Immune response to chronic Toxocara canis infection in a mice model.

AIMS: The zoonotic nematode Toxocara canis causes larva migrans syndrome that induces an immune response characterized by the production of antibodies and eosinophilia. A Th2 polarization has been associated with the infection, but there are still details of the cellular and humoral immune response that need to be described. Thus, the aim of this study was to describe the systemic host immune response to T canis chronic infection in a mouse model. METHODS AND RESULTS: BALB/c mice were inoculated once with 500 T canis embryonated eggs, per os. After 49 days, the amounts of larval found in brain and muscle tissues were statistically two and four times higher, respectively, than the amounts found in lung, liver, kidney or heart tissues. Splenic proportions of F4/80+ cells, as well as B, cytotoxic T and CD4+ Foxp3+ lymphocytes, were statistically higher (P ≤ .05, P ≤ .01, P ≤ .001 and P ≤ .001, respectively) as compared with control mice. In lymph nodes, some of these proportions changed, with the exception of F4/80+ cells. IgG1 levels in infected mice sera were increased. IL-4, IL-10 and VEGF levels were statistically higher in spleen (P ≤ .05, all) and sera (P ≤ .01, P ≤ .05 and P ≤ .05, respectively) in the infected mice. Also, in infected animals, IL-5 serum levels were increased (P ≤ .01). CONCLUSION: These results suggest that T canis chronic infection in BALB/c mice results in a type 2 response with an incipient regulatory response.

Seroprevalence and associated risk factors of Toxocara infection in Korean, Manchu, Mongol, and Han ethnic groups in northern China.

Toxocariasis is a very prevalent zoonotic disease worldwide. Recently, investigators have focused more on Toxocara spp. seroprevalence in humans. Information regarding Toxocara seroprevalence in people from different ethnic backgrounds in China is limited. For this study, blood samples were collected from a total of 802 Han, 520 Korean, 303 Manchu, and 217 Mongol subjects from Jilin and Shandong provinces. The overall Toxocara seroprevalence was 16·07% (14·21% Han, 20·58% Korean, 11·22% Manchu, 18·89% Mongol). Living in suburban or rural areas, having dogs at home, exposure to soil, and consumption of raw/undercooked meat were risk factors for Toxocara infection. Exposure to soil was identified as the major risk factor for Toxocara seropositivity in all of the tested ethnicities. To the best of our knowledge, this is the first report concerning Toxocara infection in Manchus and Mongols in China. The present study provided baseline data for effective prevention strategies of toxocariasis in northeast China and recommends improvements in personal hygiene standards to achieve this goal.

Immunoblot for the detection of Ascaris suum-specific antibodies in patients with visceral larva migrans (VLM) syndrome.

Visceral larva migrans (VLM) syndrome caused by Toxocara canis larvae was first described in the 1950s. The role of other nematode larvae, i.e. the pig roundworm Ascaris suum as a causative agent of visceral larva migrans-associated symptoms like general malaise, cough, liver dysfunction, hypereosinophilia with hepatomegaly and/or pneumonia, was discussed controversially during the last decades. Recent serological screening studies for specific A. suum antibodies carried out in the Netherlands and Sweden yielded remarkable high seroprevalences, while a number of case reports from Japan report pulmonal, hepatic and cerebral symptoms caused by A. suum larvae after ingestion of infected raw meat (liver) or contaminated vegetables. We present here a sensitive and specific larval excretory-secretory (E/S) antigen-based immunoblot (As-IB) for the serodiagnosis of A. suum-infected patients suffering from symptoms associated to the VLM syndrome. In total, 34 sera from patients with hypereosinophilia and other clinical symptoms associated to the VLM syndrome tested negative for Toxocara sp. antibodies but positive in our newly established As-IB, 30 sera from healthy volunteers, 53 sera from patients with clinically and serologically confirmed toxocarosis and other helminthoses as well as 3 sera from patients with intestinal ascariosis due to Ascaris lumbricoides were included in the study. When evaluated with 30 sera from healthy volunteers and 53 sera from patients suffering from different helminthoses, the calculated specificity of our new As-IB is 95%. Problems hampering the establishment of simple serological screening tests for specific A. suum antibodies, like extensive antigenic similarities between the nematodes Ascaris and Toxocara or the absence of suitable experimental animals, are discussed. We assume that specific serological testing for antibodies of A. suum is very important for the treatment of individual patients on one hand and seroepidemiological investigations will help to clarify routes of transmission on the other hand. Further studies will be necessary to learn more about the extent of A. suum as a causative agent of the VLM syndrome and the role of pigs and their manure as the main source of human Ascaris infections in Austria and other industrialized countries.

