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International Journal for Parasitology xxx (2013) xxx–xxx

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International Journal for Parasitology


journal homepage: www.elsevier.com/locate/ijpara

Invited Review

The epidemiology and public health importance of toxocariasis:


A zoonosis of global importance
Calum N.L. Macpherson ⇑
Windward Islands Research and Education Foundation, St George’s University, Schools of Medicine and Veterinary Medicine, P.O. Box 7, Grenada

a r t i c l e i n f o a b s t r a c t

Article history: Toxocariasis, caused by infection with larvae of Toxocara canis, and to a lesser extent by Toxocara cati and
Received 27 June 2013 other ascaridoid species, manifests in humans in a range of clinical syndromes. These include visceral and
Received in revised form 16 July 2013 ocular larva migrans, neurotoxocariasis and covert or common toxocariasis. Toxocara canis is one of the
Accepted 18 July 2013
most widespread public health and economically important zoonotic parasitic infections humans share
Available online xxxx
with dogs, cats and wild canids, particularly foxes. This neglected disease has been shown through sero-
prevalence studies to be especially prevalent among children from socio-economically disadvantaged
Keywords:
populations both in the tropics and sub-tropics and in industrialised nations. Human infection occurs
Toxocariasis
Toxocara canis
by the accidental ingestion of embryonated eggs or larvae from a range of wild and domestic paratenic
Toxocara cati hosts. Most infections remain asymptomatic. Clinically overt infections may go undiagnosed, as diagnos-
Visceral larva migrans tic tests are expensive and can require serological, molecular and/or imaging tests, which may not be
Ocular larva migrans affordable or available. Treatment in humans varies according to symptoms and location of the larvae.
Neurotoxocariasis Anthelmintics, including albendazole, thiabendazole and mebendazole may be given together with
Covert toxocariasis anti-inflammatory corticosteroids. The development of molecular tools should lead to new and improved
Epidemiology strategies for the treatment, diagnosis and control of toxocariasis and the role of other ascaridoid species
in the epidemiology of Toxocara spp. Molecular technologies may also help to reveal the public health
importance of T. canis, providing new evidence to support the implementation of national control initia-
tives which have yet to be developed for Toxocara spp. A number of countries have implemented repro-
ductive control programs in owned and stray dogs to reduce the number of young dogs in the population.
These programs would positively impact upon T. canis transmission since the parasite is most fecund and
prevalent in puppies. Other control measures for T. canis include the regular and frequent anthelmintic
treatment of dogs and cats, starting at an early age, education and enforcement of laws for the disposal
of canine faeces, dog legislation and personal hygiene. The existence of wild definitive and paratenic
hosts complicates the control of T. canis. Increasing human and dog populations, population movements
and climate change will all serve to increase the importance of this zoonosis. This review examines the
transmission, diagnosis and clinical syndromes of toxocariasis, its public health importance, epidemiol-
ogy, control and current research needs.
Ó 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

1. Introduction where dog treatment and population control is limited. Toxocara


canis infection is also an important cause of morbidity in wealthier,
Toxocariasis manifests itself in humans as a range of syn- industrialised nations, especially in children and socio-economi-
dromes. They are primarily caused by infection with larvae of the cally disadvantaged populations (Torgerson and Budke, 2006;
ascardoid nematode Toxocara canis (Werner 1782) and to a lesser Hotez, 2008; Hotez et al., 2013; Paul et al., 2010; Torgerson and
extent by Toxocara cati (Schrank 1788) and related species. Macpherson, 2011). Other species of Toxocara contribute to the
Toxocara canis is one of the most widespread public health and eco- global burden of toxocariasis, but their importance is less well
nomically important zoonoses humans share with dogs, cats and a understood or defined. This includes T. cati, which has a similar
range of wild definitive hosts, particularly foxes (Glickman and global distribution to T. canis. The importance of T. cati infection
Schantz, 1981; Schantz, 1989). Toxocariasis is particularly preva- to toxocariasis cannot be ignored (Fisher, 2003; Smith and Noor-
lent in the tropics and sub-tropics, in less industrialised nations din, 2006). Other species include Toxocara malaysiensis (Gibbons

⇑ Tel.: +1 473 444 3997; fax: +1 473 444 3041.


E-mail address: cmacpherson@sgu.edu

0020-7519/$36.00 Ó 2013 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ijpara.2013.07.004

Please cite this article in press as: Macpherson, C.N.L. The epidemiology and public health importance of toxocariasis: A zoonosis of global importance. Int.
J. Parasitol. (2013), http://dx.doi.org/10.1016/j.ijpara.2013.07.004
2 C.N.L. Macpherson / International Journal for Parasitology xxx (2013) xxx–xxx

