RESUMO
BACKGROUND: The hygiene hypothesis suggests that early life exposure to helminth infections can reduce hypersensitivity in the immune system. OBJECTIVE: The present study aims to evaluate the effects of Toxocara cati (T. cati) somatic products on allergic airway inflammation. METHODS: Between 2018 and 2020, T. cati adult worms were collected from stray cats in Mashhad, Iran (31 out of 186 cats), and their somatic extract was collected. Thirty BALB/c mice were equally divided into three groups, including the OVA group (sensitized and challenged with ovalbumin), the somatic administered group (received somatic extract along with ovalbumin sensitization), and the PBS group (sensitized and challenged with phosphate buffer saline). Bronchoalveolar lavage (BAL) fluid was collected to assess the number of cells, and lung homogenates were prepared for cytokine analysis. Histopathological analysis of the lungs was performed, and inflammatory cells and mucus were detected. Cytokine levels (IL-4, IL-5, IL-10) were measured using enzyme-linked immunosorbent assay (ELISA), and ovalbumin-specific immunoglobulin E (IgE) levels were determined using a capture ELISA. RESULTS: The somatic group significantly decreased regarding the lung pathological changes, including peribronchiolitis, perivasculitis, and eosinophil influx, compared to the group treated with ovalbumin alone. These changes were accompanied by a decrease in proinflammatory cytokines IL-4 and IL-5 and an increase in the anti-inflammatory cytokine IL-10, indicating a shift toward a more balanced immune response. The number of inflammatory cells in the BAL fluid was also significantly reduced in the somatic group, indicating a decrease in inflammation. CONCLUSION: These preclinical findings suggest that in experimental models, T. cati somatic extract exhibits promising potential as a therapeutic agent for mitigating allergic airway inflammation. Its observed effects on immune response modulation and reduction of inflammatory cell infiltration warrant further investigation in clinical studies to assess its efficacy and safety in human patients.
Assuntos
Citocinas , Camundongos Endogâmicos BALB C , Toxocara , Animais , Camundongos , Toxocara/imunologia , Toxocara/efeitos dos fármacos , Citocinas/metabolismo , Citocinas/imunologia , Imunoglobulina E/imunologia , Imunoglobulina E/sangue , Ovalbumina/imunologia , Pulmão/imunologia , Pulmão/patologia , Pulmão/parasitologia , Pulmão/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/imunologia , Asma/imunologia , Asma/tratamento farmacológico , Modelos Animais de Doenças , Gatos , Feminino , Toxocaríase/tratamento farmacológico , Toxocaríase/imunologia , Toxocaríase/parasitologiaRESUMO
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
Toxocariasis, a zoonotic infection transmitted by Toxocara canis (from dogs) and Toxocara cati (from cats) larvae, poses rare but severe risks to humans. We present a case of hepatic visceral larva migrans (VLM) caused by Toxocara canis in a 21-year-old male with a history of close contact with a pet dog. Initial symptoms and imaging findings mimicked a pyogenic liver abscess. The initial laboratory investigations revealed neutrophilia and elevated levels of IgE. Despite broad-spectrum antibiotics, persistent fever prompted further investigation. Subsequent serological testing for Toxocara antibodies and histopathological analysis of liver tissue demonstrating eosinophil infiltrates and Charcot-Leyden crystals led to a confirmed diagnosis of a liver abscess caused by Toxocara canis. Serological testing for Toxocara antibodies and histopathological analysis of liver tissue confirmed a Toxocara canis-induced liver abscess. Albendazole treatment yielded significant clinical improvement. This case highlights the necessity of considering toxocariasis in liver abscess differentials, particularly in high-seroprevalence regions like Vietnam. Relying solely on serological tests may be insufficient, emphasizing the need for corroborative evidence, including invasive procedures like liver biopsy, for accurate hepatic toxocariasis diagnosis.
