- Scoping Review
- Open Access
Toxocariasis: a silent threat with a progressive public health impact
Infectious Diseases of Poverty volume 7, Article number: 59 (2018)
Toxocariasis is a neglected parasitic zoonosis that afflicts millions of the pediatric and adolescent populations worldwide, especially in impoverished communities. This disease is caused by infection with the larvae of Toxocara canis and T. cati, the most ubiquitous intestinal nematode parasite in dogs and cats, respectively. In this article, recent advances in the epidemiology, clinical presentation, diagnosis and pharmacotherapies that have been used in the treatment of toxocariasis are reviewed.
Over the past two decades, we have come far in our understanding of the biology and epidemiology of toxocariasis. However, lack of laboratory infrastructure in some countries, lack of uniform case definitions and limited surveillance infrastructure are some of the challenges that hindered the estimation of global disease burden. Toxocariasis encompasses four clinical forms: visceral, ocular, covert and neural. Incorrect or misdiagnosis of any of these disabling conditions can result in severe health consequences and considerable medical care spending. Fortunately, multiple diagnostic modalities are available, which if effectively used together with the administration of appropriate pharmacologic therapies, can minimize any unnecessary patient morbidity.
Although progress has been made in the management of toxocariasis patients, there remains much work to be done. Implementation of new technologies and better understanding of the pathogenesis of toxocariasis can identify new diagnostic biomarkers, which may help in increasing diagnostic accuracy. Also, further clinical research breakthroughs are needed to develop better ways to effectively control and prevent this serious disease.
Please see Additional file 1 for translations of the abstract into five official working languages of the United Nations.
Toxocariasis is a prevalent zoonosis with a significant socioeconomic impact, particularly on impoverished communities around the world. It is caused by nematode parasites of the genus Toxocara, of which dog roundworm (Toxocara canis; Werner, 1782) and to a lesser extent, cat roundworm (Toxocara cati; Schrank, 1788) cause severe disease in humans . In the natural definitive hosts – dogs and cats – these parasitic roundworms colonize the intestinal tract and excrete Toxocara eggs with faeces into the environment . The roundworm Toxocara is a perfect example of a parasite moving from wild canids to their domestic counterparts and to humans [3, 4]. Dogs or cats, especially in low-income and rural regions, play important roles in the transmission of Toxocara spp. through environmental contamination, which spreads the infection to humans . Humans are considered as an accidental or aberrant host, therefore, Toxocara larvae cannot develop into adult worms inside the human body [2, 4,5,6].
Humans acquire infection via ingestion of embryonated/larvated eggs present in the soil or contaminated food, or by ingestion of encapsulated Toxocara larvae in improperly cooked tissues of paratenic hosts, such as cows, sheep and chickens [2, 4,5,6,7,8,9]. Following ingestion of embryonated eggs, larvae hatch in the small intestine, penetrate the intestinal wall, gain access to circulation, migrate throughout the body, leading to a marked inflammatory response and various clinical symptoms, depending on the organ involved [1, 7, 9, 10]. Although infection in humans can be asymptomatic, Toxocara parasite has a notorious tendency to cause extra-intestinal pathologies [7, 8]. Indeed, toxocariasis includes four clinical forms, which can lead to serious health consequences [7, 9, 10]. Due to the non-specific symptoms of this disease, its medical and public health impact might be underestimated [11, 12]. Thus, although toxocariasis can be diagnosed tentatively based on patient’s symptoms, laboratory diagnosis is required to improve the accuracy of diagnosis [13, 14].
The first human infection was reported in 1950 , and since then it has been reported in almost 100 countries [7, 8]. Over the last few years, toxocariasis has gained an increasing international attention and was listed among the five most neglected parasitic infections according to the US Centers for Disease Control and Prevention (CDC) [3, 4, 12, 16]. The newly sequenced genome of T. canis along with transcriptomic analysis has allowed an in-depth characterization of this organism’s molecular characteristics . Also, knowledge of the parasite’s genetic diversity has been improved and new diagnostic markers have been discovered [9, 18,19,20]. These achievements reflect the increased awareness of toxocariasis and recognition of its continued public health impact. In this article, we provide an updated review of data on toxocariasis, with a focus on the epidemiological, diagnostic and therapeutic aspects of the disease.
The causative agents
Toxocara spp. are classified under the super-family Ascaridoidea [21,22,23], and include four valid species, namely Toxocara canis, T. cati, T. malaysiensis, and T. vitulorum [21, 22]. Phylogenetic analyses based on the ITS-2 and 28S sequences of the nuclear ribosomal DNA (rDNA), showed that Toxocara spp. form a distinct clade, in relation to their definitive hosts, which is separate from Ascaris spp. . Moreover, phylogenetic analysis of T. vitulorum, T. canis, T. cati, T. malaysiensis, Ascaris suum, Anisakis simplex, and Onchocerca volvulus based on amino acid sequences of the entire mitochondrial (mt) genome, revealed that Toxocara spp. are more closely related to A. suum than to A. simplex and O. volvulus; and that T. malaysiensis is more closely related to T. cati than to T. canis . T. vitulorum has been shown, based on partial mt genome sequence, to be more closely related to T. malaysiensis than to T. canis and T. cati . T. vitulorum, T. canis and T. cati, have been reported worldwide, however T. malaysiensis was only reported in China, Malaysia, and Vietnam [26,27,29].
Neither nucleotide variation of ITS-1 and ITS-2 in T. canis from different hosts, including dogs, foxes, and turkey, was observed; nor was there significant intra-specific variability (with none exceeding 0.4%) between specimens from Japan, England, Australia, Sri Lanka and Poland . In regard to T. cati, no variation in IT-S sequences within one host was detected, but rDNA microheterogeneity within specimens originating from different geographical locations was reported [28, 31]. Polymorphism analysis of T. cati from different geographical locations has shown that differences between Malaysian and Australian strains are 2.9% for ITS-1 and 0.3% for ITS-2 , and the ITS sequences of T. cati from Poland and Australia differed slightly (0.3–0.4%). However, the differences were much more significant for T. cati from Malaysia (2% in ITS-1 and 0.6% in ITS-2) . Interestingly, intra-specific variation in the partial mt sequences within T. malaysiensis was only 0.0–0.9% . Microheterogeneity of T. cati appears to depend on geographical latitude and it remains to be determined if this heterogeneity plays a role in the response to therapy and potential immune protection.
Burden of disease by geographic region
Toxocariasis has been reported in many countries worldwide, with most cases occurring in France, Austria, India, Japan, Korea, China, USA, and Brazil (Additional file 2: Table S1). A total of 823 ocular toxocariasis (OT) cases have been reported, including 282 cases in Europe, 317 cases in Asia, five cases in Australia, 218 cases in Latin America, and one documented case in Tunisia (Additional file 2: Table S1). The highest number of OT cases has been reported in Japan and Korea, France, Brazil and the USA. Only 99 neurotoxocariasis (NT) cases have been recorded worldwide, of which 46 cases occurred in Europe, 32 cases in Asia, 20 cases in the Americas, and only one case in South Africa. The largest numbers of NT cases have been reported in Lebanon (17 cases), Sakha Republic in Russian Federation (20 cases) and the USA (8 cases). A total of 247 visceral larva migrans (VLM) cases have been reported worldwide, with the largest numbers reported in Spain (61 cases; 63% of European 97 cases), India (14; 29% of Asian 49 cases), Argentina and Brazil (16; 16% and 76; 75% of cases in South American 101 cases). Eating raw cows’ liver is the main route for acquiring toxocariasis in Japan and Korea, whereas stray dogs and cats spreading eggs in environment are the main source of infection for people in India and other South East Asian countries. In developed countries, including the USA, France and Austria, patients are infected via contact with soil contaminated with Toxocara eggs, for example in playgrounds, sandpits and gardens.
