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1.
Parasitol Res ; 120(11): 3633-3644, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34519871

RESUMO

Diverse Onchocerca species are present mostly parasitizing ungulates, with the exception of Onchocerca volvulus (O. volvulus) in humans and O. lupi in canids and cats. The human cases due to the O. lupi have been more highlighted during last years. So, the present review was performed to determine the detailed characteristics of confirmed human O. lupi case reports documented worldwide. Hence, a systematic search was done using English international databases (Scopus, PubMed, Web of Science, Embase, ProQuest, and Google Scholar). Totally, 14 confirmed human cases were documented during the last decade, mostly from the USA and Turkey with 7 and 3 cases, respectively. Most cases (7 individuals) were male with the age range of 22-month-old to 54-year-old. The parasite was frequently isolated from the right eye (5 cases), followed by the left eye (4 cases), cervical spinal canal (3 cases), scalp, and right forearm (one case each). Molecular identification of the isolated agent was the preferred way of diagnosis in most cases (9 records). In conclusion, human O. lupi cases have been more highlighted in recent years, whether due to the improved diagnostics and/or host-switching phenomenon, and both veterinarians and healthcare authorities should be alerted.


Assuntos
Doenças do Cão , Onchocerca volvulus , Oncocercose , Animais , Cães , Olho , Humanos , Masculino , Onchocerca , Oncocercose/epidemiologia
2.
Acta Trop ; 224: 106140, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34562429

RESUMO

Black flies (Diptera: Simuliidae) are known as vectors of disease agents in humans and livestock, with some species being vectors of Onchocerca volvulus, the filarial nematode that is the causative agent of human onchocerciasis. Nematode infections in adult female black flies have been reported from some areas in northern and western Thailand, but not from other regions of Thailand. In this study, wild-caught adult female black flies from the central region of Thailand were examined for infections with nematodes. Collections of adult females were carried out at Khlong Lan district, Kamphaeng Phet province, central Thailand. A molecular approach, based on the mitochondrial (cox1, 12S rRNA) and nuclear (18S rRNA) genes, was used to identify the species of nematodes recovered from the specimens collected. A total of 911 wild-caught adult black flies were collected. Simulium nigrogilvum was the most abundant species (n = 708), followed by S. doipuiense complex (n = 179), S. chamlongi (n = 11), S. umphangense (n = 10), S. chumpornense (n = 1), S. multistriatum species-group (n = 1), and S. maewongense (n = 1). Nematode infections were detected in nine specimens of S. nigrogilvum, of which two were positive for filarial worms (one worm each, infection rate 0.28%) and seven were positive for non-filarial nematodes (11 worms in total, infection rate 0.99%). The two filarial nematodes (third-stage larvae) were identified molecularly as Onchocerca species type I, while the 11 non-filarial nematodes were classified into ascaridoid (n = 2), tylenchid (n = 6) and mermithid (n = 3) nematodes. The results of this study demonstrated that adult female S. nigrogilvum were parasitized with diverse nematodes (filarial and non-filarial). Detection of the infective larvae of Onchocerca sp. type I in S. nigrogilvum confirms that occurrence of zoonotic onchocerciasis is highly possible in Thailand. Additional in-depth investigation of the morphology, life cycle and host-parasite relationship of nematodes that parasitized this black fly host is still needed.


Assuntos
Mordeduras e Picadas , Oncocercose , Simuliidae , Animais , Feminino , Humanos , Onchocerca/genética , Oncocercose/epidemiologia , Tailândia
3.
Exp Parasitol ; 229: 108143, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34437906

RESUMO

BACKGROUND: Current treatment options for onchocerciasis are sub-optimal, prompting research and development of a safe cure (macrofilaricide). Onchocerca ochengi, a parasite of cattle, is used as a close surrogate for the human parasite O. volvulus in a murine model for pre-clinical screening of macrofilaricides. Skin from naturally infected cattle have been used in previous studies as a reliable source of parasite material. However, there is limited knowledge on how source-related factors such as the microfilaridermia status of the cattle, the nodule load and nodular worm viability may affect survival of male O. ochengi worms implanted in the rodent hosts. Such relationships were investigated in this study. METHODS: Dermal tissue and nodules were obtained from Gudali cattle, dissected and cultured to obtain migrating microfilariae (mf) and male worms. Emerged male worms were implanted into SCID mice and Gerbils (Meriones unguiculatus) and recovery rates were determined upon 42 days post implantation. Finally, nodules were processed for histology and embryogram analyses to assess the nodular worm viability and fertility, respectively. RESULTS: Of the 69 cattle sampled, 24 (34.8%) were mf+ and 45 (65.2%) were mf-. The mean nodule loads were 180.5 ± 117.7 (mf+) and 110.6 ± 102.7 (mf-) (p = 0.0186). The mean male worm harvest from nodules were 76.8 ± 120.3 and 47.2 ± 33.4 (p = 0.2488) for mf+ and mf- cattle, respectively. The number of male worms per 100 nodules were 57/100 and 46/100 nodules for mf+ and mf- cows, respectively. Female worms from nodules of mf- cows had higher counts of both normal and abnormal embryos with higher proportions of dead nodular worms evinced by histology compared to those from mf+ cows. A total of 651 worms were implanted into mice and gerbils, out of which 129 (19.81%) were recovered. Logistic regression analysis indicated that the microfilaridermia status of the cattle (presence of mf) (OR = 4.3319; P = 0.001) is the single most important predictor of the success of male worm recovery after implantation into rodents. CONCLUSION: Microfilaridermic cattle provide a promising source of adult O. ochengi. Male worms from this group of cattle have a better success rate of survival in a murine implant model. Nevertheless, in the programmatic point of view, amicrofilaridermic Gudali cattle would still constitute an important source of O. ochengi male worms with relatively good viability after implantation into rodents.


