them by
pet owners. Recommending regular stool examinations and
the frequent use of chemotherapeutic agents such as mebenda-
zole has proven effective in controlling infection.
MEDICAL ECOLOGY
The physical environment plays a crucial role in maintaining
and distributing the infective eggs of T. canis and T. cati,
although this subject remains underappreciated. Nonetheless,
developing effective control programs may require that this
aspect be known in much greater detail. Infective ascarid eggs
of all species can last for months to years outside the host
under optimal conditions, due solely to a resistant outer shell
composed of ascarosides. This acellular layer enables eggs to
withstand various harsh chemicals (e.g., high concentrations of
formalin and various inorganic acids), extreme temperature
changes, and various degrees of moisture. Future strategies for
reducing the number of infectious eggs in soil must find novel
ways of breaching the egg shell barrier that protects the im-
mature worm from its external environment.
Earthworms and small mammals play a role in dispersing
eggs from a point source. As Darwin pointed out in his essay
“On the Formation Of Vegetable Mould through the Action of
Worms with Observations on Their Habits” (10), earthworms
dump huge quantities of processed (i.e., partially digested) soil
onto the surface of the ground, bringing it from depths as great
as 2 ft. Viable eggs become incorporated into their fecal pellets
and are then subject to random distribution throughout the
local area by rain events and wind. Peridomestic mammals,
such as dogs, cats, squirrels, and chipmunks, play a role simi-
lar to that of earthworms, albeit less efficient, in the dispersal
of embryonated eggs (14). Birds that feed primarily on the
ground (e.g., pigeons, starlings, and sparrows) can serve as
paratenic hosts, carrying eggs from place to place on their feet
and beaks, and may be responsible for depositing eggs in places
far from the original source.
CLIN. MICROBIOL. REV.
Another mechanism for egg dispersal is drinking water. In
one study, public beaches adjacent to municipal drinking water
supplies just outside the city limits of Moscow, Russia, were
implicated as a source of contamination (5). The authors spec-
ulated that by allowing dogs and cats free access to these
recreational areas, this increased the likelihood that eggs of
Toxocara would enter the water column of the lake. Bathers
frequently and inadvertently drink water while wading and
swimming, allowing for the possibility of ingesting infective
eggs. In addition, this scenario also could lead to eggs contam-
inating tap water.
Some elements of soil, saprophytic fungi for example (Pae-
cilomyces lilacinus and Paecilomyces marquandii), have been
shown under controlled conditions to have larvicidal activity
against the juvenile worm within its egg’s shell (3). However
interesting these findings may be, however, it should be cau-
tioned that their application to the control of Toxocara eggs in
soil may prove intractably difficult, due to the high degree of
unpredictability regarding the behavior of species of any kind
that are introduced into new environments (15).
MOLECULAR ASPECTS
Nematodes in the genus Toxocara are distant relatives of the
free-living, soil (and laboratory)-dwelling roundworm Caeno-
rhabditis elegans. The latter is the only member of the phylum
Nematoda whose entire genomic DNA sequence has been de-
termined (see Nobel Prizes in Medicine and Physiology, 2002).
It contains 19,099 genes (7a) and is 97 Mb in size. The genome
of T. canis is approximately the same size as that of A. lumbri-
coides, which is about three times larger than that of C. elegans
(3 ⫻ 109 bp) (33). T. canis has 18 chromosomes, compared to
24 for Ascaris.
Investigations into the molecular biology of Toxocara have
mainly focused on the secreted proteins of the migrating juve-
nile stages. These proteins have proven useful in immunodi-
agnosis of VLM, and OLM. Speculation favors these same
proteins in aiding the worm regarding its capacity to evade
potentially protective immune responses. This idea derives
from the fact that the juvenile stage wanders about the tissues
for months to years without apparent interference from the
host. Presumably, the worms eventually die of old age. The fact
that many of the excretory-secretory proteins from the juvenile
stages constitute a family of at least six highly antigenic mucins
(13) associated with the cuticular surface reinforces this con-
cept (29). Secreted mucins temporarily coat the surface of the
worm (43) and are shed into the host periodically (2). It is
thought that this shedding behavior represents an attempt on
the part of the parasite to confuse the host’s immune system,
leaving behind it a trail of slime, not unlike that of a snail (34).
