Recent advances in chest computed tomograhy (CT) scan screening have led to an increase in the detection of unexplained multiple pulmonary patchy infiltrate (1, 2). Various kinds of diseases, such as infections, allergic diseases and malignancies, should be considered to be causes of unexplained pulmonary infiltrate. Parasitic infection is one of these causes, especially in combination with eosinophilia. A recent report on toxocariasis in Korea presents that 32 of 141 toxocariasis patients had pulmonary involvement (3). Toxocariasis is a zoonosis caused by ascarids from dogs or cats, Toxocara canis or Toxocara catis, in which animals they live as adults within the lumen of the small intestine. Human infection is aberrant and usually asymptomatic, but can cause visceral larva migrans to spread to specific target organs such as the liver, lung, eye, and central nerve systems. Visceral larva migrans may result in patients who present with fever, hepatosplenomegaly, lower respiratory symptoms such as bronchospasm, eosinophilia sometimes approaching 70%, and hypergammaglobulinemia of immunoglobulin M, G, and E.

Definitive diagnosis of visceral larva migrans in the lung can be made by tissue biopsy, but this is difficult to perform in the clinical setting. Therefore, the diagnosis of toxocariasis is primarily reached immunologically. The enzyme-linked immunosorbent assay (ELISA) using antigens secreted by second stage larva is the best indirect test for diagnosing this infection (4). The seroprevalence of toxocara is high in tropical areas and developing countries, but relatively low in developed countries. The seroprevalence among adult populations is 2.4% in the U.S.A. and 4.0% in Switzerland, but 20.5% in Brazil and 30.4% in Nigeria (5). The toxocara seroprevalence is closely related to the practice of eating raw liver (6). The seroprevalence among Korean rural adults is reported to be 5% (female: 6.1%, male: 4.0%) (7).

Toxocara larva migrans in lung is usually asymptomatic or elicits only nonspecific mild symptoms, although it can also cause pulmonary infiltrate due to a hypersensitive reaction to larva. However, the prevalence and clinical importance of toxocariasis among patients with unexplained pulmonary patchy infiltrate is unknown, and would be expected to vary along with the eating habits of the population.

Recently, many patients with unexplained pulmonary infiltrate have been referred to the Respiratory Center of Seoul National University Bundang Hospital from among the total patients screened by low dose chest CT scan at the Health Care Promotion Center of Seoul National University Bundang Hospital. Many of these patients displayed transient or migratory infiltrate on follow-up chest CT scan that were suggested to be of a transient immunologic or inflammatory nature. Therefore, we designed this study to identify the prevalence of toxocariasis in unexplained multiple pulmonary patchy infiltrate and to evaluate the clinical and laboratory factors associated with toxocariasis.

Toxocarial infection in humans can occur by the ingestion of viable, embryonated eggs from contaminated soil or hands (8, 9). Therefore, the seroprevalence of toxocara is high in younger children and low in adults. The risk factors of toxocariasis in children are local animal population, high prevalence of toxocara species in dogs and cats, soil contamination by infective toxocara eggs, low socioeconomic condition, and high frequency of pet ownership (10). However, a major risk factor for toxocariasis in adults is the ingestion of viable eggs from the uncooked internal organs or meat of parasitic hosts, especially raw cow liver (5, 6, 11-13). Visceral larva migrans to the liver, lung, eye and central nerve systems are largely dependent upon the death of larvae. Their death occurs due to both delayed and immediate hypersensitivity responses and results in an eosinophilic granulomatous reaction and pulmonary infiltrate in the lung (4).

In present study, a positive result on ELISA for toxocara was higher among patients with pulmonary infiltrate, compared with people with normal findings on chest CT scan, even after the adjustment for eosinophilia and intake of raw cow liver.