Assuntos
Albendazol , Larva Migrans Visceral , Tomografia Computadorizada por Raios X , Toxocara canis , Humanos , Toxocara canis/isolamento & purificação , Larva Migrans Visceral/diagnóstico , Larva Migrans Visceral/tratamento farmacológico , Masculino , Animais , Adulto Jovem , Albendazol/uso terapêutico , Cães , Fígado/parasitologia , Fígado/patologia , Anticorpos Anti-Helmínticos/sangue , Ultrassonografia , Abscesso Hepático/diagnóstico , Abscesso Hepático/parasitologia , Abscesso Hepático/tratamento farmacológico , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológico , Imunoglobulina E/sangue , Anti-Helmínticos/uso terapêuticoRESUMO
INTRODUCTION: Ocular toxocariasis is a rare disease, predominantly affecting children and young adolescents, and usually presenting as unilateral posterior uveitis. We report the case of a child with toxocariasis associated with serous retinal detachment. OBSERVATION: A 8-year-old child with no previous history of toxocariasis was referred for a 1-year decline in visual acuity, unimproved by optical correction, with vitreous condensation on examination, without central or peripheral granulomas, and serous retinal detachment on OCT. The diagnosis was made after extensive questioning, with evidence of contact with dogs and positive serology. Medical treatment combining corticosteroid therapy and antiparasitic therapy was initiated, and the clinical picture improved. DISCUSSION: Ocular toxocariasis is a rare infection, unilateral in 90% of cases. Its clinical manifestation in children is pars planitis, posterior uveitis with a posterior pole chorioretinal focus associated with vitreoretinal traction and/or peripheral granuloma. In our case, the patient presented with vitreous condensation only, with OCT serous retinal detachment and no peripheral or central granulomas. Positive plasma serology or ocular samples confirmed the diagnosis. CONCLUSION: Ocular toxocariasis should not be ruled out in the absence of a typical clinical picture, and seropositivity enables confirmation of the diagnosis when clinical suspicion arises.
Assuntos
Infecções Oculares Parasitárias , Descolamento Retiniano , Toxocaríase , Humanos , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológico , Toxocaríase/complicações , Criança , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/parasitologia , Infecções Oculares Parasitárias/tratamento farmacológico , Descolamento Retiniano/diagnóstico , Descolamento Retiniano/parasitologia , Masculino , Cães , AnimaisRESUMO
Toxocara canis (T. canis) is a gastrointestinal nematode in dogs, and its larvae also infect humans, causing severe larval migratory disease. Anthelmintic drugs have become the primary means to combat T. canis. In this study, the efficacy of nitazoxanide (NTZ) was tested against all the internal stages of T. canis, including L3 larval stage in vitro experiments and gastrointestinal worm in vivo experiments. In the in vitro experiment, after treatment with NTZ at 7.81 and 62.5 µg/mL for 12 h, the larval mortality efficacy reached 90.0 and 100.0%, respectively. In the in vivo experiments, 100 mg/kg NTZ possessed good anthelmintic efficacy against T. canis, with an egg per gram (EPG) reduction of 99.19%, and 90.00% of dogs cleared with residual worms. These results were comparable to those of the positive control drug. The highest anthelmintic efficacy was observed in the group treated with 150 mg/kg NTZ. Based on faecal egg counts, the number of T. canis eggs decreased by 100.00%, and the percentage of dogs cleared with residual worms achieved 90.00% after 7 days of treatment in the 150-mg/kg NTZ treatment group. In general, NTZ showed great potential to be applied as an anthelmintic against T. canis.
