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1.
Parasit Vectors ; 15(1): 306, 2022 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-36038928

RESUMO

BACKGROUND: Current recommendations for diagnosis of Dirofilaria immitis infection in dogs rely on the detection of antigen produced largely by adult females coupled with the visualization of microfilariae (mf) in the circulation via a microfilaria detection test (MFDT). It is hypothesized that qPCR assays used in parallel with antigen detection tests will perform better in detecting mf than modified Knott's test (MK), when combined with antigen detection. This study compares probe-based qPCR and MK techniques for mf detection used in parallel with the DiroCHEK® antigen test to screen for heartworm infection in shelter dogs. METHODS: Matching blood and serum samples were collected from 300 shelter dogs in Brazos and Harris counties, Texas, USA. Blood was assessed for the presence of mf via MK and the presence of D. immitis DNA by a species-specific probe-based qPCR assay. Serum samples were tested for the presence of heartworm antigen using DiroCHEK® before and after immune complex dissociation (ICD) via heat treatment. In addition, the performance of each diagnostic test was evaluated via Chi-square test, Cochran's Q test, and post hoc analysis. RESULTS: Qualitatively, MK detected mf in 22.0% (66/300) of samples, 55 of which were morphologically identified as D. immitis and 11 as Acanthocheilonema reconditum. The range of heartworm mf was 28 to 88,803 mf/ml (median: 6627.5). Real-time PCR detected D. immitis DNA in 20.7% (62/300) of samples. Heartworm antigen was detected in 24.7% (74/300) of samples pre-ICD, and in 29.3% (88/300) post-ICD. When comparing tests, the Chi-square and McNemar's tests showed that the difference between positive and negative proportions was statistically significant. The Cochran test showed the difference in the distributions of cases and non-cases was significant when individual tests were combined (χ2 = 62.3, df = 3, P < 0.0001) and when parallel methods were combined (χ2 = 43.1, df = 4, P < 0.0001). CONCLUSION: Considering individual and combined test performances, practicality, and efficient use of bench time, this heartworm-specific probe-based qPCR method is a viable option as a mf detection test to be used in parallel with antigen tests for canine heartworm infection in diagnostic and research settings.


Assuntos
Acanthocheilonema , Dirofilaria immitis , Dirofilariose , Doenças do Cão , Acanthocheilonema/genética , Animais , Antígenos de Helmintos , Dirofilaria immitis/genética , Dirofilariose/diagnóstico , Doenças do Cão/diagnóstico , Cães , Feminino , Microfilárias/genética , Reação em Cadeia da Polimerase em Tempo Real/veterinária
2.
Sci Rep ; 12(1): 14078, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35982240

RESUMO

The seal heartworm Acanthocheilonema spirocauda (Nematoda: Onchocercidae) parasitizes the heart and pulmonary arteries of various phocid seals of the Northern Hemisphere. Over many decades, potential vectors of this parasite have been discussed, and to this date, the life cycle is not fully known. The seal louse Echinophthirius horridus (Anoplura: Echinophthiriidae) is an obligatory, permanent and haematophagous ectoparasite of phocids that has been hypothesized to function as obligate intermediate host for A. spirocauda. We examined 11 adult E. horridus specimens collected from stranded harbour seals (Phoca vitulina) in rehabilitation at the Sealcentre Pieterburen by X-ray microCT imaging, aiming to illustrate larval A. spirocauda infection sites in situ. In three of these specimens, thread-like larvae were detected in insect organs. Detailed imaging of the most infected louse revealed a total of 54 A. spirocauda larvae located either in fat bodies or the haemocoel. Histological analysis of the same specimen illustrated nematode cross-sections, confirming X-ray microCT data. The current data strongly suggest that E. horridus is a natural intermediate host for A. spirocauda. Moreover, we demonstrate the potential of X-ray microCT-based imaging as a non-destructive method to analyze host-parasite interactions, especially in the neglected field of marine mammal parasitology.


Assuntos
Acanthocheilonema , Anoplura , Dirofilaria immitis , Nematoides , Phoca , Animais , Larva , Microtomografia por Raio-X
3.
PLoS Pathog ; 17(11): e1010069, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34748611