Several seroepidemiological features of human toxocariasis are shown in Additional file 2: Table S2. Some risk factors of toxocariasis, such as gender, age, household’s design and construction material, and the presence of domestic animals, have been identified. However, current knowledge of important epidemiological features of toxocariasis, such as the global burden of the disease, disability-adjusted life years, and populations at risk, are still to be determined. Since many infections are asymptomatic and thus can be misdiagnosed, the global burden of toxocariasis is likely to have been underestimated . The global prevalence of human toxocariasis can be influenced by a number of potentially confounding variables that can contribute to differences in the reported toxocariasis prevalence [3, 33]. To improve consistency of the results obtained from prevalence surveys, future studies should consider using standardized diagnostic criteria and should be performed by trained clinicians who can apply a standardized set of toxocariasis case definitions.
Sources of contamination, route of transmission and reservoirs
Dogs and cats are the most important animal hosts for toxocariasis, especially in developing countries where most cats and dogs have access to public parks and playgrounds, serving as the main source of soil contamination, and posing a huge risk of human exposure to infective eggs (Additional file 2: Table S3). However, in some developed countries, e.g. the UK, urban and rural foxes are the primary source of eggs and infections to humans. Although dogs under six weeks of age excrete more eggs than dogs older than 1 year of age, their lack of access to public areas and the removal of their faeces resulted in ranking foxes as the biggest contributor to eggs (Additional file 2: Table S3). Toxocara prevalence is usually higher in cubs, but the prevalence can be high even in adult foxes .
Environmental contamination with Toxocara eggs is common in most countries, mainly in urban public parks, with positive rates of soil samples obtained from parks ranging from 17.4 to 60.3% in Brazil, 14.4 to 20.6% in the USA, 13.0 to 87.1% in Europe, 30.3 to 54.5% in Africa and 6.6 to 63.3% in Asia [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,44]. In some temperate countries, such as Germany and England, although a few cases of human toxocariasis have been reported [39, 44], environmental contamination with Toxocara eggs has been found to be high. The presence of embryonated Toxocara eggs attached to the hair of dogs, cats and foxes, represent another route by which humans can acquire infection from dogs or cats [45,46,47,48]. Although the total numbers of eggs detected on animal hair varies, puppies and stray animals had higher egg numbers in their coat than others [47, 48].
Evidence suggests that only a handful of animal species might function as paratenic hosts, within which no further development occurs. Paratenic hosts can disseminate infective stages of the parasite and/or aid these stages in avoiding unfavourable conditions during absence of the natural host . These paratenic hosts (animals) include the common shrew (Sorex araneus), Eurasian harvest mouse (Sorex minutes), Eurasian water shrew (Neomys fodiens), Mediterranean water shrew (Neomy sanomalus), lesser white-toothed shrew (Crocidura suaveolens), common dormouse (Muscardinus avellanarius), house mouse (Mus musculus), harvest mouse (Micromys minutus), striped field mouse (Apodemus agrarius), yellow-necked mouse (Apodemus flavicollis), wood mouse (Apodemus silvaticus), Ural field mouse (Apodemus microps), brown rat (Rattus norvegicus), bank vole (Clethrionomys glareolus), common pine vole (Pitymys subterraneus), and common vole (Microtus arvalis) . To date, a few studies have identified the prevalence of infection in these animals. In Slovak Republic, 10 non-commensal rodents from suburban locations were confirmed to have higher seropositivity, with the highest seropositivity being found in Apodemus agrarius (21%) . In an urban area of Switzerland, four species of non-commensal rodents had a 13.2% Toxocara seroprevalence .
Clinical presentation and associated disease syndromes
Toxocara infections are often associated with considerable variability in clinical presentation. Because T. canis larvae migrate to various body organs, such as the liver, heart, lungs, kidneys, brain, muscle and eyes, a broad range of clinical symptoms can be developed (Table 1) . In general, human toxocariasis is categorized into four clinical forms: VLM, OT, Covert or Common Toxocariasis (CT), and NT, depending on which organs are affected. The severity of disease is dependent on the parasite burden, the duration of larval migration, and age- and immune-mediated responses of the affected individuals [7, 9, 15, 33, 52].
VLM is the consequence of a systemic migration of Toxocara larvae through the tissue of human viscera. It occurs in children aged 2–7 years and results from high intensity or repeated infections by T. canis larvae. Infections in adult individuals have been reported in East Asia (e.g. South Korea and Japan), through ingestion of raw beef, lamb, chicken, or ostrich liver [53, 54]. The liver is the most commonly affected organ in VLM, and is associated with the formation of granulomatous lesions and hepatitis [55,56,57]. Less frequently, larvae may invade other organs, such as heart, lungs, kidneys and muscle, resulting in myocarditis, myalgia with eosinophilic polymyositis, arthritis and nephritis [58,59,60,61,62]. Dermatological changes, such as rash, pruritus, eczema, panniculitis, urticaria and vasculitis, have also been detected in some VLM cases .
Common pathologies observed in OT include posterior pole and peripheral retinochoroiditis with granuloma, scleritis, chronic endophthalmitis and panuveitis [7, 8]. Other abnormalities include vitreous opacities, yellowish-white intraretinal lesions in the optic disc with papilledema, live intraocular worm, papillitis, and a tractional retinal detachment, and diffuse unilateral subacute neuroretinitis. The level of visual impairment is dependent on the location of the larvae, the extent of eosinophilia and the fibrotic granulomatous response involved in the induction of distortion, heterotopia and/or detachment of the macula [64, 65].
In this form of toxocariasis, patients exhibit non-specific symptoms, such as abdominal pain, fever, anorexia, nausea, headache, vomiting, pharyngitis, pneumonia, cough, wheeze and cervical lymphadenitis, which can be accompanied with eosinophilia and positive Toxocara serology [4, 7].
NT is caused by invasion of Toxocara larvae to the brain and spinal cord, leading to cerebral lesions and neurological damage, predominantly located in the cerebral and cerebellar white matter, with occlusion of cerebral blood vessels (Table 1). The associated clinical symptoms include myelitis, encephalitis, mental confusion and/or meningitis. NT can be influenced by many factors, such as host genetics, the number of ingested ova and prior exposure [8, 66].
