Adult human case of toxocariasis with pulmonary migratory infiltrate and eosinophilia

Introduction. Toxocariasis is a zoonosis which is in Serbia characterized with a very high infection rate of dogs and excessive contamination of the soil with the eggs of Toxocara canis, the agent of the disease. Toxocara-induced infections have in recent years been established in a few hundreds of children, but toxocariasis has rather rarely been diagnosed in adults. Case report. We reported toxocariasis (visceral larva migrans) in an adult, manifested by migratory pulmonary infiltrates and positive serological test finding to Toxocara. Conclusion. Human toxocariasis is a rare disease in adults, therefore it should be considered in adult patients presented with eosinophilia and migratory pulmonary infiltrates.


Introduction
Toxocariasis is a well-known parasitic zoonosis caused by Toxocara canis, with the soil transmission cycle which includes dogs and other canis as natural hosts and many mammals and birds as paratenic or transport hosts.Toxocariasis is present in nearly 100% of the dog population in Serbia, due to transplacental infection of puppies and climate conditions suitable for embryonation of Toxocara ova in the soil, especially in urban places and children playgrounds 1,2 .The major route of transmission to humans is through the ingestion of embryonated ova from the soil.As in other regions with a temperate climate, in Serbia toxocariasis has been diagnosed mostly in children, as visceral and rarely ocular involvement [3][4][5] .However, in adults toxocariasis has obscure symptoms and in Serbia it has been extremely rarely confirmed, mostly in its ocular form 5 .Migratory eosinophilic pneumonia induced by the visceral larva migrans in adults is not a common manifestation of toxocariasis, motivating us to report the case of a 20year the female patient.
Although most human infections are asymptomatic, two well-defined clinical syndromes are classically recognized: visceral larva migrans and ocular larva migrans.Additional two less severe syndromes have also been described one mostly in children (covert toxocariasis), and the other pravailing in adults (common toxocariasis) [6][7][8] .The diagnosis is established on the basis of laboratory findings of excessive eosinophilia, particularly the finding of specific antibodies to Toxocara in blood.Exceptianally polymorphic clinical pres- entation makes the clinical diagnosis of toxocariasis difficult, so the diagnostic algorithm should be strictly applied 9 .

Považan
We reported case of an adult toxocariasis with pulmonary involvement, the diagnosis difficult to establish.

Case report
In 2006, a 20-year old female patient was admitted to the Institute for Pulmonary Diseases of Vojvodina (IPDV) in Sremska Kamenica, Serbia, with a few months long history of symptoms, including occasional subfebrile body temperatures, fatigue, hyperhydrosis and bilateral lung lesions seen on chest computerized tomography (CT) finding, accompanied with persisting eosinophilia in the blood.Due to these symptoms, the patient visited the doctor several times and had total blood count analyses.Having performed CT screening of the chest to more accurately enlighten the morphology of lung lesions seen on the chest radiography, the patient was referred to the Insitute for Pulmonary Diseases of Vojvodina (IPDV).
On admission, the patient was conscious, oriented, subfebrile, withouth cardiac disease, with a slightly enlarged lymph node on the left neck, complaining about fatigue and excessive sweating, free of cough or skin lesions.The anamnestical data revealed the patient came from the country and had puppy pets.
The chest radiography finding was presented with an excessively marked bronchovascular contour and a tiny, roundish, inhomogeneous lesions partially in the intermediary and lower lung portions bilaterally and one infiltrate on the left basal field (Figure 1).The CT finding obtained immediately prior to admission was presented with roundish, uncleanly delineated to the periphery, inhomogeneous, hyperdense lesions of 6-8 mm in the diameter, localized on the left, in the projection of the basal and the Fowler ' s segment.The finding suggested micronodular infiltrative lesions were involved in these localizations, and one infiltrate over 1 cm on the left (Figure 1).
The following blood test findings were obtained: erythrocyte sedimentation rate was 20/35, C-reactive protein (CRP) level < 6 mg/L, and white blood count (WBC) 5.3  10 9 /L, with 18% of eosinophils, and immunoglobulin levels of IgA 4.4 g/L, IgM 3.6 g/L, IgG 13.1 g/L.The tuberculin and virological tests were negative.The sputum and catheter biopsy samples examined for Mycobacterium tuberculosis by smear and by culture were negative.Bacteriological findings of the nose and throat swab samples, as well as the sputum ones were negative, as well.The cytological sputum analysis recurrently suggested the presence of eosinophil granulocytes.The stool assay for parasite eggs and larvae was negative.
Lung function tests were normal, and the bronchial challenge with carbachol was negative, as well.Blood gas analyses at rest and on exertion of 80 W were normal.Allergy examination by a prick test revealed no hypersensitivity to examined standard inhalant allergens.
Ultrasound (US) scanning of the upper abdomen showed the liver approximated 151 mm in diameter, with a homogeneous structure, and the pancreas, spleen and gall bladder were normal, as well.
The bronchoscopy finding was normal, and all the histological samples (catheter biopsy and transbronchial biopsy) taken from the left lung in the course of bronchoscopy had normal features, excluding the presence of few eosinophils.Bronchoalveolar lavage (BAL) of the middle lobe revealed the increased presence of eosinophils (24%), with 64% macrophages, 8% lymphocytes and 4% segmented neutrophils.
To better enlighten descrete lung lesions, a control CT screening of the chest was performed three weeks later, revealing infiltrative migratory lesions of an altered localization and density as compared to those seen in the former CT finding.
Due to enlarged cervical lymph nodes and as recommended by the hematologist, magnetic resonance (MR) imaging of the neck and endocranium was performed, revealing cervical lymphadenomegaly (enlarged nuchal lymph nodes bilaterally with the largest diameter of 12.8 mm, as well as the supraclavicular ones on the right, reaching 11.8 mm in diameter), without pathological lesions in the endocranium.
A high percentage of eosinophils (17%) persisted in blood.Taking into account the age of the patient, laboratory and chest CT findings, the diagnosis of the hypereosinophilic syndrome and eosinophilic pneumonia was established.
Corticosteroid therapy (prednisone 30 mg per day) was initiated resulting in a complete radiological regression and eosinophil count reduction in ten days.The patient's general condition was satisfactory, but elevated eosinophil counts in the peripheral blood persisted.After a 6-month corticosteroid treatment, eosinophil count was normalized (5% of eosinophils), so corticosteroids were discontinued.But, as the eosinophil count increased to 28% as soon as the corticosteroid treatment had been discontinued (Figure 2), corticosteroids were reintroduced into the treatment to include daily pronisone doses of 30 mg per day.