RESUMO

ES-62 is the major secreted protein of the parasitic filarial nematode, Acanthocheilonema viteae. The molecule exists as a large tetramer (MW, ~240kD), which possesses immunomodulatory properties by virtue of multiple phosphorylcholine (PC) moieties attached to N-type glycans. By suppressing inflammatory immune responses, ES-62 can prevent disease development in certain mouse models of allergic and autoimmune conditions, including joint pathology in collagen-induced arthritis (CIA), a model of rheumatoid arthritis (RA). Such protection is associated with functional suppression of "pathogenic" hyper-responsive synovial fibroblasts (SFs), which exhibit an aggressive inflammatory and bone-damaging phenotype induced by their epigenetic rewiring in response to the inflammatory microenvironment of the arthritic joint. Critically, exposure to ES-62 in vivo induces a stably-imprinted CIA-SF phenotype that exhibits functional responses more typical of healthy, Naïve-SFs. Consistent with this, ES-62 "rewiring" of SFs away from the hyper-responsive phenotype is associated with suppression of ERK activation, STAT3 activation and miR-155 upregulation, signals widely associated with SF pathogenesis. Surprisingly however, DNA methylome analysis of Naïve-, CIA- and ES-62-CIA-SF cohorts reveals that rather than simply preventing pathogenic rewiring of SFs, ES-62 induces further changes in DNA methylation under the inflammatory conditions pertaining in the inflamed joint, including targeting genes associated with ciliogenesis, to programme a novel "resolving" CIA-SF phenotype. In addition to introducing a previously unsuspected aspect of ES-62's mechanism of action, such unique behaviour signposts the potential for developing DNA methylation signatures predictive of pathogenesis and its resolution and hence, candidate mechanisms by which novel therapeutic interventions could prevent SFs from perpetuating joint inflammation and destruction in RA. Pertinent to these translational aspects of ES-62-behavior, small molecule analogues (SMAs) based on ES-62's active PC-moieties mimic the rewiring of SFs as well as the protection against joint disease in CIA afforded by the parasitic worm product.


Assuntos
Anti-Inflamatórios/farmacologia , Artrite Experimental/prevenção & controle , Epigênese Genética , Fibroblastos/metabolismo , Proteínas de Helminto/farmacologia , Inflamação/prevenção & controle , Sinoviócitos/metabolismo , Acanthocheilonema/metabolismo , Animais , Artrite Experimental/etiologia , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Células Cultivadas , Metilação de DNA , Fibroblastos/efeitos dos fármacos , Fibroblastos/imunologia , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Camundongos Endogâmicos DBA , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/imunologia
4.
Parasit Vectors ; 14(1): 390, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362416

RESUMO

BACKGROUND: During the last decades, filarial infections caused by Dirofilaria spp. have spread rapidly within dog populations of several European countries. Increasing scientific interest in filariasis, and the availability of new diagnostic tools, has led to improved knowledge of the biology, morphology, and epidemiology of different species of filarial worms. However, data are still scarce for a number of countries, including the Republic of Moldova. Thus, we assessed the epidemiological status of canine filariasis in the Republic of Moldova to address part of this knowledge gap. METHODS: A total of 120 blood samples were collected between June 2018 and July 2019 from dogs originating from the cities of Cahul and Chisinau. The samples were examined microscopically, and multiplex polymerase chain reaction was performed to evaluate filarioid species diversity. RESULTS: Microscopic examination revealed that 12 dogs (10.0%) were positive for circulating microfilariae. The molecular test showed that one dog was positive for Acanthocheilonema reconditum (0.8%), one for Dirofilaria immitis (0.8%), six for Dirofilaria repens (5.0%), and four (3.3%) harboured a co-infection with D. immitis and D. repens. Prevalence was significantly higher in dogs aged ≥ 2 years. CONCLUSIONS: The epidemiological survey presented here for the Republic of Moldova confirmed the presence D. immitis, D. repens and A. reconditum in dogs that had not received any heartworm preventive.


Assuntos
Acanthocheilonema/genética , Acantoqueilonemíase/veterinária , Dirofilaria/genética , Doenças do Cão/epidemiologia , Filariose/epidemiologia , Filariose/veterinária , Acanthocheilonema/classificação , Acantoqueilonemíase/epidemiologia , Animais , Dirofilaria/classificação , Dirofilaria immitis/genética , Dirofilaria repens/genética , Doenças do Cão/parasitologia , Cães , Feminino , Filariose/sangue , Masculino , Moldávia , Prevalência
5.
Parasitol Res ; 120(6): 2109-2124, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33963428