Misdiagnosis due to the nonspecific clinical presentation, may lead to prolonged morbidity and development of health complications. A high index of suspicion is therefore necessary to establish an early diagnosis and start appropriate treatment. Also, diagnosis of toxocariasis should rely on clinical, radiographic and laboratory evidence of the disease [13, 14]. In general, diagnosis of toxocariasis is based on history (e.g. individuals consumed raw or undercooked meat [7, 13]), clinical examination, direct microscopic examination of tissues (eosinophilic granuloma surrounding live or degenerated roundworm larvae), and blood analysis (leukocytosis and eosinophilia). A range of serological and molecular methods are also available (Table 2) and can be used to confirm the diagnosis.
Demonstrating the presence of Toxocara larvae in tissue biopsy, cerebrospinal fluid (CSF) or ocular fluids using direct microscopy remains the “gold standard” for the diagnosis of toxocariasis . However, this method is invasive, insensitive and time-consuming . Also, it can be difficult to distinguish between larvae of Toxocara and those of other ascarids, especially when the larvae are degenerated or when only parts of the larva can be recovered from tissues [9, 67].
Serological tests are used to support the clinical diagnosis of toxocariasis. Immunoelectrophoresis (IEP) has shown an excellent specificity, but its low sensitivity has limited its utility in clinical settings . Enzyme-linked immunosorbent assay (ELISA), based on excretory and secretory antigens of the third stage larvae (L3) of T. canis, is commonly used for diagnosis of human toxocariasis . A limitation of T. canis antigen testing is the significant cross-reactivity with other helminths, such as Ascaris lumbricoides, particularly in endemic areas [13, 14]. Also, the level of serum IgG can remain elevated for years, which precludes the discrimination between active and persistent infections, especially in patients with high infection intensity . Despite the potential false-positive reaction, these assays have clinical significance that should not be ignored. Although a positive test does not imply causation, a negative test can help to rule out toxocariasis. Serological tests for detecting T. canis antibodies may have less value in the evaluation of disease progression in the CNS because results of ELISA for T. canis antibodies can be positive in serum, but negative in the CSF of NT patients . Recombinant Toxocara antigens have been shown to improve the sensitivity and specificity of serological testing . A combination of diagnostic tests is generally used in seroepidemiological studies (e.g. ELISA is initially used as a fast and relatively inexpensive method, followed by Western blotting to improve the sensitivity and specificity) . Specific detection of total anti-Toxocara IgG antibodies and subclasses (e.g. IgG1, IgG2, IgG3 and IgG4) are also possible . Various parasite antigens, semi-purified, and crude antigens from T. canis larvae (TCLA), have been used to detect IgM, IgG or IgG4 using ELISA tests with satisfactory sensitivity and specificity [70, 71]. In addition, IgE- and IgM- based ELISAs can be used to evaluate the effect of treatment by monitoring the antibody titer post-treatment .
Molecular techniques have high analytical specificity, and shorter turnaround times than other diagnostics. PCR-based assays using a variety of genetic markers (e.g. ITS-1 and ITS-2 regions of rDNA) have been developed and have enabled the identification and phylogenetic analysis of T. canis, T. cati and other ascarids [72,73,74]. PCR-based testing has been utilized to identify T. canis larvae collected from human biopsies in ocular larva migrans (OT) and from CSF in NT [9, 75, 76]. PCR-based assays, including quantitative real-time PCR (qPCR), PCR-RFLP and PCR-RAPD have been used for accurate identification and diagnosis of Toxocara eggs isolated from faeces or soil (Table 2) . The development of loop-mediated isothermal amplification (LAMP) of nucleic acid has provided a rapid and cheap approach for assessing the contamination of soil with Toxocara eggs [77, 78]. Molecular methods with improved performance characteristics have the potential to advance the diagnosis of toxocariasis.
A variety of imaging modalities have been used for the detection of lesions caused by infection with Toxocara larvae, such as magnetic resonance imaging (MRI), computed tomography (CT), ultrasound, fundus photography, fluorescein angiography, ophthalmic ultrasound and optical coherence tomography (OCT) [79,80,81,82,83,84,85].
Imaging findings in OT
Fundus photography, fluorescein angiography, ophthalmic ultrasound and OCT can assist in the detection of eye granulomas and in the differentiation of OT from similar ocular conditions, such as retinoblastoma. Routine fundus photography can reveal the location and effects of focal granulomas in eyes with clear media, and in monitoring changes related to disease progression or in response to treatment . Wide-field imaging may aid in the management of patients with peripheral visual involvement. Angiography is used to document the effects of focal and diffuse inflammation on retinal vasculature. Ultrasound biomicroscopy (UBM) can be valuable in detecting the location and extent of vitreous bands and/or traction affecting the anterior segment including the ciliary body, pars plana and peripheral retina [85, 87]. High-penetration optical coherence tomography (HP-OCT) is useful for examining intraretinal lesions, noninvasively. HP-OCT provides clear and continuous scanning from the retina to the choroid , compared with conventional OCT.
Imaging findings in NT
In NT patients, MRI and CT can be used to detect lesions caused by migrating Toxocara larvae in neural tissues. The diagnostic features of NT on MRI include single or multiple, subcortical, cortical or white matter hyperintense lesions on T2-weighted and FLAIR images, and hypointense on T1-weighted images [68, 88]. However, these imaging features are only suggestive, not specific to NT. Therefore, serologic studies of blood and CSF, eosinophilia in the serum or CSF, and clinical and radiological improvement after anthelmintic treatment are necessary to establish the diagnosis.
Imaging findings in VLM
VLM lesions appeared on the ultrasound (US) scan as multiple ill-defined, non-spherical hypoechoic lesions . Contrast-enhanced computed tomography of the liver revealed VLM as fluid-attenuating conglomerate lesions [89, 90]. On MRI scan hepatic lesions caused by Toxocara L3 larvae migration appeared hypointense on T1-weighted (T1W) images and hyperintense on T2-weighted (T2W) images . VLM lesions exhibited reduced signal intensity on superparamagnetic iron oxide-enhanced T2-weighted MRI images . Based on the radiographic features, fine needle aspiration cytology through the hepatic lesion can be used to characterize the lesion’s content. The presence of mixed inflammatory cells predominantly eosinophils along with Charcot-Leydon crystals in a necrotic background can suggest VLM .
Despite growing efforts to develop a range of diagnostic methods for detection of human toxocariasis, accurate diagnosis remains a challenge. To improve the management of toxocariasis, we must distinguish this disease from similar conditions. Hence, NT should be differentiated from neural larva migrans (NLM) caused by the nematode Baylisascaris procyonis. Also, in clinical cases of meningeal, cerebral, or spinal cord disease with hypereosinophilia of unknown origin and cerebral granulomatous, differential diagnosis of NT should not be overlooked. Differential diagnosis of OT should consider excluding proliferative and neoplastic pathologies (retinoblastoma), and other coexisting parasitic zoonoses (e.g. angiostrongyliasis, toxoplasmosis, cysticercosis, gnathostomiasis, thelaziasis, trichinosis), bacterial infections (e.g. Lyme borreliosis) or viral infections (e.g. cytomegaly). Future research is required to develop better diagnostic methods for detecting the causative parasite, so as to best direct appropriate resources.