et al., 2001) which occurs in cats in Malaysia and China (Li et al., 7 years (Beaver et al., 1952; Salem and Schantz, 1992; Taira
2006; Gasser, 2013; Mohd Zain et al., 2013), Toxocara vitulorum et al., 2004; Lloyd, 2006; Choi et al., 2012; Strube et al., 2013).
of cattle, buffalo and other ruminants (Rast et al., 2013; Woodbury L3s may also be found in a range of invertebrate hosts including
et al., 2012), Baylisascaris procyonis from raccoons in the USA, Eur- earthworms. Dogs which ingest paratenic hosts can develop adult
ope and Japan (Chavez et al., 2012), other Baylisascaris spp. (Gavin worms but there is no tracheal migration (Overgaauw and van
et al., 2005; Bauer, 2013) and Ascaris suum of pigs (Pinelli et al., Knapen, 2013). L3s ingested by omnivorous or carnivorous parate-
2011). Many other ascaridoids including Toxocara pteropodis (bats) nic hosts can migrate to the tissues of a new paratenic host.
and members of the genera Lagochilascaris (opossums), Porrocae- Ingestion of paratenic hosts plays an important role in T. cati
cum sp. (birds of prey) and Ophidascaris, Polydelphis, Travassoascaris infection for adult cats. Transmission of the parasite from infected
(snakes), have zoonotic potential but their importance is likely to rodents may be facilitated by behavioral changes induced in ro-
be very limited due, inter alia, to the lack of human exposure to dents infected with T. canis, which may impair survival and fitness
these parasites (Lloyd and Morgan, 2011). Toxascaris leonina, which relative to the intensity of infection (Cox and Holland, 2001). Post
occurs in dogs, cats and various wild canids and felids throughout mortem examination of rats (Rattus norvegicus) which had been
the world, is also considered to have limited zoonotic potential experimentally infected with T. canis revealed L3s in muscle, eye,
(Morgan, 2013). liver, kidney, brain and lung (Santos et al., 2009). The same situa-
tion may apply to T. cati.

2. Veterinary aspects
2.3. Survival and distribution of eggs of Toxocara spp.

2.1. Definitive hosts


Once expelled, T. canis eggs require 2–6 weeks at temperatures
of 10–30 °C before the eggs are fully embryonated and contain
Toxocara canis is transmitted predominantly among canids
infective L3s. Increasing temperature accelerates the development
(dogs, foxes, wolves and coyotes) and T. cati by felids through a
as well as the degradation of T. canis eggs while temperatures
wide variety of routes. These include vertical transmission, trans-
colder than 10 °C or warmer (>37 °C) are inimical to the matura-
placental (not cats) and/or trans-mammary (lactogenic) as well
tion or survival of eggs (Gamboa, 2005; Azam et al., 2012). Embry-
as horizontal transmission through the ingestion of embryonated
onation is therefore seasonal in temperate climates but year-round
eggs from the environment or ingestion of larvae via vertebrate
in tropical areas. Toxocara canis eggs do not embryonate in dark-
and/or invertebrate paratenic hosts (Overgaauw and van Knapen,
ness (Feney-Rodriguez et al., 1988), and infections have yet to be
2000). It is the ability of T. canis to survive for many years in the
reported from the Arctic (Jenkins et al., 2013).
tissues of a substantial number of vertebrate species, as well as
Eggs are very resistant and survive well over most winters in tem-
to develop to sexual maturity in the intestinal tract of its definitive
perate climates, surviving for 6–12 months. Some eggs may be able
canid hosts, especially dogs, that has facilitated its global
to survive in moist, cool conditions for 2–4 years or longer (Azam
distribution.
et al., 2012). Soil type, pH and percentage of vegetation cover impact
Pups are infected in utero by reactivated, somatic larvae of
upon contamination and viability with clay soils negatively impact-
T. canis from the mother from day 42 of gestation (Lloyd et al.,
ing on egg viability (Trejo et al., 2012). In sandy soils in Perth, Austra-
1983). This efficient trans-placental infection route results in egg
lia, eggs disappeared over 6 months, despite favorable conditions
excretion 16 days after parturition (Lloyd, 1993). More limited,
(Dunsmore et al., 1984). In Poland, 1 year after deposition in sandy
lactogenic transmission continues to occur for 5 weeks. Kittens
soils a few eggs were recovered with 60–90% viability and >94% were
are infected by vertical, lactogenic transmission of T. cati and com-
found in the top centimeter (Mizgajska-Wiktor and Uga, 2006). The
mence fecal egg excretion 47 days after birth (Overgaauw and
substrate, light, temperature, humidity, pH and vegetation cover
van Knapen, 2013). Once infected, pups shed millions of eggs per
are important factors for egg availability, development and survival;
day into the environment, depending on the intensity of T. canis
the proportion of deposited eggs that survive and/or are available to
infection and host immune status (Glickman and Schantz, 1981).
hosts is unknown. Eggs can be physically dispersed by movements of
Dogs and other canids also become infected by ingesting embry-
definitive hosts, rainfall, birds, beetles, earthworms, slugs and flies.
onated eggs from the environment. Toxocara canis undergoes a tra-
The role of water-borne transmission of eggs of Toxocara spp. is un-
cheal migration and has a prepatent period of 4–5 weeks. In cats,
known (Beer et al., 1999) and requires further investigation.
the prepatent period is 8 weeks. Toxocara canis infections can be
Studies have concentrated on assessing egg contamination of
acquired at any age, although adult worm infections are generally
playgrounds, parks, sandpits, and backyards/gardens and have shown
less common in dogs less than 6 months of age, and fecal egg counts
contamination to be prevalent (Manini et al., 2012; reviewed by
are much lower than in pups (Claerebout et al., 2009). Paradoxically,
Lloyd and Morgan, 2011; Manini et al., 2012). Although such areas
low levels of egg exposure are more successful for the establish-
seem to provide opportunities for infection, the role of different
ment of patent infections in juvenile/adult dogs than large numbers
domestic and wild definitive hosts in the contamination of these
of eggs. This finding may have long term implications for control
areas is unclear. One issue has been the inability to unequivocally
programs (Overgaauw and van Knapen, 2013).
identify eggs to species using a microscope; even though the eggs
Toxocara spp. do not usually cause pathological changes in
of T. canis are usually larger than those of T. cati (74.8  86.0 lm ver-
definitive host species, although high infection intensities in trans-
sus 62.3  72.7 lm), it is difficult and time consuming to distinguish
placentally infected puppies can result in a pot-bellied appearance,
Toxocara eggs at a species level. Fortunately, PCR utilising the second
failure to thrive and, in some instances, death (Lloyd and Morgan,
internal transcribed spacer (ITS-2) of rDNA allows specific identifica-
2011; Overgaauw and van Knapen, 2013).
tion (Jacobs et al., 1997). A recent study (Fahrion et al., 2011), in
which eggs shed by dogs were identified by PCR, showed that 24
2.2. Paratenic hosts (68.5%) were T. canis and 11 (31.5%) were T. cati. Coprophagy was
suggested as a possible explanation for this finding. The development
Mammals (rodents, lagomorphs, birds and domestic livestock) of molecular techniques to identify and differentiate Toxocara spp.
are susceptible to infection by embryonated eggs containing infec- eggs from, for example, playgrounds may now be carried out using
tive L3s (Araujo, 1972), which migrate to the tissues, where they a high throughput, quantitative real-time PCR (qPCR) assay, which
undergo no further development and remain infective for up to should help to evaluate environmental contamination (Durant

