Nanoparticles as Alternatives for the Control of Haemonchus contortus: A Systematic Approach to Unveil New Anti-haemonchiasis Agents

Haemonchus contortus is an infectious gastrointestinal nematode parasite of small ruminants. This study addresses the in vitro/in vivo anti-haemonchiasis potential, toxicological effects, and mechanism of action of nanoparticles. Online databases were used to search and retrieve the published literature (2000 to 2021). A total of 18 articles were selected and reviewed, out of which, 13 (72.2%) studies reported in vitro, 9 (50.0%) in vivo, and 4 (22.2%) both in vitro/in vivo efficacy of different nanoparticles. Mostly, organic nanoparticles (77.7%) were used including polymeric (85.7%) and lipid nanoparticles (14.3%). The highest efficacy, in vitro, of 100% resulted from using encapsulated bromelain against eggs, larvae, and adult worm mortality at 4, 2, and 1 mg/ml, respectively. While in vivo, encapsulated Eucalyptus staigeriana oil reduced worm burden by 83.75% and encapsulated Cymbopogon citratus nano-emulsion by 83.1%. Encapsulated bromelain, encapsulated Eucalyptus staigeriana oil, and encapsulated Cymbopogon citratus nano-emulsion were safe and non-toxic in vivo. Encapsulated bromelain damaged the cuticle, caused paralysis, and death. Nanoparticles could be a potential source for developing novel anthelmintic drugs to overcome the emerging issue of anthelmintic resistance in H. contortus. Studies on molecular effects, toxicological consequences, and different pharmacological targets of nanoparticles are required in future research.

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Effect of Jatropha curcas Latex on L3 Haemonchus contortus Larval Motility

International Journal of Pharmaceutical and Clinical Research ◽

10.25258/ijpcr.v9i3.8317 ◽

2017 ◽

Vol 9 (3) ◽

Cited By ~ 1

Author(s):

Noorzaid Muhamad ◽

Syahirah Sazeli ◽

Resni Mona ◽

Jannathul Firdous

Keyword(s):

Larvicidal Activity ◽

Jatropha Curcas ◽

Haemonchus Contortus ◽

Anthelmintic Resistance ◽

Small Ruminants ◽

Gastrointestinal Nematodes ◽

Dose Dependent ◽

Plants Extract

The anthelmintic resistance has limited the control of gastrointestinal nematodes of small ruminants and thus has awakened interest in the study of plants extract as a source of anthelmintics. These experiments were carried out to evaluate the in vitro efficacy of Jatrophacurcas latex extract against Haemonchuscontortus larval motility. To evaluate the larvicidal activity, H.contortus L3 were incubated with the extracts with varying concentration of 5 mg/mL, 10 mg/mL, 15 mg/mL and 20 mg/mL at 27°C for 48, 72 and 96 hrs. The results were subjected to the Kruskal-Wallis test (P less than 0.05). The extracts showed dose-dependent larvicidal effects. These results suggest that J.curcas can be used to control gastrointestinal nematodes of small ruminants.

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Comparison of two in vitro methods for the detection of ivermectin resistance in Haemonchus contortus in sheep

Helminthologia ◽

10.1515/helmin-2015-0002 ◽

2016 ◽

Vol 53 (2) ◽

pp. 120-125 ◽

Cited By ~ 2

Author(s):

M. Urda Dolinská ◽

A. Königová ◽

M. Babják ◽

M. Várady

Keyword(s):

Drug Resistance ◽

Haemonchus Contortus ◽

Anthelmintic Resistance ◽

Economic Losses ◽

Parasitic Nematodes ◽

Migration Inhibition ◽

In Vitro Methods ◽

Parasitic Helminths

SummaryGastrointestinal parasitic nematodes in sheep cause severe economic losses. Anthelmintics are the most commonly used drugs for prophylaxis and therapy against parasitic helminths. The problem of drug resistance has developed for all commercially available anthelmintics in several genera and classes of helminths. In vitro and in vivo tests are used to detect anthelmintic resistance. Two in vitro methods (larval migration inhibition test and micromotility test) for the detection of ivermectin (IVM) resistance were compared using IVM-resistant and IVM-susceptible isolates of Haemonchus contortus. The degree of resistance for each test was expressed as a resistance factor (RF). The micromotility test was more sensitive for quantitatively measuring the degree of resistance between susceptible and resistant isolates. The RFs for this test for IVM and eprinomectin ranged from 1.00 to 108.05 and from 3.87 to 32.32, respectively.

