Background
Human toxocariasis is a zoonotic disease caused by several species of the nematode round worm
Toxocara.
Toxocara spp. are common intestinal round worms parasitizing a wide range of domestic, agricultural, and wild animals. The species include
T. canis of dogs and wild canids,
T. cati of cats,
T. leonina found in both cats and dogs and
T. vitulorum of ruminants. The disease is most frequently caused due to
T. canis [
1]. The definitive hosts of these parasites include the domestic and peridomestic cats and dogs, particularly puppies that have been infected transplacentally [
1,
2]. The adult worms in the intestines of canines and felids lay eggs that are shed along with faeces into the environment.
Toxocara eggs, when voided by dogs are unembryonated, and need 10–14 days to develop into infective larvae [
3]. Therefore, contact with eggs in soil is a very important risk factor in the transmission of toxocariasis to humans.
Toxocara infection has been associated with pica and pet ownership [
4,
5]. Age, sex, geographical location, and poor socioeconomical status are other risk factors for acquiring the disease [
6,
7]. The clinical spectrum of human toxocariasis ranges from asymptomatic cases to systemic infections. The recognized clinical manifestations include classic and incomplete visceral toxocarisis (VLM), ocular toxocarisis (OLM), neurological toxocarisis (NLM), covert toxocariasis and asymptomatic toxocarisis [
8].
Ocular larva migrans was first recognized by Wilder (1950) when 24 cases in which eyes enucleated for suspected retinoblastoma were found to have nematodes [
1].
Toxocara larvae are capable of invading almost all the structures of the eye; granuloma either in the posterior pole or in the periphery of the eye has been identified as the most common clinical presentation of OLM [
9‐
11]. The consequences of fibrosis were the most important causes of visual loss in more chronic lesions [
11]. Other less common causes of visual loss in OLM include hypopyon, vitreous abscess, optic neuritis and keratitis [
1,
9]. Eosinophilia which is both pronounced and persistent with VLM is virtually absent with OLM [
12]. Toddlers and teenagers are the most common victims of this disease and if left untreated it may result in permanent loss of vision in the affected eye [
13,
14]. OLM is typically characterized by unilateral vision impairment which may be accompanied less frequently with strabismus. Critical infection leads to invasion of the retina which leads to granuloma formation either peripherally or in the posterior pole. The granuloma drags the retina and leads to distortions, heteropia or detachment of the macula. Depending on the region of infection in the eye, the patient may have minor visual impairment or blindness. Other clinical manifestations of OLM include diffuse endophthalmitis, papillitis, or secondary glaucoma [
1].
Toxocariasis represents an ‘ongoing and poorly recognized parasitic infection’ in many developing countries including Sri Lanka [
15]. The first seroepidemiological study on toxocariasis in Sri Lankan population was conducted in 2003 on 1020 children in the age group 1–12 years of age revealed 43% of seropositivity [
5]. Studies conducted in Sri Lanka have focused mainly on the paediatric population and VLM. No studies have yet been carried out regarding the OLM infection status in Sri Lanka, thus the current study was carried out on 250 cases that clinicians had suspected as having ocular toxocariasis and whose serum samples had been sent for testing to determine the presence of
Toxocara antibodies and to describe demographic factors and clinical manifestations of seropositive patients.