RESUMO

Acanthocheilonema reconditum is a filarial parasite transmitted by arthropods (fleas, lice, and ticks) that infect dogs. There is minimal published data available to date on potential haematological and biochemical changes associated with this parasitic infection. Study aims were (i) provide an overview of A. reconditum in Europe, (ii) define A. reconditum prevalence and risk factors in a specific dog population (hunting) from southern Italy, and (iii) assess the frequency of haemato-biochemical abnormalities associated with infection. Blood samples collected from 3020 dogs were tested by a modified Knott's technique to count and identify microfilariae. Eighty-four dogs were infected by A. reconditum (2.78%; 95% CI 2.19-3.37%). Microfilariae ranged from 1 to 212/ml. Based on clinical examination, all but six dogs with non-specific symptoms were healthy. Haematological abnormalities included leucocytosis (n = 15), with eosinophilia (n = 14) and monocytosis (n = 13). Serum biochemical abnormalities included increased total serum proteins (n = 19), albumins (n = 7), total globulins (n = 14), ALT (n = 1), and ALP (n = 1); one dog was hypoalbuminemic, and BUN was mildly increased in 2 dogs. Risk factors included the province origin (Napoli, OR=5.4, 95%CI: 2.1-14.0; Caserta, OR=5.1, 95%CI: 2.5-10.6), hunting wild mammals (OR=2.8, 95% 95%CI: 1.6-4.8), and ectoparasite infestation (OR=1.9, 95%CI: 1.1-3.1). There was a negative correlation between microfilaraemic load and decreased albumin level (-0.37; p=0.021). Our results showed that A. reconditum circulates within the hunting dog population of southern Italy, with seemingly low pathogenic potential.


Assuntos
Acanthocheilonema/patogenicidade , Acantoqueilonemíase/veterinária , Doenças do Cão/parasitologia , Doenças Hematológicas/veterinária , Cães Trabalhadores/parasitologia , Acanthocheilonema/isolamento & purificação , Acantoqueilonemíase/sangue , Acantoqueilonemíase/epidemiologia , Acantoqueilonemíase/parasitologia , Animais , Doenças do Cão/sangue , Doenças do Cão/epidemiologia , Cães , Doenças Hematológicas/sangue , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/parasitologia , Itália/epidemiologia , Masculino , Microfilárias/isolamento & purificação , Microfilárias/patogenicidade , Prevalência , Fatores de Risco
6.
Parasitol Res ; 120(12): 4125-4143, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33547508

RESUMO

Filariae are vector-borne parasitic nematodes that are endemic worldwide, in tropical and subtropical regions. Important human filariae spp. include Onchocerca volvulus, Wuchereria bancrofti and Brugia spp., and Loa loa and Mansonella spp. causing onchocerciasis (river blindness), lymphatic filariasis (lymphedema and hydrocele), loiasis (eye worm), and mansonelliasis, respectively. It is estimated that over 1 billion individuals live in endemic regions where filarial diseases are a public health concern contributing to significant disability adjusted life years (DALYs). Thus, efforts to control and eliminate filarial diseases were already launched by the WHO in the 1970s, especially against lymphatic filariasis and onchocerciasis, and are mainly based on mass drug administration (MDA) of microfilaricidal drugs (ivermectin, diethylcarbamazine, albendazole) to filarial endemic areas accompanied with vector control strategies with the goal to reduce the transmission. With the United Nations Sustainable Development Goals (SDGs), it was decided to eliminate transmission of onchocerciasis and stop lymphatic filariasis as a public health problem by 2030. It was also requested that novel drugs and treatment strategies be developed. Mouse models provide an important platform for anti-filarial drug research in a preclinical setting. This review presents an overview about the Litomosoides sigmodontis and Acanthocheilonema viteae filarial mouse models and their role in immunological research as well as preclinical studies about novel anti-filarial drugs and treatment strategies.


Assuntos
Acanthocheilonema , Filariose Linfática , Filarioidea , Loíase , Animais , Filariose Linfática/tratamento farmacológico , Filariose Linfática/epidemiologia , Humanos , Loíase/tratamento farmacológico , Loíase/epidemiologia , Masculino , Camundongos , Modelos Animais
7.
Parasite Immunol ; 43(3): e12803, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33091157

RESUMO

AIMS: ES-62 is a well-studied anti-inflammatory molecule secreted by L4-adult stage Acanthocheilonema viteae. We maintain the life cycle of A viteae using Meriones libycus as the definitive host. Here, we investigated whether the full life cycle could be maintained, and functional ES-62 produced, in a related jird species-Meriones shawi. METHODS AND RESULTS: Adult worms were produced in comparable numbers in the two species, but very few microfilariae (MF) were observed in the M shawi bloodstream. M shawi ES-62 produced ex vivo was functional and protective in a mouse model of arthritis. Myeloid-derived cells from naïve and infected jirds of both species were compared with respect to ROS production and osteoclast generation, and some differences between the two species in both the absence and presence of infection were observed. CONCLUSIONS: The life cycle of A viteae cannot be successfully completed in M shawi jirds but L3 stage worms develop to adulthood and produce functional ES-62. Preliminary investigation into jird immune responses suggests that infection can differentially modulate myeloid responses in the two species. However, species-specific reagents are required to understand the complex interplay between A viteae and its host and to explain the lack of circulating MF in infected M shawi jirds.