Please cite this article in press as: Macpherson, C.N.L. The epidemiology and public health importance of toxocariasis: A zoonosis of global importance. Int.
J. Parasitol. (2013), http://dx.doi.org/10.1016/j.ijpara.2013.07.004
C.N.L. Macpherson / International Journal for Parasitology xxx (2013) xxx–xxx 3

et al., 2012). Molecular techniques can also be useful in identifying conditions, will provide ideal transmission opportunities, particu-
Toxocara spp. in paratenic hosts (Marucci et al., 2013). larly if coupled with poor hygiene and geophagia or pica. Such risk
factors are widely appreciated and documented for many parts of
2.4. Diagnosis in definitive hosts the world (Dunsmore et al., 1984; Overgaauw, 1997; Won et al.,
2008; Lee et al., 2010). A recent study in the USA, where there
Ante mortem diagnosis of adult Toxocara spp. infections are are more than 77 million dogs and 93 million cats (Esch and Peter-
routinely conducted by faecal flotation techniques using solutions sen, 2013), assessed the risk factors associated with poverty, geog-
with a high specific gravity (1.2–1.3) and the identification of the raphy and demographics, and confirmed that both individual-level
characteristic eggs. Such techniques are sensitive for diagnosis in risk factors and geographic factors affected the transmission of tox-
young animals shedding large numbers of eggs, but lack sensitivity ocariasis (Congdon and Lloyd, 2011). Children, due to their behav-
in older animals which shed eggs intermittently and/or in low ior and their close contact with dogs, eating soil, putting objects in
numbers. their mouths, eating earthworms and/or their poor hygiene, are
most at risk of toxocariasis.
2.5. Treatment of companion animals Less understood is the relative contribution of infective eggs
and their spatial distribution in the environment by different sym-
Dogs and cats can be effectively treated by administration of patric definitive host species (Luty, 2001; Mizgajska et al., 2001;
any of a wide variety of commercially available anthelmintics Morgan et al., 2013). A recent case study in the city of Bristol in
including milbemycin, nitroscanate, piperazine and pyrantel, all the UK (Morgan et al., 2013) found that although pups less than
of which kill or paralyse adult worms. Emodepside, ivermectin, 12 weeks of age dominated total egg excretion, their lack of access
moxidectin, elamectin and fenbendazole are all effective in treat- to public areas and the removal of their faeces resulted in foxes
ing both adult worms and larvae (Ramsey, 2011). Fenbendazole, being the primary source of eggs. In many cities in Europe, public
moxidectin and the avermectins can be used to prevent vertical environments including parks and playgrounds pose the main area
transmission of Toxocara in pregnant and lactating females. How- for risk of human exposure to eggs (Deplazes et al., 2011).
ever, there are no drugs that are effective against arrested, somatic Embryonated Toxocara spp. eggs have been recovered from the
larvae. Puppies should be treated at 2, 4, 6 and 8 weeks of age, fol- hair of dogs, which demonstrates that direct human-dog contact
lowed by a monthly regimen until the age of 6 months and then could also be a route of infection for humans (Wolfe and Wright,
followed by annual, biannual or tri-annual treatment, depending 2003; Roddie et al., 2008; Aydenizoz-Ozkayhan et al., 2008; Amaral
on the individual animal’s exposure to risk factors. The recommen- et al., 2010; El-Tras et al., 2011). One study (Tavassoli et al., 2012)
dation for cats is that kittens are treated at 3, 5, 7 and 9 weeks of implicated contact with sheepdog pups as a potential source of di-
age (www.cdc.gov/healthypets/diseases/toxocariasis.htm). rect transmission of embryonated eggs. Other authorities in the
field rarely, if ever, find embryonated eggs on the hair of dogs
3. Epidemiology and believe that this route of transmission is rare (Nagy et al.,
2011). A recent study showed that embryonation is slower on
3.1. Human infection and risk factors the hair of dogs but can occur and the authors suggest that trans-
mission by direct contact, even for well-groomed dogs, should not
Humans become infected with L3s of Toxocara spp. through the be ruled out (Keegan and Holland, 2013).
accidental ingestion of embryonated eggs shed by definitive hosts The importance of human infection via ingestion of paratenic
and through the consumption of L3s in raw or undercooked parate- hosts has yet to be determined. Meat-borne transmission through
nic hosts. the consumption of raw or undercooked viscera or meat has been
Many biological factors inherent to the parasite’s life cycle suc- incriminated (Salem and Schantz, 1992; Yoshikawa et al., 2008;
cessfully facilitate the perpetuation of Toxocara spp. These include Antolova et al., 2013; Strube et al., 2013). The use of molecular
the numerous advantages of vertical transmission, ensuring the techniques and the rapid identification of larvae in paratenic hosts
early onset of egg production in young definitive hosts, the fecun- will aid in identifying the range and epidemiological importance of
dity of the adult female, the prolonged survival of eggs in the envi- such hosts (Gasser, 2013; Marucci et al., 2013). Some well-docu-
ronment and the diversity of its domestic and wild definitive and mented instances of ingestion of paratenic hosts have provided
paratenic host species. These factors, coupled with the ubiquitous valuable information on the incubation period of visceral larva mi-
distribution of definitive hosts, have resulted in Toxocara spp. being grans (VLM) (Cianferoni et al., 2006), and infection rates in small
one of the world’s most widespread and prevalent parasitic rodents may provide shared indicators for Toxocara spp. (Reperant
zoonoses. et al., 2009).
The global prevalence of Toxocara spp. in humans is influenced
by a wide and complex number of variables which are linked at a 3.1.1. Risk of infection with other ascaridoids
population level to environmental, geographic, cultural and socio- In the USA, the risk of infection with B. procyonis relates mainly
economic factors and at the individual level by the heterogeneity to the contact with embryonated eggs passed by raccoons, which
of susceptibility to infection influenced by immunity, co-infection, are sometimes kept as pets, or contact with ‘raccoon latrines’ in
genetics, age, gender, nutrition and behavior of the (human and wooded areas.
definitive) hosts (Macpherson, 2013; Viney and Graham, 2013). Toxocara vitulorum eggs are likely to occur in soil and water in
These factors, together with the increasing human population, glo- tropical environments as cattle and water buffalo calves are fre-
bal migration and rural:urban migration with more than 50% of the quently infected (e.g., Rast et al., 2013).
global population now residing in urban areas and the ever closer
and denser human-definitive host interactions suggest that, for the 4. Clinical manifestations in humans
majority of the world’s population, Toxocara/toxocariasis is an ever
changing public health problem. The clinical syndromes of human toxocariasis are caused by the
Transmission and risk factors will vary considerably in different migration of L3s of Toxocara spp. via the bloodstream to the inter-
parts of the world. Poverty, a lack of education and problems with nal organs including muscle, liver, brain and eye. Such migration
uncontrolled and untreated definitive host populations will lead to may be asymptomatic or can lead to a wide variety of clinical
heavily contaminated environments which, under warm climatic symptoms, depending on the organs invaded, the duration of

