RESUMO
Human toxocariasis is a neglected anthropozoonosis with global distribution. Treatment is based on the administration of anthelmintics; however, their effectiveness at the tissue level is low to moderate, necessitating the discovery of new drug candidates. Several groups of synthetic compounds, including coumarin derivatives, have demonstrated bioactivity against fungi, bacteria, and even parasites, such as Dactylogyrus intermedius, Leishmania major, and Plasmodium falciparum. The aim of this study was to evaluate the effect of ten coumarin-derived compounds against Toxocara canis larvae using in vitro, cytotoxicity, and in silico tests for selecting new drug candidates for preclinical tests aimed at evaluating the treatment of visceral toxocariasis. The compounds were tested in vitro in duplicate at a concentration of 1 mg/mL, and compounds with larvicidal activity were serially diluted to obtain concentrations of 0.5 mg/mL; 0.25 mg/mL; 0.125 mg/mL; and 0.05 mg/mL. The tests were performed in a microculture plate containing 100 T. canis larvae in RPMI-1640 medium. One compound (COU 9) was selected for cytotoxicity analysis using J774.A1 murine macrophages and it was found to be non-cytotoxic at any concentration tested. The in silico analysis was performed using computational models; the compound presented adequate results of oral bioavailability. To confirm the non-viability of the larvae, the contents of the microplate wells of COU 9 were inoculated intraperitoneally (IP) into female Swiss mice at 7-8 weeks of age. This confirmed the larvicidal activity of this compound. These results show that COU 9 exhibited larvicidal activity against T. canis larvae, which, after exposure to the compound, were non-viable, and that COU 9 inhibited infection in a murine model. In addition, COU 9 did not exhibit cytotoxicity and presented adequate bioavailability in silico, similar to albendazole, an anthelmintic, which is the first choice for treatment of human toxocariasis, supporting the potential for future investigations and preclinical tests on COU 9.
Assuntos
Cumarínicos , Larva , Toxocara canis , Animais , Larva/efeitos dos fármacos , Toxocara canis/efeitos dos fármacos , Cumarínicos/farmacologia , Cumarínicos/química , Anti-Helmínticos/farmacologia , Anti-Helmínticos/química , Disponibilidade Biológica , Camundongos , Simulação por Computador , Toxocaríase/tratamento farmacológico , Toxocaríase/parasitologiaRESUMO
PURPOSE: Animal hoarding has been associated with unhealthy human, animal and environmental conditions that predispose such individuals to serious life-threatening risks such as arson, malnutrition, cruelty and zoonosis. The study aimed to evaluate the presence of anti-Toxocara spp. antibodies among individuals with animal hoarding disorder in Curitiba, Brazil. METHODS: 65 residences with register of animal hoarder behavior were visited and 11 residences were included in the study, with a total of 19 individuals consenting participation. A short questionnaire was applied to gather information regarding hoarders and their dogs/cats, and serum samples were screened to detect antibodies (IgG) against antigens of Toxocara spp. RESULTS: Overall, 14/19 individuals (73.7%) presented anti-Toxocara spp. antibodies. In 8/11 (72.7%) households at least one person was seropositive. Seropositivity was higher among women (10/13; 76.9%) than men (4/6; 66.7%). A total of 442 dogs (14-30 dogs; average = 23.3 per household) and 31 cats (1-20 cats; average = 4.8 per household) were observed. To the authors' knowledge, this was the first study to survey occurrences of toxocariasis among animal hoarders. The high population densities of dogs observed during visits, in conjunction with absence of veterinary care and unsanitary conditions, may indicate that situations of high levels of animal infection and soil contamination were present. CONCLUSION: In summary, the seroprevalence observed in this study indicated that there was a high risk of Toxocara spp. infection among individuals with animal hoarding disorder. Provision of educational programs to reduce the risk of infection in this population is warranted.