We showed GGO, GGO combined with consolidation, or GGO combined with nodules to be a common finding in the multiple pulmonary patchy infiltrate. Kim et al. have reported the most common finding on chest CT scan in patients with toxocariasis to be randomly distributed GGO (3). Also in toxocara seropositive patients, the peripheral eosinophil count is reported to be higher than in seronegative patients. This finding is correlated with the finding that toxocariasis is one of the causes of pulmonary infiltrate with eosinophilia (14).

In Korea, there are dietary habits that include eating of raw meat, including raw animal liver, especially cow liver, for the promotion of health, among adults. According to the responses to our questionnaire, 88 of the 102 patients with unexplained pulmonary infiltrate and 52 of 116 in the control group had a history of intake of raw cow liver that explained the relatively high seropositivity. This study shows that intake of raw cow liver and eosinophilia are major predictors for toxocara seropositivity among patients with unexplained pulmonary patchy infiltrate. These results indicate that physicians should consider testing for toxocariasis in patients with unexplained pulmonary infiltrate and a history of intake of raw cow liver, especially with peripheral blood eosinophilia.

Most toxocariasis is self-limiting, but the treatment of choice is albendazole (10 mg/kg of body weight/day for 10-14 days) and/or corticosteroids. In the present study, the pulmonary infiltrate of patients (over 80%) with toxocara seropositivity improved with or without treatment. This strongly suggests that ELISA test for toxocariasis and follow-up chest CT scan at 3 month intervals might reduce unnecessary diagnostic workups for unexplained pulmonary patchy infiltrate.

There are limitations of this study which should be acknowledged. First, it was difficult to identify the exact causal relationship between seropositivity of toxocara and pulmonary toxocariasis. This problem is inevitable because the diagnosis of toxocariasis is dependent on an immunologic assay such as ELISA. A definitive laboratory diagnosis of human toxocarial infection can be achieved by pathology examination of involved organ specimens, including the liver, brain, lung or enucleated eye. However, such a direct parasitologic assessment is difficult because larva is mobile as well as invasive. Therefore, serologic methods are the mainstay for the diagnosis. Although previous studies have been rare (15), ELISA and eosinophil counts in bronchoscopic lavage fluid can be helpful. Second, toxocara IgG detected with ELISA method can persist several months after infection (16, 17). Therefore, in this study history of raw cow liver intake was restricted within previous one year. Third, the seroprevalence (22.4%) in the control group is higher than the reported seroprevalence (5%) in rural districts of Korea in a previous study (7). This difference could be explained by differences in the ELISA kits and also the different populations. Both studies used toxocara excretory-secretory antigen (TES). A previous study (7) defined the seroprevalence of toxocariasis as a positive reaction to a self-made ELISA kit against TES and a positive reaction on immunoblot to toxocara in case of positive patients with ELISA. However, the present study used the toxocara ELISA kit from Bordier Affinity products (Crissier), which is well standardized and has a reasonably high sensitivity (86%) and specificity (91%) (18). In another study on the prevalence of toxocariasis among patients with unknown eosinophilia in Korea using the same ELISA kit as used in this study, 68% of patients with unknown eosinophilia were diagnosed as having toxocariasis (11). Although there was an epidemiologic study using this kit in developed countries (18), further epidemiologic study using this kit is required in Korean population. Furthermore, the control group of this study specifically included the adult patients receiving low-dose chest CT scan for lung cancer screening in Seoul National University Bundang Hospital with a history of raw cow liver ingestion (45%). The male predominance of those who received low dose chest CT scan for lung cancer screening would be another likely factor, as men reportedly more frequently ingest raw cow liver than women do. Seropositive subjects with eosinophilia in control group may have toxocariasis without lung involvement.

In conclusion, the prevalence of toxocara seropositivity was high in patients with unexplained pulmonary multiple patchy infiltrate, and a strong relationship was found between toxocara seropositivity and raw cow liver intake. We recommend that toxocara ELISA should be performed in patients with unexplained multiple pulmonary patchy infiltrate with peripheral blood eosinophilia and the eating of raw cow liver should be actively discouraged.