Assuntos
Doenças dos Bovinos/parasitologia , Onchocerca/fisiologia , Oncocercose/veterinária , Animais , Bovinos , Modelos Animais de Doenças , Feminino , Fertilidade , Gerbillinae , Masculino , Camundongos , Camundongos SCID , Microfilárias/crescimento & desenvolvimento , Microfilárias/fisiologia , Análise Multivariada , Onchocerca/crescimento & desenvolvimento , Oncocercose/parasitologia , Análise de Regressão
4.
Parasit Vectors ; 14(1): 305, 2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34099047

RESUMO

BACKGROUND: Drugs currently used for controlling onchocerciasis and lymphatic filariasis (LF) are mainly microfilaricidal, with minimal or no effect on the adult worms. For efficient management of these diseases, it is necessary to search for new drugs with macrofilaricidal activities that can be used singly or in combination with existing ones. Daniellia oliveri and Psorospermum febrifugum are two plants commonly used in the local management of these infections in Bambui, a township in the North West Region of Cameroon, but there is currently no documented scientific evidence to support their claimed anthelmintic efficacy and safety. The aim of this study was to provide evidence in support of the search for means to eliminate these diseases by screening extracts and chromatographic fractions isolated from these plants for efficacy against the parasitic roundworms Onchocerca ochengi and Brugia pahangi. METHODS: The viability of O. ochengi adult worms was assessed using the MTT/formazan assay. Fully confluent monkey kidney epithelial cells (LLC-MK2) served as the feeder layer for the O. ochengi microfilariae (mfs) assays. Viability of the mfs was assessed by microscopic examination for mean motility scoring (relative to the negative control) every 24 h post addition of an extract. The Worminator system was used to test the effects of the extracts on adult B. pahangi motility, and mean motility units were determined for each worm. Cytotoxicity of the active extracts on N27 cells was assessed using the MTS assay. RESULTS: Extracts from D. oliveri and P. febrifugum were effective against the adult roundworms O. ochengi and B. pahangi. Interestingly, extracts showing macrofilaricidal activities against O. ochengi also showed activity against O. ochengi mfs. The hexane stem bark extract of D. oliveri (DOBHEX) was more selective for adult O. ochengi than for mfs, with a half maximal and 100% inhibitory concentration (IC50 and IC100, respectively) against adult O. ochengi of 13.9 and 31.3 µg/ml, respectively. The in vitro cytotoxicity of all active extracts on N27 cells showed selective toxicity for parasites (selectivity index > 1). Bioassay-guided fractionation of the extracts yielded fractions with activity against adult B. pahangi, thus confirming the presence of bioactive principles in the plant extracts. CONCLUSIONS: Our study supports the use of D. oliveri and P. febrifugum in the traditional treatment of onchocerciasis and LF. The further purification of active extracts from these plants could yield lead compounds for filarial drug discovery and development.


Assuntos
Clusiaceae/química , Fabaceae/química , Filaricidas/farmacologia , Onchocerca/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Camarões , Linhagem Celular , Haplorrinos , Humanos , Onchocerca/crescimento & desenvolvimento , Oncocercose/tratamento farmacológico , Oncocercose/parasitologia , Casca de Planta/química
5.
PLoS Pathog ; 17(6): e1009601, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34077488

RESUMO

Onchocerciasis (river blindness), caused by the filarial worm Onchocerca volvulus, is a neglected tropical disease mostly affecting sub-Saharan Africa and is responsible for >1.3 million years lived with disability. Current control relies almost entirely on ivermectin, which suppresses symptoms caused by the first-stage larvae (microfilariae) but does not kill the long-lived adults. Here, we evaluated emodepside, a semi-synthetic cyclooctadepsipeptide registered for deworming applications in companion animals, for activity against adult filariae (i.e., as a macrofilaricide). We demonstrate the equivalence of emodepside activity on SLO-1 potassium channels in Onchocerca volvulus and Onchocerca ochengi, its sister species from cattle. Evaluation of emodepside in cattle as single or 7-day treatments at two doses (0.15 and 0.75 mg/kg) revealed rapid activity against microfilariae, prolonged suppression of female worm fecundity, and macrofilaricidal effects by 18 months post treatment. The drug was well tolerated, causing only transiently increased blood glucose. Female adult worms were mostly paralyzed; however, some retained metabolic activity even in the multiple high-dose group. These data support ongoing clinical development of emodepside to treat river blindness.