Assuntos
Anticorpos Anti-Helmínticos , Doenças do Cão , Transtorno de Acumulação , Toxocara , Toxocaríase , Animais , Brasil/epidemiologia , Humanos , Cães , Toxocara/imunologia , Gatos , Feminino , Masculino , Toxocaríase/epidemiologia , Transtorno de Acumulação/epidemiologia , Estudos Soroepidemiológicos , Doenças do Cão/parasitologia , Doenças do Cão/epidemiologia , Anticorpos Anti-Helmínticos/sangue , Adulto , Doenças do Gato/parasitologia , Doenças do Gato/epidemiologia , Saúde Pública , Pessoa de Meia-Idade , Adulto Jovem , Inquéritos e Questionários , AdolescenteRESUMO
Introduction: Despite human toxoplasmosis and toxocariasis having been listed among the top six most neglected parasitic zoonoses worldwide, presenting similar associated risk factors and transmission routes, few studies have been conducted in pregnant women and the consequences of concurrent infection remain to be fully established. Accordingly, the present study has serologically assessed the co-infection and associated risk factors for Toxoplasma gondii and Toxocara spp. in pregnant women, assisted by the public Unified National Health System (SUS) in southeastern Brazil. Materials and Methods: Blood samples were collected and tested for IgG antibodies against Toxoplasma gondii by chemiluminescence immunoassay and against Toxocara spp. by enzyme-linked immunosorbent assay (ELISA). An epidemiological questionnaire was applied to gather socioeconomic information to assess the risk factors associated with seropositivity to toxocariasis/toxoplasmosis by univariate analysis followed by logistic regression. Results: Overall, seropositivity was 69/280 (24.6, 95% CI: 19.96-30.01) for T. gondii and 56/280 (20.0, 95% CI: 15.73-25.08) for Toxocara spp. Co-infection was observed in 25/280 (8.9, 95% CI: 6.12-12.85) pregnant women, with increased odds (OR: 3.3, CI 95%: 1.77-6.14, p = 0.0002). Logistic regression revealed that a higher educational level (high school or college) significantly reduced the likelihood of co-infection seropositivity, owning cats increased the odds of toxocariasis, and older pregnant women presented significantly higher T. gondii seropositivity. Conclusion: Co-infection herein highlights the importance of educational programs in the prevention of toxocariasis and toxoplasmosis in pregnant women and other high-risk populations.
Assuntos
Coinfecção , Toxocaríase , Toxoplasma , Toxoplasmose , Animais , Humanos , Feminino , Gravidez , Toxocaríase/epidemiologia , Toxocara , Gestantes , Brasil/epidemiologia , Coinfecção/epidemiologia , Anticorpos Antiprotozoários , Toxoplasmose/epidemiologiaRESUMO
INTRODUCTION: Toxocariasis is caused by nematodes of Toxocara genus, which infest dogs and cats, with humans serving as paratenic hosts. METHODS: The epidemiological profile of patients examined for toxocariasis between October 2014 and October 2019 at Evandro Chagas Institute (IEC) was outlined. The frequency of anti-T. canis IgG antibodies were evaluated using the Enzyme Linked Immunosorbent Assay (ELISA) method. RESULTS: From a total of 734 samples, 56% were from male (p < 0.05). Regarding age, the group with the most solicitations were from ≤11 years old individuals (p < 0.05). Pará state had the highest number of exams requested (92%), with the majority from residents of urban areas, accounting for 81.5% of samples (p < 0.05). The overall toxocariasis seroprevalence was 41.8%, the male sex being the most frequent with 60.9% (p < 0.05). The most affected age group was ≤11 years old, with a total of 67.8% of positive samples (p < 0.05). CONCLUSION: The high rates obtained emphasize the need for complementary studies on toxocariasis in Brazil, especially in Pará state, contributing to epidemiological surveillance actions in the control of this infection. Besides, health campaigns for domestic and stray animals, also can contribute to a more effective surveillance in controlling parasitic infections and encourages the One Health approach.
Assuntos
Doenças do Gato , Doenças do Cão , Toxocaríase , Humanos , Masculino , Animais , Cães , Gatos , Criança , Toxocaríase/epidemiologia , Toxocaríase/parasitologia , Estudos Soroepidemiológicos , Doenças do Gato/epidemiologia , Toxocara , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Anticorpos Anti-Helmínticos , Fatores de RiscoRESUMO
PURPOSE: To describe the most important cause of infectious posterior uveitis in pediatric patients. METHODS: Review of the literature. RESULTS: The most important causes of infectious uveitis in pediatric patients are: cat-scratch disease, toxocariasis, tuberculosis, viral diseases and toxoplasmosis. Ocular manifestations include retinitis, neuroretinitis, choroidal granulomas, peripheral granulomas and posterior pole granulomas. CONCLUSION: Infectious posterior uveitis is a challenging subject and should be considered in the differential diagnosis of any posterior uveitis in children. Infectious uveitis must be excluded before initiating immunosuppressive therapy.