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Anthelmintic activity of Cymbopogon citratus against Haemonchus contortus

Revista Brasileira de Parasitologia Veterinária ◽

10.1590/s1984-29612015059 ◽

2015 ◽

Vol 24 (3) ◽

pp. 268-275 ◽

Cited By ~ 14

Author(s):

Iara Tersia Freitas Macedo ◽

Lorena Mayana Beserra de Oliveira ◽

Wesley Lyeverton Correia Ribeiro ◽

Jessica Maria Leite dos Santos ◽

Kaline das Chagas Silva ◽

...

Keyword(s):

Essential Oil ◽

Haemonchus Contortus ◽

Anthelmintic Activity ◽

Meriones Unguiculatus ◽

Parasitic Nematodes ◽

Control Group ◽

Cymbopogon Citratus ◽

Egg Hatching

Parasitic nematodes are of major economic importance in livestock. An alternative for the control of parasites is phytotherapy. This study evaluated the efficacy of Cymbopogon citratus decoction (CcD), C. citratus essential oil (CcEo) and citral against Haemonchus contortus using in vitro egg hatch test (EHT) and larval development test (LDT) and an in vivo test using a Meriones unguiculatus (gerbil) model. The effect of 800 mg/kg CcEo was evaluated in gerbils that had been artificially infected with 5,000 third-stage H. contortus larvae. The effective concentrations required to inhibit 50% (EC50) of egg hatching were 0.46, 0.14 and 0.13 mg/mL for CcD, CcEo and citral, respectively. The EC50 values in the LDT were 5.04, 1.92 and 1.37 mg/mL for CcD, CcEo and citral, respectively. H. contortus population in the group treated with C. citratus essential oil was reduced by 38.5% (P< 0.05) in comparison to the control group. These results suggest that it may be possible to use C. citratusessential oil to control of H. contortus parasite of small ruminant.

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Characterization of a Rhodanese Homologue from Haemonchus Contortus and its Immune-Modulatory Effects on Goat Immune Cells in Vitro

10.21203/rs.3.rs-34082/v1 ◽

2020 ◽

Author(s):

Yujian Wang ◽

Muhammad Ehsan ◽

Jianmei Huang ◽

Kalibixiati Aimulajiang ◽

RuoFeng Yan ◽

...

Keyword(s):

Haemonchus Contortus ◽

Mononuclear Cells ◽

Small Ruminants ◽

Parasitic Nematodes ◽

Dependent Manner ◽

Peripheral Blood Mononuclear ◽

Nematode Parasites ◽

Wide Range

Abstract Background: Suppression and modulation of the immune response of the host by nematode parasites have been reported widely. Rhodaneses or thiosulfate: cyanide sulfurtransferases are present in a wide range of organisms, such as archea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homology could bind by goat peripheral blood mononuclear cells (PBMCs) in vivo.Results: In the present study, we cloned and produced recombinant rhodanese protein originated from Haemonchus contortus (rHCRD), which was one of the parasitic nematodes of small ruminants. The effect of this protein on modulating the immunity of goat PBMC and monocyte was studied in the current work. The predominant localization of the natural HCRD protein was verified as the bowel wall and body surface of worms, according to the immunohistochemical tests. It was proved in this study that the serum produced by artificially infecting goats with H. contortus successfully recognized rHCRD which conjugated goat PBMCs. The rHCRD was co-incubated with goat PBMCs to observe the immunomodulatory effect on proliferation, apoptosis and secretion of cytokines exerted by HCRD. The results showed that the interaction of rHCRD suppressed proliferation of goat PBMCs stimulated by ConA but did not induce the apoptosis of goat PBMCs. After rHCRD exposure, the production of TNF-α and IFN-γ were significantly decreased, however, it significantly increased the secretion of IL-10 and TGF-β1 in goat PBMCs. Phagocytotic assay by FITC-dextran internalization showed that rHCRD inhibited the phagocytosis of goat monocytes. Moreover, rHCRD could down-regulate the expression of MHC-II on goat monocytes in a dose-dependent manner. Conclusions: These discoveries proposed a possible target as immunomodulator, which was potentially beneficial to illuminate the interaction between parasites and hosts in the molecular level and hunt for innovative protein species as candidate targets of drug and vaccine.