Alterations of plasma circulating microRNAs in BALB/c mice with Toxocara canis visceral and cerebral larva migrans.

BACKGROUND: Human toxocariasis is a neglected parasitic disease characterised by the syndromes visceral, cerebral, and ocular larva migrans. This disease is caused by the migrating larvae of Toxocara roundworms from dogs and cats, affecting 1.4 billion people globally. Via extracellular vesicles (EVs), microRNAs have been demonstrated to play roles in host-parasite interactions and proposed as circulating biomarkers for the diagnosis and follow-up of parasitic diseases. METHODS: Small RNA-seq was conducted to identify miRNAs in the infective larvae of T. canis and plasma EV-containing preparations of infected BALB/c mice. Differential expression analysis and target prediction were performed to indicate miRNAs involved in host-parasite interactions and miRNAs associated with visceral and/or cerebral larva migrans in the infected mice. Quantitative real-time polymerase chain reaction (PCR) was used to amplify circulating miRNAs from the infected mice. RESULTS: This study reports host and parasite miRNAs in the plasma of BALB/c mice with visceral and cerebral larva migrans and demonstrates the alterations of these miRNAs during the migration of larvae from the livers through the lungs and to the brains of infected mice. After filtering unspecific changes in an irrelevant control, T. canis-derived miRNAs and T. canis infection-induced differential miRNAs are predicted to modulate genes consistently involved in mitogen-activated protein kinase (MAPK) signalling and pathways regulating axon guidance and pluripotency of stem in the infected mice with visceral and cerebral larva migrans. For these plasma circulating miRNAs predicted to be involved in host-parasite crosstalk, two murine miRNAs (miR-26b-5p and miR-122-5p) are experimentally verified to be responsive to larva migrans and represent circulating biomarker candidates for visceral and cerebral toxocariasis in BALB/c mice. CONCLUSIONS: Our findings provide novel insights into the crosstalk of T. canis and the mammalian host via plasma circulating miRNAs, and prime agents and indicators for visceral and cerebral larva migrans. A deep understanding of these aspects will underpin the diagnosis and control of toxocariasis in humans and animals.

Alteration of cytokine production during visceral larva migrans by Toxascaris leonina in mice.

To determine alteration of immune responses during visceral larva migrans (VLM) caused by Toxascaris leonina at several time points, we experimentally infected mice with embryonated eggs of T. leonina and measured T-helper (Th) cell-related serial cytokine production after infection. At day 5 post infection (PI), most larvae were detected from the lungs, spleen, intestine, and muscle. Expression of thymic stromal lymphopoietin (TSLP) and CCL11 (eotaxin) showed a significant increase in most infected organs, except the intestine. However, expression of the CXCL1 (Gro-α) gene was most highly enhanced in the intestine at day 14 PI. Th1-related cytokine secretion of splenocytes showed increases at day 28 PI, and the level showed a decrease at day 42 PI. Th2-related cytokine secretion of splenocytes also showed an increase after infection; in particular, IL-5 level showed a significant increase at day 14 PI, and the level showed a decrease at day 28 PI. However, levels of Th17-related cytokines, IL-6 and IL-17A, showed gradual increases until day 42 PI. In conclusion, Th1, Th2, and Th17-related cytokine production might be important in immune responses against T. leonina VLM in experimental mice.

Liver abscesses caused by visceral larva migrans: Aimless wanderer separated from the host.

Visceral larva migrans (VLM) is a systemic zoonotic parasitic disease caused by migration of the second stage larva through viscera of humans. Despite being a foremost public health problem in low- and middle-income countries (LMICs) such as India, larva migrans remains an untended zoonosis. Here, we report two cases of VLM who presented with fever and abdominal pain for a prolonged duration. On further investigation, marked peripheral eosinophilia with multiple confluent necrotizing eosinophilic granulomas were identified on histopathological examination of the liver.