Assuntos
Infecções Oculares Bacterianas , Infecções Oculares , Retinite , Uveíte Posterior , Uveíte , Animais , Humanos , Criança , Uveíte Posterior/diagnóstico , Uveíte Posterior/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Retinite/diagnóstico , Retinite/tratamento farmacológico , Infecções Oculares/diagnóstico , Infecções Oculares/tratamento farmacológico , Infecções Oculares Bacterianas/diagnóstico , Corioide , GranulomaRESUMO
Introduction: The current study aimed to quantitatively synthesize available evidence regarding the seroprevalence of human toxocariasis in Latin America and the Caribbean. Methods: A systematic research involving six electronic databases was conducted using a research strategy that combined MeSH terms with free terms. Article selection and information extraction were performed using a double and independent approach. The Newcastle-Ottawa tool was used to assess the risk of bias in the included articles. The meta-analysis used the random-effects approach, with subgroup analysis and sensitivity analysis for risk of bias also being performed. Results: We included 101 articles with a total of 31,123 participants. The studies were conducted between 1990 and 2022, with Brazil accounting for the largest number of studies (n = 37). The overall seroprevalence of human toxocariasis was 31.0% (95% CI: 27.0-35.0%, I2 = 99%). The prevalence of the main characteristics observed in seropositive patients were as follows: ocular toxocariasis (30.0%), asymptomatic (26.0%), and presence of dogs at home (68.0%). In addition, the seroprevalence was lower in studies including only adults than in those including children or both. In contrast, no differences in seroprevalences were found between studies conducted in the community and hospital. Conclusion: The overall seroprevalence of human toxocariasis in Latin America and the Caribbean was high. Notably, our findings showed that the seroprevalence was increased among populations who kept a dog at home but was decreased in populations comprising only adults. Our findings can be used to establish epidemiological surveillance strategies for the prevention and early identification of toxocariasis.
Assuntos
Toxocaríase , Criança , Adulto , Humanos , Animais , Cães , Toxocaríase/epidemiologia , América Latina/epidemiologia , Estudos Soroepidemiológicos , Região do Caribe/epidemiologia , EtnicidadeRESUMO
Objetivo: Caracterizar clínica y epidemiológicamente la toxocariasis ocular. Métodos: Se realizó un estudio observacional, descriptivo, de corte transversal con pacientes diagnosticados de toxocariasis ocular, atendidos en el Instituto Cubano de Oftalmología Ramón Pando Ferrer en el período de abril de 2019 a diciembre de 2022. Resultados: Predominó el sexo masculino (53,7 por ciento) y el grupo etario de 0 a 10 años (73,1 por ciento). El 56,1 por ciento de los pacientes vivían en área rural. La convivencia con animales domésticos representó el 75,6 por ciento. El síntoma más referido fue la disminución de la agudeza visual (48,8 por ciento). La forma de presentación más frecuente fue el granuloma periférico de forma unilateral en ojo derecho (52,4 por ciento). La complicación más observada fue el desprendimiento de retina (58,5 por ciento). Conclusiones: La infección ocular por Toxocara spp. es una enfermedad prevenible e incapacitante que limita el desenvolvimiento educacional, laboral y de la vida en general de los pacientes afectados, particularmente la población infantil, el sexo masculino y los que residen en área rural en convivencia con animales domésticos, en especial perros(AU)
Objective: To characterize ocular toxocariasis clinically and epidemiologically. Methods: An observational, descriptive and cross-sectional study was conducted with patients diagnosed with ocular toxocariasis, attended at the Instituto Cubano de Oftalmología Ramón Pando Ferrer in the period from April 2019 to December 2022. Results: The male sex predominated (53.7 percent), together with the age group 0-10 years (73.1 percent). 56.1 percent of the patients lived in rural areas. Cohabitation with domestic animals accounted for 75.6 percent. The most frequently reported symptom was decreased visual acuity (48.8 percent). The most frequent form of presentation was peripheral granuloma in the right eye (52.4 percent). The most observed complication was retinal detachment (58.5 percent). Conclusions: Ocular infection by Toxocara spp. is a preventable, as well as incapacitating, disease that limits the educational, occupational and general life development of affected patients, particularly children, males and those living in rural areas cohabitating with domestic animals, especially dogs(AU)
Assuntos
Humanos , Lactente , Pré-Escolar , Descolamento Retiniano/complicações , Toxocaríase/epidemiologia , Epidemiologia Descritiva , Estudos Observacionais como AssuntoRESUMO
BACKGROUND: Despite being one of the most prevalent helminth parasitic zoonoses worldwide and particularly in socioeconomically vulnerable populations, toxocariasis remains to be fully investigated in persons experiencing homelessness. Accordingly, the present study has aimed to assess the seroprevalence and associated risk factors of Toxocara spp. exposure in persons experiencing homelessness and shelter workers from a day-shelter in São Paulo city, Brazil. METHODS: Anti-Toxocara IgG antibodies were detected by enzyme-linked immunosorbent assay (ELISA). Univariable and multivariable logistic regression models were performed to assess the risks for toxocariasis. RESULTS: Overall, anti-Toxocara IgG antibodies were detected in 89/194 (45.9%, 95% CI: 39.0-52.9%) persons experiencing homelessness, twice as high (OR = 2.2; 95% CI = 1.245-3.873; P = 0.0089) than the frequency of 22/79 (27.8%, 95% CI: 19.2-38.6) in shelter workers. College education was the only protective factor for Toxocara spp. exposure (OR: 0.23; P = 0.018) revealed by logistic regression. CONCLUSIONS: Although indicating a multifactorial origin of toxocariasis, the present study has assessed a highly vulnerable population with high disease risks and premature death. Thus, the living conditions of the homeless population have influenced the high prevalence of anti-Toxocara antibodies verified here compared with domiciled shelter workers. Despite being less exposed, shelter and other outdoor workers may present an occupational risk to toxocariasis. Future studies should establish whether such environmental exposure might occur in persons experiencing homelessness in other regions worldwide.