Fig. 2 -Eosinophilia: course and levels with and without corticosteroid therapy
To enlighten the etiology of persisting eosinophilia, additional analyses were performed: antistreptolysin titre, antiechinococcal antibodies, antinuclear, antimitochondrial, antithyroid, antiparietal, anti-smooth muscle and anticardiac antibodies, and they were negative.Complement 3 (C 3 ) and complement 4 (C 4 ) findings were normal, too.The ultrasound (US) and hormone findings of the thyroid were normal, as well.The cytological finding of the bone marrow sample was presented with an elevated percentage (15%) of eosinophil cells.The repeate examinations of the stool and perianal print samples revealed no eggs of intestinal parasites.The assay for eosinophils of the nose secretion sample established 300 eosinophils per low magnification microscopic field.
Cytological analysis of the sputum and nose secretion sample, and the histological assay of the transbronchial biopsy sample established the presence of eosinophils, accompanied with an increased percentage of eosinophils in the BAL and bone marrow sample and eosinophilia in blood suggest idiopathic hypereosinophilic syndrome with pulmonary involvement.
At the and, the indirect immunofluorescent test for toxocariasis in the serum was significantly positive, in the titre of 1 : 80 in the course of corticosteroid treatment.
A team of experts including a pulmologist, hematologist, parasitologist and an immunologist, indicated that the treatment with low-dose prednisolone accompanied with a further follow-up of the patient, should also include an anthelmintic drug (albendazole in the dose of 15 mg/kg/body mass over 30 days), establishing the final diagnosis: Toxocariasis, Pneumonia eosinophilica, Eosinophilia persistens.
At subsequent controls the patient was free of symptoms, with normal eosinophil count in blood, without patho-logical lesions in radiograpy, and the negative finding of the immunofluorescent test for toxocariasis was achieved after two years.