Please cite this article in press as: Macpherson, C.N.L. The epidemiology and public health importance of toxocariasis: A zoonosis of global importance. Int.
J. Parasitol. (2013), http://dx.doi.org/10.1016/j.ijpara.2013.07.004
4 C.N.L. Macpherson / International Journal for Parasitology xxx (2013) xxx–xxx

migration, the intensity of infection, and age- and immune-medi- sessed; it is likely to occur where pig slurry is used as fertiliser or
ated host responses. The long-term survival of T. canis larvae has in countries where there are free-roaming pigs and poor hygiene.
been attributed to two molecular strategies evolved by the para-
site. The larvae release significant quantities of ‘excretory–secre- 4.2. Ocular larva migrans (OLM)/ocular toxocariasis (OT)
tory’ products including lectins, mucins and enzymes that
interact with and modulate host immunity, and secondarily the OLM is considered to be rare compared with VLM, is thought to
larvae produce a specialised mucin-rich surface coat, loosely at- result from low intensity of infection with T. canis and, similar to
tached to the parasite epicuticle. This ‘coat’ permits the parasite VLM, is most frequently reported in children (Despommier,
to escape, when host antibodies and cells adhere, resulting in an 2003). The clinical consequences of OLM elicit emotive reactions
inflammatory reaction around a newly vacated focus (Maizels, from those involved, which increases the awareness of the public
2013). Toxocariasis is rarely fatal but the inflammatory responses health importance of toxocariasis. Cases of OLM are usually unioc-
to the migrating larvae have been associated with generalised lym- ular and are caused by the migration of L3s in the eye and resultant
phadenopathy, granulomatous hepatitis, endomyocarditis, immune reactions. Visual impairment occurs over days or weeks,
endophthalmitis, asthma and leukocytosis including high eosino- and the level of impairment is dependent on the location of the lar-
philia (>30% or >2  109/L) is often seen (Despommier, 2003; Men- vae, the eosinophilia and later the fibrotic granulomatous response
donça et al., 2012; Fan et al., 2013). Many patients have IgG/IgE as granulomatas create a distortion, heterotopia and/or detach-
hyper-gamma-globulinaemia; cutaneous manifestations and, ment of the macula, which can result in blindness (CDC, 2011). Vi-
rarely, meningoencephalitis can occur. Infections are usually self- sual impairment depends on the specific area involved (CDC, 2011;
limiting and larvae become encapsulated in the musculature and Woodhall et al., 2012). OLM can also cause diffuse endophthalmitis
liver, and symptoms subside. The syndromes of infection with Tox- or papillitis. Long-term infection with Toxocara spp. may lead to
ocara spp. are thus related to the migration of larvae and the im- choroidal neovascular membrane formation following chorioreti-
mune response to them (Despommier, 2003; Gavignet et al., nitis (Despommier, 2003).
2008; Lopez Mde et al., 2010; Salvador et al., 2010; Damasceno Baylisascaris procyonis has also been implicated in subacute uni-
and Damasceno, 2012; Caldera et al., 2013; Fan et al., 2013; Mai- lateral neuroretinitis (Goldberg et al., 1993).
zels, 2013). Originally, two classifications of toxocariasis were de- Co-infection of T. canis with other parasites that may impair vi-
fined: VLM or visceral toxocariasis (VT) and ocular larva migrans sion is not uncommon. One study using multivariate analysis to
(OLM) or ocular toxocariasis (OT) (Fan et al., 2013). Our under- control for demographic and risk factors (Jones et al., 2008)
standing of the variability in the clinical signs and symptoms of showed that persons infected with Toxocara spp. were also more
toxocariasis has evolved over the last 30 years. With the introduc- likely to be infected with Toxoplasma gondii (Odds Ratio
tion of improved diagnostic tests and seroepidemiological screen- (OR) = 1.93, 95% Confidence Limits (CL) = 1.61–2.31), and similarly,