Assuntos
Acanthocheilonema/crescimento & desenvolvimento , Acantoqueilonemíase/parasitologia , Gerbillinae/parasitologia , Proteínas de Helminto/biossíntese , Animais , Modelos Animais de Doenças , Feminino , Estágios do Ciclo de Vida , Masculino , Camundongos , Microfilárias/crescimento & desenvolvimento , Especificidade da Espécie
8.
Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi ; 34(2): 204-211, 2021 Nov 01.
Artigo em Chinês | MEDLINE | ID: mdl-35537846

RESUMO

ES-62 is a phosphorylcholine-containing, 62 kDa glycoprotein derived from the excretory-secretory product of Acanthocheilonema viteae, which is effective for the prevention and treatment of immune dysregulation diseases through triggering activation of immune cells, such as dendritic cells, mononuclear macrophages and regulatory B cells and mediating immune responses. Recently, the role of the ES-62 protein in the management of allergic, autoimmune and metabolic diseases has been paid much attention. This review summarizes the regulatory role of the ES-62 protein in immune dysregulation diseases and the underlying mechanisms, so as to provide insights into future experimental studies.


Assuntos
Acanthocheilonema , Dipetalonema , Acanthocheilonema/metabolismo , Animais , Dipetalonema/metabolismo , Glicoproteínas , Proteínas de Helminto , Fosforilcolina/metabolismo
9.
Parasit Vectors ; 13(1): 501, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004047

RESUMO

BACKGROUND: Dirofilaria immitis is responsible for heartworm disease in dogs in endemic areas worldwide. Screening for this infection is done by blood tests. Antigen testing is the most sensitive method to detect an infection with adult (female) worms. Microscopic examination of a blood smear or Knott's test can be used to detect circulating microfilariae, the infective larvae. To increase the sensitivity of the antigen test by decreasing the false negative test results, heating of the blood sample has been recommended in recent guidelines. Heating is believed to remove blocking immune-complexes. Circulating microfilariae are not specific findings for heartworm infection, as other nematodes (among others, Acanthocheilonema dracunculoides) can also result in microfilaremia. Although the type of microfilariae cannot be determined by microscopy alone, real-time PCR can reliably identify the infecting nematode species. Correct identification of the parasite is of major importance, as an infection with D. immitis requires antiparasitic therapy, whereas A. dracunculoides is thought to be a clinically irrelevant coincidental finding. The present case report describes a microfilaremic dog where the initial antigen test for D. immitis turned positive after heat treatment, whereas real-time PCR revealed that the microfilariae were A. dracunculoides (syn. Dipetalonema dracunculoides). RESULTS: A circa 5-year old, asymptomatic Spanish mastiff dog was referred for heartworm therapy because microfilariae were found via a screening blood test. The dog was recently imported to the Netherlands from Spain, where it had been a stray dog. Antigen tests on a plasma sample for D. immitis were performed with three different test kits, which all turned out to be negative. However, heat treatment of two of these samples were carried out and both of them led to a positive antigen test result. Real-time PCR showed that the circulating microfilariae belonged to A. dracunculoides species. Three administrations of moxidectin spot-on at monthly intervals resulted in a negative antigen and a negative Knott's tests one month after the last treatment. CONCLUSIONS: We conclude that heat treatment of initially negative blood samples for D. immitis could lead to false positive antigen test results if the dog is infected with A. dracunculoides.


Assuntos
Acanthocheilonema/isolamento & purificação , Acantoqueilonemíase/veterinária , Antígenos de Helmintos/sangue , Dirofilaria immitis/isolamento & purificação , Dirofilariose/parasitologia , Doenças do Cão/parasitologia , Microfilárias/isolamento & purificação , Acanthocheilonema/genética , Acanthocheilonema/imunologia , Acantoqueilonemíase/sangue , Acantoqueilonemíase/parasitologia , Animais , Sangue/parasitologia , Dirofilaria immitis/genética , Dirofilaria immitis/imunologia , Dirofilariose/sangue , Dirofilariose/diagnóstico , Doenças do Cão/sangue , Doenças do Cão/diagnóstico , Cães , Reações Falso-Positivas , Feminino , Temperatura Alta , Testes Imunológicos , Microfilárias/genética , Microfilárias/imunologia
10.
Vet Parasitol Reg Stud Reports ; 20: 100404, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32448535

RESUMO

This paper reports the presence of various species of filarial nematodes in dogs in an area of central Italy at the border between two regions (Tuscany-Latium), which had previously been free of infection and for which there are no epidemiological data in the literature. Blood and serum samples from a total of 363 adult dogs were collected during in 2016/17 and 2018/19 in the provinces of Grosseto (Tuscany) and Viterbo (Latium). The dogs were of different breeds or mixed breeds, randomly selected, and living in public kennels or privately owned. Of the 363 samples tested, 55 dogs were positive to Knott's test for microfilariae (prevalence 15.1%; 95% confidence interval: 11.5-18.8%). Dirofilaria immitis was found in 25 cases (prevalence 6.9%; 95% CI 4.3-9.5%), D. repens in 27 (7.4%, 95% CI 4.7-10.1%) and Acanthocheilonema reconditum in 3 (0.8%, 95% CI 0.1-1.7%). Out of 55 dogs, only four were infested with both D. immitis and D. repens (1.1%, 95% CI 0.001-2.2%).