Assuntos
Doenças dos Bovinos/tratamento farmacológico , Depsipeptídeos/uso terapêutico , Filaricidas/uso terapêutico , Canais de Potássio Ativados por Cálcio de Condutância Alta/efeitos dos fármacos , Oncocercose/tratamento farmacológico , Oncocercose/veterinária , Animais , Bovinos , Onchocerca/efeitos dos fármacos
6.
PLoS Negl Trop Dis ; 15(6): e0009489, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34115752

RESUMO

BACKGROUND: Onchocerciasis (river-blindness) in Africa is targeted for elimination through mass drug administration (MDA) with ivermectin. Onchocerciasis may cause various types of skin and eye disease. Predicting the impact of MDA on onchocercal morbidity is useful for future policy development. Here, we introduce a new disease module within the established ONCHOSIM model to predict trends over time in prevalence of onchocercal morbidity. METHODS: We developed novel generic model concepts for development of symptoms due to cumulative exposure to dead microfilariae, accommodating both reversible (acute) and irreversible (chronic) symptoms. The model was calibrated to reproduce pre-control age patterns and associations between prevalences of infection, eye disease, and various types of skin disease as observed in a large set of population-based studies. We then used the new disease module to predict the impact of MDA on morbidity prevalence over a 30-year time frame for various scenarios. RESULTS: ONCHOSIM reproduced observed age-patterns in disease and community-level associations between infection and disease reasonably well. For highly endemic settings with 30 years of annual MDA at 60% coverage, the model predicted a 70% to 89% reduction in prevalence of chronic morbidity. This relative decline was similar with higher MDA coverage and only somewhat higher for settings with lower pre-control endemicity. The decline in prevalence was lowest for mild depigmentation and visual impairment. The prevalence of acute clinical manifestations (severe itch, reactive skin disease) declined by 95% to 100% after 30 years of annual MDA, regardless of pre-control endemicity. CONCLUSION: We present generic model concepts for predicting trends in acute and chronic symptoms due to history of exposure to parasitic worm infections, and apply this to onchocerciasis. Our predictions suggest that onchocercal morbidity, in particular chronic manifestations, will remain a public health concern in many epidemiological settings in Africa, even after 30 years of MDA.


Assuntos
Anti-Helmínticos/administração & dosagem , Oftalmopatias/tratamento farmacológico , Ivermectina/administração & dosagem , Oncocercose/tratamento farmacológico , Dermatopatias/tratamento farmacológico , Adolescente , Adulto , África/epidemiologia , Animais , Criança , Pré-Escolar , Oftalmopatias/epidemiologia , Oftalmopatias/parasitologia , Feminino , Humanos , Masculino , Administração Massiva de Medicamentos , Pessoa de Meia-Idade , Onchocerca/efeitos dos fármacos , Onchocerca/fisiologia , Oncocercose/epidemiologia , Oncocercose/parasitologia , Dermatopatias/epidemiologia , Dermatopatias/parasitologia , Adulto Jovem
7.
PLoS Negl Trop Dis ; 15(5): e0009011, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33979331

RESUMO

BACKGROUND: The existence of locations with low but stable onchocerciasis prevalence is not well understood. An often suggested yet poorly investigated explanation is that the infection spills over from neighbouring locations with higher infection densities. METHODOLOGY: We adapted the stochastic individual based model ONCHOSIM to enable the simulation of multiple villages, with separate blackfly (intermediate host) and human populations, which are connected through the regular movement of the villagers and/or the flies. With this model we explore the impact of the type, direction and degree of connectedness, and of the impact of localized or full-area mass drug administration (MDA) over a range of connected village settings. PRINCIPAL FINDINGS: In settings with annual fly biting rates (ABR) below the threshold needed for stable local transmission, persistence of onchocerciasis prevalence can well be explained by regular human traffic and/or fly movement from locations with higher ABR. Elimination of onchocerciasis will then theoretically be reached by only implementing MDA in the higher prevalence area, although lingering infection in the low prevalence location can trigger resurgence of transmission in the total region when MDA is stopped too soon. Expanding MDA implementation to the lower ABR location can therefore shorten the duration of MDA needed. For example, when prevalence spill-over is due to human traffic, and both locations have about equal populations, then the MDA duration can be shortened by up to three years. If the lower ABR location has twice as many inhabitants, the reduction can even be up to six years, but if spill-over is due to fly movement, the expected reduction is less than a year. CONCLUSIONS/SIGNIFICANCE: Although MDA implementation might not always be necessary in locations with stable low onchocerciasis prevalence, in many circumstances it is recommended to accelerate achieving elimination in the wider area.