Assuntos
Anti-Helmínticos , Doenças do Cão , Toxocara canis , Toxocaríase , Humanos , Animais , Cães , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Nitrocompostos/uso terapêutico , Tiazóis/uso terapêutico , Toxocaríase/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Contagem de Ovos de Parasitas/veterináriaRESUMO
Toxocariasis is a prevalent zoonosis caused by infection with the larvae of Toxocara canis or Toxocara cati. It ranges in severity from mundane to life-threatening, depending on organ involvement. The lungs are often affected, manifesting as coughing, wheezing, and chest pain. However, pleural effusions rarely occur in patients with pulmonary toxocariasis. We report the case of a 74-year-old man with highly suspected toxocariasis who presented with an eosinophilic pleural effusion and eosinophilia. He developed dyspnea and a right-sided pleural effusion. Thoracentesis revealed an exudative effusion containing numerous eosinophils. The pleural effusion continued to increase, and the eosinophilia rapidly progressed. Although the patient had not recently had contact with animals or known exposure to contaminated food, water, or soil, toxocariasis was confirmed by positive serological test results for anti-Toxocara antibodies in the serum and pleural effusion. The patient was cured with albendazole treatment for 28 days. The pleural effusion and eosinophilia resolved and did not recur. Clinicians should consider toxocariasis in the differential diagnosis of patients presenting with eosinophilic pleural effusions.
Assuntos
Eosinofilia , Derrame Pleural , Toxocaríase , Masculino , Animais , Humanos , Idoso , Toxocaríase/complicações , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológico , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Toxocara , Albendazol/uso terapêutico , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológicoRESUMO
Food-borne toxocariasis caused by the consumption of raw meat or liver has occasionally been reported from East Asia. We treated a 38-year-old Japanese man who was infected with Toxocara in China and underwent a four-week treatment with albendazole. The liver and lung lesions disappeared after the treatment, suggesting that the treatment was successful. One month after the end of the treatment, the patient relapsed, and albendazole was administered again for eight weeks. The patient has remained relapse-free for one year. Although toxocariasis can heal spontaneously, in some cases, such as the present case, the disease relapses even after long-term treatment. In conclusion, different durations of treatment are recommended by various guidelines, and the duration of treatment needs to be modified with each case, considering the response to the treatment.
Assuntos
Albendazol , Recidiva , Toxocaríase , Humanos , Albendazol/uso terapêutico , Albendazol/administração & dosagem , Masculino , Toxocaríase/tratamento farmacológico , Adulto , Animais , Anti-Helmínticos/uso terapêutico , Anti-Helmínticos/administração & dosagemRESUMO
DESIGN: Case Report Case description: This report describes the case of a female patient diagnosed with oculo-cerebral toxocariasis manifesting initially in the form of isolated bilateral cystoid macular edema. Diagnosis was made by means of positive anterior chamber and lumbar puncture western blots. The unusual presentation, ancillary findings and treatment are discussed. The control of intraocular inflammation that was only partially responsive to steroids was eventually achieved with pegylated interferon alfa-2a. CONCLUSION: Isolated macular edema is a rare presentation of ocular toxocariasis. Interferon alfa-2a may prove useful in case of insufficient control of inflammation.
Assuntos
Edema Macular , Toxocaríase , Uveíte , Animais , Humanos , Feminino , Edema Macular/diagnóstico , Edema Macular/tratamento farmacológico , Edema Macular/etiologia , Toxocaríase/complicações , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológico , Uveíte/complicações , Interferon alfa-2 , Inflamação/complicaçõesRESUMO
Toxocariasis is a zoonosis that represents a serious threat to public health particularly in tropical and subtropical areas. Currently, albendazole, the most effective drug for treating visceral toxocariasis, shows moderate efficacy against the larvae in tissues and has some adverse effects. Artemether is an antiparasitic drug mainly used in the treatment of malaria and showed effectiveness against numerous helminthic infections. Besides, it possesses potent anti-inflammatory, antiapoptotic, antifibrotic, and neuroprotective properties. Thus, the study's aim was to investigate artemether's effects in comparison with albendazole on the therapeutic outcome of experimental toxocariasis. For this aim, 140 laboratory-bred mice were divided into four main groups: uninfected control, treatment control, albendazole-treated, and artemether-treated groups. The treatment regimens were started at the 15th dpi (early treatment), and at the 35th dpi (late treatment). The effectiveness of treatment was determined by brain larval count, histopathological, immunohistochemical, and biochemical examination. Artemether showed more effectiveness than albendazole in reducing brain larval counts, markers of brain injury including NF-κB, GFAP, and caspase-3, the diameter and number of hepatic granulomas, hepatic oxidative stress, hepatic IL-6, and TG2 mRNA, and pulmonary inflammation and fibrosis. The efficacy of artemether was the same when administered early or late in the infection. Finally, our findings illustrated that artemether might be a promising therapy for T. canis infection and it could be a good substitution for albendazole in toxocariasis treatment.