Assuntos
Acantoqueilonemíase/veterinária , Dirofilariose/epidemiologia , Doenças do Cão/epidemiologia , Filariose/veterinária , Acanthocheilonema/isolamento & purificação , Acantoqueilonemíase/epidemiologia , Acantoqueilonemíase/parasitologia , Animais , Dirofilaria immitis/isolamento & purificação , Dirofilariose/parasitologia , Doenças do Cão/parasitologia , Cães , Feminino , Filariose/epidemiologia , Filariose/parasitologia , Itália/epidemiologia , Masculino , Prevalência
11.
Parasitol Res ; 119(4): 1281-1290, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32166425

RESUMO

At least two species of filarial worms, Dirofilaria immitis and Acanthocheilonema (Dipetalonema) odendhali, infect otariid pinnipeds, including the California sea lion (Zalophus californianus). To date, evidence of infection in sea lions has come from dead or captive animals, and little is known about filariasis in free-living populations. We sampled 45 California sea lion adults and 197 pups captured at 12 rookeries from different ecological regions within the Gulf of California and detected and quantified D. immitis and A. odendhali microfilariae in blood smears. We investigated differences in prevalence and parasite load (intensity of infection) among ecological regions. Microfilariae were detected in the blood of 35 of the 45 (77.78%) adult females and in 1 of the 197 (0.51%) pups examined. The average burden of A. odendhali per microlitre of blood was nearly twice that of D. immitis. Prevalence and intensity of infection differed significantly among regions, being highest for colonies within the northern and northcentral regions and lowest in the southern region. Dirofilaria immitis and A. odendhali infections displayed a similar spatial pattern of prevalence. Colony density inversely predicted the prevalence of microfilariae. Based on the clinical parameters typically associated with filarial infections in carnivores and physical examinations, none of the sea lions appeared to have evidence of disease. This is a first approximation to investigate the prevalence of microfilaria infections in free-ranging California sea lions and to explore their relevance to population health.


Assuntos
Acanthocheilonema/isolamento & purificação , Acantoqueilonemíase/veterinária , Dirofilaria immitis/isolamento & purificação , Dirofilariose/parasitologia , Leões-Marinhos/parasitologia , Acantoqueilonemíase/parasitologia , Animais , California , Feminino , México , Carga Parasitária
12.
PLoS Pathog ; 16(3): e1008391, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163524

RESUMO

Improvements in hygiene and health management have driven significant increases in human lifespan over the last 50 years. Frustratingly however, this extension of lifespan has not been matched by equivalent improvements in late-life health, not least due to the global pandemic in type-2 diabetes, obesity and cardiovascular disease, all ageing-associated conditions exacerbated and accelerated by widespread adoption of the high calorie Western diet (HCD). Recently, evidence has begun to emerge that parasitic worm infection might protect against such ageing-associated co-morbidities, as a serendipitous side-effect of their evolution of pro-survival, anti-inflammatory mechanisms. As a novel therapeutic strategy, we have therefore investigated the potential of ES-62, an anti-inflammatory secreted product of the filarial nematode Acanthocheilonema viteae, to improve healthspan (the period of life before diseases of ageing appear) by targeting the chronic inflammation that drives metabolic dysregulation underpinning ageing-induced ill-health. We administered ES-62 subcutaneously (at a dose of 1 µg/week) to C57BL/6J mice undergoing HCD-accelerated ageing throughout their lifespan, while subjecting the animals to analysis of 120 immunometabolic responses at various time-points. ES-62 improved a number of inflammatory parameters, but markedly, a range of pathophysiological, metabolic and microbiome parameters of ageing were also successfully targeted. Notably, ES-62-mediated promotion of healthspan in male and female HCD-mice was associated with different mechanisms and reflecting this, machine learning modelling identified sex-specific signatures predictive of ES-62 action against HCD-accelerated ageing. Remarkably, ES-62 substantially increased the median survival of male HCD-mice. This was not the case with female animals and unexpectedly, this difference between the two sexes could not be explained in terms of suppression of the chronic inflammation driving ageing, as ES-62 tended to be more effective in reducing this in female mice. Rather, the difference appeared to be associated with ES-62's additional ability to preferentially promote a healthier gut-metabolic tissue axis in male animals.