The mainstay of toxocariasis therapies includes anthelmintics (e.g. albendazole [ABZ], mebendazole [MBZ] and thiabendazole) and anti-inflammatory drugs . These drugs are used to achieve a clinical resolution or to reduce the damage caused by larval migration to various organs, particularly the brain and eyes [92,93,94]. ABZ at 400 mg twice a day for five days is the first choice for treatment of VLM patients [1, 13], but MBZ has been indicated as the second therapeutic option for VLM, due to its lower absorption rate outside the gastrointestinal tract compared to ABZ [11, 52]. Other anthelmintic drugs such as diethylcarbamazine (DEC) and ivermectin have been explored to treat VLM, but ivermectin has uncertain efficacy [11, 52]. In cases with cardiac involvement, regimens involving 800 mg/day for two weeks, 50 mg/(kg·day) for 28 days, 600 mg/day for 14 days, or 1000 mg/day for four weeks have been used . Corticosteroids have been used in cases of pulmonary toxocariasis and toxocariasis-associated cardiac diseases [95, 96].
Despite the lack of an optimal treatment for OT, some patients can be treated successfully with anthelmintic drugs or surgically (Table 3), depending on the severity of intraocular inflammation and retinal comorbidities [97–99]. Current standard treatment for OT with active intraocular inflammation includes systemic corticosteroid in combination with ABZ . Periocular or systemic steroids can limit the inflammation, fibrosis, or cicatrization in eyes with active vitritis. Surgery is advised for treatment of structural complications [101–103]. Cryotherapy can be used to treat granulomas, with the administration of steroids following the procedure .
Combinations of corticosteroids with DEC, MBZ, orthiabendazole have been used for the treatment of NT . Although NT may resolve from treatment using ABZ, MBZ, thiabendazole and DEC, ABZ used for at least three weeks, which often needed to be repeated is the preferable choice because it can penetrate the CSF with a minimal toxicity [105, 106]. Corticosteroids can be used for reducing inflammation and controlling hypersensitivity reactions caused by degenerated larvae following the treatment of NT . Encouraging results have been reported recently where a long-term administration of ABZ (10–15 mg/[kg·day]) for four weeks or eight weeks resulted in recovery rate of 78.9 and 81.3%, respectively [11, 108]. Monitoring of side effects post-treatment is recommended especially in patients who might be at a high risk of treatment complications, including people with allergies, pregnant or lactating women, children weighing less than 15 kg, older patients, and those concurrently taking other medicines.
The rapid increase in the number of dogs and cats, especially uncontrolled feral and stray populations and their close proximity to humans, has increased the risk of human infection with Toxocara . The lack of an effective method to kill Toxocara eggs makes it impossible to eradicate this parasite from the environment . Therefore, strategies for preventing infection should include measures to prevent initial contamination of the environment . Various measures can be implemented to interrupt the transmission of Toxocara eggs from animals to humans. These involve de-worming household pets frequently and from a young age. Particular attention and prophylactic anthelmintics should be given to puppies, kittens, or pregnant bitches, which are most likely to transmit the disease. Owners should also safely collect and hygienically dispose of pet faeces, before the eggs become infective. The World Health Organization (WHO) published useful recommendations for disposal of faeces of infected dogs and cats in order to break the dog-soil-human transmission cycle of toxocariasis .
Prevention of human infections can also be achieved by washing hands after touching or playing with pets, or following exposure to potentially contaminated sites. Parents should educate children about basic personal hygienic precautions, such as the need for frequent hand washing and the dangers of eating dirt. Children’s play areas should be regularly cleaned and pets kept out of outdoor play areas (e.g. sandboxes) by covering or fencing them off. In addition to measures mentioned above, other interventions have been tested in animal models and may provide alternatives for the prevention of toxocariasis. For example, probiotics (Enterococcus faecalis CECT 7121 and Saccharomyces boulardii) and DNA-based vaccines (pcDNA3/CpG and pcDNA3/IL-12) have been tested in animal models. E. faecalis CECT 7121 and S. boulardii significantly reduced the burden of larvae in the liver, lungs and brain significantly [112,113,114]. DNA vaccination with pcDNA3/CpG and pcDNA3/IL-12 reduced eosinophilia and airway hyper-responsiveness, respectively . Solid lipid nanoparticles of ABZ has been suggested as a promising formulation for the treatment of T. canis infection in mice .
Despite extraordinary progress during the past two decades, toxocariasis continues to pose a significant challenge to the public health. This challenge includes a need for continued surveillance to better define the burden of toxocariasis, which requires timely, efficient diagnosis; a need to develop and deploy new drugs and vaccines to combat clinical disease; and a need for ongoing research not only in developing appropriately-targeted prevention strategies, but also in understanding the infection biology of Toxocara spp. and human responses to them. Future directions in basic and applied research likely will include: (i) molecular characterization of Toxocara isolates from clinical and environmental sources to identify novel biomarkers for diagnosis and epidemiological surveys; (ii) better understanding of humoral, innate, and cell-mediated immunity to Toxocara infection for development of prophylactic or therapeutic vaccines; and (iii) establishment of a database that includes behavioural, climatic, demographic, ecological, and socioeconomic factors, crucial data for prediction of infection risk, and for improving the effectiveness of public health interventions by focusing on populations with the highest probability of benefit. Successful realization of these research priorities can advance the understanding of toxocariasis and promote the development of new interventions to prevent Toxocara infection and minimize its impact on society.
Covert or common toxocariasis
Fluid-attenuated inversion recovery
Magnetic resonance imaging
Neural larva migrans
Optical coherence tomography
Ocular larva migrans
Crude antigens from T. canis larvae
Visceral larva migrans
World Health Organization
Despommier D. Toxocariasis: clinical aspects, epidemiology, medical ecology, and molecular aspects. Clin Microbiol Rev. 2003;16:265–72.
Overgaauw PA, van Knapen F. Veterinary and public health aspects of Toxocara spp. Vet Parasitol. 2013;193:398–403.
Holland CV. Knowledge gaps in the epidemiology of Toxocara: the enigma remains. Parasitology. 2017;144:81–94.
Macpherson CN. The epidemiology and public health importance of toxocariasis: a zoonosis of global importance. Int J Parasitol. 2013;43:999–1008.
Zibaei M. Helminth infections and cardiovascular diseases: Toxocara species is contributing to the disease. Curr Cardiol Rev. 2017;13:56–62.
Strube C, Heuer L, Janecek E. Toxocara spp. infections in paratenic hosts. Vet Parasitol. 2013;193:375–89.
Fan CK, Holland CV, Loxton K, Barghouth U. Cerebral toxocariasis: silent progression to neurodegenerative disorders? Clin Micobiol Rev. 2015;28:663–86.
Fan CK, Liao CW, Cheng YC. Factors affecting disease manifestation of toxocariasis in humans: genetics and environment. Vet Parasitol. 2013;193:342–52.
Chen J, Zhou DH, Nisbet AJ, Xu MJ, Huang SY, Li MW, Wang CR, Zhu XQ. Advances in molecular identification, taxonomy, genetic variation and diagnosis of Toxocara spp. Infect Genet Evol. 2012;12:1344–8.
Nicoletti A. Toxocariasis. Handb Clin Neurol. 2013;114:217–28.
Chen J, Xu MJ, Zhou DH, Song HQ, Wang CR, Zhu XQ. Canine and feline parasitic zoonoses in China. Parasit Vectors. 2012;5:152.