Assuntos
Pessoas Mal Alojadas , Toxocaríase , Animais , Anticorpos Anti-Helmínticos , Brasil/epidemiologia , Ensaio de Imunoadsorção Enzimática , Humanos , Imunoglobulina G , Fatores de Risco , Estudos Soroepidemiológicos , Toxocara , Toxocaríase/parasitologiaRESUMO
Infections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on a limited set of drugs, many of which have become less effective, necessitating the search for novel anthelmintic agents. In this study, a simplified compound, N-(4-methoxyphenyl)pentanamide (N4MP), based on the structure of the most widely used anthelmintic (albendazole), was chemically prepared using 4-anisidine and pentanoic acid. N-(4-Methoxyphenyl)pentanamide was evaluated in vitro against the nematode Toxocara canis, an ascarid roundworm of animals that can infect humans. Similar to albendazole, bioassays showed that N-(4-methoxyphenyl)pentanamide affected the viability of parasites in a time- and concentration-dependent manner. Interestingly, N-(4-methoxyphenyl)pentanamide showed a profile of lower cytotoxicity to human and animal cell lines than albendazole. Pharmacokinetic, drug-likeness, and medicinal chemistry friendliness studies demonstrated an excellent drug-likeness profile for N-(4-methoxyphenyl)pentanamide as well as an adherence to major pharmaceutical companies' filters. Collectively, the results of this study demonstrate that the molecular simplification of albendazole to give N-(4-methoxyphenyl)pentanamide may be an important pipeline in the discovery of novel anthelmintic agents. IMPORTANCE Infections caused by parasitic helminths have enormous health, social, and economic impacts worldwide. The treatment and control of these diseases have been dependent on a limited set of drugs, many of which have become less effective, necessitating the search for novel anthelmintic agents. Considering this scenario, the present study reports the preparation of N-(4-methoxyphenyl)pentanamide (N4MP), a simplified molecule based on the structure of the most widely used anthelmintic (albendazole). N4MP was evaluated in vitro against the nematode Toxocara canis, a common ascarid roundworm of domestic animals that can infect humans. Similar to albendazole, bioassays showed that N4MP affected the viability of parasites in a time- and concentration-dependent manner but displayed a profile of lower cytotoxicity to human and animal cell lines than albendazole. Therefore, this study demonstrates that the molecular simplification of albendazole to give N4MP may be an important pipeline in the discovery of novel anthelmintic agents.
Assuntos
Anti-Helmínticos , Toxocara canis , Toxocaríase , Albendazol/farmacologia , Albendazol/uso terapêutico , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Humanos , Toxocaríase/tratamento farmacológico , Toxocaríase/parasitologiaRESUMO
IL-17 is a cytokine produced by innate and acquired immunity cells that have an action against fungi and bacteria. However, its action in helminth infections is unclear, including in Toxocara canis infection. Toxocariasis is a neglected zoonosis representing a significant public health problem with an estimated seroprevalence of 19% worldwide. In the present study, we describe the immunopathological action of IL-17RA in acute T. canis infection. C57BL/6j (WT) and IL-17RA receptor knockout (IL-17RA-/-) mice were infected with 1000 T. canis eggs. Mice were evaluated 3 days post-infection for parasite load and white blood cell count. Lung tissue was harvested for histopathology and cytokine expression. In addition, we performed multiparametric flow cytometry in the BAL and peripheral blood, evaluating phenotypic and functional changes in myeloid and lymphoid populations. We showed that IL-17RA is essential to control larvae load in the lung; however, IL-17RA contributed to pulmonary inflammation, inducing inflammatory nodular aggregates formation and presented higher pulmonary IL-6 levels. The absence of IL-17RA was associated with a higher frequency of neutrophils as a source of IL-4 in BAL, while in the presence of IL-17RA, mice display a higher frequency of alveolar macrophages expressing the same cytokine. Taken together, this study indicates that neutrophils may be an important source of IL-4 in the lungs during T. canis infection. Furthermore, IL-17/IL-17RA axis is important to control parasite load, however, its presence triggers lung inflammation that can lead to tissue damage.