Assuntos
Anti-Helmínticos , Toxocaríase , Animais , Camundongos , Toxocaríase/tratamento farmacológico , Toxocaríase/parasitologia , Toxocaríase/patologia , Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Artemeter/uso terapêutico , Fígado/patologia , Encéfalo/parasitologia , Encéfalo/patologia , PulmãoRESUMO
PURPOSE: To report the clinical features and treatment outcomes in adult Caucasians with ocular toxocariasis (OT) and investigate their prognosis depending on their serological status. METHODS: Retrospective observational cohort study (2016-2021) including consecutive adults with uveitis and positive western blot (WB) in the aqueous humor or vitreous. The presence of serum antibodies was not necessary for inclusion, allowing to compare the outcomes depending on the serological status. RESULTS: Seventeen eyes of 15 patients were included. Mean age at diagnosis was 51.9 years. Vitreous inflammation was the most frequent sign (100%). Vitreoretinal tractions (41.2%) and chorioretinal granulomas (58.8%) were less prevalent. Atypical features were: spontaneous intravitreal hemorrhage (23.5%), exudative retinal detachment (11.8%), isolated macular edema (17.6%), papillitis (29.4%) and vasculitis (47.1%). Twenty percent of patients had a positive serum serology. Baseline clinical features did not differ statistically depending on the serological status; however, the degree of inflammation was numerically higher in patients with negative serology. Overall, macular thickness, anterior and posterior segment inflammation improved significantly after treatment with oral albendazole, systemic ± local corticosteroids. Vitrectomy (47.1%) was performed in case of persistent vitritis (62.5%), retinal detachment (12.5%) and intravitreous hemorrhage (25%). CONCLUSION: OT has no pathognomonic sign and atypical presentations were not infrequent in this adult Caucasian cohort. Serum antibodies were rarely positive, stressing on the importance of ocular sample analysis, especially in case of atypical features. Serum antibodies may prove useful in forecasting the rapidity of inflammation clearance. Antiparasitic and anti-inflammatory treatment was safe and efficient in most cases.
Assuntos
Albendazol , Humor Aquoso , Infecções Oculares Parasitárias , Toxocaríase , Humanos , Estudos Retrospectivos , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológico , Masculino , Feminino , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/tratamento farmacológico , Infecções Oculares Parasitárias/parasitologia , Pessoa de Meia-Idade , Adulto , Humor Aquoso/parasitologia , Idoso , Albendazol/uso terapêutico , Animais , Resultado do Tratamento , População Branca , Anticorpos Anti-Helmínticos/sangue , Corpo Vítreo/parasitologia , Corpo Vítreo/patologia , Acuidade Visual/fisiologia , Anti-Helmínticos/uso terapêutico , Vitrectomia , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/parasitologia , Glucocorticoides/uso terapêutico , Tomografia de Coerência Óptica , Western BlottingRESUMO
There are currently insufficient anthelmintic medications available for the treatment of toxocariasis. For instance, Albendazole (ABZ) is the preferred medication, but its effectiveness against tissue-dwelling parasites is limited. In addition, Metformin (MTF) is a widely used oral antidiabetic medication that is considered to be safe for treatment. This study aimed to investigate any potential effects of MTF, alone or in combination with ABZ, on mice infections caused by Toxocara canis (T. canis). The efficacy of the treatment was assessed in the acute and chronic phases of the infection by larval recovery and histopathological, immunohistochemical, and biochemical studies. The results showed that combined therapy significantly reduced larval counts in the liver, brain, and muscles and ameliorated hepatic and brain pathology. It reduced oxidative stress and TGF-ß mRNA expression and increased FGF21 levels in the liver. It decreased TNF-α levels and MMP-9 expression in the brain. In addition, it increased serum levels of IL-12 and IFN-γ and decreased serum levels of IL-4 and IL-10. In the acute and chronic phases of the infection, the combined treatment was more effective than ABZ alone. In conclusion, this study highlights the potential role of MTF as an adjuvant in the treatment of experimental T. canis infection when administered with ABZ.