Rubinsky-Elefant G, Hirata CE, Yamamoto JH, Ferreira MU. Human toxocariasis: diagnosis, worldwide seroprevalences and clinical expression of the systemic and ocular forms. Ann Trop Med Parasitol. 2010;104:3–23.
Hotez PJ, Wilkins PP. Toxocariasis: America’s most common neglected infection of poverty and a helminthiasis of global importance? PLoS Negl Trop Dis. 2009;3:e400.
Fillaux J, Magnaval JF. Laboratory diagnosis of human toxocariasis. Vet Parasitol. 2013;193:327–36.
Moreira GM, TelmoPde L, Mendonça M, Moreira AN, McBride AJ, Scaini CJ, Conceição FR. Human toxocariasis: current advances in diagnostics, treatment, and intervention. Trends Parasitol. 2014;30:456–64.
Wilder HC. Nematode endophthalmitis. Trans Am Acad Ophthalmol Otolaryngol. 1950;55:99–104.
Parise ME, Hotez PJ, Slutsker L. Neglected parasitic infections in the United States: needs and opportunities. Am J Trop Med Hyg. 2014;90:783–5.
Zhu XQ, Korhonen PK, Cai H, Young ND, Nejsum P, von Samson-Himmelstjerna G, et al. Genetic blueprint of the zoonotic pathogen Toxocara canis. Nat Commun. 2015;6:6145.
Gasser RB, Korhonen PK, Zhu XQ, Young ND. Harnessing the Toxocara genome to underprin toxocariasis research and new interventions. Adv Parasitol. 2016;91:87–110.
Li MW, Lin RQ, Song HQ, Wu XY, Zhu XQ. The complete mitochondrial genomes for three Toxocara species of human and animal health significance. BMC Genomics. 2008;9:224.
Gasser RB. A perfect time to harness advanced molecular technologies to explore the fundamental biology of Toxocara species. Vet Parasitol. 2013;193:353–64.
Mizgajska-Wiktor H, Jarosz W. A comparison of soil contamination with Toxocara canis and Toxocara cati eggs in rural and urban areas of Wielkopolska district in 2000-2005. Wiad Parazytol. 2007;53:219–25. (in Polish)
Gawor J, Borecka A. The contamination of the environment with Toxocara eggs in Mazowieckie voivodship as a risk of toxocarosis in children. Wiad Parazytol. 2004;50:237–41.
Borecka A, Gawor J, Niedworok M, Sordyl B. Occurrence of Toxocara spp. eggs in household environment of children with diagnosed toxocariasis in Łodz´ voivodeship. Wiad Parazytol. 2010;56:141–4.
Wickramasinghe S, Yatawara L, Rajapakse RP, Agatsuma T. Toxocara canis and Toxocara vitulorum: molecular characterization, discrimination, and phylogenetic analysis based on mitochondrial (ATP synthase subunit 6 and 12S) and nuclear ribosomal (ITS-2 and 28S) genes. Parasitol Res. 2009;104:1425–30.
Wickramasinghe S, Yatawara L, Rajapakse RP, Agatsuma T. Toxocara vitulorum (Ascaridida: Nematoda): mitochondrial gene content, arrangement and composition compared with other Toxocara species. Mol Biochem Parasitol. 2009;166:89–92.
Le TH, Anh NT, Nguyen KT, Nguyen NT, do TT T, Gasser RB. Toxocara malaysiensis infection in domestics cats in Vietnam--an emerging zoonotic issue? Infect Genet Evol. 2016;37:94–8.
Zhu XQ, Jacobs DE, Chilton NB, Sani RA, Cheng NABY, Gasser RB. Molecular characterization of a Toxocara variant from cats in Kuala Lumpur, Malaysia. Parasitology. 1998;117:155–64.
Gibbons LM, Jacobs DE, Sani RA. Toxocara malaysiensis n. Sp. (Nematoda: Ascaridoidea) from the domestic cat (Feliscatus Linnaeus, 1758). J Parasitol. 2001;87:660–5.
Fogt-Wyrwas R, Mizgajska-Wiktor H, Pacoń J, Jarosz W. Intraspecific variation between the ITS sequences of Toxocara canis, Toxocara cati and Toxascaris leonine from different hosts species in South-Western Poland. J Helminthol. 2013;87:432–42.
Zhu XQ, Gasser RB, Jacobs DE, Hung GC, Chilton NB. Relationships among some ascaridoid nematodes based on ribosomal DNA sequence data. Parasitol Res. 2000;86:738–44.
Li MW, Lin RQ, Song HQ, Sani RA, Wu XY, Zhu XQ. Electriphoretic analysis of sequence variability in three mitochondrial DNA regions for ascaridoid parasites of human and animal health significance. Electrophoresis. 2008;29:2912–7.
Smith H, Holland C, Taylor M, Magnaval JF, Schantz P, Maizels R. How common is human toxocariasis? Towards standardizing our knowledge. Trends Parasitol. 2009;25:182–8.
Saeed I, Taira K, Kapel CM. Toxocara canis in experimentally infected silver and arctic foxes. Parasitol Res. 2005;97:160–6.
Guimarães AM, Alves EG, de Rezendede GF, Rodrigues MC. Toxocara sp. eggs and Ancylostoma sp. larvae in public parks, Brazil. Rev Saude Publica. 2005;39:293–5. (in Portuguese)
Tiyo R, Guedes TA, Falavigna DL, Falavigna-Guilherme AL. Seasonal contamination of public squares and lawns by parasites with zoonotic potential in southern Brazil. J Helminthol. 2008;82:1–6.
Dada BJ, Lindquist WD. Prevalence of Toxocara spp. eggs in some public grounds and highway rest areas in Kansas. J Helminthol. 1979;53:145–6.
Chorazy ML, Richardson DJ. A survey of environmental contamination with ascarid ova, Wallingford, Connecticut. Vector Borne Zoonotic Dis. 2005;5:33–9.
Düwel D. The prevalence of Toxocara eggs in the sand of children’s playgrounds in Frankfurt/M. Ann Trop Med Parasitol. 1984;78:633–6.
Rokicki J, Kucharska AP, Dzido J, Karczewska D. Contamination of playgrounds in Gdan’sk city with parasite eggs. Wiad Parazytol. 2007;53:227–30. (in Polish)
Emehelu CO, Fakae BB. Prevalence of Toxocara canis ova on playgrounds of nursery schools in Nsukka, Nigeria. In J Zoonoses. 1986;13:158–61.
Oteifa NM, Moustafa MA. The potential risk of contracting toxocariasis in Heliopolis district, Cairo, Egypt. J Egypt Soc Parasitol. 1997;27:197–203.
Gunaseelan L, Ganesan PI, Ramadass P, Basheer MA, Raghavan N. Incidence of Toxocara ova in the environment. J Indian Vet. 1992;69:308–9.
Shimizu T. Prevalence of Toxocara eggs in sandpits in Tokushima city and its outskirts. J Vet Med Sci. 1993;55:807–11.
Keegan JD, Holland CV. A comparison of Toxocara canis embryonation under controlled conditions in soil and hair. J Helminthol. 2013;87:78–84.
