RESUMEN
BACKGROUND: Ovine psoroptic mange (sheep scab), caused by an infestation of the mite Psoroptes ovis, leads to clinical disease, economic loss and severely compromised animal welfare. Here, a community-based approach to the management of scab in three high-risk areas of England is described. METHODS: For each of the 254 farms included in the study, an initial survey of their clinical sheep scab history was followed up by a blood test (ELISA) to detect the presence of antibodies to P. ovis. This facilitated the coordination of treatment across groups of farms in each region. Blood testing was then repeated at the end of the treatment programme. RESULTS: On the first blood test in 2021/2022, 25.6% (±5.5%) of the flocks were positive for sheep scab. On the second test in 2022/2023, 9% (±3.94%) of the flocks tested were positive, showing a highly statistically significant reduction in prevalence overall, but with strong regional variation. LIMITATIONS: generating an understanding of the flock-level nature of the blood test and confidence in its detection of scab where clinical signs were not apparent provided ongoing challenges. CONCLUSIONS: The programme demonstrated that a focused community-based approach can be used to significantly reduce the prevalence of sheep scab in high-risk areas of England. The use of the blood test on all farms allowed the identification of subclinical sheep scab. The programme provides an effective model for sheep scab management on a national scale.
Asunto(s)
Crianza de Animales Domésticos , Infestaciones por Ácaros , Enfermedades de las Ovejas , Ovinos , Psoroptidae , Infestaciones por Ácaros/diagnóstico , Infestaciones por Ácaros/epidemiología , Infestaciones por Ácaros/prevención & control , Infestaciones por Ácaros/veterinaria , Inglaterra , Enfermedades de las Ovejas/diagnóstico , Enfermedades de las Ovejas/epidemiología , Enfermedades de las Ovejas/prevención & control , Anticuerpos/sangre , Prevalencia , Crianza de Animales Domésticos/métodosRESUMEN
Sheep scab, caused by infestation with the ectoparasitic mite Psoroptes ovis, is an endemic disease in the Northern Ireland (NI) sheep flock and constitutes significant economic and welfare burdens for the NI farming industry. Despite its endemic nature, historically, little research has been undertaken to support the control of the disease in NI. This study offers the first attempt to analyse the psychological and behavioural factors influencing farmers' intentions to implement effective sheep scab control measures in NI. To achieve our objective, quantitative data from a sample of 126 sheep farmers were statistically analysed using an extended theory of planned behaviour approach in an ordered logistic regression modelling framework. Our analyses showed that sheep scab remains an issue of concern in Northern Ireland. The attitudes of the farmers, as well as perceived behavioural control, emotional effect, membership of Business Development Groups (BDGs), and higher education qualifications, were found to be statistically significant factors influencing farmers' intentions to adopt sheep scab control measures. This study provides a solid foundation for how to promote behavioural changes among sheep farmers to improve their ability to implement effective disease control measures, helping to tackle this challenging disease in a more sustainable way in the future.
RESUMEN
Teladorsagia circumcincta is an abomasal parasitic nematode that can cause serious issues in small ruminant production, which are aggravated by drug resistance. Vaccines have been suggested as a feasible, long-lasting alternative for control since adaptation to the host's immune mechanisms by helminths develops at a much slower pace than anthelmintic resistance. Recently, a T. circumcincta recombinant subunit vaccine yielded over a 60% reduction in egg excretion and worm burden and induced strong humoral and cellular anti-helminth responses in vaccinated 3-month-old Canaria Hair Breed (CHB) lambs, but Canaria Sheep (CS) of a similar age were not protected by the vaccine. Here, we compared the transcriptomic profiles in the abomasal lymph nodes of such 3-month-old CHB and CS vaccinates 40 days after infection with T. circumcincta to understand differences in responsiveness at the molecular level. In the CS, differentially expressed genes (DEG) identified were related to general immunity processes such as antigen presentation or antimicrobial proteins and down-regulation of inflammation and immune response through regulatory T cell-associated genes. However, upregulated genes in CHB vaccinates were associated with type-2 oriented immune responses, i.e., immunoglobulin production, activation of eosinophils, as well as tissue structure and wound repair-related genes and protein metabolism pathways such as DNA and RNA processing. These results highlight potentially more optimal timing and orientation of immune responses in CHB sheep compared to CS associated with vaccine-induced protection. The data obtained in this study thus deepens our understanding of variations in responsiveness to vaccination in young lamb and provides insights for vaccine refinement strategies.