Assuntos
Metformina , Toxocara canis , Toxocaríase , Camundongos , Animais , Toxocaríase/tratamento farmacológico , Toxocaríase/parasitologia , Metformina/farmacologia , Metformina/uso terapêutico , Albendazol/farmacologia , Albendazol/uso terapêutico , Encéfalo/patologia , Fígado/patologiaRESUMO
Toxocariasis is a cosmopolitan helminthiasis linked to contamination with Toxocara cati or Toxocara canis. Only six isolated cases of pleural toxocariasis have been reported in the literature. We describe a case of pleurisy with isolated eosinophilia varying between 600 and 1500/mm3 likely linked o presumptive toxocariasis in a 72-year-old patient. Our patient was admitted to hospital with severe dyspnoea, asthenia and diarrhoea. Imaging studies confirmed right unilateral pleurisy without any parenchymal involvement. Serology of serum and pleural fluid was positive for anti-Toxocara antibodies by ELISA and immunoblotting. Treatment by pleural drainage and anti-parasitic medication with albendazole for 8 days resulted in the resolution of symptoms. A decrease in the levels of polynuclear eosinophils and total IgE confirmed the clinical resolution. The presence of hypereosinophilia in pleural fluid should evoke a diagnosis of pleural toxocariasis. Clinical symptoms and imaging are non-specific, but positive serology for anti-Toxocara antibodies in serum and pleural fluid can confirm the diagnosis.
Assuntos
Eosinofilia , Pleurisia , Toxocaríase , Animais , Humanos , Idoso , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológico , Toxocara , Albendazol/uso terapêutico , Ensaio de Imunoadsorção Enzimática , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Pleurisia/tratamento farmacológicoRESUMO
Infections caused by parasitic helminths rank among the most prevalent infections of humans and animals. Toxocariasis, caused by nematodes of the genus Toxocara, is one of the most widespread and economically important zoonotic parasitic infections that humans share with dogs and cats. Despite the completion of the Toxocara canis draft genome project, which has been an important step towards advancing the understanding of this parasite and the search for drug targets, the treatment of toxocariasis has been dependent on a limited set of drugs, necessitating the search for novel anthelmintic agents, specially against Toxocara larvae in tissues. Given that research, development, and innovation are crucial to finding appropriate solutions in the fight against helminthiasis, this paper reviews the progress made in the discovery of anthelmintic drug candidates for toxocariasis. The main compounds reported in the recent years regards on analogues of albendazole, reactive quinone derivatives and natural produts and its analogues. Nanoparticles and formulations were also reviewed. The in vitro and/or in vivo anthelmintic properties of such alternatives are herein discussed as well as the opportunities and challenges for treatment of human toxocariasis. The performed review clarify that the scarcity of validated molecular targets and limited chemical space explored are the main bottlenecks for advancing in the field of anti-Toxocara agents.