Assuntos
Acanthocheilonema/imunologia , Acantoqueilonemíase/imunologia , Dieta Ocidental/efeitos adversos , Proteínas de Helminto/imunologia , Longevidade/imunologia , Modelos Imunológicos , Animais , Feminino , Masculino , Camundongos
13.
Parasitol Int ; 76: 102070, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32036036

RESUMO

Canine filarioids are worldwide distributed nematodes transmitted by arthropods with variable virulence depending on the species. Dirofilaria immitis is the most virulent and serological antigen tests are commonly employed to detect it. This study reports on the heaviest cavity filariasis recorded so far in a dog, which showed no apparent clinical signs of infection. The 6-year-old male was positive to a D. immitis antigen test. Blood samples collected and analyzed with the modified Knott's test for microfilariae revealed 264,367 microfilariae/ml. In a post-mortem examination 791 adult filarial nematodes were found in the dog's thoracic and peritoneal cavities. Morphological and molecular analysis identified the nematode as Acanthocheilonema dracunculoides and no other species were present. This is evidence that massive A. dracunculoides infections in dogs may not be clinically evident, they may cause serologic cross-reaction with D. immitis infection and become a life-threatening condition if dogs are treated with a microfilaricidal treatment without previously performing an adequate diagnosis.


Assuntos
Acanthocheilonema/isolamento & purificação , Acantoqueilonemíase/veterinária , Doenças do Cão/diagnóstico , Acantoqueilonemíase/diagnóstico , Acantoqueilonemíase/parasitologia , Animais , Doenças do Cão/parasitologia , Cães , Filariose/diagnóstico , Filariose/parasitologia , Filariose/veterinária , Masculino , Microfilárias/isolamento & purificação , Espanha
14.
Vet Parasitol Reg Stud Reports ; 18: 100330, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31796181

RESUMO

The current study investigated for the first time the occurrence of filarial infections in dogs in Cyprus. Blood samples of dogs from five districts of Cyprus (Lefkosia, Lemessos, Larnaka, Pafos and Ammochostos) were examined by the modified Knott's method and by serology, and the morphological classification of microfilariae was confirmed by molecular methods. A total of 200 dogs, 153 living in shelters and 47 owned dogs, were included in the study. Acanthocheilonema reconditum microfilariae were found in 9 (4.5%) samples and one (0.5%) sample was seropositive for D. immitis. No statistical significance was observed between microfilaraemic samples and the evaluated variables apart from the district (p = .005). The present study showed that dogs in Cyprus can be infected with blood circulating microfilariae and for the first time A. reconditum was reported as autochthonous infection in dogs in the country. No microfilariae of Dirofilaria spp. were detected. However, veterinarians should remain vigilant regarding Dirofilaria infections and should consider preventive protection to the animals, at least in case of travel in enzootic areas.


Assuntos
Acanthocheilonema/isolamento & purificação , Dirofilaria immitis/isolamento & purificação , Dirofilariose/epidemiologia , Doenças do Cão/epidemiologia , Microfilárias/isolamento & purificação , Acanthocheilonema/crescimento & desenvolvimento , Acantoqueilonemíase/epidemiologia , Acantoqueilonemíase/parasitologia , Acantoqueilonemíase/veterinária , Animais , Chipre/epidemiologia , Dirofilaria immitis/crescimento & desenvolvimento , Dirofilariose/parasitologia , Doenças do Cão/parasitologia , Cães , Feminino , Masculino , Prevalência
15.
Glycobiology ; 29(8): 562-571, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31094418

RESUMO

ES-62 is the major secreted product of the parasitic filarial nematode Acanthocheilonema viteae and has potent anti-inflammatory activities as a consequence of posttranslational decoration by phosphorylcholine (PC). Previously, we showed that ES-62's PC was attached to N-linked glycans, and using fast atom bombardment mass spectrometry, we characterized the structure of the glycans. However, it was unknown at this time which of ES-62's four potential N-glycosylation sites carries the PC-modified glycans. In the present study, we now employ more advanced analytical tools-nano-flow liquid chromatography with high-definition electrospray mass spectrometry-to show that PC-modified glycans are found at all four potential N-glycosylation sites. Also, our earlier studies showed that up to two PC groups were detected per glycan, and we are now able to characterize N-glycans with up to five PC groups. The number per glycan varies in three of the four glycosylation sites, and in addition, for the first time, we have detected PC on the N-glycan chitobiose core in addition to terminal GlcNAc. Nevertheless, the majority of PC is detected on terminal GlcNAc, enabling it to interact with the cells and molecules of the immune system. Such expression may explain the potent immunomodulatory effects of a molecule that is considered to have significant therapeutic potential in the treatment of certain human allergic and autoimmune conditions.