Visceral larva Migrans in a Young Italian Patient: A Diagnostic Dilemma.

BACKGROUND: The association of fever, focal hepatic lesions and peripheral hyper-eosinophilia (FHLH) can be observed in both infectious and non-infectious conditions. Fascioliasis, capillariasis, toxocariasis, all causes of visceral larva migrans (VLM), represent most of the former, whilst lymphomas, eosinophilic leukemias and mastocytosis belong in the non-infectious conditions. METHODS: We prospectively followed a young patient presenting with FHLH in the Tuscany region of Italy. RESULTS: The patient was subject to serological and parasitological examination in an attempt to clarify the origin of the lesions. Serologies for both Fasciola hepatica and Toxocara spp. were positive, with the latter presenting a higher index. We opted for treatment with a prolonged course of albendazole due to the serological results and being toxocariasis more frequent in our setting. The patient was then subject to radiological follow-up. The patient responded to treatment with albendazole as shown by a decrease in eosinophils, seronegativization for Toxocara spp., clinical and radiological improvement. Toxocariasis was hence considered the most likely diagnosis. CONCLUSIONS: Parasitic infections cannot be disregarded in the presence of FHLH. Differential diagnosis between these parasitic infections can be challenging due to the presence of similar clinical presentations and serological cross-reactions, and follow-up of the patient is needed to ensure optimal treatment outcomes.

Visceral larva migrans in immigrants from latin america.

To determine whether increased migration is associated with an increase in incidence of toxocariasis (visceral larva migrans), we analyzed clinical data obtained from immigrants from Latin America. Although infection with Toxocara sp. roundworm larvae is distributed worldwide, seroprevalence is highest in tropical and subtropical areas.

[Occurrence of Toxocara spp. eggs in household environment of children with diagnosed toxocariasis in Lódz voivodeship]. / Czestosc wystepowania jaj inwazyjnych Toxocara spp. w srodowisku przydomowym dzieci ze zdiagnozowana toksokaroza w woj. lódzkim.

Toxocariasis is a zoonosis due to infection of humans by dog or cat roundworm (Toxocara canis, T. cati). Humans become infected by ingestion of infective eggs either from soil, dirty hands, raw fruits and vegetables or larvae from undercooked meat of paratenic hosts. The aim of the study was to evaluate the level of contamination of soil samples from households of children with diagnosed toxocariasis in rural and urban areas of Lódz voivodeship. In the years 2004-2007 toxocariasis was confirmed in 178 patients of the Polish Memorial Hospital in Lódz. The soil samples were collected from 53 courtyards of patients' domiciles. Toxocara spp. eggs were isolated from the samples using flotation technique (Dada 1979). The examinations revealed the high prevalence of ground contamination with Toxocara eggs in both, rural (30.4%) and urban areas (23.3%). The presence of Toxocara eggs in households enlarges the risk of re-infection for children with diagnosed toxocariasis, especially in rural areas where the high level of contamination was detected.

Visceral larval migrans of Toxocara canis and Toxocara cati in non-canid and non-felid hosts.

Toxocara canis and Toxocara cati are considered the most ubiquitous gastrointestinal helminths in domesticated canids and felids. Ascarid eggs passed in the faeces of canids and felids in a suitable environment may remain infective for years and are capable of infecting not only canids and felids, but a large range of other vertebrate paratenic hosts, including man. Infection with Toxocara species also occurs following the ingestion of paratenic hosts containing infective larvae. As infective larvae are incapable of completing their lifecycle in these hosts, they instead travel to different parts of the body, sometimes inducing inflammatory responses, and in some cases remaining entrapped in the body for years. Migration routes depend on the host species; however, nearly all organs may be affected with varying quantities of larval burdens.

Status of human toxocariasis, a neglected parasitic zoonosis in Iran: a systematic review from past to current.