Roddie G, Holland C, Stafford P, Wolfe A. Contamination of fox hair with eggs of Toxocara canis. J Helminthol. 2008;82:293–6.
Roddie G, Stafford P, Holland CV, Wolfe A. Contamination of dog hair with eggs of Toxocara canis. Vet Parasitol. 2008;152:85–93.
Lee AC, Schantz PM, Kazacos KR, Montgomery SP, Bowman DD. Epidemiologic and zoonotic aspects of ascarid infections in dogs and cats. Trends Parasitol. 2010;26:155–61.
Dubinský P, Havasiová-Reiterová K, Petko B, Hovorka I, Tomasovicová O. Role of small mammals in the epidemiology of toxocariasis. Parasitology. 1995;110:187–93.
Antolova D, Reiterova K, Miterpakova M, Stanko M, Dubinsky P. Circulation of Toxocara spp. in suburban and rural ecosystems in the Slovak Republic. Vet Parasitol. 2004;126:317–24.
Reperant LA, Hegglin D, Tanner I, Fischer C, Deplazes P. Rodents as shared indicators for zoonotic parasites of carnivores in urban environments. Parasitology. 2009;136:329–37.
Magnaval JF, Glickman LT, Dorchies P, Morassin B. Highlights of human toxocariasis. Korean J Parasitol. 2001;39:1–11.
Akao N, Ohta N. Toxocariasis in Japan. Parasitol Int. 2007;56:87–93.
Yoshikawa M, Nishiofuku M, Moriya K, Ouji Y, Ishizaka S, Kasahara K, et al. A familial case of visceral toxocariasis due to consumption of raw bovine liver. Parasitol Int. 2008;57:525–9.
Stoicescu RM, Mihai CM, Giannakopoulou AD. Marked hypereosinophilia in a toddler: a case report. J Med Life. 2011;4:105–8.
Musso C, Castelo JS, Tsanaclis AM, Pereira FE. Prevalence of Toxocara-induced liver granulomas, detected by immunohistochemistry, in a series of autopsies at a Children’s reference Hospital in Vitória, ES, Brazil. Virchows Arch. 2007;450:411–47.
Hartleb M, Januszewski K. Severe hepatic involvement in visceral larva migrans. Eur J Gastroenterol Hepatol. 2001;13:1245–9.
Kuenzli E, Neumayr A, Chaney M, Blum J. Toxocariasis-associated cardiac diseases-a systematic review of the literature. Acta Trop. 2016;154:107–20.
Kayes SG, Oaks JA. Development of the granulomatous response in murine toxocariasis. Initial events Am J Pathol. 1978;93:277–94.
Dromer C, Constantin A, Amar J, Caulier M, Billey T, Chamontin B, et al. Rheumatologic aspects of toxocariasis (visceral larva migrans), apropos of 2 cases. Rev Rhum Ed Fr. 1993;60:621–4.
Shetty AK, Aviles DH. Nephrotic syndrome associated with Toxocara canis infection. Ann Trop Paediatr. 1999;19:297–300.
Prunier F, Delepine S, Victor J, de Gentile L, Moreau C, Laporte J, et al. Loffler’s fibroblastic endocarditis. A report of a case complicating toxocarosis. Arch Mal Coeur Vaiss. 2001;94:226–30. (in French)
Ismail MA, Khalafallah O. Toxocara canis and chronic urticaria in Egyptian patients. J Egypt Soc Parasitol. 2005;35:833–40.
Stewart JM, Cubillan LD, Cunningham ET Jr. Prevalence, clinical features, and causes of vision loss among patients with ocular toxocariasis. Retina. 2005;25:1005–13.
Centers for Disease Control and Prevention. Ocular toxocariasis--United States, 2009 –2010. MMWR Morb Mortal Wkly Rep. 2011;60:734–6.
Quinnell RJ. Genetics of susceptibility to human helminth infection. Int J Parasitol. 2003;33:1219–31.
Norhaida A, Suharni M, Liza Sharmini AT, Tuda J, Rahmah N. rTES-30USM: cloning via assembly PCR, expression, and evaluation of usefulness in the detection of S228 toxocariasis. Ann Trop Med Parasitol. 2008;102:151–60.
Xinou E, Lefkopoulos A, Gelagoti M, Drevelegas A, Diakou A, Milonas I, Dimitriadis AS. CT and MR imaging findings in cerebral toxocaral disease. AJNR Am J Neuroradiol. 2003;24:714–8.
Watthanakulpanich D, Smith HV, Hobbs G, Whalley AJ, Billington D. Application of Toxocara canis excretory-secretory antigens and IgG subclass antibodies (IgG1-4) in serodiagnostic assays of human toxocariasis. Acta Trop. 2008;106:90–5.
Noordin R, Smith HV, Mohamad S, Maizels RM, Fong MY. Comparison of IgG-ELISA and IgG4-ELISA for Toxocara serodiagnosis. Acta Trop. 2005;93:57–62.
Jin Y, Shen C, Huh S, Sohn WM, Choi MH, Hong ST. Serodiagnosis of toxocariasis by ELISA using crude antigen of Toxocara canis larvae. Korean J Parasitol. 2013;51:433–9.
Jacobs DE, Zhu XQ, Gasser RB, Chilton NB. PCR-based methods for identification of potentially zoonotic ascaridoid parasites of the dog, fox and cat. Acta Trop. 1997;68:191–200.
Li MW, Lin RQ, Chen HH, Sani RA, Song H, Zhu XQ. PCR tools for the verification of the specific identity of ascaridoid nematodes from dogs and cats. Mol Cell Probes. 2007;21:349–54.
Rai SK, Uga S, Wu Z, Takahashi Y, Matsumura T. Use of polymerase chain reaction in the diagnosis of toxocariasis: an experimental study. Southeast Asian J Trop Med Public Health. 1997;28:541–4.
Van De N, Trung NV, le Duyet V, Chai JY. Molecular diagnosis of an ocular toxocariasis patient in Vietnam. Korean J Parasitol. 2013;51:563–7.
Lim SJ, Lee SE, Kim SH, Hong SH, You YS, Kwon OW, et al. Prevalence of Toxoplasma gondii and Toxocara canis among patients with uveitis. Ocul Immunol Inflamm. 2014;22:360–6.
Macuhova K, Kumagai T, Akao N, Ohta N. Loop-mediated isothermal amplification assay for detection and discrimination of Toxocara canis and Toxocara cati eggs directly from sand samples. J Parasitol. 2010;96:1224–7.
Tomita N, Mori Y, Kanda H, Notomi T. Loop-mediated isothermal amplification (LAMP) of gene sequences and simple visual detection of products. Nat Protoc. 2008;3:877–82.
Arevalo JF, Espinoza JV, Arevalo FA. Ocular toxocariasis. J Pediatr Ophthalmol Strabismus. 2012;50:76–86.
Campbell JP, Wilkinson CP. Imaging in the diagnosis and management of ocular toxocariasis. Int Ophthalmol Clin. 2012;52:145–53.
Morais FB, MacielAL ATE, Muccioli C, Al-lemann N. Ultrasonographic findings in ocular toxocariasis. Arq Bras Ophthalmol. 2012;75:43–7.