Assuntos
Antiparasitários/uso terapêutico , Controle de Doenças Transmissíveis/métodos , Ivermectina/uso terapêutico , Administração Massiva de Medicamentos/métodos , Oncocercose , Animais , Erradicação de Doenças , Humanos , Mordeduras e Picadas de Insetos/parasitologia , Ivermectina/administração & dosagem , Onchocerca/efeitos dos fármacos , Oncocercose/epidemiologia , Oncocercose/prevenção & controle , Oncocercose/transmissão , Simuliidae/parasitologia
8.
Parasit Vectors ; 14(1): 199, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849643

RESUMO

BACKGROUND: Onchocerca lupi and Cercopithifilaria spp. are vector-borne filarioids of dogs, which harbour skin microfilariae (mfs), the former being of zoonotic concern. Proper treatment studies using compounds with microfilaricidal activity have not been performed. Therefore, this study aimed to assess the efficacy of a commercially available spot-on formulation containing moxidectin 2.5%/imidacloprid 10% for the treatment of O. lupi or Cercopithifilaria spp. skin-dwelling mfs in naturally infected dogs. METHODS: Privately owned dogs (n = 393) from southern Portugal were sampled via skin biopsies to identify and count mfs in 20 µl of skin sediment. A total of 22 mfs-positive dogs were allocated to treatment group (n = 11; G1) or left untreated as a control (n = 11; G2). As a pilot investigation to test the treatment efficacy, five dogs assigned to G1 were treated four times at monthly intervals with moxidectin 2.5%/imidacloprid 10% spot-on formulation on SDs 0, 28 (± 2), 56 (± 2), and 84 (± 2). Based on the negative results for both O. lupi and/or Cercopithifilaria spp. mfs of dogs in the pilot study from SD28 onwards, the remaining six dogs in G1 were treated at SD0 and assessed only at SD28. RESULTS: Of the 393 animals sampled, 78 (19.8%) scored positive for skin-dwelling mfs. At the pilot investigation, a mean number of 19.6 mfs for O. lupi was recorded among five infected dogs whereas no mfs were detected at SD28. At SD0, the mean number of Cercopithifilaria spp. larvae was 12.6 for G1 and 8.7 for G2. The mean number of mfs for G2 was 20.09. CONCLUSIONS: Results herein obtained suggest that a single treatment with moxidectin 2.5%/imidacloprid 10% spot-on formulation is efficacious against skin-dwelling mfs in dogs. The microfilaricidal effect of moxidectin could also be useful in reducing the risk of O. lupi infection for humans.


Assuntos
Anti-Helmínticos/farmacologia , Doenças do Cão/tratamento farmacológico , Filariose/veterinária , Filarioidea/efeitos dos fármacos , Macrolídeos/farmacologia , Neonicotinoides/farmacologia , Nitrocompostos/farmacologia , Onchocerca/efeitos dos fármacos , Oncocercose/veterinária , Animais , Anti-Helmínticos/química , Doenças do Cão/parasitologia , Cães , Composição de Medicamentos , Feminino , Filariose/tratamento farmacológico , Filariose/parasitologia , Filarioidea/crescimento & desenvolvimento , Macrolídeos/química , Masculino , Neonicotinoides/química , Nitrocompostos/química , Onchocerca/crescimento & desenvolvimento , Oncocercose/tratamento farmacológico , Oncocercose/parasitologia , Projetos Piloto , Portugal , Resultado do Tratamento
9.
Parasit Vectors ; 14(1): 203, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33858497

RESUMO

BACKGROUND: Onchocerca lupi is an emerging, zoonotic filarioid nematode associated with ocular disease in companion animals in North America and the Old World. The areas where this parasite is assumed to be endemic in the USA comprise southwestern states. Thus far, all cases reported outside of the southwest are associated with travel or animal movement. METHODS: An 11-year-old, castrated male Pitbull dog from McAllen, Hidalgo County, southern Texas, with no travel history, was diagnosed with a perforating corneal ulceration of the right eye. Enucleation was performed and tissues submitted for histopathology. RESULTS: Histologically, sections of two filarioid nematodes were observed. DNA was extracted from formalin-fixed paraffin-embedded tissue using a commercial kit. We performed PCR targeting the cox1 gene of the mitochondrial DNA, followed by sequencing and phylogenetic analysis. Altogether, these results confirmed the identification of the nematode specimens as O. lupi, phylogenetically belonging to haplotype 1. CONCLUSION: We report the first autochthonous case of O. lupi in a dog from Hidalgo County, southern Texas, USA. Our finding suggests Texas as an additional state where this zoonotic nematode is endemic. Further investigations are required to understand the epidemiology of this parasite along the USA/Mexico border.


Assuntos
Doenças do Cão/parasitologia , Onchocerca/fisiologia , Oncocercose Ocular/veterinária , Animais , Cães , Olho/parasitologia , Humanos , Masculino , Onchocerca/classificação , Onchocerca/genética , Onchocerca/isolamento & purificação , Oncocercose Ocular/parasitologia , Filogenia , Texas , Zoonoses/parasitologia
10.
Parasitol Res ; 120(6): 2087-2094, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33864105

RESUMO

Control and treatment of onchocerciasis, a devastating tropical filarial disease caused by Onchocerca volvulus, rely solely on the community directed treatment with ivermectin. However, ivermectin is only microfilaricidal with evidence of resistance of the parasite among other limitations, which necessitate the search for new efficacious and safe filaricides. Ten synthetic thienylazoryl dyes were screened in vitro against adult and microfilariae worm stages of Onchocerca ochengi based on worm motility and MTT formazan assay. Cytotoxicity of active compounds was assessed on monkey kidney epithelial cells (LLC-MK2) using the MTT formazan assay. Seven (7) compounds showed both macrofilaricidal activity against adult male worms and microfilaricidal activity among which three 4a, 4c and 4e recorded the highest activity (IC50 = 4.2 to 8.8µM) against adult male worms, comparable to some standard anthelmintics. Five compounds showed rapid activity against microfilariae with 100% inhibition after 24-h incubation. The active compounds were nontoxic on monkey kidney cells (CC50> 4µg/mL), but their selectivity index values were relatively low (≤ 3). The thienylazoaryls with both macrofilaricidal and microfilaricidal activities may yield molecules which could be used for eradication of onchocerciasis following further medicinal chemistry modification of their structures to enhance their selectivity.