Assuntos
Acanthocheilonema/metabolismo , Proteínas de Helminto/química , Processamento de Proteína Pós-Traducional , Proteoma/química , Glicosilação , Proteínas de Helminto/metabolismo , Proteoma/metabolismo , Via Secretória
16.
Rio de Janeiro; s.n; 2019. 78 p. ilus.
Tese em Português | LILACS | ID: biblio-1045986

RESUMO

Dirofilaria immitis é o bioagente patogênico da dirofilariose, agravo frequente à saúde dos cães, principalmente em áreas costeiras de regiões tropicais e subtropicais. A dirofilariose humana é uma zoonose considerada acidental, presente em diferentes países, inclusive no Brasil. O objetivo deste estudo foi analisar a ocorrência da infecção canina por filarídeos nos municípios de Magé, Duque de Caxias, Guapimirim e Nova Iguaçu, na Baixada Fluminense, Estado do Rio de Janeiro. O estudo foi desenvolvido a partir de amostras de sangue de cães nascidos, criados e atendidos em serviços veterinários. Amostras diagnosticadas como positivas após análise pelos testes laboratoriais foram submetidas à PCR-Multiplex e sequenciamento, para identificação específica. Em todos os municípios estudados foram detectados cães infectados. A frequência geral em relação aos casos positivos de cães microfilarêmicos foi de 76,9% (113/147) e deste total, 100 amostras (88,5%) amplificaram o fragmento do gene 12S. As maiores frequências de animais parasitados das amostras do laboratório de patologia clínica foram observadas em Magé (51%; 51/100) e Duque de Caxias (40%; 40/100) (p<0,00; χ2=23,7; OR=8,71)


Cães machos foram os mais parasitados (62,3%; χ2=1,26; p=0,25), a faixa etária entre 1 a 6 anos foi a mais acometida (62,1%; χ2=1,96; p=0,16), e a chance de um animal de porte grande ser parasitado é 3,6 vezes maior em relação a um cão de porte médio (63,6%; χ2=7,47; p=0,02; OR=3,64). Das amostras submetidas à reação de sequenciamento, 93,6% (73/78) foram identificadas como D. immitis e 6,4% (5/78) como Achantocheilonema reconditum. A alta frequência e a consideração de que as áreas onde vivem os cães com D. immitis são ambientes naturais para criadouros dos vetores culicídeos, permitem inferir sobre o estabelecimento e a manutenção do ciclo enzoótico na região analisada, sinalizam sua vulnerabilidade para a ocorrência do ciclo epidêmico e apontam para a possibilidade de ocorrência de casos humanos. O estudo permitiu caracterizar e determinar a ocorrência de filarioses caninas na região e possibilitou a avaliação de risco para a população humana e orientações de medidas integradas de prevenção. (AU)


Assuntos
Animais , Zoonoses , Dirofilaria immitis , Cães , Acanthocheilonema , Filariose , Promoção da Saúde
17.
Molecules ; 23(10)2018 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-30336585

RESUMO

Parasitic helminths and their isolated secreted products show promise as novel treatments for allergic and autoimmune conditions in humans. Foremost amongst the secreted products is ES-62, a glycoprotein derived from Acanthocheilonema viteae, a filarial nematode parasite of gerbils, which is anti-inflammatory by virtue of covalently-attached phosphorylcholine (PC) moieties. ES-62 has been found to protect against disease in mouse models of rheumatoid arthritis, systemic lupus erythematosus, and airway hyper-responsiveness. Furthermore, novel PC-based synthetic small molecule analogues (SMAs) of ES-62 have recently been demonstrated to show similar anti-inflammatory properties to the parent molecule. In spite of these successes, we now show that ES-62 and its SMAs are unable to provide protection in mouse models of certain autoimmune conditions where other helminth species or their secreted products can prevent disease development, namely type I diabetes, multiple sclerosis and inflammatory bowel disease. We speculate on the reasons underlying ES-62's failures in these conditions and how the negative data generated may help us to further understand ES-62's mechanism of action.


Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Proteínas de Helminto/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Acanthocheilonema/química , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Diabetes Mellitus Tipo 1/patologia , Modelos Animais de Doenças , Proteínas de Helminto/química , Helmintos/química , Humanos , Doenças Inflamatórias Intestinais/patologia , Camundongos , Esclerose Múltipla/patologia
18.
PLoS One ; 13(7): e0200419, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29995959

RESUMO

Dirofilaria immitis and Acanthocheilonema reconditum are common parasites in dogs but have also been reported parasitizing humans. The differential diagnosis and epidemiological evaluation of these zoonoses are important to the development of efficient public health policies and control strategies. The purpose of this study was to carry out an epidemiological survey by using molecular methods for the specific identification of filarid parasites of domestic dogs in the Marajó mesoregion, State of Pará (PA), Brazil. A total of 418 canine blood samples from Marajó mesoregion (Northern Brazil) were collected, submitted to DNA extraction, polymerase chain reaction (PCR) with "pan filarial" primer, subsequent sequencing and sequence analysis using BLASTn software comparison with previously deposited sequences in GenBank. After that, a phylogenetic analysis by Maximum Parsimony was performed to aid the specific diagnosis. The obtained sequences showed the occurrence of 9 (2.15%) dogs infected with D. immitis and 30 (7.18%) by A. reconditum, with a confidence interval of 95%, there were no cases of co-infection. We observed that male dogs were more likely to D. immits and A. reconditum infection. However, age was not significant to both infections. This study reports for the first time the occurrence of A. reconditum in the northern region of Brazil and confirmed the presence of D. immitis in the Marajó mesoregion.