Discussion
Seroepidemiological surveys, done in various countries of the world indicate that larva migrans due to
Toxocara spp. is a relatively common infection in the general population and at times it can lead to serious or life threatening conditions in human [
16]. Clinical features associated with toxocariasis are common and non-specific. Therefore, diagnosis of toxocariasis based solely on the clinical findings is unreliable. Since the
Toxocara larva fails to complete their migratory cycle in the human, eggs are not passed in the stool. Also, the definitive diagnosis of toxocariasis by histological examination for
Toxocara larvae in biopsy material is very difficult. Thus, the confirmatory diagnosis of toxocariasis depends heavily on immunological tests. The successful in vitro culture of
T. canis larvae has enabled the collection of excretory secretory antigens of the second stage larva [
17] and introduction of ELISA based on these antigens [
18]. The lack of sensitivity and specificity associated with many of the early serodiagnostic techniques were rectified, resulting in considerable improvement in immunodiagnosis. A seroepidemiological study on toxocariasis carried out in children aged 1–12 years in Sri Lanka has reported 43% of seropositivity, indicating high level of transmission. This is the first study on ocular toxocariasis carried out in a Sri Lankan population. The present study showed considerably high
Toxocara IgG antibody carriage (62%) among clinically suspected OLM patients. This pattern of antibody carriage is much higher than the prevalence of 21% and 28% reported among clinically suspected OLM patients reported in North India [
19] and Slovenia [
20] respectively. In Sri Lanka, although rabies is a high public health priority little attention is paid to other zoonotic diseases that humans could acquire from dogs. A survey in an urban area has shown dog to human population ratio of 1:8 [
21] with 20% of these dogs being un-owned or group as strays. Thus the risk of soil contamination with
Toxocara spp. is an increasing threat throughout human habitations in Sri Lanka. This could be the reason for our community to have high seroprevalence rate compared to prevalence rate reported elsewhere in the world.
The present study showed high prevalence of OLM among children aged between 10 and 14 years. This is in contrast to a study published in 2009, where the infection was most frequently seen in children of ages below 10 years [
22]. The current study observed high incidence of OLM in males. Similarly, several prior studies have documented that OLM is more common among males [
23,
24].
The most common symptoms and signs include reduced vision, peripheral posterior pole retinal granuloma, tearing, leukokoria and redness of the eye. Only a single eye was affected in most of the patients which is in line with a study done to determine the worldwide seroprevalence of OLM [
25]. The major cause of visual acuity loss is uveitis (34.2%). However only vitritis (
P = 0.003) was significantly associated with seropositivity. A larger case-controlled study is required to study the ocular manifestations in seropositive cases. A prior study reported vitritis, cystoid macular oedema and tractional retinal detachment as the major causes of visual acuity loss.However, in the present study, only a small proportion of the patients harbored macular oedema (1.29%) or retinal detachment (3.23%) [
26]. Although the exact reason for the clinical presentation is not known the most possible reason may be due to a toxic or immunoallergic reaction against the larva antigens which leads to inflammatory reactions and granuloma formation. An immunological response to highly immunogenic antigens is considered to cause vitritis.
Diagnosis was performed by In-house TES-ELISA specific to
Toxocara canis coupled with the clinical features observed in the patient. In the current study 34.2% of the seronegative cases presented with uveitis while 7/22 granuloma cases were seronegative. Toxoplasmosis and tuberculosis are possible differential diagnosis for uveitis and granuloma. However, we could not perform any laboratory investigations to exclude these diseases in our study. One limitation of this study was that clinicians have not specified the type of granulomas and uveitis. Posterior pole granuloma (27) and posterior uveitis (11) are shown to be frequent clinical presentations of OLM. Those seronegative cases could be due to some other reasons. It has been reported that the diagnosis of ocular toxocariasis is challenging since the levels of antibodies in serum may be low or undetectable [
27]. Hence even a low level of antibody maybe of diagnostic value, but the cut-off value for such an instance has not been established so far [
25]. Sensitivity of
Toxocara ELISA can be improved by analyzing intraocular fluid [
28]. In such cases it is worthwhile to obtain vitreous or aqueous humor fluid to perform ELISA. However, even the use of these fluids cannot be 100% accurate since it was observed that those who had clear signs of OLM did not show seropositivity in the eye fluid. Therefore it is advisable to detect antibodies by ELISA in both serum and eye fluid to enhance the sensitivity of detecting OLM [
29].
Our study had a few limitations that need further consideration. This was a retrospective descriptive study. Toxocara antibodies can be positive among healthy people; however there is no data for the prevalence of seropositivity of T.canis in asymptomatic individuals. Therefore a case control study comparing seropositive rates in healthy, asymptomatic patients and those with ocular manifestations of ocular toxocariasis is required. Also, after laboratory diagnosis, we were unable to conduct a follow up on the individuals after treatment, since they were sent to us only for serological testing. Further studies with proper serological follow up with treatment are essential to establish proper treatment in our country.
Acknowledgements
Ms. Lakmali Bandara, technical officer at the department of Parasitology, Faculty of Medicine, Univeristy of Peradeniya.