In this model, the worm periodically switches its secreted an-
tigenic identity, thus avoiding harm.
Many other novel coding regions for other expressed pro-
teins of the resting (dauer) larva have also been reported,
including those encoding four different C-type lectins, five
varieties of superoxide dismutase, phosphatidylethanolamine
binding protein, prohibin, olfactomedin, aquaporin, three unique
venom allergen/ASP homologues, and an asparaginyl endo-
peptidase. Functions for these gene products await further in-
vestigation. Another interesting group of proteins has been
VOL. 16, 2003
described from various stages of T. canis and may help explain
the mechanism employed by the parasite to migrate through
host tissues. Cathepsin-z-like protease genes have been cloned
and their cDNAs have been sequenced, identifying a cysteine
protease coding region expressed both in the adult and infec-
tive larva (16).
Molecular vaccines could prove useful in aiding in the con-
trol of infection in domestic dogs and cats. The search so far
has identified the myosins of Toxocara as potential candidates
(40). Several fragments of myosin proved highly antigenic
when used in combination in the ELISA for IgG antibodies
resulting from naturally occurring infections. In that study,
over 85% of the patients previously diagnosed with VLM were
positive. To date, however, no molecular vaccines have been
described.
Ascarid nematodes are well-known for their ability to induce
strong allergic responses, and laboratory investigators working
with Ascaris spp. have frequently had to cease research on
them solely for this reason. Allergens have been partially char-
acterized from Ascaris spp. and constitute a group of lipid-
binding polypeptides expressed as a large aggregate polypro-
tein referred to as nematode polyprotein allergens (64). The
parent nematode polyprotein allergen molecule is typically
secreted as a large polymer and then undergoes digestion at
regular intervals along its length, producing a series of poly-
peptides of ca. 15 kDa. Each of these smaller molecules is
structurally related to one of two subgroups, A or B. It is these
smaller subunits of the parent molecule that induce allergic
responses in a wide variety of mammalian hosts. A group of
polyprotein allergens have been identified from T. canis, des-
ignated TBA-1 (65), and are similar in structure to those al-
ready described in Ascaris.
CONCLUDING REMARKS
Toxocariasis remains a problem throughout the world, in-
ducing multisystem disease in young people. Overcrowding
and the inevitable cohabitation of our peridomestic environ-
ment by dogs and cats reinforces the transmission cycle in an
already-dismal situation in many regions. Public parks and
playgrounds have become zones of disease acquisition, not at
all fitting their original purpose. At the present time, control
programs aimed at reducing the number of domestic animals,
or, at the very least, limiting their access to areas frequented by
small children, appear to be effective in a few cases. Control of
the spread of dog feces, and to a lesser extent cat feces, also
helps limit exposure. Regular treatment of pets with benzimi-
dazoles helps reduce worm burdens and limits the number of
eggs deposited in soil. However, for the most part, these hearty
nematodes appear to be more than holding their own. What is
needed in terms of future control programs is the development
of radically new approaches, such as effective molecular or
DNA-based vaccines that offer the possibility of lifelong pro-
tection. Oral baits laced with vaccine would be ideal for dealing
with semiwild dog and cat populations, an approach similar to
ones that already exist for the large-scale control of rabies in
wild animal populations. To augment vaccine development,
rapid, highly sensitive and specific diagnostic tests employing
recombinant, antigenic peptides that can be executed in the
field are essential elements needed to formulate any future
TOXOCARIASIS 271
control program. Finally, more effective single-dose treatment
regimens with safer (over-the-counter?) drugs for pediatric
patients would help limit the time of illness, provided of course
that adequate medical infrastructure is already in place. Killing
Toxocara eggs in contaminated soils is seen by most epidemi-
ologists as a nearly impossible task, but if such a strategy could
be found and safely implemented, vast numbers of acres of
now potentially dangerous city landscape could be rendered
Toxocara-free.
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