Assuntos
Acantoqueilonemíase/veterinária , Dirofilariose/epidemiologia , Dirofilariose/parasitologia , Doenças do Cão/epidemiologia , Doenças do Cão/parasitologia , Acanthocheilonema , Acantoqueilonemíase/sangue , Acantoqueilonemíase/epidemiologia , Acantoqueilonemíase/parasitologia , Animais , Brasil , Dirofilaria immitis , Dirofilariose/sangue , Doenças do Cão/sangue , Cães , Feminino , Masculino , Epidemiologia Molecular , Doenças Negligenciadas/sangue , Doenças Negligenciadas/epidemiologia , Doenças Negligenciadas/parasitologia , Doenças Negligenciadas/veterinária , Filogenia , Zoonoses/sangue , Zoonoses/epidemiologia , Zoonoses/parasitologia
19.
Front Immunol ; 9: 1016, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29867986

RESUMO

The immunomodulatory actions of parasitic helminth excretory-secretory (ES) products that serendipitously protect against development of chronic inflammatory disorders are well established: however, knowledge of the interaction between ES products and the host musculoskeletal system in such diseases is limited. In this study, we have focused on ES-62, a glycoprotein secreted by the rodent filarial nematode Acanthocheilonema viteae that is immunomodulatory by virtue of covalently attached phosphorylcholine (PC) moieties, and also two synthetic drug-like PC-based small molecule analogues (SMAs) that mimic ES-62's immunomodulatory activity. We have previously shown that each of these molecules prevents development of pathology in collagen-induced arthritis (CIA), a model of the musculoskeletal disease rheumatoid arthritis (RA) and reflecting this, we now report that ES-62 and its SMAs, modify bone remodeling by altering bone marrow progenitors and thus impacting on osteoclastogenesis. Consistent with this, we find that these molecules inhibit functional osteoclast differentiation in vitro. Furthermore, this appears to be achieved by induction of anti-oxidant response gene expression, thereby resulting in reduction of the reactive oxygen species production that is necessary for the increased osteoclastogenesis witnessed in musculoskeletal diseases like RA.


Assuntos
Artrite Experimental/prevenção & controle , Proteínas de Helminto/farmacologia , Fatores Imunológicos/farmacologia , Osteogênese/efeitos dos fármacos , Acanthocheilonema/química , Animais , Masculino , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo
20.
Sci Rep ; 8(1): 2123, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29391452

RESUMO

ES-62 is a protein secreted by the parasitic worm Acanthocheilonema viteae that is anti-inflammatory by virtue of covalently attached phosphorylcholine. Previously we have reported that drug-like Small Molecule Analogues (SMAs) of its phosphorylcholine moiety can mimic ES-62 in protecting against disease development in certain mouse models of autoimmune and allergic conditions, due to them causing partial degradation of the TLR/IL-1R adaptor MyD88. We have now taken a molecular modelling approach to investigating the mechanism underlying this effect and this predicts that the SMAs interact directly with the MyD88 TIR domain. Further support for this is provided by assay of LPS-induced MyD88/NF-κB-driven secreted alkaline phosphatase (SEAP) reporter activity in commercially-available stably transfected (TLR4-MD2-NF-κB-SEAP) HEK293 cells, as SMA12b-mediated inhibition of such SEAP activity is blocked by its pre-incubation with recombinant MyD88-TIR domain. Direct binding of SMA12b to the TIR domain is also shown to inhibit homo-dimerization of the adaptor, an event that can explain the observed degradation of the adaptor and inhibition of subsequent downstream signalling. Thus, these new data identify initial events by which drug-like ES-62 SMAs, which we also demonstrate are able to inhibit cytokine production by human cells, homeostatically maintain "safe" levels of MyD88 signalling.


Assuntos
Acanthocheilonema/metabolismo , Anti-Inflamatórios/farmacologia , Proteínas de Helminto/farmacologia , Inflamação/tratamento farmacológico , Fator 88 de Diferenciação Mieloide/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos , Acanthocheilonema/crescimento & desenvolvimento , Células HEK293 , Humanos , Inflamação/metabolismo , Inflamação/patologia , Fator 88 de Diferenciação Mieloide/genética , NF-kappa B/genética , Domínios Proteicos , Fator de Necrose Tumoral alfa
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