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Characterization of a rhodanese homologue from Haemonchus contortus and its immune-modulatory effects on goat immune cells in vitro

10.21203/rs.3.rs-34082/v4 ◽

2020 ◽

Author(s):

Yujian Wang ◽

Muhammad Ehsan ◽

Jianmei Huang ◽

Kalibixiati Aimulajiang ◽

RuoFeng Yan ◽

...

Keyword(s):

Haemonchus Contortus ◽

Mononuclear Cells ◽

Small Ruminants ◽

Dependent Manner ◽

Peripheral Blood Mononuclear ◽

Mhc I ◽

Nematode Parasites ◽

Wide Range

Abstract Background: Modulation of the host immune response by nematode parasites has been widely reported. Rhodaneses (thiosulfate: cyanide sulfurtransferases) are present in a wide range of organisms, such as archaea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homologue could be bound by goat peripheral blood mononuclear cells (PBMCs) in vivo.Methods: In the present study, we cloned and produced a recombinant rhodanese protein originating from Haemonchus contortus (rHCRD), a parasitic nematode of small ruminants. rHCRD was co-incubated with goat PBMCs to assess its immunomodulatory effects on proliferation, apoptosis and cytokine secretion.Results: We verified that the natural HCRD protein localized predominantly to the bowel wall and body surface of the parasite. We further demonstrated that serum produced by goats artificially infected with H. contortus successfully recognized rHCRD, which bound to goat PBMCs. rHCRD suppressed proliferation of goat PBMCs stimulated by concanavalin A but did not induce apoptosis in goat PBMCs. The production of TNF-α and IFN-γ decreased significantly, whereas secretion of IL-10 and TGF-β1 increased, in goat PBMCs after exposure to rHCRD. rHCRD also inhibited phagocytosis by goat monocytes. Moreover, rHCRD downregulated the expression of major histocompatibility complex (MHC)-II on goat monocytes in a dose-dependent manner, but did not alter MHC-I expression.Conclusions: These results propose a possible immunomodulatory target that may help illuminate the interactions between parasites and their hosts at the molecular level and reveal innovative protein species as candidate drug and vaccine targets.

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Multiple anthelmintic resistance at a goat farm in Slovakia

Helminthologia ◽

10.2478/helm-2021-0014 ◽

2021 ◽

Vol 58 (2) ◽

pp. 173-178

Author(s):

M. Babják ◽

A. Königová ◽

M. Várady

Keyword(s):

Inhibitory Concentration ◽

Anthelmintic Resistance ◽

Small Ruminants ◽

Threshold Concentration ◽

Faecal Egg Count ◽

Goat Farm ◽

Threshold Criteria ◽

Larval Development Test

Summary Cases of parasite resistance to the main classes of anthelmintics are increasingly reported from small ruminants at farms in Europe. We visited a goat farm in Slovakia in November 2019 with suspected parasite problems that reduced productivity and performed an in vivo faecal egg count reduction test (FECRT) and an in vitro larval development test (LDT) for all three main classes of anthelmintics. The lowest efficacy (60 %) detected by FECRT was for ivermectin (IVM). Benzimidazole (BZ) efficacy ranged between 80.3 and 86.5 %, and levamisole (LEV) efficacy was 94 %. The results from the in vivo FECRT test were confirmed by the in vitro LDT. Minimum inhibitory concentration (MIC) 173.6 ng/ml for IVM several times exceeded the recommended threshold of 21.6 ng/ml. Mean LD50 for BZ was equal to the threshold concentration, but the other threshold criteria indicated a low level of resistance in the population. The LDT did not indicate the presence of resistance only for LEV. The MIC 1.0 μg/ml for LEV was evaluated as susceptible with respect to species composition. Teladorsagia was the dominant genus after treatment with BZ, IVM, and LEV. Haemonchus contortus was identifi ed after treatment with BZ and LEV.