Assuntos
Pneumonia , Receptores de Interleucina-17 , Toxocara canis , Toxocaríase , Animais , Citocinas/imunologia , Interleucina-17/imunologia , Interleucina-4/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/imunologia , Pneumonia/parasitologia , Receptores de Interleucina-17/imunologia , Toxocara canis/imunologia , Toxocaríase/imunologia , Toxocaríase/parasitologiaRESUMO
Toxocariasis is an infection caused by the round worms Toxocara canis and Toxocara cati. It occurs worldwide though it is more prevalent in developing countries. For the diagnosis of toxocariasis, the most used method is the indirect enzyme-linked immunosorbent assay (indirect ELISA), based on the detection of specific antibodies using the excreted/secreted products from T. canis larvae (TES) as antigens, but it cross-reacts with several helminth infections. For this reason, there is a need to investigate species-specific immunoreactive proteins, which can be used for the development of a more sensitive and specific diagnosis. This study aims to investigate immunoreactive protein candidates to be used for the development of a more sensitive and specific diagnosis of Toxocara spp. infection in humans. We have used immunoblotting and mass spectrometry to select four Toxocara canis immunoreactive proteins that were recombinantly expressed in bacteria and evaluated as potential new diagnostic antigens (rMUC3, rTES 26, rTES32 and rCTL4). The recognition of these recombinant proteins by total serum IgG and IgG4 was assayed using the purified proteins in an isolated manner or in combination. The IgG ELISAs performed with individual recombinant antigens reached values of sensitivity and specificity that ranged from 91.7% to 97.3% and 94.0% to 97.9%, respectively. Among the analyses, the IgG4 immunoassay was proven to be more effective, revealing a sensitivity that ranged from 88.8% to 98.3% and a specificity of 97.8%-97.9%. The IgG4 ELISA was shown to be more effective and presented no cross-reactivity when using combinations of the rTES 26 and rCTL4 recombinant proteins. The combination of these two molecules achieved 100% sensitivity and specificity. The use of only two recombinant proteins can contribute to improve the current panorama of toxocariasis immunodiagnosis for, with a better optimization and reduced cost.
Assuntos
Toxocara canis , Toxocaríase , Animais , Antígenos de Helmintos , Ensaio de Imunoadsorção Enzimática/métodos , Ensaio de Imunoadsorção Enzimática/veterinária , Humanos , Immunoblotting/veterinária , Imunoglobulina G , Testes Imunológicos/veterinária , Proteômica , Proteínas Recombinantes , Toxocara , Toxocaríase/diagnósticoRESUMO
Biological control is considered one of the most used alternative measures to combat helminths of relevance in veterinary medicine and public health. Among these parasites, Toxocara canis stands out for its high prevalence and worldwide distribution, in addition to being the main cause of visceral larva migrans in man. The present work aimed the fungus Pochonia chlamydosporia (isolate Pc-10) on eggs of T. canis. In order to do this, fertile nematode eggs were obtained by dissection of adult females fertilized specimens. After obtaining the eggs, they were inserted into 24 well plates previously À lled with different concentrations of enzymatic extract of the fungus (100, 200, 400 and 500 µL). In addition, the behavior of P. chlamydosporia hyphae on Toxocara canis eggs was also observed in 2% wateragar medium (2% WA+ fungal isolate) when compared to the control group (2% WA + water). It was veriÀ ed ovicidal activity with the enzymatic extract of P. chlamydosporia at concentrations of 400 and 500 µL. At the same time, after 12 days of exposure of the T. canis eggs to P. chlamydosporia mycelia it was possible to observe the fungus action on eggshells, including penetration of the hyphae and colonization of the egg inside. The results conÀ rm the ovicidal potential of the fungus and suggest its applicability in toxocariasis control programs.(AU)
Assuntos
Ativação Enzimática , Hypocreales/enzimologia , Inseticidas/toxicidade , Toxocara canisRESUMO
The intense contact of children with domestic animals or environments contaminated with faeces of these animals, together with habits related to lack of hygiene, can facilitate infection by zoonoses. The study evaluated the seroprevalence and risk factors associated with toxoplasmosis and toxocariasis in schoolchildren in the city of Jataizinho, Paraná. Of the 412 children aged 4-15 years, 56.8% (234/412) presented antibodies reactive to Toxoplasma gondii, 42.5% (175/412) presented antibodies reactive to Toxocara canis, and 27.4% (113/412) were reactive for the two species. The analysis of risk factors showed that prevalence of toxoplasmosis and toxocariasis was associated with the level of education of the child's mother (less than eight years of schooling), age range (10-15 years) and the presence of cats in the residence. In addition, family income (up to a minimum wage), presence of a dog, the habit of playing in soil/sand and eosinophilia were associated with Toxocara canis infection. There was an association between the two zoonoses (p < .01), indicating the existence of coinfection. The results show high prevalence of these two important zoonoses, alerting to the need of implementing control measures in order to reduce the incidence and risks of sequelae in children.