Although human toxocariasis can lead to serious complications including neurological, ocular and visceral complications, there is a lack of comprehensive epidemiological information about the seroprevalence of Toxocara species in humans. In the present study, we analysed and reviewed the overall seroprevalence of human toxocariasis in Iran. The data collection was systematically undertaken on published articles using the PubMed, Google Scholar, ScienceDirect and Scopus databases. A total of 27 studies from the past two decades reporting seroprevalence of human toxocariasis met our eligibility criteria. The pooled proportion of Toxocara infection was estimated as 6.58% (95% confidence interval = 3.98-9.77). A wide variation between different studies was observed (Q statistic = 799.37, df = 26, P < 0.0001, and I2 = 96.7%). The seroprevalence rate of toxocariasis in the Iranian population is relatively high; contamination of the environment by eggs from the host as well as from household dogs and cats should be blamed.

A familial case of visceral toxocariasis due to consumption of raw bovine liver.

We present 3 adult cases of visceral toxocariasis from the same family, who each consumed thin slices of raw bovine liver weekly, and developed eosinophilia and multiple small lesions in their livers and lungs. Serological examinations using the larval excretory-secretory product of Toxocara canis strongly indicated infection with Toxocara species larvae. The patients responded well to treatment with albendazole. Ingestion of raw liver from paratenic animals is considered to be a common transmission route of human toxocariasis, especially in adults.

Toxocariasis of the liver: visceral larva migrans.

Toxocariasis is caused by dog ascarid, Toxocara canis, forming eosinophilic inflammation such as eosinophilic abscess or granuloma in the liver and lungs. The lesions move slowly and thus the disease is called as visceral larva migrans. On CT or MR imaging, hepatic lesions are seen as multiple, ill-defined, oval lesions that measure 1.0-1.5 cm in diameter. Sometimes, the lesion may be angular or trapezoid. The lesions are usually best seen on the portal venous phase in dynamic contrast-enhanced CT and MR imaging; the lesions are either not seen or only faintly seen on arterial and equilibrium phases. Either an enhancing rim or enhancing nodules are sometimes observed. On sonography, the lesions appear as multiple, small, oval hypoechoic lesions in the liver parenchyma. The lesions differ from metastatic nodules is as much as they have fuzzy margins, are uniform in size, non-spherical shape and are best seen on portal venous phase. On follow-up imaging, the lesions may improve, or sometimes a change positions, reflecting migration of larva in the liver, supporting the phenomenon of visceral larva migrans.

[Analysis of children with a presumptive diagnosis of toxocariasis in Santa Fe, Argentina]. / Estudio en niños con diagnóstico presuntivo de toxocariasis en Santa Fe, Argentina.

Human toxocariasis is a parasitic disease found worldwide. The most important etiological agent is Toxocara canis, a dog parasite. Humans are infected by the ingestion of their eggs; the eggs hatch in the small intestine and the larvae migrate through the capillaries, taking up residence in different tissues. Clinical manifestations are associated with mechanical and/or reaction damage caused by these parasites larvae. Clinical diagnosis is difficult. The method applied in this work is the demonstration of antibodies against the helminth in the blood of children, target host population of this parasitic disease. An ELISA test was performed using T. canis larval excretory-secretory products as antigen. A total of 100 children presumptively diagnosed of toxocariasis that had been derived from different services of the Regional Children's Hospital for complementary studies, were included in the analysis. The test detected two different populations: infected (59) and non-infected (41). The statistical analysis showed a non significant association between infection and sex (p = 0.279). Infected subjects tended to be older than the non infected (p = 0.009). Eosinophilia was detected in 100% of seropositive children and in 85.2% of the seronegative. There was no significant association between infection and leucocytosis (p = 0.950). The association of these two parameters was significantly higher among infected patients (R = 0.918). Respiratory symptoms and signs were more frequently detected in the positive population (p = 0.05). Dogs tenancy was as frequent among infected as in the non infected homes (p = 0.53). According to these results, prevention, early diagnosis and opportune treatment for toxocariasis should be considered as priority health activities in this region.

[Case of toxocariasis showing migratory nodular shadows with halos].

A 30-year-old man, who had kept a dog for nine years and often ate raw beef liver, visited a hospital because of a chest nodular shadow in the left lung field found on a checkup examination. Chest computed tomography obtained 8 days after the checkup showed no abnormal shadow in the left lung but two nodular shadows with halos in the right upper and lower lobes. Peripheral blood eosinophil counts and serum IgE values were elevated. Immunological examination including microplate ELISA showed a high titer of specific antibody against Toxocara canis in the serum. He was successfully treated with albentazole. Parasitic disease, especially toxocariasis, is an important consideration in the differential diagnosis of migratory nodular shadow with a halo on chest computed tomography, and serology is useful in diagnosis screening.