Assuntos
Compostos Azo/farmacologia , Filaricidas/farmacologia , Microfilárias/efeitos dos fármacos , Onchocerca/efeitos dos fármacos , Tiofenos/farmacologia , Animais , Compostos Azo/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Concentração Inibidora 50 , Masculino , Tiofenos/química
11.
Parasitol Int ; 83: 102313, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33662527

RESUMO

Reports of zoonotic infections with Onchocerca japonica (Nematoda: Filarioidea), which parasitizes the Japanese wild boar, Sus scrofa leucomystax, have recently increased in Japan. To predict the occurrence of infection in humans, it is necessary to determine the prevalence of O. japonica infection in the natural host animals. We investigated the presence of adult worms in the footpads, and of microfilariae in skin snips, taken from the host animals, between 2000 and 2018. Onchocerca japonica was found in 165 of 223 (74%) Japanese wild boars in Honshu and Kyushu. Among the nine regions studied, the highest prevalence of O. japonica infection was found in Oita, Kyushu, where 47 of 52 (90.4%) animals were infected. The ears were the predilection sites for O. japonica microfilariae. Adult worms of O. japonica were found more frequently in the hindlimbs than in the forelimbs of the host animals. Onchocerca takaokai was found in 14 of 52 (26.9%) Japanese wild boars in Oita. In Kakeroma Island among the Nansei Islands, both O. japonica and O. takaokai were isolated from the Ryukyu wild boar, S. s. riukiuanus. These observations could help predict future occurrences of human zoonotic onchocercosis in Japan.


Assuntos
Onchocerca/isolamento & purificação , Oncocercose/veterinária , Doenças dos Suínos/epidemiologia , Zoonoses/epidemiologia , Animais , Japão/epidemiologia , Oncocercose/epidemiologia , Oncocercose/parasitologia , Prevalência , Sus scrofa , Suínos , Doenças dos Suínos/parasitologia , Zoonoses/parasitologia
12.
Parasit Vectors ; 14(1): 118, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-33627171

RESUMO

BACKGROUND: Onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis) are two human neglected tropical diseases that cause major disabilities. Mass administration of drugs targeting the microfilarial stage has reduced transmission and eliminated these diseases in several countries but a macrofilaricidal drug that kills or sterilizes the adult worms is critically needed to eradicate the diseases. The causative agents of onchocerciasis and lymphatic filariasis are filarial worms that harbor the endosymbiotic bacterium Wolbachia. Because filarial worms depend on Wolbachia for reproduction and survival, drugs targeting Wolbachia hold great promise as a means to eliminate these diseases. METHODS: To better understand the relationship between Wolbachia and its worm host, adult Brugia pahangi were exposed to varying concentrations of doxycycline, minocycline, tetracycline and rifampicin in vitro and assessed for Wolbachia numbers and worm motility. Worm motility was monitored using the Worminator system, and Wolbachia titers were assessed by qPCR of the single copy gene wsp from Wolbachia and gst from Brugia to calculate IC50s and in time course experiments. Confocal microscopy was also used to quantify Wolbachia located at the distal tip region of worm ovaries to assess the effects of antibiotic treatment in this region of the worm where Wolbachia are transmitted vertically to the microfilarial stage. RESULTS: Worms treated with higher concentrations of antibiotics had higher Wolbachia titers, i.e. as antibiotic concentrations increased there was a corresponding increase in Wolbachia titers. As the concentration of antibiotic increased, worms stopped moving and never recovered despite maintaining Wolbachia titers comparable to controls. Thus, worms were rendered moribund by the higher concentrations of antibiotics but Wolbachia persisted suggesting that these antibiotics may act directly on the worms at high concentration. Surprisingly, in contrast to these results, antibiotics given at low concentrations reduced Wolbachia titers. CONCLUSION: Wolbachia in B. pahangi display a counterintuitive dose response known as the "Eagle effect." This effect in Wolbachia suggests a common underlying mechanism that allows diverse bacterial and fungal species to persist despite exposure to high concentrations of antimicrobial compounds. To our knowledge this is the first report of this phenomenon occurring in an intracellular endosymbiont, Wolbachia, in its filarial host.