ing surveys there is a greater understanding of the molecular persons infected with T. gondii were more likely to be infected with
basis of immune recognition and evasion. Therefore, additional Toxocara spp. (OR = 1.91, 95% CL = 1.59 2.28). Other parasites that
major syndromes have been described, including common or cov- may impact on vision include Plasmodium falciparum, Taenia soli-
ert toxocariasis (CT) (Taylor et al., 1988; Nathwani et al., 1992) and um, Echinococcus granulosus and Onchocerca volvulus (Benazzou
neurotoxocariasis (NT) (Finsterer and Auer, 2007; Smith et al., et al., 2010; Ziaei et al., 2011; Ejere et al., 2012; Postels et al., 2013).
2009; Salvador et al., 2010).
Other parasites are involved in the spectrum of toxocariasis, 4.3. Covert or common toxocariasis (CT)
including T. cati, which are known to cause both VLM and OLM,
but the importance of these species awaits clarification (Fisher, As with most other parasitic infections, the vast majority may
2003; Lee et al., 2010). In addition, B. procyonis infections may be go undiagnosed due to the asymptomatic, mild or non-specific
severe due to the aggressive migrations of the L3s, which increase clinical nature of their features. The same appears to be the case
in size as they migrate slowly through the brain and spinal chord, for many Toxocara spp. infections. Cross-sectional community-
and encapsulate slowly (Gavin et al., 2005). The L3s of T. vitulorum based seroepidemiological surveys often detect individuals who
are likely only to have a short-lived migration, but infection could test positive for anti-Toxocara antibodies, but who are asymptom-
induce cross-reactive-antibody and eosinophilia and, in repeated atic or only have non-specific or mild symptoms (Taylor et al.,
infections, disease. Clinical cases of VLM suspected to be caused 1988). These findings prompted the terms ‘covert’ or ‘common’
by A. suum have been described (Izumikawa et al., 2011). Molecu- toxocariasis (Taylor et al., 1987, 1988; Magnaval et al., 1994; Paw-
lar diagnosis may provide the best opportunity to evaluate the lowski, 2001). Magnaval et al. (1994) characterised CT in children
importance of T. cati and other ascaridoids in human toxocariasis by fever, anorexia, headache, abdominal pain, nausea, vomiting,
(Chen et al., 2012; Gasser, 2013). lethargy, sleep and behavioral disorders, pulmonary symptoms,
limb pains, cervical lymphadenitis and hepatomegaly, and com-
mon toxocariasis in adults by weakness, pruritus, rash, pulmonary
4.1. Visceral larva migrans (VLM)/visceral toxocariasis (VT) symptoms and/or abdominal pain.

VLM is most commonly diagnosed in children less than 8 years 4.4. Neurotoxocariasis (NT)
of age and is associated with high intensity or repeated larval
infection by T. canis which can persist for weeks or months (Kayes, NT arises from the invasion of L3s of T. canis to the brain and
1997). Classical signs include fever, hepatosplenomegaly, abdomi- spinal cord (Ruttinger and Hadidi, 1991; Finsterer and Auer,
nal pain, vomiting, diarrhoea, respiratory signs (cough/wheeze), 2007; Caldera et al., 2013), causing meningitis, encephalitis, mye-
asthma, anorexia, weight loss, fatigue, neurological manifestations, litis, cerebral vasculitis and seizures.
pallor and, occasionally, urticaria (Despommier, 2003).
A serological survey of sera from VLM and OLM suspected pa- 4.5. Toxocara canis associated with other clinical manifestations
tients in the Netherlands using IgG-ELISA suggested that human
exposure to A. suum may occur in those countries where pig slur- Toxocara canis infection has also been associated with asthma
ry/sludge is used as a fertiliser on farms and gardens (Pinelli et al., and may be linked to the rise in asthma observed in inner city chil-
2011). The importance of A. suum as a zoonosis needs to be as- dren in cities in the USA (Sharghi et al., 2001; Busse and Mitchell,