Assuntos
Doenças do Gato , Doenças do Cão , Toxocara canis , Toxocaríase , Toxoplasma , Toxoplasmose , Animais , Gatos , Cães , Humanos , Estudos Soroepidemiológicos , Fatores Socioeconômicos , Toxocaríase/epidemiologia , Toxoplasmose/epidemiologia , Zoonoses/epidemiologiaRESUMO
Toxocariasis is a zoonotic disease of worldwide distribution. The connection between parasitic diseases and conditions that depress the immune system, such as the use of immunosuppressive drugs, has been studied. The purpose of this study was to evaluate the effect of Cyclosporine A (CsA) on the intensity of infection, humoral response and gene transcription of interleukins IL-4, IL-10 and IL-12 in mice experimentally infected with Toxocara canis. To this end, mice were divided into two groups treated with CsA (G1: 10 mg/Kg and G2: 50 mg/kg), the G3 and G4 group received PBS. After the last administration of the drug or PBS (orally every 48 hours for 15 days), groups G1, G2 and G3 were inoculated with 1200 eggs of T. canis. Was collected blood samples on days zero, 15 and 30 days post-inoculation (PI), for ELISA test and the mice were euthanized 30 days PI. The organs and striated muscle tissue were collected for the recovery of larvae. The splenocytes were analyzed by RT-PCR. The intensity of infection in the mice treated with 50 mg/kg of CsA was 65.5% higher than in the control group (p=0.001). An analysis of the kinetics of anti-Toxocara antibody revealed that the groups treated with CsA showed significantly higher mean levels of antibodies on day 15 PI. The transcription of the three tested interleukins showed no statistical difference between G2 and G3 (control). It was concluded that the immunosuppression triggered by CsA (50 mg/Kg) favored the establishment of a larger number of T. canis larvae without, however, altering immunoglobulin production and IL-4, IL-10 and IL-12 transcription on day 30 PI.
A toxocaríase é uma zoonose de distribuição mundial. A conexão entre doenças parasitárias e condições que deprimem o sistema imunológico, como o uso de drogas imunossupressoras, tem sido estudada. O objetivo deste estudo foi avaliar o efeito da Ciclosporina A (CsA) na intensidade da infecção, resposta humoral e transcrição gênica das interleucinas IL-4, IL-10 e IL-12 em camundongos experimentalmente infectados com Toxocara canis. Para tanto, os camundongos foram divididos em dois grupos tratados com CsA (G1: 10 mg/Kg e G2: 50 mg/kg), os grupos G3 e G4 receberam PBS. Após a última administração da droga ou PBS (via oral a cada 48 horas por 15 dias), os grupos G1, G2 e G3 foram inoculados com 1200 ovos de T. canis. Foram coletadas amostras de sangue nos dias zero, 15 e 30 dias pós-inoculação (PI), para teste de ELISA e os camundongos foram eutanasiados 30 dias PI. Os órgãos e tecido muscular estriado foram coletados para a recuperação das larvas. Os esplenócitos foram analisados por RT-PCR. A intensidade da infecção nos camundongos tratados com 50 mg/kg de CsA foi 65,5% maior do que no grupo controle (p=0,001). Uma análise da cinética do anticorpo anti-Toxocara revelou que os grupos tratados com CsA apresentaram níveis médios de anticorpos significativamente maiores no dia 15 PI. A transcrição das três interleucinas testadas não apresentou diferença estatística entre G2 e G3 (controle). Concluiu-se que a imunossupressão desencadeada pela CsA (50 mg/Kg) favoreceu o estabelecimento de um maior número de larvas de T. canis sem, no entanto, alterar a produção de imunoglobulinas e a transcrição de IL-4, IL-10 e IL-12 no dia 30 PI.