[Visceral larva migrans syndrome and hepatic abscess: A case report]. / Síndrome de larva migrans visceral y absceso hepático: Reporte de un caso.

Toxocariasis canis or catis is a zoonotic infection disseminated in humans. Human beings can act as non-natural hosts in which the parasite can survive for long periods of time and they become infected by the ingestion of geohelminth eggs. These can be located on the ground, playgrounds and children's games, and are mostly eliminated by dogs or cats. There are different spectra in the clinical presentation of this infection, which can vary from an asymptomatic host to the production of serious organic lesions; some of them are ocular toxocariasis, visceral larva migrans, covert toxocariasis and neurotoxocariasis. In this case report a patient who presents with a history of respiratory problems, prolonged fever, and hepatomegaly. Laboratory analyses show hypereosinophilia, hypergammaglobulinemia and serodiagnosis is positive for toxocariasis. Preliminary diagnosis: Visceral Larva Migrans Syndrome.

La infección por T oxocara canis o catis es una zoonosis diseminada en el ser humano. La toxocariasis puede coexistir con otras parasitosis endémicas. El hombre actúa como huésped no natural y adquiere la infección a través de la ingesta de huevos del geohelminto. Estos pueden localizarse en la tierra, los patios y los juegos de los niños, y son eliminados, principalmente, por perros o gatos. Existen distintos espectros en la presentación clínica; algunos de ellos son toxocariasis ocular, larva migrans visceral, toxocariasis encubierta y neurotoxocariasis. Se presenta el caso de un paciente de 2 años y 3 meses de edad, con antecedente de síntomas respiratorios, fiebre prolongada y hepatomegalia, con resultados de laboratorio que informa hipereosinofilia, hipergammaglobulinemia y serología positiva para toxocariasis (ensayo por inmunoabsorción ligado a enzimas). Se plantea el diagnóstico de síndrome de larva migrans visceral.

Space Occupying Lesion in the Liver Caused by Hepatic Visceral Larva Migrans: A Case Report.

Visceral larva migrans (VLM) is one of the clinical syndromes of human toxocariasis. We report a case of hepatic VLM presenting preprandial malaise and epigastric discomfort in a 58-year-old woman drinking raw roe deer blood. The imaging studies of the abdomen showed a 74-mm hepatic mass featuring hepatic VLM. Anti-Toxocara canis immunoglobulin G (IgG) was observed in enzyme-linked immunosorbent assay (ELISA) and western blot. Despite anthelmintic treatment, the patient complained of newly developed cough and skin rash with severe eosinophilia. Hepatic lesion increased in size. The patient underwent an open left lobectomy of the liver. After the surgery, the patient was free of symptoms such as preprandial malaise, epigastric discomfort, cough, and skin rash. Laboratory test showed a normal eosinophilic count at postoperative 1 month, 6 months, 1 year, and 4 years. The initial optical density value of 2.55 of anti-T. canis IgG in ELISA was found to be negative (0.684) at postoperative 21 months. Our case report highlights that a high degree of clinical suspicion for hepatic VLM should be considered in a patient with a history of ingestion of raw food in the past, presenting severe eosinophilia and a variety of symptoms which reflect high worm burdens. Symptom remission, eosinophilia remission, and complete radiological resolution of lesions can be complete with surgery.

Eosinophilic cholecystitis as a rare manifestation of visceral larva migrans.

Eosinophilic cholecystitis is an infrequent form of cholecystitis. The etiology of eosinophilic cholecystitis is still obscure, and it is sometimes accompanied with several complications, but a simultaneous onset with pericarditis is very rare. We would like to make an alternative interpretation of our recent report "Kaji K, Yoshiji H, Yoshikawa M, Yamazaki M, Ikenaka Y, Noguchi R, Sawai M, Ishikawa M, Mashitani T, Kitade M, Kawaratani H, Uemura M, Yamao J, Fujimoto M, Mitoro A, Toyohara M, Yoshida M, Fukui H. Eosinophilic cholecystitis along with pericarditis caused by Ascaris lumbricoides: A case report. World J Gastroenterol 2007; 13: 3760-3762."