We searched PubMed and Scopus databases for articles published between Jan 1, 1950, and April 16, 2016, with the terms “toxocar*” AND (“clinical manifestation” OR “syndrome”); “toxocar*” AND “diagnosis”; “toxocar*” AND (“epidemiology” OR “public health”); “toxocar*” AND (“treatment” OR “chemotherapy”); “toxocar*” AND (“immunol*” OR “vaccine”); “toxocar*” AND (“prevention” OR “control”); “toxocar*” AND (“genom*” OR “transcriptom*”). We screened the titles and abstracts and identified articles
ReviewHuman toxocariasis
Introduction
The first diagnosis of human toxocariasis was the detection of Toxocara larvae in enucleated eyes from children with suspected retinoblastoma more than 60 years ago.1, 2 Histological examination of the retinas of these diseased eyes revealed granulomatous lesions that likely contained Toxocara canis larvae.2 Since then, various clinical forms of human toxocariasis have been recognised: ocular larva migrans, visceral larva migrans, covert or common toxocariasis, and neurotoxocariasis.3, 4, 5 Despite the clinical recognition of these syndromes and the rising awareness that human toxocariasis is causing an increasing burden to public health, particularly in subtropical and tropical regions and in disadvantaged communities in some countries,6, 7, 8, 9, 10, 11 there are still major gaps in the understanding of this disease.7, 12, 13, 14, 15, 16, 17, 18, 19 Indeed, evidence from recent investigations suggests that human toxocariasis is seriously neglected because limited attention has been paid to its prevention, treatment, and surveillance and because it is a non-notifiable disease.20, 21, 22
A major challenge in preventing toxocariasis is the complexity of infection sources of Toxocara spp and routes of transmission, about which still relatively little is known. Adult worms of Toxocara spp live in the small intestines of various wild or domestic definitive hosts (figure 1). For instance, T canis infects canid hosts, including coyotes, dogs, foxes, and wolves, and Toxocara cati (previously Toxocara mystax) and Toxocara malaysiensis infect felids.9, 23, 24, 25 Related species, such as Toxocara vitulorum, Toxascaris leonina, and Baylisascaris procyonis, infect various carnivorous or ruminant hosts.9 Human toxocariasis acquired from cats and Toxoplasma gondii co-infection might be more common than previously thought.24, 26 Infected definitive hosts, such as dogs and cats, excrete eggs in the faeces, which then contaminate the environment under suitable conditions (humidity and temperature)27, 28, 29 where they can remain infective for many months or even years. T canis larvae can also undergo arrested development in the tissues of female canids and reactivate during pregnancy to infect pups through both transplacental and transmammary routes.30, 31
Eggs containing infective third-stage larvae are accidentally ingested by human beings through contact with contaminated food, water, soil, or utensils. In the small intestine, the larvae are released from the eggs, penetrate the intestinal wall, and travel via the circulatory system to various organs, including the lungs, liver, muscles, and CNS. Except in the definitive canid host, third-stage larvae do not mature but can arrest in development within tissues for many years. Tissue infection evokes an inflammatory immune response in the body that can lead to (usually non-specific) symptoms of disease, such as fever, headaches, coughing, and pains.3, 8, 32 Infective eggs ingested by paratenic or transport hosts (eg, mice, rats, rabbits, pigs, cattle, or chickens, and earthworms or other invertebrates) undergo a similar fate, with third-stage larvae arresting in tissues.33 Although larvae never develop to adult worms in the intestine of human beings or other paratenic hosts, larvae-infected tissues from paratenic hosts can serve as food for human beings and definitive hosts, leading to infection or disease. For instance, the consumption of undercooked or raw liver from infected animals has been implicated in toxocariasis.34, 35
Although eliminating or reducing intestinal infections in definitive hosts (dogs and cats) by chemotherapy is probably the most efficient way of decreasing environmental contamination and subsequent transmission to human beings and other paratenic hosts, the high prevalence of anti-T canis serum antibodies in human beings in many regions of the world, particularly disadvantaged communities,20, 22 indicates that this approach is not being adequately implemented. In this Review, we introduce salient aspects of human toxocariasis and Toxocara infections, emphasise key knowledge gaps, and discuss future prospects and research areas to improve insights into what is still a neglected parasitic disease of major public health importance.