Assuntos
Anti-Helmínticos , Doenças do Gato , Doenças do Cão , Toxocaríase , Animais , Humanos , Gatos , Cães , Toxocaríase/tratamento farmacológico , Toxocaríase/parasitologia , Doenças do Gato/tratamento farmacológico , Doenças do Cão/tratamento farmacológico , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Albendazol/uso terapêutico , ToxocaraRESUMO
BACKGROUND: Toxocariasis is a common parasitic infection worldwide. Although it can present as several clinical syndromes, neurological manifestation is rare. Only a few reports are available on spinal cord involvement of toxocariasis. We report a case that presented with gait disturbance due to progressive lower limb spasticity. The patient had had visceral toxocariasis infection 8 years before. A spine magnetic resonance image (MRI) showed syringomyelia along the entire thoracic cord with small nodular enhancing lesions in the mid-portion of the syrinx, which led to the suspicion of ependymoma. Surgical mass removal was performed. However, histopathological examination of the mass did not show any malignant cells; instead, there were numerous axonal retraction balls with an eosinophilic granular body-like appearance. The serum antibody titer against toxocariasis was borderline high. Taken together, these observations led to a diagnosis of Toxocara infection, and the patient was treated with albendazole. CONCLUSION: To the best of our knowledge, this is the first case report of tumor-like spinal toxocariasis involving extensive lesions. A solid enhancing mass with accompanied syrinx and hemorrhage might be a Toxocara infection. It can easily be diagnosed with serologic tests and simply be treated with oral albendazole if suspected.
Assuntos
Anti-Helmínticos , Neoplasias , Siringomielia , Toxocaríase , Animais , Humanos , Toxocaríase/complicações , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológico , Albendazol/uso terapêutico , Anti-Helmínticos/uso terapêutico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Coluna Vertebral , Siringomielia/complicaçõesRESUMO
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
BACKGROUND: Toxocariasis is a worldwide distributed zoonosis that affects characteristically children. Clinical presentation is highly variable, often asymptomatic, and treatment duration is controversial. METHODS: A retrospective descriptive study (January 2014-December 2019) was performed in a referral Unit for Pediatric Tropical Diseases. Patients younger than 18 years of age diagnosed with toxocariasis were included. RESULTS: Out of 931 children screened for toxocariasis, 49 (5.3%) were seropositive. The median age was 11.0 years, 55.1% male and 30.6% referred contact with puppies. Overall, 34.7% were Latin-American, 24.5% Asiatic, 20.4% European, and 20.4% African. Only 34.7% presented symptoms, gastrointestinal the most common (52.9%). The 57.1% of children presented eosinophilia and 50% elevated total IgE. Most cases (95.9%) corresponded to covert toxocariasis. All children were treated with albendazole for 5, 14 or 21 days, and 4 children required a second course. Follow-up data were available in 32 children (65.3%) for a median of 7 months, showing a progressive decline in eosinophils, IgE-titers and ELISA optical density. CONCLUSION: Toxocariasis is mostly asymptomatic in children and eosinophilia is not always present. Serological tests should be included in migrant health screening and in the diagnostic assessment of eosinophilia. Eosinophil count, IgE-titers and ELISA optical-density could be useful during follow-up.
Assuntos
Eosinofilia , Toxocara canis , Toxocaríase , Migrantes , Animais , Cães , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Eosinofilia/epidemiologia , Feminino , Humanos , Imunoglobulina E , Masculino , Estudos Retrospectivos , Espanha/epidemiologia , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológico , Toxocaríase/epidemiologiaRESUMO
Parasitic infections are the leading cause of hypereosinophilia in the paediatric population in tropical countries. We report an unusual case of Toxocara infection in an eight-year-old boy who presented with intermittent fever, hypereosinophilia complicated by massive pericardial effusion and a mycotic aneurysm. This child received treatment with four weeks of albendazole and steroids.