Assuntos
Zoonoses , Ciclosporina , Toxocara canis , CamundongosRESUMO
The objective of this work was to evaluate the early and late immunological modulation of an experimental infection of T. canis larvae in mice. Mice were infected with 100 infective larvae and euthanized at different period: 24, 48 hours post infection (HPI), 15- and 30 days post infection (DPI). The humoral response was evaluated by indirect ELISA. Quantitative RT-PCR (qPCR) was used to quantify the mRNA transcription of cytokines IL4, IL10, IL12 and Ym1 in the early and late infection periods. Infection with T. canis was able to generate specific total IgG at 15- and 30- DPI. Analyzing the IgG isotype revealed a significant differentiation for IgG1 compared with IgG2a, IgG2b and IgG3, characterizing a Th-2 response. Evaluating the gene transcription at the early phase of infection, higher transcription levels of IL10, IL4 and Ym1 and a downregulation of IL12 were observed. By the late phase, increased transcription levels of IL4, Ym1 and IL12 were observed, and downregulation of IL-10 transcription was observed. The data obtained suggest that during experimental infection with T. canis, the participation of the IL4, IL10, IL12 cytokines and Ym1 can play an important role in T. canis immunomodulation.(AU)
O objetivo deste trabalho foi avaliar a modulação imunológica precoce e tardia da infecção experimental de larvas de T. canis em camundongos. Estes foram infectados com 100 larvas infectantes e eutanasiados em diferentes períodos: 24 e 48 horas pós infecção (HPI), 15 e 30 dias após a infecção (DPI). A resposta humoral foi avaliada por ELISA indireto. RT-PCR quantitativo (qPCR) foi usado para quantificar a transcrição de mRNA das citocinas IL4, IL10, IL12 e Ym1 nos períodos de infecção precoce e tardia. A infecção por T. canis foi capaz de gerar IgG total específico aos 15 e 30 DPI. A análise do isótipo IgG revelou uma diferenciação significativa para IgG1 em comparação com IgG2a, IgG2b e IgG3, caracterizando uma resposta Th-2. Avaliando-se a transcrição gênica na fase inicial da infecção, foram observados níveis mais elevados de transcrição de IL10, IL4 e Ym1 e a regulação negativa de IL12. Na fase tardia, foram observados níveis aumentados de transcrição de IL4, Ym1 e IL12, e foi observada regulação negativa da transcrição de IL-10. Os dados obtidos sugerem, que durante a infecção experimental com T. canis, a participação das citocinas IL4, IL10, IL12 e Ym1 podem desempenhar um papel importante na imunomodulação de T. canis.(AU)
Assuntos
Animais , Camundongos , Toxocaríase/diagnóstico , Toxocara canis/imunologia , Imunomodulação , Camundongos/parasitologia , Larva Migrans/imunologiaRESUMO
ABSTRACT The Western-blotting technique was applied to identify antigenic fractions of excretory-secretory Toxocara canis antigen recognized by IgG antibodies throughout an experimental infection in mice challenged by different inocula. Mice were inoculated with 5, 50 and 500 embryonated eggs and serum samples were collected 15, 30, 60, 90 and 120 days post-infection. Serum samples were analyzed using an excretory-secretory Toxocara antigen. Antibodies recognized antigenic fractions from 30 to 90 kDa. The protein fraction of 30-35 kDa was the most frequently recognized regardless of the size of inoculum and the stage of infection represented by the different collection times, but the antigenic recognition was more evident in groups infected with 50 and 500 eggs. This study presents an antigenic panel of the excretory-secretory antigen of T. canis and suggests that the 30-35 kDa antigenic fraction is a promising marker of the infection and should be further explored in future studies on experimental toxocariasis.
RESUMO
Toxocariasis, caused by Toxocara spp. nematodes, is among the top 5 neglected parasitic diseases worldwide; however, no comprehensive study to date has serologically compared infections in people and their dogs and environmentally contaminated soil or sand of mainland and island locations. Accordingly, this study aimed to assess the seroprevalence of anti-Toxocara antibodies in traditional human seashore populations, the presence of eggs in dogs' feces and hair, and the presence of eggs in environmental samples from islands compared to the adjacent mainland of southern Brazil. Overall, 212/328 (64.6%) people were positive for Toxocara spp. antibodies, including 125/190 (65.8%) island and 87/138 (63.0%) mainland residents. For dog samples, 12/115 (10.43%) were positive for the presence of Toxocara spp. eggs, all from dogs living in islands, and 22/104 (21.15%) dog hair samples contained eggs of Toxocara spp. Environmental contamination with Toxocara spp. eggs was observed in 50/130 (38.46%) samples from all sampled sites. No significant association was found between risk factors (age, sex, educational level, monthly income, owning dogs or cats, ingestion of treated water, and consumption of raw or uncooked meat) and Toxocara spp. seropositivity. The present study is the first concurrent report on people, their dogs, and environmental contamination of Toxocara spp. The high prevalence we observed in the seashore populations of both in island and mainland areas may be caused by exposure to contaminated sand and climatic factors favoring frequent exposure to Toxocara spp. In conclusion, seashore lifestyle and living conditions of both island and mainland areas may have predisposed higher contact with infected pets and contaminated soil, favoring the high prevalence of toxocariasis.