Hashida N, Nakai K, Nishida K. Diagnostic evaluation of ocular toxocariasis using high-penetration optical coherence tomography. Case Rep Ophthalmol. 2014;5:16–21.
Ahmed AS, Biswas J. Uveitis: a search for a cause. Taiwan J Ophthalmol. 2013;3:134–40.
Kim YJ, Moon CH, Chang JH. Toxocariasis of the optic disc. J Neuroophthalmol. 2013;33:151–2.
Tran VT, Lumbroso L, LeHoang P, Herbort CP. Ultrasound biomicroscopy in peripheral retinovitreal toxocariasis. Am J Ophthal. 1999;127:607–9.
Rodman J, Pizzimenti J. In vivo diagnostic imaging of ocular toxocariasis. Clin Exp Optom. 2009;92:146–9.
Chen Q, Gu J, Jiang R, Zhou M, Chang Q. Role of ultrasound biomicroscopy in diagnosis of ocular toxocariasis. Br J Ophthalmol. 2018 May;102(5):642–6.
Sánchez SS, García HH, Nicoletti A. Clinical and magnetic resonance imaging findings of neurotoxocariasis. Front Neurol. 2018;9:53.
Rohilla S, Jain N, Yadav R, Dhaulakhandi DB. Hepatic visceral larva migrans. BMJ Case Rep. 2013;13:2013.
Rajesh S, Patidar Y, Rastogi A, Bihari C. Image of the month: hepatic visceral larva migrans. Am J Gastroenterol. 2015;110:497.
Kim YK, Kim CS, Moon WS, Cho BH, Lee SY, Lee JM. MRI findings of focal eosinophilic liver diseases. AJR Am J Roentgenol. 2005;184:1541–8.
Magnaval JF, Charlet JP. Comparative efficacy of thiabendazole and mebendazole in the treatment of toxocariasis. Therapie. 1987;42:541–4. (in French)
Stürchler D, Schubarth P, Gualzata M, Gottstein B, Oettli A. Thiabendazole vs albendazole in treatment of toxocariasis: a clinical trial. Ann Trop Med Parasitol. 1989;83:473–8.
Pawlowski Z. Toxocariasis in humans: clinical expression and treatment dilemma. J Helminthol. 2001;75:299–305.
Woodhall DM, Fiore AE. Toxocariasis: a review for pediatricians. J Pediatric Infect Dis Soc. 2014;3:154–9.
Ranasuriya G, Mian A, Boujaoude Z, Tsigrelis C. Pulmonary toxocariasis: a case report and literature review. Infection. 2014;42:575–8.
Hrˇckova G. Novel approaches to immunoprophylaxis in toxocariasis. In: Holland CV, Smith HV, editors. Toxocara: the enigmatic parasite. Oxfordshire: CAB International; 2006. p. 174–94.
Martínez-Pulgarín DF, Muñoz-Urbano M, Gomez-Suta LD, Delgado OM, Rodriguez-Morales AJ. Ocular toxocariasis: new diagnostic and therapeutic perspectives. Recent Pat Antiinfect Drug Discov. 2015;10:35–41.
Frazier M, Anderson ML, Sophocleous S. Treatment of ocular toxocariasis with albendezole: a case report. Optometry. 2009;80:175–80.
Satou T, Horiuchi A, Akao N, Koike K, Fujita K, Nikaido T. Toxocara canis: search for a potential drug amongst beta-carboline alkaloids-in vitro and mouse studies. Exp Parasitol. 2005;110:134–9.
Othman AA. Therapeutic battle against larval toxocariasis: are we still far behind? Acta Trop. 2012;124:171–8.
Wiśniewska-Ligier M, Woźniakowska-Gęsicka T, Sobolewska-Dryjańska J, Markiewicz-Jóźwiak A, Wieczorek M. Analysis of the course and treatment of toxocariasis in children: a long-term observation. Parasitol Res. 2012;110:2363–71.
Woodhall D, Starr MC, Montgomery SP, Jones JL, Lum F, Read RW, et al. Ocular toxocariasis: epidemiologic, anatomic, and therapeutic variations based on a survey of ophthalmic subspecialists. Ophthalmology. 2012;119:1211–7.
Choi KD, Choi JH, Choi SY, Jung JH. Toxocara optic neuropathy: clinical features and ocular findings. Int J Ophthalmol. 2018;11:520–3.
Eberhardt O, Bialek R, Nagele T, Dichgans J. Eosinophilic meningomyelitis in toxocariasis: case report and review of the literature. Clin Neurol Neurosurg. 2005;107:432–8.
Graeff-Teixeira C, da Silva AC, Yoshimura K. Update on eosinophilic meningoencephalitis and its clinical relevance. Clin Microbiol Rev. 2009;22:322–48.
Goffette S, Jeanjean AP, Duprez TP, Bigaignon G, Sindic CJ. Eosinophilic pleocytosis and myelitis related to Toxocara canis infection. Eur J Neurol. 2000;7:703–6.
Hombu A, Yoshida A, Kikuchi T, Nagayasu E, Kuroki M, Maruyama H. Treatment of larva migrans syndrome with long-term administration of albendazole. J Microbiol Immunol Infect. 2017;S1684-1182(17):30142–1.
Deplazes P, van Knapen F, Schweiger A, Overgaauw PA. Role of pet dogs and cats in the transmission of helminthic zoonoses in Europe, with a focus on echinococcosis and toxocarosis. Vet Parasitol. 2011;24:41–53.
Parsons JC. Ascarid infections of cats and dogs. Vet Clin North Am Small Anim Pract. 1987;17:1303–7.
WHO. Action to reduce human health hazards arising from animals. WHO Chron. 1978;32:307–10.
Malheiro A, Aníbal FF, Martins-Filho OA, Teixeira-Carvalho A, Perini A, Martins MA, Medeiros AI, Turato WM, Acencio MP, Brandão IT, Nomizo A, Silva CL, Faccioli LH. pcDNA-IL-12 vaccination blocks eosinophilic inflammation but not airway hyperesponsiveness following murine Toxocara canis infection. Vaccine. 2008;26:305–15.
Basualdo J, Sparo M, Chiodo P, Ciarmela M, Minvielle M. Oral treatment with a potential probiotic (Enterococcus faecalis CECT 7121) appears to reduce the parasite burden of mice infected with Toxocara canis. Ann Trop Med Parasitol. 2007;101:559–62.
Chiodo PG, Sparo MD, Pezzani BC, Minvielle MC, Basualdo JA. In vitro and in vivo effects of Enterococcus faecalis CECT7121 on Toxocara canis. Mem Inst Oswaldo Cruz. 2010;105:615–20.
de Avila LF, Conceição FR, Telmo Pde L, Dutra GF, de los Santos DG, Martins LH, Berne ME, da Silva PE, Scaini CJ. Saccharomyces boulardii reduces infection intensity of mice with toxocariasis. Vet Parasitol. 2012;187:337–40.
Kudtarkar A, Shinde UP, Bharkad G, Singh K. Solid lipid nanoparticles of albendazole for treatment of Toxocara canis infection: in-vivo efficacy studies. Nanosci Nanotechnol-Asia. 2017;7:80–91.