Section snippets
Clinical manifestations and disease
In human beings, Toxocara larvae penetrate the intestinal mucosa and migrate to liver, lungs, and other organ systems (eg, skeletal muscle, heart, brain, and eyes) by mechanical means and protease digestion.4, 5, 34 Migrating larvae are attacked by host immune responses, resulting in local inflammation associated with eosinophilia and increased production of cytokines and specific antibodies. Although many T canis infections are subclinical in nature, human toxocariasis can manifest itself as
Diagnosis
The diagnosis of toxocariasis and Toxocara infection in paratenic or accidental hosts can be made by histopathological examination, morphometric assessment of larvae (if present), or the specific detection of larval DNA from tissue or body fluid samples.45 As serological or immunological methods alone do not allow for an unequivocal diagnosis of infection,18, 45 PCR-based tools, using genetic markers in the first and second internal transcribed spacers (ITS-1 and ITS-2) of nuclear ribosomal RNA
Epidemiology and public health importance
T canis and T cati have a worldwide distribution.24, 76 For this Review, we assessed the prevalence of T canis infections or exposure in human beings, as determined using serological assays (figure 2); the studies are summarised in the appendix. The prevalence of T canis and T cati in dogs and cats, respectively, has been reported as 1·2% and 3·2% in Australia,77 4·4% and 4·6% in the Netherlands,28 and 6·1% and 4·7% in Germany.78 In some surveys in countries including Nigeria, Portugal, India,
Treatment
The two major obstacles to the successful treatment of toxocariasis in human beings are: the requirement for drugs to reach larvae across a range of tissues; and the difficulty in verifying drug efficacy in patients. Nevertheless, treatment with anthelmintics is advocated for acute toxocariasis, particularly to prevent Toxocara larvae from reaching the brain and eyes.32, 90 Albendazole and mebendazole are commonly used to treat visceral larva migrans, despite their limited efficacy against
Immunology and prospect for vaccines
There is increasing interest in vaccines against helminth infections and, specifically, for vaccines to prevent transmission of zoonotic diseases to human beings. A recent example is the development of a vaccine against Taenia solium in pigs to prevent human cysticercosis.102 Like many other helminthic diseases, however, protective immunity is often forestalled by the parasites' ability to block and evade the host immune system.103 For T canis, immune evasion is mediated by surface coat and
Prevention and control
The remarkably broad geographical distribution of T canis, its multiple infection routes (eg, human–dog contact and through neonatal and food-borne transmission), and potential associations of toxocariasis with allergic and neurological disorders have raised considerable public concern. However, community awareness of toxocariasis is still inadequate. Enhancing education will be essential to improve the public's understanding of toxocariasis and its prevention, treatment, and control (figure 3).
New molecular insights using genomic and transcriptomic tools
The completion of the T canis draft genome project was an important step towards advancing the understanding of this parasite and toxocariasis at the molecular and biochemical levels. These data could assist in developing a next generation of diagnostic and intervention methods.113, 114 The draft genome (317 Mb) was predicted to encode 18 596 genes, with 14 583 (78·4%) genes annotated and 5406 (29·1%) genes having homologues in known biological KEGG pathways.113, 114 Specifically, 870 excretory
Future prospects and conclusions
Although branded as “America's most common neglected infection of poverty”,7, 134 the global importance of toxocariasis remains to be critically assessed.7, 9 No estimate of the global disease burden of toxocariasis exists, and although epidemiological studies and reports of toxocariasis have been done all over the world, major knowledge gaps remain in the epidemiology of T canis and T cati infections and of T malaysiensis, the zoonotic importance of which is unknown, and considerable
Search strategy and selection criteria
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