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Measuring the effect of avermectins and milbemycins on somatic muscle contraction of adult Haemonchus contortus and on motility of Ostertagia circumcincta in vitro

Parasitology ◽

10.1017/s0031182013002291 ◽

2014 ◽

Vol 141 (7) ◽

pp. 948-956 ◽

Cited By ~ 10

Author(s):

JANINA DEMELER ◽

GEORG VON SAMSON-HIMMELSTJERNA ◽

NICHOLAS C. SANGSTER

Keyword(s):

Muscle Contraction ◽

Haemonchus Contortus ◽

Anthelmintic Resistance ◽

Parasitic Nematodes ◽

Response Curves ◽

Drug Potency ◽

The Right ◽

Sites Of Action

SUMMARYThe mechanism of anthelmintic resistance against the widely used macrocyclic lactones (MLs) is still not fully understood. Pharyngeal, somatic body muscles and the ovijector have been proposed as putative sites of action as well as resistance. In the present study the effects of three avermectins and three milbemycins on adult parasitic nematodes were evaluated in vitro. The Muscle Transducer system was used to investigate the effects of MLs on muscle contraction in female Haemonchus contortus and effects on motility were measured in Ostertagia (Teladorsagia) circumcincta using the Micromotility Meter. Concentration-response curves for all substances in both systems shifted to the right in the resistant isolates. Resistance was present to ivermectin (IVM) and its components IVM B1a and IVM B1b, suggesting that both components are involved in the mode of action and resistance. No consistent patterns of potency and resistance of the substances were observed except that milbemycins generally showed lower resistance ratios (RRs) than IVM. IVM and IVM B1b were the most potent inhibitors of contraction and motility in both susceptible isolates and also showed the highest RR in both species. Low RRs for milbemycins recorded in vitro for highly resistant isolates in vivo suggest that other factors such as pharmacokinetics influence drug potency in vivo.

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Resistencia a los antihelmínticos: origen, desarrollo y control.

Ciencia y Tecnología Agropecuaria ◽

10.21930/rcta.vol4_num1_art:14 ◽

2003 ◽

Vol 4 (1) ◽

pp. 55 ◽

Cited By ~ 6

Author(s):

Dildo Márquez Lara

Keyword(s):

Anthelmintic Resistance ◽

Control Strategies ◽

Small Ruminants ◽

Nematode Resistance ◽

Development Of Resistance ◽

Helminth Infections ◽

Wide Range ◽

And Control

Una variada gama de antihelmínticos modernos, con espectro amplio y alto grado de eficacia, como los benzimidazoles, los agonistas nicotínicos y las lactonas macrocíclicas, se encuentran disponibles comercialmente en el mundo para el control de las infecciones causadas por helmintos en rumiantes. El uso intensivo y la administración inadecuada de antihelmínticos, en épocas y grupos de rumiantes no apropiados, han contribuido al desarrollo de resistencia a estas sustancias, lo que constituye un obstáculo importante para el control de los endoparásitos. La resistencia antihelmíntica se ha reportado principalmente en pequeños rumiantes y es escasa la información relacionada con los nemátodos de bovinos. Se han identificado algunos factores aceleradores del proceso de desarrollo de resistencia, entre ellos factores genéticos, reproductivos y ecológicos de los parásitos, así como factores de orden antrópico, siendo la resistencia una característica heredable. El aumento de la resistencia a los antihelmínticos en la última década, así como los requerimientos de información sobre su ocurrencia e incidencia, han señalado la necesidad de desarrollar y estandarizar técnicas más sensibles para su detección. Hay varias técnicas disponibles in vivo e in vitro útiles para detectar la resistencia antihelmíntica, si bien la prueba de Reducción del Conteo de Huevos Fecales (RCH) es la más usada. La detección temprana de esta condición es un factor esencial para el control estratégico de los endoparásitos a fin de preservar la eficacia de los antihelmínticos. La presente revisión propone diferentes alternativas, químicas y no químicas, para el control de helmintos con el objeto de retardar la aparición de resistencia. Anthelmintic resistance: origin, development and controlA wide range of modern anthelmintics, with broad-spectrum and high efficacy to control helminth infections in ruminants, are commercially available, such as benzimidazoles, nicotinic agonist and macrocyclic lactones.The intensive use and inadequated dosages of anthelmintics in ruminants have contributed to develop resistance, becoming the main threat to control endoparasites. Anthelmintic resistance has been reported mainly in small ruminants, but there is scarce information about it in nematodes of cattle. Genetic, reproductive, ecological and anthropic factors have been found to enhance the development of resistance. Because nematode resistance has increased in the last decade, it is necessary to investigate about its occurrence and incidence; so, developing and standarization of improved techniques for detection of the resistance should be carried out. There are several techniques (in vivo and in vitro) available for detection of anthelmintic resistance, being the Faecal Egg Count Reduction Test (FECRT) the most commonly used. Early detection of resistance is an essential factor on parasite control strategies in order to preserve the effectiveness of anthelmintics. Different chemical and non-chemical helminth control strategies have been suggested in order to slow the onset of resistance.