Wilkinson CP, Welch RB. Intraocular Toxocara. Am J Ophthalmol. 1971;71:921–30.
Yokoi K, Goto H, Sakai J, Usui M. Clinical features of ocular toxocariasis in Japan. Ocul Immunol Inflamm. 2003;11:269–75.
do Lago A, Andrade R, Muccioli C, Belfort R Jr. Optical coherence tomography in presumed subretinal Toxocara granuloma: case report. Arq Bras Oftalmol. 2006;69:403–5.
Gass JD, Gilbert WR, Guerry RK, Scelfo R. Diffuse unilateral subacute neuroretinitis. Ophthalmology. 1978;85:521–45.
de Souza EC, Nakashima Y. Diffuse unilateral subacute neuroretinitis. Report of transvitreal surgical removal of a subretinal nematode. Ophthalmology. 1995;102:1183–6.
Brown DH. Ocular Toxocara canis. I Experimental immunology. Ann Ophthalmol. 1971;3:907–10.
Gillespie SH, Dinning WJ, Voller A, Crowcroft NS. The spectrum of ocular toxocariasis. Eye (Lond). 1993;7:415–8.
Ahn SJ, Ryoo NK, Woo SJ. Ocular toxocariasis: clinical features, diagnosis, treatment, and prevention. Asia Pac Allergy. 2014;4:134–41.
Ahn SJ, Woo SJ, Jin Y, Chang YS, Kim TW, Ahn J, et al. Clinical features and course of ocular toxocariasis in adults. PLoS Negl Trop Dis. 2014;8:e2938.
Glickman LT, Magnaval JF, Domanski LM, Shofer FS, Lauria SS, Gottstein B, et al. Visceral larva migrans in French adults: anew disease syndrome? Am J Epidemiol. 1987;125:1019–34.
Finsterer J, Auer H. Neurotoxocarosis. Rev Inst Med Trop Sao Paulo. 2007;49:279–87.
Richartz E, Buchkremer G. Cerebral toxocariasis: a rare cause of cognitive disorders. A contribution to differential dementia diagnosis. Nervenarzt. 2002;73:458–62. (in German)
Bachli H, Minet JC, Gratzl O. Cerebral toxocariasis: a possible cause of epileptic seizure in children. Childs NervSyst. 2004;20:468–72.
Moreira-Silva SF, Rodrigues MG, Pimenta JL, Gomes CP, Freire LH, Pereira FE. Toxocariasis of the central nervous system: with report of two cases. Rev Soc Bras Med Trop. 2004;37:169–74.
Fortenberry JD, Kenney RD, Younger J. Visceral larva migrans producing static encephalopathy in an infant. Pediatr Infect Dis J. 1991;10:403–6.
Caldera F, Burlone ME, Genchi C, Pirisi M, Bartoli E. Toxocara encephalitis presenting with autonomous nervous system involvement. Infection. 2013;41:691–4.
Gasser RB, Zhu XQ, Jacobs DE, Hu M, Chilton NB. Molecular genetic characterisation of members of the genus Toxocara – taxonomic, population genetic and epidemiological considerations. In: Holland CV, Smith HV, editors. Toxocara: the enigmatic parasite. United Kingdom: Wallingford; 2006. p. 18–31.
Magnaval JF, Faufingue JH, Morassin B, Fabre R. Eosinophil cationic protein, specific IgE and IgG4 in human toxocariasis. J Helminthol. 2006;80:417–23.
Magnaval JF, Berry A, Fabre R, Morassin B. Eosinophil cationic protein as a possible marker of active human Toxocara infection. Allergy. 2001;56:1096–9.
Mohamad S, Azmi NC, Noordin R. Development and evaluation of a sensitive and specific assay for diagnosis of human toxocariasis by use of three recombinant antigens (TES-26, TES-30USM, and TES-120). J Clin Microbiol. 2009;47:1712–7.
Peixoto PL, Nascimento E, Cançado GG, Miranda RR, Rocha RL, Araújo RN, et al. Identification of candidate antigens from adult stages of Toxocara canis for the serodiagnosis of human toxocariasis. Mem Inst Oswaldo Cruz. 2011;106:200–6.
Magnaval JF, Fabre R, Maurières P, Charlet JP, de Larrard B. Application of the western blotting procedure for the immunodiagnosis of human toxocariasis. Parasitol Res. 1991;77:697–702.
Yamasaki H, Araki K, Lim PK, Zasmy N, Mak JW, Taib R, Aoki T. Development of a highly specific recombinant Toxocara canis second-stage larva excretory-secretory antigen for immunodiagnosis of human toxocariasis. J Clin Microbiol. 2000;38:1409–13.
Magnaval JF. Comparative efficacy of diethylcarbamazine and mebendazole for the treatment of human toxocariasis. Parasitology. 1995;110:529–33.
Barrera MG, Leonardi D, Bolmaro RE, Echenique CG, Olivieri AC, Salomon CJ, et al. In vivo evaluation of albendazole microspheres for the treatment of Toxocara canis larva migrans. Eur J Pharm Biopharm. 2010;75:451–4.
Leonardi D, Echenique C, Lamas MC, Salomon CJ. High efficacy of albendazole–PEG 6000 in the treatment of Toxocara canis larva migrans infection. J Antimicrob Chemother. 2009;64:375–8.
Horiuchi A, Satou T, Akao N, Koike K, Fujita K, Nikaido T. The effect of free and polyethylene glycol-liposome-entrapped albendazole on larval mobility and number in Toxocara canis infected mice. Vet Parasitol. 2005;129:83–7.
Hrckova G, Velebny S. Treatment of Toxocara canis infections in mice with liposome-incorporated benzimidazole carbamates and immunomodulator glucan. J Helminthol. 2001;75:141–6.
Hrˇckova G, Velebny S, Obwaller A, Auer H, Kogan G. Evaluation of follow-up therapy with fenbendazole incorporated into stabilized liposomes and immunomodulator glucan in mice infected with Toxocara canis larvae. Acta Trop. 2007;104:122–32.
The authors thank colleagues Paul Goodwin and Luke Mathews at the University of Nottingham for copy-editing this manuscript.
This study was financially supported by the Elite Program of Chinese Academy of Agricultural Sciences, the International Science &Technology Cooperation Program of China (grant No. 2013DFA31840) and the Agricultural Science and Technology Innovation Program (ASTIP) (Grant No. CAAS-ASTIP-2016-LVRI-03).
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The authors declare that they have no competing interests.
Multilingual abstracts in the five official working languages of the United Nations. (PDF 254 kb)
Table S1. Number of clinical cases of human toxocariasis by clinical form and country. Table S2. Epidemiological characteristics and risk factors for human toxocariasis and references. Table S3. Prevalence of Toxocara spp. in definitive hosts by country and animal host species. (PDF 780 kb)
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Chen, J., Liu, Q., Liu, GH. et al. Toxocariasis: a silent threat with a progressive public health impact. Infect Dis Poverty 7, 59 (2018). https://doi.org/10.1186/s40249-018-0437-0
- Toxocara canis
- Larva migrans