Assuntos
Brugia Malayi/fisiologia , Microfilárias/microbiologia , Onchocerca/fisiologia , Simbiose , Wolbachia/fisiologia , Animais , Antibacterianos/farmacologia , Brugia Malayi/efeitos dos fármacos , Brugia Malayi/microbiologia , Doxiciclina/farmacologia , Feminino , Masculino , Microfilárias/efeitos dos fármacos , Microfilárias/fisiologia , Onchocerca/efeitos dos fármacos , Onchocerca/microbiologia , Simbiose/efeitos dos fármacos , Wolbachia/efeitos dos fármacos
13.
PLoS Negl Trop Dis ; 15(2): e0009027, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33566799

RESUMO

Onchocerca lupi (Spirurida: Onchocercidae) is a filarial worm parasitizing domestic carnivores and humans. Adult nematodes usually localize beneath in the sclera or in the ocular retrobulbar of infected animals, whilst microfilariae are found in the skin. Therefore, diagnosis of O. lupi is achieved by microscopic and/or molecular detection of microfilariae from skin biopsy and/or surgical removal of adults from ocular tissues of infected hosts. An urgent non-invasive diagnostic tool for the diagnosis of O. lupi in dog is mandatory. In this study, an immunoproteomic analyses was performed using a combination of immunoblotting and mass spectrometry techniques. Onchocerca lupi major antigen (Ol-MJA) and paramyosin (Ol-PARA) proteins were identified as potential biomarkers for serodiagnosis. Linear epitopes were herein scanned for both proteins using high-density peptide microarray. Sera collected from dog infected with O. lupi and healthy animal controls led to the identification of 11 immunodominant antigenic peptides (n = 7 for Ol-MJA; n = 4 for Ol-PARA). These peptides were validated using sera of dogs uniquely infected with the most important filarioids infesting dogs either zoonotic (Dirofilaria repens, Dirofilaria immitis) or not (Acanthocheilonema reconditum and Cercopithifilaria bainae). Overall, six antigenic peptides, three for Ol-MJA and for Ol-PARA, respectively, were selected as potential antigens for the serological detection of canine O. lupi infection. The molecular and proteomic dataset herein reported should provide a useful resource for studies on O. lupi toward supporting the development of new interventions (drugs, vaccines and diagnostics) against canine onchocercosis.


Assuntos
Doenças do Cão/diagnóstico , Onchocerca/química , Oncocercose Ocular/diagnóstico , Oncocercose/diagnóstico , Tropomiosina/genética , Tropomiosina/imunologia , Animais , Biomarcadores/sangue , Doenças do Cão/parasitologia , Cães , Feminino , Masculino , Microfilárias/genética , Microfilárias/isolamento & purificação , Onchocerca/imunologia , Onchocerca/isolamento & purificação , Oncocercose/imunologia , Oncocercose/parasitologia , Oncocercose Ocular/sangue , Oncocercose Ocular/imunologia , Oncocercose Ocular/parasitologia , Testes Sorológicos , Tropomiosina/sangue , Tropomiosina/isolamento & purificação
14.
BMC Microbiol ; 21(1): 5, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407120

RESUMO

BACKGROUND: During the last two decades research on animal filarial parasites, especially Onchocerca ochengi, infecting cattle in savanna areas of Africa revealed that O. ochengi as an animal model has biological features that are similar to those of O. volvulus, the aetiological agent of human onchocerciasis. There is, however, a paucity of biochemical, immunological and pathological data for O. ochengi. Galectins can be generated by parasites and their hosts. They are multifunctional molecules affecting the interaction between filarial parasites and their mammalian hosts including immune responses. This study characterized O. ochengi galectin, verified its immunologenicity and established its immune reactivity and that of Onchocerca volvulus galectin. RESULTS: The phylogenetic analysis showed the high degree of identity between the identified O. ochengi and the O. volvulus galectin-1 (ß-galactoside-binding protein-1) consisting only in one exchange of alanine for serine. O. ochengi galectin induced IgG antibodies during 28 days after immunization of Wistar rats. IgG from O. ochengi-infected cattle and O. volvulus-infected humans cross-reacted with the corresponding galectins. Under the applied experimental conditions in a cell proliferation test, O. ochengi galectin failed to significantly stimulate peripheral blood mononuclear cells (PBMCs) from O. ochengi-infected cattle, regardless of their parasite load. CONCLUSION: An O. ochengi galectin gene was identified and the recombinantly expressed protein was immunogenic. IgG from Onchocerca-infected humans and cattle showed similar cross-reaction with both respective galectins. The present findings reflect the phylogenetic relationship between the two parasites and endorse the appropriateness of the cattle O. ochengi model for O. volvulus infection research.