Please cite this article in press as: Macpherson, C.N.L. The epidemiology and public health importance of toxocariasis: A zoonosis of global importance. Int.
J. Parasitol. (2013), http://dx.doi.org/10.1016/j.ijpara.2013.07.004
C.N.L. Macpherson / International Journal for Parasitology xxx (2013) xxx–xxx 5

2007; Walsh and Haseeb, 2012) and other countries (Cobzaru et al.,
2012; Kanobana et al., 2013). There is also growing evidence that
implicates Toxocara spp. infection in epilepsy (Nicoletti et al.,
2007; Quattrocchi et al., 2012). One small cohort of children with
a diagnosis of OLM also had a strong association with seizures
(Good et al., 2004). The aetiological connection between Toxocara
spp. infection and epilepsy requires additional studies (Holland
and Hamilton, 2013) particularly in areas with other sympatrically
occurring infections that also cause epilepsy. In a large study in five
countries in sub-Saharan Africa (where epilepsy is common), epi-
lepsy in children (<18 years) was associated with difficulties in
feeding or breathing after birth, crying, abnormal antenatal periods
and head injury, whilst in adults (P18 years), risk factors included
malaria or fever, exposure to T. canis, T. gondii, O. volvulus, T. solium
or hypertension (Ngugi et al., 2013).
Children seropositive for T. canis have been linked in a few stud-
ies to impaired cognitive development (Stewart et al., 2005; Jarosz
et al., 2010; Holland and Hamilton, 2013). Walsh and Haseeb
(2012) reported statistically lower cognitive scores on both the
Wechsler Intelligence Scale for Children-Revised (WISC-R) and
the Wide Range Achievement Test-Revised (WRAT-R) in the USA
compared with seronegative children. This finding was indepen- Fig. 1. Ultrasound of the liver showing multiple hypoechoic areas which show L3
dent of socio-economic status, ethnicity, gender, rural residence, Toxocara spp. larvae (arrowed). Repeat ultrasound images over time can reveal their
cytomegalovirus infection and lead levels in blood. These results migration.

require additional longitudinal data to confirm an aetiological con-


nection between toxocariasis and cognitive function. pathogenesis of toxocariasis in paratenic hosts, including hu-
mans, has been reviewed by Fan et al. (2013).
Imaging techniques can be useful in aiding diagnosis in patients
with VLM and OLM. In VLM patients multiple, ill-defined, oval he-
5. Diagnosis in humans patic lesions measuring 1.0–1.5 cm in diameter can be detected on
computerised tomography, magnetic resonance imaging (MRI) or
Direct microscopic diagnosis of Toxocara spp. larval infection as oval hypoechoic lesions upon sonographic examination
in humans is difficult and rarely attempted. PCR-based sequenc- (Fig. 1). The lesions differ from metastatic nodules is as much as
ing of ITS-1 and ITS-2 sequences of nuclear rDNA enables the they have fuzzy margins, are uniform in size and have a non-spher-
identification of T. canis, T. cati and other ascaridoids which ical shape (Lim, 2008).
can occur in human tissue biopsies (Jacobs et al., 1997; Zhu The diagnosis of NT is difficult but should include an examina-
et al., 2001; Li et al., 2007, 2008; Norhaida et al., 2008). tion of serum and CSF for anti-T. canis antibodies and eosinophils
Diagnosis of VLM and CT is problematic, particularly in trop- in the CSF. Computerised tomography and MRI scans reveal cortical
ical countries where polyparasitism is common. Diagnosis is or sub-cortical granulomata as diffuse lesions or circumscribed hy-
based on clinical presentation, history and serological antibody per-intense areas on T2-weighted images with resolution following
tests. Immunodiagnosis based on the use of ELISA employing treatment (Ruttinger and Hadidi, 1991; Zachariah et al., 1994; Fin-
Toxocara excretory/excretory (TES) antigens (de Savigny et al., sterer and Auer, 2007). In different regions of the world, care should
1979; Maizels et al., 1984) as well as commercially produced be exercised in making a differential diagnosis of other parasites
test kits (ELISA NOVUM, ELISA PU and Toxocara CHEK) are avail- that can infect the CNS including protozoans (Acanthamoeba spp.,
able and are widely used for diagnosis and in seroepidemiologi- Naegleria spp., Entamoeba histolytica, P. falciparum, T. gondii, Trypan-
cal studies. Differences in the quality of antigens used and lack osoma spp.), trematodes (Paragonimus spp., Schistosoma spp.), ces-
of standardisation of results coupled to differences in human todes (Echinococcus spp., T. solium, Spirometra spp.) and nematodes
populations (polypararasitism), cross-reactivity, diet and expo- (Angiostrongylus spp., Gnathostoma spp.) (Finsterer and Auer, 2012).
sure to other pathogens makes it challenging to compare survey Similarly the diagnosis of OLM is problematic as specific anti-T.
outcomes (Smith and Noordin, 2006). Positive serum samples canis serum antibody titres may be low or absent (Despommier,
must be confirmed by western blotting (WB) (Fillaux and Mag- 2003). The detection of specific anti-T. canis antibody in vitreous
naval, 2013). WB, based on the use of fractionated, native, TES and/or aqueous humor helps to confirm a diagnosis (Yokoi et al.,
antigens of T. canis larvae has been shown to increase specificity, 2003). A wide range of imaging techniques can assist with the
with reactivity to bands of low molecular weight (24–32 kDa) diagnosis and treatment of OLM. Optical coherence tomography,
shown previously to be specific for T. canis (Mohamad et al., fluorescein angiography, computerised tomography and ocular
2009; Smith et al., 2009). Polypararasitism with gastrointestinal ultrasound using transducers (>10 MHz) can be used to infer the
helminths can reduce specificity to 650%, and an ELISA for the location of the L3s (Fig. 2) and in providing a differential diagnosis
detection of IgG subclasses including specific IgG2 serum anti- of other ocular diseases including retinoblastoma (Cella et al.,
bodies to glycan of TES antigens, has sensitivities of IgG, 50%; 2004; Brennan et al., 2012; Arevalo et al., 2013).
IgG1, 60%; IgG2, 98%; IgG3, 78%; IgG4, 64% and specificities of
IgG, 73%; IgG1, 76%; IgG2, 71%; IgG3, 81%; IgG4, 71% (Watt- 6. Treatment in humans
hanakulpanich et al., 2008). An ELISA for the specific detection
of anti-Toxocara IgG4 serum antibodies achieves increased spec- The chemotherapy of toxocariasis in people varies according to
ificity (Noordin et al., 2005). IgE- and IgM-ELISAs may be used the severity and location of symptoms. Patients with VLM and
post-treatment to show a decline in antibody titre but are not symptomatic NT or CT are administered anthelmintics such as
highly specific or sensitive (Smith et al., 2009). The immuno- albendazole, thiabendazole and mebendazole, and may also be gi-