Assuntos
Aneurisma Infectado , Eosinofilia , Derrame Pericárdico , Toxocaríase , Albendazol/uso terapêutico , Aneurisma Infectado/diagnóstico , Aneurisma Infectado/tratamento farmacológico , Aneurisma Infectado/etiologia , Animais , Criança , Humanos , Masculino , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/tratamento farmacológico , Derrame Pericárdico/etiologia , Toxocaríase/complicações , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológicoRESUMO
BACKGROUND: Toxocariasis is a neglected tropical disease caused by Toxocara canis and Toxocara cati. Toxocara species can involve many organs, such as the brain, heart and lungs, however, the urinary system involvement of toxocariasis is largely unknown. METHODS: We performed a systematic review to identify cases infected with urinary tract toxocariasis. RESULTS: We identified seven cases that were eligible to be reviewed. Among the included citations, four studies reported bladder involvement and three reported kidney involvement. Fever, urinary, and abdominal presentations were amongst the most important clinical symptoms. Eosinophilic cystitis and nephrotic syndrome were the most common diagnoses.. The treatment regimen included a combination of anthelmintic drugs and steroids. CONCLUSIONS: In cases of urinary tract presentations accompanied by eosinophilia or histopathologic findings suggestive of parasitic infection, toxocariasis should be included in the list of differential diagnoses, especially in endemic areas.
Assuntos
Anti-Helmínticos , Eosinofilia , Toxocara canis , Toxocaríase , Animais , Anti-Helmínticos/uso terapêutico , Eosinofilia/diagnóstico , Humanos , Doenças Negligenciadas/complicações , Toxocara , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológico , Toxocaríase/epidemiologiaRESUMO
Human toxocariasis is a helminthozoonosis caused by the migration of Toxocara species larvae through an organism. The infection in humans is transmitted either by direct ingestion of the eggs of the parasite, or by consuming undercooked meat infested with Toxocara larvae. This parasitosis can be found worldwide, but there are significant differences in seroprevalence in different areas, depending mainly on hot climate conditions and on low social status. However, the literature estimates of seroprevalence are inconsistent. Infected patients commonly present a range of symptoms, e.g., abdominal pain, decreased appetite, restlessness, fever, and coughing. This manuscript presents a case report of a polytraumatic patient who underwent a two-phase spinal procedure for a thoracolumbar fracture. After the second procedure, which was a vertebral body replacement via thoracotomy, the patient developed a pathologic pleural effusion. A microscopic cytology examination of this effusion revealed the presence of Toxocara species larvae. Although the patient presented no specific clinical symptoms, and the serological exams (Enzyme-linked immunosorbent assay (ELISA), Western blot) were negative, the microscopic evaluation enabled a timely diagnosis. The patient was successfully treated with albendazole, with no permanent sequelae of the infection.
Assuntos
Parasitos , Toxocaríase , Animais , Ensaio de Imunoadsorção Enzimática , Humanos , Estudos Soroepidemiológicos , Status Social , Toxocara , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológicoRESUMO
BACKGROUND: Toxocariasis is a helminthic infection caused by a nematode that mainly affects populations in tropical and subtropical latitudes. Humans are potential paratenic hosts, and clinical disease occurs as a result of parasite migration through intestinal tissue. We present a clinical case of otorhinolaryngological affectation by Toxocara canis. CASE PRESENTATION: A 60-year-old male from Ecuador, resident in Spain for 5 years, evaluated in the emergency department for presenting headache, otorrhea and left ear pain. Computed tomography (CT) and magnetic resonance imaging (MRI) reported a large mass of the nasopharynx with infiltration of the skull base, intracranial extension and a lesion in the left pons without being able to exclude metastases. Two Functional Endoscopic Sinus Surgery (FESS) biopsies were negative for malignancy. Despite not meeting the diagnostic criteria established by the existing literature, the clinical and radiological presentation, the presence of risk factors, a positive serology for Toxocara canis (IgGELISA) and the absence of alternative diagnosis were considered sufficient criteria to establish toxocariasis with inflammatory lesions in the nasopharynx and pons as the most probable diagnosis. Treatment with albendazole (400 mg / 12 h) and corticosteroids (1 mg / kg for 5 days) was started and continued for one month. Post treatment negative serology, and MRI and CT post treatment controls were performed after one year, both showing a decrease in lesion of the clivus as well as the pons. CONCLUSIONS: With the appropriate personal history, toxocariasis should be included in the differential diagnosis of infiltrating lesions of the skull base with a negative study of tumor histology. Albendazole treatment has been shown to control and cure the disease.