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Comparative in vitro efficacy of kefir produced from camel, goat, ewe and cow milk on Haemonchus contortus

Journal of Helminthology ◽

10.1017/s0022149x18000378 ◽

2018 ◽

Vol 93 (04) ◽

pp. 440-446

Author(s):

D. Alimi ◽

M. Rekik ◽

H. Akkari

Keyword(s):

Haemonchus Contortus ◽

Therapeutic Potential ◽

Small Ruminants ◽

Gastrointestinal Parasites ◽

Camel Milk ◽

Alternative Methods ◽

Cow Milk ◽

Egg Hatching

AbstractOne of the great challenges of veterinary parasitology is the search for alternative methods for controlling gastrointestinal parasites in small ruminants. Milk kefir is a traditional source of probiotic, with great therapeutic potential. The objective of this study was to investigate the anthelmintic effects of kefir on the abomasal nematode Haemonchus contortus from sheep. The study used camel, goat, ewe and cow milk as a starting material, to produce camel, goat, cow and ewe milk kefir. All kefirs showed a significant concentration-dependent effect on H. contortus egg hatching at all tested concentrations. The highest inhibition (100%) of eggs was observed with camel milk kefir at a concentration 0.125 mg/ml. In relation to the effect of kefirs on the survival of adult parasites, all kefirs induced concentration-dependent mortality in adults, with variable results. The complete mortality (100%) of adults of H. contortus occurred at concentrations in the range 0.25–2 mg/ml. The highest inhibition of motility (100%) of worms was observed after 8 h post exposure with camel milk kefir at 0.25 mg/ml. These findings indicate that kefir can be considered a potential tool to control haemonchosis in sheep. Further investigations are needed to assess the active molecules in kefir responsible for its anthelmintic properties and to investigate similar in vivo effects.

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Characterization of a rhodanese homologue from Haemonchus contortus and its immune-modulatory effects on goat immune cells in vitro

10.21203/rs.3.rs-34082/v2 ◽

2020 ◽

Author(s):

Yujian Wang ◽

Muhammad Ehsan ◽

Jianmei Huang ◽

Kalibixiati Aimulajiang ◽

RuoFeng Yan ◽

...

Keyword(s):

Haemonchus Contortus ◽

Mononuclear Cells ◽

Small Ruminants ◽

Dependent Manner ◽

Peripheral Blood Mononuclear ◽

Mhc I ◽

Nematode Parasites ◽

Wide Range

Abstract Background: Modulation of the host immune response by nematode parasites has been widely reported. Rhodaneses (thiosulfate: cyanide sulfurtransferases) are present in a wide range of organisms, such as archaea, bacteria, fungi, plants and animals. Previously, it was reported that a rhodanese homologue could be bound by goat peripheral blood mononuclear cells (PBMCs) in vivo.Methods: In the present study, we cloned and produced a recombinant rhodanese protein originating from Haemonchus contortus (rHCRD), a parasitic nematode of small ruminants. rHCRD was co-incubated with goat PBMCs to assess its immunomodulatory effects on proliferation, apoptosis and cytokine secretion.Results: We verified that the natural HCRD protein localized predominantly to the bowel wall and body surface of the parasite. We further demonstrated that serum produced by goats artificially infected with H. contortus successfully recognized rHCRD, which bound to goat PBMCs. rHCRD suppressed proliferation of goat PBMCs stimulated by concanavalin A but did not induce apoptosis in goat PBMCs. The production of TNF-α and IFN-γ decreased significantly, whereas secretion of IL-10 and TGF-β1 increased, in goat PBMCs after exposure to rHCRD. rHCRD also inhibited phagocytosis by goat monocytes. Moreover, rHCRD down-regulated the expression of major histocompatibility complex (MHC)-II on goat monocytes in a dose-dependent manner, but did not alter MHC-I expression. Conclusions: These results propose a possible immunomodulatory target that may help illuminate the interactions between parasites and their hosts at the molecular level and reveal innovative protein species as candidate drug and vaccine targets.

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