Please cite this article in press as: Macpherson, C.N.L. The epidemiology and public health importance of toxocariasis: A zoonosis of global importance. Int.
J. Parasitol. (2013), http://dx.doi.org/10.1016/j.ijpara.2013.07.004
6 C.N.L. Macpherson / International Journal for Parasitology xxx (2013) xxx–xxx

ven anti-inflammatory corticosteroids to relieve symptoms caused should be addressed (Hotez, 2008; Hotez et al., 2013). The benefits
by severe allergic responses (Despommier, 2003; Magnaval and of control have been calculated (Torgerson and Budke, 2006) and
Glickman, 2006). Cases of OLM are usually treated with corticoste- suggest that there would be significant human health and animal
roids and may also require delicate ophthalmologic procedures production (T. vitulorum) gains if implemented.
(Despommier, 2003; Magnaval and Glickman, 2006).
8. Control
7. Public health importance
The wide range of domestic and wild definitive and paratenic
Toxocariasis is not a notifiable disease but is of major impor- host species and modes of transmission of Toxocara spp. means
tance as a public health problem. Epidemiological studies demon- that the control of T. canis is complicated. To date no specific na-
strate that T. canis is one of the most prevalent and ubiquitous tional control programs against this zoonosis have ever been
zoonotic parasite species occurring from the sub-Arctic to the tro- attempted.
pics (Rubinsky-Elefant et al., 2011; Pinelli et al., 2011; Messier
et al., 2012; Fan et al., 2013; Jenkins et al., 2013). Serological sur- 8.1. Control in pet dogs and cats
veys, conducted mostly in children, suggest that prevalences in
industrialised countries vary between 0.7% in New Zealand, 1.6% Of the four main reservoirs of parasite infection, viz, intestinal
in Japan, 2.4% in Denmark, 7.5% in Australia, 14% in the USA and infections in definitive hosts, eggs in the environment, larvae in
15% in Poland (Jarosz et al., 2010; Fan et al., 2013). In contrast, paratenic hosts and somatic larvae in the host (Schnieder et al.,
higher seroprevalences have been reported in less industrialised, 2011), the easiest populations in which to control Toxocara spp.
tropical countries including in Africa: 30% in Nigeria, 45% in Swazi- infection are the pet dogs and cats. There are excellent treatment
land and 93% in La Reunion (Africa), 81% in Nepal, 63.2% in Indone- options for dogs and cats. Compliance with treatment regimens
sia and 58% in Malaysia (Asia) and 36% in Brazil and 37% in Peru will reduce environmental contamination from this potential
(South America) (Smith and Noordin, 2006; Liao et al., 2010; Rol- source. The role of education, as with all other Toxocara spp. related
dan et al., 2010; Schoenardie et al., 2013). control activities, is pivotal to the reduction of human infection
A recent web-based survey involving eye specialists throughout and for compliance with reducing infection for others. Veterinari-
the USA was used to collect epidemiological, demographic and ans play an important role in educating pet owners and the general
clinical information on patients with OLM (CDC, 2011). The survey public on zoonoses. The multi-billion dollar small animal health
found 68 patients with OLM diagnosed between September 2009 companies which historically played a major role in education pro-
and September 2010. The median patient age was 8.5 years (range: grams should be encouraged to revitalise this role. Such companies
1–60 years), and 25 patients (57%) were from the south. The most together with others involved in the pet industry such as some of
common symptom was vision loss, reported by 25 (83%) patients; the pharmaceutical companies, trusts and foundations could also
of these, 17 (68%) had suffered permanent vision loss. The results play a more active role in the control of Toxocara spp. in the pet
of this first national web-based survey demonstrated the useful- population. Australia in particular has seen a reduction in the prev-
ness of using such an approach to obtain national data which alence and importance of T. canis infections in dogs and cats
might be applicable in other countries. throughout the country (Palmer et al., 2008, 2010).
The high seroprevalence (13.9%) of Toxocara infection reported Reduction in the number of pet dogs contaminating the envi-
by Won et al. (2008) and the estimated 1.3–2.8 million people in- ronment, particularly in cities where recreational areas are shared
fected in the USA (Hotez, 2008) indicate that, even in the richest by many people and pets, has been achieved to some extent in
country in the world, toxocariasis poses an important burden on North America, Europe and Australia. This reduction was enforced
society and at the individual level. This zoonosis together with through the introduction, over 30 years ago, of the ‘‘scoop laws’’
those caused by other helminths such as strongyloidiasis, ascaria- (Beck, 1979). The regulations required dog owners to collect faeces
sis and cysticercosis are regarded as the neglected diseases dispro- deposited by their dog when in public areas. This has allowed peo-
portionately affecting impoverished human populations. Their ple and dogs to share the public areas in cities in ways that benefit
existence continues to entrap people in generational poverty and them both. Studies of interventions on dog fouling are lacking and
would be useful to fill gaps in our approaches to this method of
control (Atenstaedt and Jones, 2011). Restricting dogs from play-
grounds, squares and gardens would also be useful. Such methods
have not always proved effective, with some surveys failing to find
lower egg densities inside such restricted areas than outside them
(Kirchheimer and Jacobs, 2008).