Discussion
Migratory pulmonary infiltrates, eosinophilia in blood and bronchial exudate and positive serology suggested the diagnosis of toxocariasis in our patient.After the hospital treatment and a long-term outpatient treatment and control, a regression of eosinophilia and negative serological assay two years later, strongly confirmed the diagnosis of the classical larva migrans syndrome caused by Toxocara canis.A long diagnostic procedure in our patient was due to a great rarity of toxocariasis in adult population in Serbia.So far, just a few cases of ocular involvement in adults have been registered 5 , in contrast to a great number of cases in children with diverse clinical manifestations 2 .
The infection of children is easy to explain.The geooral transmission, especially in children with geophagia, is well-known.In adult patients without risky behavior, with good hygienic standards, the Toxocara infection is possible by ingestion of infected meat of other paratenic hosts.Meat as a source of infection has been mentioned in the literature.Serological investigations in Britain have shown that the pig serves as a paratenic host for Toxocara canis, with 4.5% of pigs having antibodies against Toxocara canis 10,11 .Seroepidemiological studies throughout the world have shown the most common prevalence of the general population is 2%-7% in moderate climate, but significantly higher in tropical regions.In spite of numerous studies in this field performed in Serbia, we lack accurate data, but it has been well established that toxocariasis is a rare disease in adulthood 9 .
Parasitic infections may induce pulmonary eosinophilia and pulmonary lesions, so it is necessary to have a good knowledge on inducing agents of pulmonary eosinophilia, its manifestations, diagnostic approach and treatment 12 .
Toxocariasis is one of the inducing agents of eosinophilic lung infiltrates.A study carried out in Korea reports 102 patients with pulmonary infiltrates diagnosed by CT screening of the chest who also had a positive serological finding in toxocariasis and blood eosinophilia.On the control chest CT finding, 35% of the patients had migratory infiltrates, and 48% of them were presented with regression of pulmonary lesions 13 .Computerized tomography chest screening provides a better morphological presentation of pulmonary lesions, so we apply this imaging technique as other authors.Our reported patient also had migratory infiltrates seen on the control chest CT finding, as described in this case report.Migratory nodular lesions were also seen on the control CT finding in a 30-year old male patient with eosinophilia and a positive serological finding of Toxocara canis 14 .
The relevance of an elevated percentage of eosinophils in the BAL fluid has also been recognized by the authors from Osaka, who reported a 38-year old female patient with the symptoms of cough, blood eosinophilia, lung infiltrates and 94% of eosinophils in the BAL fluid, while we found 24%.The diagnosis of visceral larva migrans (VLM) was made on the basis of the positive results in the enzymelinked immunosorbent assay for Toxocara canis, supported by the clinical symptoms and laboratory findings 15 .
The relevance of chest CT screening and BAL analysis has also been recognized by Polish authors who reported a 32-year old patient with Toxocara infection.The diagnosis was confirmed by serological tests with anti-Toxocara canis antibodies, bronchial lavage and chest CT scan with disseminated lung lesions 16 .
Toxocariasis is one of the inducing agents of eosinophilia in the peripheral blood and eosinophilic infiltrates in an organism.The authors from Israel report that many cases may be diagnosed just as hypereosinophilia syndrome in case the serological test with Toxocara is not applied 17 .It was the case in our patient who, despite the applied corticosteroid treatment developed an increase and persistence of eosinophils, indicating a larger-scale investigations including an immunofluorescent assay which confirmed toxocariasis.There is no doubt it is crucial to establish an accurate diagnosis, requiring a good knowledge diagnostic algorithm for eosinophilia.Due to an activated immunoinflammatory reaction, our patient developed enlarged lymph nodes of the neck.
The diagnosis of larval migrans is usually done by immunodiagnostic methods 18 .
Serological tests with Toxocara are recommended in patients with pulmonary infiltrates of unknown etiology 13 , and the diagnosis of VLM is established by positive serological findings for Toxocara canis, together with the clinical symptoms and laboratory findings [14][15][16] .
Having obtained a significantly positive indirect immunofluorescent test finding of toxocariasis in serum in our patient, we introduced albendazole in the treatment.The authors from Osaka reported an adult patient with VLM and pulmonary infiltrates, with histologically established eosinophilic pneumonia persisting for seven weeks prior to introducing the antihelminthic therapy with albendazole 15 , that was also the case in our patient in whom all blood findings did not regain normal levels before albendazole had been applied.
The duration of the treatment with albendozole, which is diversely approached, is also analyzed by the authors who report a 42-year old patient with fever, productive cough, dyspnea, ground glass opacities mainly in the upper and middle lung fields on chest radiography.The symptoms dis-appeared on antibiotic treatment, but eosinophilia persisted, so the investigations were, as in our case, extended and Toxocara canis larva migrans was diagnosed.Four-week albendazole treatment was applied, but as eosinophilia reoccur after one month discontinuation, the treatment was prolonged for additional eight weeks 19 .
Numerous studies investigated undesirable side effects of albendazole.Some authors, however, recognize its efficacy without side effects for the tratment of toxocariasis in children 20 .Jevtić et al. 21analyze a long-term treatment with high albendazole doses in patients with cystic echinococcosis, establishing significantly elevated transaminase levels in serum, which in most patients regain to normal in six months.New efficient drugs of this group should therefore be discovered 21,22 .
The clinical forms are non-specific but frequent and varied (neurological, opthalmologic, pulmonary, cutaneous and sometimes rheumatological) 23 .The following skin manifestations have been described in patients with toxocariasis: chronic urticaria, chronic pruritis and eczema.In many cases, these skin manifestations appear as sole symptoms of the disease, developing after antihelmitic treatment 7 .Ocular toxocariasis is usually a unilateral disease and the authors report a 71-year old female patient with ocular toxocariasis of the left eye and unilaterally deteriorated sight and strabism, pointing out the exposure to pets -dogs and cats, as risk factors for Toxocara infection 8 .
Our patient had cervical lymphadenopathy, which was resolved after the applied treatment.It correlates with a case report of a 7-year old boy with toxocariasis reporting that the initial corticosteroid cotreatment succeeded by thiabendazole resulted in a regression of lymphadenopathy and normalization of a total blood and eosinophil count 24 .It is therefore suggested that infection with Toxocara canis should be considered in cases with generalized lymphadenopathy accompanied with fever, hepatosplenomegaly and eosinophilia.

Conclusion
We reported a case of visceral larva migrans in an adult patient with migratory pulmonary infiltrates and positive serology.Due to a prolonged diagnostic management of our patient, we emphasize this little known zoonosis in adult patients which should be considered in case of eosinophilia and pulmonary infiltrates.