Assuntos
Galectinas/administração & dosagem , Galectinas/genética , Imunoglobulina G/sangue , Leucócitos Mononucleares/imunologia , Onchocerca/imunologia , Animais , Bovinos , Clonagem Molecular/métodos , Feminino , Galectinas/imunologia , Perfilação da Expressão Gênica , Proteínas de Helminto/administração & dosagem , Proteínas de Helminto/genética , Proteínas de Helminto/imunologia , Humanos , Imunização , Leucócitos Mononucleares/parasitologia , Onchocerca/genética , Filogenia , Ratos , Ratos Wistar , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/imunologia , Análise de Sequência de DNA
15.
PLoS Negl Trop Dis ; 15(1): e0008926, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33465080

RESUMO

BACKGROUND: The impact of large scale Mass Drug Adminstration (MDA) of ivermectin on active onchocerciasis transmission by Simulium damnosum, which transmits the parasite O. volvulus is of great importance for onchocerciasis control programmes. We investigated in the Mbam river system area, the impact of MDA of ivermectin on entomological indices and also verify if there are river system factors that could have favoured the transmission of onchocerciasis in this area and contribute to the persistence of disease. We compared three independent techniques to detect Onchocerca larvae in blackflies and also analyzed the river system within 9 months post-MDA of ivermectin. METHOD: Simulium flies were captured before and after 1, 3, 6 and 9months of ivermectin-MDA. The biting rate was determined and 41% of the flies dissected while the rest were grouped into pools of 100 flies for DNA extraction. The extracted DNA was then subjected to O-150 LAMP and real-time PCR for the detection of infection by Onchocerca species using pool screening. The river system was analysed and the water discharge compared between rainy and dry seasons. PRINCIPAL FINDINGS: We used human landing collection method (previously called human bait) to collect 22,274 adult female Simulium flies from Mbam River System. Of this number, 9,134 were dissected while 129 pools constituted for molecular screening. Overall biting and parous rates of 1113 flies/man/day and 24.7%, respectively, were observed. All diagnostic techniques detected similar rates of O. volvulus infection (P = 0.9252) and infectivity (P = 0.4825) at all monitoring time points. Onchocerca ochengi larvae were only detected in 2 of the 129 pools. Analysis of the river drainage revealed two hydroelectric dams constructed on the tributaries of the Mbam river were the key contributing factor to the high-water discharge during both rainy and dry seasons. CONCLUSION: Results from fly dissection (Microscopy), real-time PCR and LAMP revealed the same trends pre- and post-MDA. The infection rate with animal Onchocerca sp was exceptionally low. The dense river system generate important breeding sites that govern the abundance of Simulium during both dry and rainy seasons.


Assuntos
Onchocerca/isolamento & purificação , Oncocercose/prevenção & controle , Oncocercose/transmissão , Simuliidae/parasitologia , Animais , Antiparasitários/uso terapêutico , Camarões/epidemiologia , Feminino , Humanos , Mordeduras e Picadas de Insetos/epidemiologia , Insetos Vetores/parasitologia , Ivermectina/uso terapêutico , Proteína 3 de Membrana Associada ao Lisossomo , Administração Massiva de Medicamentos , Onchocerca/classificação , Onchocerca/genética , Oncocercose/diagnóstico , Reação em Cadeia da Polimerase em Tempo Real , Rios , Estações do Ano , Simuliidae/fisiologia
16.
Med Vet Entomol ; 35(3): 231-238, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33480060

RESUMO

Onchocerciasis is a neglected tropical disease (NTD) caused by Onchocerca Diesing 1841 (Spirurida: Onchocercidae) nematodes transmitted by blackflies. It is associated with poverty and imposes a significant health, welfare and economic burden on many tropical countries. Current methods to visualize infections within the vectors rely on invasive methods. However, using micro-computed tomography techniques, without interference from physical tissue manipulation, we visualized in three dimensions for the first time an L1 larva of an Onchocerca species within the thoracic musculature of a blackfly, Simulium damnosum s.l. Theobald 1903 (Diptera: Simuliidae), naturally infected in Ghana. The possibility that thicker peritrophic membranes in savannah flies could account for their lower parasite loads was not supported, but there were limits to our analysis. While there were no statistically significant differences between the mean thicknesses of the peritrophic membranes, in the anterior, dorsal and ventral regions, of forest and savannah blackflies killed 34-48 min after a blood-meal, the thickness of the peritrophic membrane in the posterior region could not be measured. Micro-computed tomography has the potential to provide novel information on many other parasite/vector systems and impactful images for public engagement in health education.


Assuntos
Oncocercose , Simuliidae , Animais , Florestas , Insetos Vetores , Onchocerca , Oncocercose/veterinária , Microtomografia por Raio-X
17.
Vet Pathol ; 58(2): 401-404, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33356968

RESUMO

Three donkeys were presented with progressive lameness and distal suspensory ligament breakdown in multiple limbs. Treatment with nonsteroidal anti-inflammatory drugs was only partially effective and eventually the donkeys were euthanized due to further progression of the lameness and concerns for their welfare. At necropsy, the distal part of the suspensory ligaments in multiple limbs, including the suspensory ligament branches, was markedly thickened, enlarged, and mottled white and brown on cut section. In one case, adult Onchocerca sp. nematodes were grossly identified embedded within the suspensory ligaments. Histopathologic examination revealed chronic, multifocal to coalescing, moderate to severe, lymphoplasmacytic, eosinophilic, and fibrosing desmitis and tendinitis with intralesional, coiled adult nematodes of Onchocerca sp., accompanied by osseous and cartilaginous metaplasia. To the authors' knowledge, this is the first histopathologic description of suspensory ligament desmitis and tendinitis associated with Onchocerca sp. in donkeys.