RESUMO
INTRODUCCIÓN: La toxocariasis es una enfermedad parasitaria ampliamente distribuida. Las formas clínicas descritas son la asintomática (TA), larva migrans visceral (LMV), larva migrans ocular (LMO) y encubierta (TE). OBJETIVOS: Describir las características clínicas, de laboratorio, evolución y tratamiento de los casos y comparar las diversas formas clínicas de presentación. PACIENTES Y MÉTODOS: Análisis retrospectivo de todos los pacientes pediátricos con diagnóstico de toxocariasis atendidos en el Servicio de Infectología del Hospital General de Niños Pedro de Elizalde entre 2012 y 2019. RESULTADOS: Se incluyeron 85 pacientes. El 63,5 % fueron varones y la mediana de edad fue de 60 meses. Cuarenta y nueve pacientes presentaron TA, 14 LMV, 15 LMO y 7 TE. Los pacientes con LMV presentaron menor edad y recuento de eosinófilos más altos. Todos los casos de LMO presentaron mal pronóstico visual. Se indicó tratamiento con albendazol en todos los casos de LMV, en los casos activos de LMO, en 4 TE y en 3 TA. CONCLUSIÓN: Este estudio representa uno de los más grandes llevados a cabo en el país. Todas las formas clínicas excepto las LMO tuvieron buena evolución. Resulta fundamental enfatizar en la prevención y en el diagnóstico precoz de la enfermedad para instaurar de manera oportuna el tratamiento y evitar secuelas.
BACKGROUND: Toxocariasis is a widely spread parasitic disease. The most frequent clinical form is asymptomatic (AT) although it may present with visceral larva migrans (VLM), ocular larva migrans (OLM) or covert (TE) involvement. Aims: To describe the clinical presentation, laboratory, evolution and treatment characteristics of the cases and to compare the various clinical forms of presentation. PATIENTS AND METHODS: Retrospective analysis of all children diagnosed with toxocariasis attended at the Infectology Service of the Pedro de Elizalde Children's General Hospital between 2012-2019. RESULTS: We included 85 patients. 63.5% were males and the median age was 60 months. 49 patients presented AT, 14 VLM, 15 OLM and 7 TE. Children with LMV had lower age and higher eosinophil count. All the cases of OLM evolved with a poor visual prognosis. Treatment with albendazole was indicated in all cases of LMV, in active cases of LMO, in 4 TE and in 3 AT. CONCLUSION: This study represents one of the largest conducted in our country. The ocular forms had bad prognosis, while the visceral and covert forms had good evolution. It is essential to emphasize the prevention and early diagnosis of the disease in order to establish timely treatment and avoid sequelae.
Assuntos
Humanos , Animais , Masculino , Feminino , Pré-Escolar , Criança , Larva Migrans Visceral , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológico , Toxocaríase/epidemiologia , Argentina/epidemiologia , Toxocara , Estudos Retrospectivos , Hospitais PediátricosRESUMO
RESUMEN El objetivo de este estudio fue determinar manifestaciones oculares de la toxocariasis en escolares. Se realizó un estudio en dos escuelas del estado Anzoátegui en Venezuela en el 2019. Se empleó la prueba de ELISA para determinar los anticuerpos IgG contra Toxocara spp. Las familias completaron un cuestionario y los niños fueron evaluados clínicamente por pediatras y oftalmólogos. Participaron 118 niños, el 18,6% presentó anticuerpos anti-Toxocara spp. Las manifestaciones clínicas con asociación estadísticamente significativa fueron las reacciones alérgicas, epífora y disminución de la agudeza visual. En la evaluación oftalmológica se encontró queratitis, uveítis, iritis, granuloma retiniano, endoftalmitis, amaurosis, leucocoria, desprendimiento de retina y endotropía. Los hallazgos muestran una alta frecuencia de enfermedad ocular en niños con toxocariasis de un estado de Venezuela.
ABSTRACT The objective of this study was to determine ocular manifestations of toxocariasis in schoolchildren. A study was conducted in two schools in the Anzoátegui state in Venezuela in 2019. The ELISA test was used to determine IgG antibodies against Toxocara spp. The families completed a questionnaire, and the children were clinically evaluated by pediatricians and ophthalmologists. 118 children participated, 18.6% presented anti-Toxocara spp. The clinical manifestations with a statistically significant association were allergic reactions, epiphora, and decreased visual acuity. The ophthalmological evaluation found keratitis, uveitis, iritis, retinal granuloma, endophthalmitis, amaurosis, leukocoria, retinal detachment and endotropia. The findings show a high frequency of eye disease in children with toxocariasis from a state of Venezuela.