Clinical Features

Clinical toxocaral infection in humans occurs in three forms, viceral larva migrans (VLM), ocular larva migrans (OLM) and covert toxocariasis (CT).

Visceral Larva Migrans

Viceral larva migrans (VLM) is predominantly a disease of children. The essentials for clinical diagnosis in the past have been regarded as an eosinophilia of over 30% in children with a history of eating dirt and with no other cause for eosinophilia (Snyder, 1961). Beaver (1956) reported that an eosinophilia of over 50% was common, but regarded other evidence of infection as variable. Initially the diagnosis was made by biopsy (usually of the liver) and histological examination to confirm the presence of Toxocara larvae, usually in granulomata (Beaver, 1956; Snyder, 1961). The two reported studies of experimental toxocariasis in humans have both noted an eosinophilia, although the features of true visceral larva migrans were not documented. An adult was infected with 100 embryonated eggs. On the 13th day after ingestion he developed a blood eosinophilia of 2704/mm3, which rose to 13 516 by the 30th day and fell to 6144 by 4.5 months. He subsequently developed a chronic cough (Chaudri and Saha, 1959). Two mentally retarded children were given 200 T. canis eggs. They developed a blood eosinophilia that was still present 13 months after ingestion (Smith and Beaver, 1953).

The other characteristics of visceral larva migrans are geophagia, anaemia, cough, wheeze, pulmonary infiltrates on X-ray, hepatospleno-megaly, fever and anorexia. Suspicion of the diagnosis is normally aroused by the raised eosinophilia. Histological confirmation of the diagnosis is now not commonly undertaken, and a finding of a raised Toxocara titre in conjunction with the characteristic features and history is normally taken as diagnostic. Ideally a changing titre should be sought.

Clinical Diagnosis

The diagnosis of visceral larva migrans in an appropriately aged child is relatively straightforward. The extreme eosinophilia usually draws attention to the possibility of a diagnosis of toxocaral infection and the other features of anaemia, fever, hepatosplenomegaly, pulmonary infiltrates and wheeze usually result in a more detailed history being taken to enquire about dog ownership and geophagia.

A Toxocara-specific ELISA titre will normally confirm the diagnosis. Ideally, a rising or falling titre will provide firmer grounds for diagnosis than a single estimate. The titre is likely to rise rapidly in the early stages of the disease but falls slowly and may take as long as a year to return to a negative value (Taylor, 1993; Taylor et al., 1988). The gold standard for diagnosis is histological examination and confirmation of the presence of a T. canis larva. T. canis larvae have been identified in enucleated eyes and also in liver granulomata. While in the past liver biopsies have been carried out to make the diagnosis, reliance is now placed on antibody titres rather than histology.

Toxocaral Eye Disease

Toxocaral eye disease is usually referred to as ocular larva migrans (OLM) because the larva migrates to the eye and, at its most acute, infection may result in blindness (Sheilds, 1984). Reaction to its presence and to its shed antigens may cause local or widespread damage to the retina and to other intra-ocular structures. Intraocular infection usually occurs unilaterally in children, but occasionally both eyes are affected and adults develop the condition (Sheilds, 1984).

Pollard et al. (1979) reported the following presenting complaints in 41 cases: decreased vision, 83%; strabismus, 10%; leukokoria, 7%.

The ocular lesions in these patients were: posterior pole mass; peripheral mass (unilateral pars planitis); posterior pole and peripheral mass; peripheral mass with retinal detachment; diffuse endophthalmitis. Gillespie et al. (1993a) recorded the following causes of severe visual loss in ocular toxocariasis: fibrous traction band; endophthalmitis; macular lesion; retinal detachment; pars planitis; papillitis.

Covert Toxocariasis

Taylor et al. (1988) suggested that the term 'covert toxocariasis' might be used for toxocar-iasis which did not fall into the categories of visceral larva migrans or ocular larva migrans. They reported 18 clinical features in an investigation of 221 subjects and added a further four clinical features detected on clinical examination of 167 subjects. The features most commonly associated with a raised Toxocara titre were abdominal pain, hepatomegaly, anorexia, nausea, vomiting, sleep and behaviour disturbance, pneumonia, cough, wheeze, pharyngitis, cervical adenitis and limb pains. These studies were carried out on children attending hospital and on their families. Glickman et al. (1987) had reported 15 signs and symptoms in 37 French adults with visceral larva migrans. Ten of the features they described were the same as those reported by Taylor et al. (1988) but with different frequency, which may be due to differences of age, race, atopic background, duration of infection or parasite differences between the two countries.

Other Associated Illnesses

Social, Learning and Behavioural Abnormalities

Behavioural and learning abnormalities have been demonstrated in mice infected with Tox-ocara canis (Cox, 1997; Cox and Holland, 1998). Infected mice perform less exploration, respond less to novelty and exhibit impaired learning ability. Aggression is reduced in infected animals, which may lead to a reduction in dominance. In humans the situation is less clear. Lower academic performance was recorded in infected children, but this effect was not significant when social class was taken into account (Worley et al., 1984). Marmor et al. (1987) reported small deficits in neuropsychological testing of Toxocara-positive children. Taylor et al. (1988) reported higher rates of behaviour disturbance in children with raised Toxocara titres. Nelson et al. (1996) assessed the risk factors for toxocariasis in a prospective study of disadvantaged pre-school children in addition to testing the hypothesis that T. canis exposure is associated with lower intelligence. Their findings suggested that for disadvantaged children, lower initial intelligence and less advantageous child rearing are risk factors for Toxocara exposure, but they failed to show a significant association between lower intelligence and infection.

Epilepsy

There have been conflicting reports regarding an association or lack of association between epilepsy and Toxocara titres (Woodruff et al., 1966; Arpino and Curatolo, 1988; Glickman et al., 1979). Glickman et al. (1979) noted that, while raised Toxocara titres were more common in those with epilepsy, pica was reported in 64% of this group compared to 19% of controls. Geophagia (earth-eating) is associated with a raised Toxocara titre (Holland et al., 1995), which may well explain why Glickman and colleagues found more raised Toxocara titres in their epilepsy group than in controls. Arpino et al. (1990) reported a significant association between seropositivity and epilepsy, but noted that that pica was more common in children with seizures. Logistic regression for risk factors was not reported in this study.

Good, Holland and Taylor (unpublished observations) have found no association between convulsions and a raised Toxocara titre in a community study of over 100 000 schoolchildren but have found an association between convulsions and toxocaral eye disease in a case-control study. In a case-control investigation of human Toxocara infection of the central nervous system, Magnaval et al. (1997) failed to find an association between case status and clinical signs but did record a signification association between case

Table 19a.3 Comparison studies investigating a relationship between asthma and Toxocara seropositivity

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