8.2. Control of ingestion of eggs and larvae

Good hygiene and the proper cooking of food can prevent the
accidental ingestion of eggs from the environment and larvae from
paratenic hosts. Unfortunately such hygiene measures are almost
impossible to implement, especially with children and with few
options to destroy Toxocara spp. eggs in the environment, this
route of infection persists. The increasing global proclivity for eat-
ing meat, liver and vegetables raw, undercooked, smoked, pickled
or dried facilitates transmission of a number of parasitic zoonoses
(Macpherson, 2005). Changes in human behaviour to reduce para-
site transmission are difficult due in part to the long prepatent
Fig. 2. Ultrasound of the eye showing a Toxocara spp. L3 in the choroid. Visual
periods and lack of correlation between disease and infection.
impairment depends on the location of the larvae and the host’s reaction to its There have been a few exceptions to this, including the remarkable
presence. reduction in vertical transmission of T. gondii infection in T. gondii

Please cite this article in press as: Macpherson, C.N.L. The epidemiology and public health importance of toxocariasis: A zoonosis of global importance. Int.
J. Parasitol. (2013), http://dx.doi.org/10.1016/j.ijpara.2013.07.004
C.N.L. Macpherson / International Journal for Parasitology xxx (2013) xxx–xxx 7

IgG seronegative women. The women were counseled on the risks and who are most at risk of infection. The geographic distribution
of T. gondii during pregnancy and its prevention (Breugelmans of T. canis is expanding as a consequence of human and animal
et al., 2004). Since toxocariasis is predominantly an infection of movements, together with the effects of global warming which
young children, education, especially targeted at new parents, has seen, for example, the northern migration of red foxes (Jenkins
would be an important part of a control program. et al., 2013). The rapid growth of the human and dog populations
and their increasing densities in urban areas means that, without
8.3. Control in wild and domestic animals specific control initiatives, the importance of toxocariasis is likely
to grow. There is a need for a greater understanding of the molec-
A wide range of wild animal definitive hosts for Toxocara spp. ular biology, biochemistry, genetics, epidemiology and ecology of
exists. In addition, large populations of untreated owned, stray of Toxocara spp. (Jex et al., 2008; Gasser, 2013). Future research activ-
feral dogs and cats in most developing and also many developed ities that focus on the development of molecular tools for specific
countries provide a continuous reservoir of infection, environmen- identification and genetic analysis should lead to new and im-
tal egg contamination and potential sources of infection to humans proved strategies for the treatment, diagnosis and control of toxo-
and other paratenic hosts. cariasis, and the role of other ascaridoids in the epidemiology of
The role of wild definitive hosts in human infection is uncertain Toxocara spp. These molecular technologies should help to reveal
although it has been demonstrated that they could be an important the true extent and therefore the public health importance of
source of environmental contamination in the UK (Morgan et al., T. canis; information which would provide the evidence and
2013). It is interesting to note that despite the wide variety of wild- justification for the introduction of national control initiatives.
life involved in rabies, the vast majority (>99%) of human rabies Development of a vaccine and/or effective ovicidal agent, which
cases throughout the world are transmitted by dogs (Knobel have long been goals of the scientific community, would greatly
et al., 2005). Thus our close environmental association with dogs improve the chances of controlling this most challenging zoonotic
may be more important for the majority of human infections either infection.
directly or indirectly, especially in areas around the world where
the majority of dogs are never treated for Toxocara spp. (Macpher-
Acknowledgements
son, 2013).
National control programs to control or reduce stray and feral
The author thanks Kareem Coomansingh for his help in the
dog populations are mainly restricted to a few developed coun-
preparation of the manuscript. Images were kindly provided by
tries. National control programs have been developed in some
Dr Carmen Cretu.
areas of the world against two important parasitic zoonoses, Leish-
mania donovani and Echinococcus spp., and rabies. As all of these
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