Assuntos
Doenças dos Cavalos , Coxeadura Animal , Animais , Equidae , Cavalos , Ligamentos , Onchocerca
18.
Molecules ; 26(1)2020 Dec 25.
Artigo em Inglês | MEDLINE | ID: mdl-33375687

RESUMO

A new iboga-vobasine-type isomeric bisindole alkaloid named voacamine A (1), along with eight known compounds-voacangine (2), voacristine (3), coronaridine (4), tabernanthine (5), iboxygaine (6), voacamine (7), voacorine (8) and conoduramine (9)-were isolated from the stem bark of Voacangaafricana. The structures of the compounds were determined by comprehensive spectroscopic analyses. Compounds 1, 2, 3, 4, 6, 7 and 8 were found to inhibit the motility of both the microfilariae (Mf) and adult male worms of Onchocerca ochengi, in a dose-dependent manner, but were only moderately active on the adult female worms upon biochemical assessment at 30 µM drug concentrations. The IC50 values of the isolates are 2.49-5.49 µM for microfilariae and 3.45-17.87 µM for adult males. Homology modeling was used to generate a 3D model of the O. ochengi thioredoxin reductase target and docking simulation, followed by molecular dynamics and binding free energy calculations attempted to offer an explanation of the anti-onchocercal structure-activity relationship (SAR) of the isolated compounds. These alkaloids are new potential leads for the development of antifilarial drugs. The results of this study validate the traditional use of V. africana in the treatment of human onchocerciasis.


Assuntos
Alcaloides/química , Onchocerca/efeitos dos fármacos , Oncocercose/tratamento farmacológico , Voacanga/química , Alcaloides/farmacologia , Animais , Humanos , Onchocerca/patogenicidade , Oncocercose/parasitologia
19.
PLoS Negl Trop Dis ; 14(12): e0008919, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33382717

RESUMO

BACKGROUND: Ghana is endemic for some neglected tropical diseases (NTDs) including schistosomiasis, onchocerciasis and lymphatic filariasis. The major intervention for these diseases is mass drug administration of a few repeatedly recycled drugs which is a cause for major concern due to reduced efficacy of the drugs and the emergence of drug resistance. Evidently, new treatments are needed urgently. Medicinal plants, on the other hand, have a reputable history as important sources of potent therapeutic agents in the treatment of various diseases among African populations, Ghana inclusively, and provide very useful starting points for the discovery of much-needed new or alternative drugs. METHODOLOGY/PRINCIPAL FINDINGS: In this study, extracts of fifteen traditional medicines used for treating various NTDs in local communities were screened in vitro for efficacy against schistosomiasis, onchocerciasis and African trypanosomiasis. Two extracts, NTD-B4-DCM and NTD-B7-DCM, prepared from traditional medicines used to treat schistosomiasis, displayed the highest activity (IC50 = 30.5 µg/mL and 30.8 µg/mL, respectively) against Schistosoma mansoni adult worms. NTD-B2-DCM, also obtained from an antischistosomal remedy, was the most active against female and male adult Onchocera ochengi worms (IC50 = 76.2 µg/mL and 76.7 µg/mL, respectively). Antitrypanosomal assay of the extracts against Trypanosoma brucei brucei gave the most promising results (IC50 = 5.63 µg/mL to 18.71 µg/mL). Incidentally, NTD-B4-DCM and NTD-B2-DCM, also exhibited the greatest antitrypanosomal activities (IC50 = 5.63 µg/mL and 7.12 µg/mL, respectively). Following the favourable outcome of the antitrypanosomal screening, this assay was selected for bioactivity-guided fractionation. NTD-B4-DCM, the most active extract, was fractionated and subsequent isolation of bioactive constituents led to an eupatoriochromene-rich oil (42.6%) which was 1.3-fold (IC50 <0.0977 µg/mL) more active than the standard antitrypanosomal drug, diminazene aceturate (IC50 = 0.13 µg/mL). CONCLUSION/SIGNIFICANCE: These findings justify the use of traditional medicines and demonstrate their prospects towards NTDs drug discovery.


Assuntos
Filaricidas/farmacologia , Onchocerca/efeitos dos fármacos , Schistosoma mansoni/efeitos dos fármacos , Esquistossomicidas/farmacologia , Tripanossomicidas/farmacologia , Trypanosoma brucei brucei/efeitos dos fármacos , Animais , Gana , Medicina Tradicional Africana , Doenças Negligenciadas/tratamento farmacológico , Doenças Negligenciadas/parasitologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química
20.
Emerg Infect Dis ; 26(12): 2989-2993, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33219658

RESUMO

The Onchocerca lupi nematode infects dogs, cats, and humans, but whether it can be spread by coyotes has been unknown. We conducted surveillance for O. lupi nematode infection in coyotes in the southwestern United States. We identified multiple coyote populations in Arizona and New Mexico as probable reservoirs for this species.


Assuntos
Coiotes , Doenças do Cão , Oncocercose , Animais , Arizona/epidemiologia , Reservatórios de Doenças , Doenças do Cão/epidemiologia , Cães , New Mexico , Onchocerca/genética , Oncocercose/epidemiologia , Oncocercose/veterinária , Sudoeste dos Estados Unidos , Estados Unidos/epidemiologia , Zoonoses
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