Asunto(s)
Antihelmínticos , Enfermedades de las Ovejas , Animales , Ovinos , Transcriptoma , Ostertagia , Vacunas Sintéticas , Perfilación de la Expresión Génica/veterinaria , Enfermedades de las Ovejas/parasitología , Heces/parasitología , Recuento de Huevos de Parásitos/veterinariaRESUMEN
The poultry red mite (PRM), Dermanyssus gallinae, is a major threat for the poultry industry worldwide. Chemical compounds have been extensively used for PRM control, leading to selection of resistant mites. Molecular mechanisms of resistance have been investigated in arthropods, showing the role of target-site insensitivity and enhanced detoxification. Few studies are available about those mechanisms in D. gallinae, and none have yet focused on the expression levels of detoxification enzymes and other defense-related genes through RNA-seq. We tested PRM populations from Italy for their susceptibility to the acaricidal compounds phoxim and cypermethrin. Mutations in the voltage-gated sodium channel (vgsc) and in acetylcholinesterase (AChE) were investigated, detecting mutations known to be associated with acaricide/insecticide resistance in arthropods, including M827I and M918L/T in the vgsc and G119S in the AChE. RNA-seq analysis was performed to characterize metabolic resistance in fully susceptible PRM and in cypermethrin-resistant PRM exposed and unexposed to cypermethrin as well as phoxim resistant PRM exposed and unexposed to phoxim. Detoxification enzymes (including P450 monooxygenases and glutathione-S-transferases), ABC transporters and cuticular proteins were constitutively overexpressed in phoxim and cypermethrin resistant mites. In addition, heat shock proteins were found constitutively and inductively upregulated in phoxim resistant mites, while in cypermethrin resistant mites esterases and an aryl hydrocarbon receptor were constitutively highly expressed. The findings suggest that acaricide resistance in D. gallinae is due to both target-site insensitivity and overexpression of detoxification enzymes and other xenobiotic defense-related genes, which is mostly constitutive and not induced by treatment. Understanding the molecular basis of resistance could be useful to screen or test PRM populations in order to select targeted acaricides and to avoid the abuse/misuse of the few available compounds.
Asunto(s)
Acaricidas , Infestaciones por Ácaros , Ácaros , Enfermedades de las Aves de Corral , Trombiculidae , Animales , Acaricidas/farmacología , Acetilcolinesterasa/genética , Ácaros/genética , Aves de Corral , Pollos , Infestaciones por Ácaros/veterinariaRESUMEN
BACKGROUND: Ovine psoroptic mange (sheep scab) is an infectious condition caused by an allergen-induced hypersensitivity response to the mite Psoroptes ovis. Infestation results in clinical disease, economic loss and welfare issues in many sheep-producing countries. The aim of this study was to compare the prevalence and spatial pattern of sheep scab on contiguous farms, using both self-reported clinical outbreak history (2012-2020) and serological testing with an enzyme-linked immunosorbent assay (2021/2022). METHODS: Farms included in the study were located in three regions of known high scab prevalence in North, Central and Southwest England. In total, 254 farms completed both a questionnaire, which provided the clinical scab history of the farm, and submitted results of serological testing with the ELISA. RESULTS: A scab outbreak was reported by 17.4% (± confidence interval [CI]: 4.6%; n = 48) of farms in 2020 based on clinical diagnosis; scab was diagnosed by the ELISA on 25.6% (± 5.5%; n = 65) of farms in 2021/2022. Comparison of self-reported clinical scab cases with the ELISA test results identified a group of farms (n = 52) that did not report scab in 2020, or in some cases did not report having scab over the previous 8 years (n = 20), but whose flocks were nevertheless seropositive in 2021/2022. CONCLUSION: A small number of flocks, particularly those using common grazings in North England, where handling is infrequent, often comprising less susceptible sheep breeds, may have persistent scab infestations that are generally undetected by clinical inspection. The data highlight the advantages of serological testing to identify exposure to scab in flocks where clinical signs are less easily detected.
Asunto(s)
Infestaciones Ectoparasitarias , Infestaciones por Ácaros , Ácaros , Psoroptidae , Enfermedades de las Ovejas , Ovinos , Animales , Infestaciones por Ácaros/diagnóstico , Infestaciones por Ácaros/epidemiología , Infestaciones por Ácaros/veterinaria , Enfermedades de las Ovejas/diagnóstico , Enfermedades de las Ovejas/epidemiología , Ensayo de Inmunoadsorción Enzimática/métodosRESUMEN
Individuals vary broadly in their response to vaccination and subsequent challenge infection, with poor vaccine responders causing persistence of both infection and transmission in populations. Yet despite having substantial economic and societal impact, the immune mechanisms that underlie such variability, especially in infected tissues, remain poorly understood. Here, to characterise how antihelminthic immunity at the mucosal site of infection developed in vaccinated lambs, we inserted gastric cannulae into the abomasa of three-month- and six-month-old lambs and longitudinally analysed their local immune response during subsequent challenge infection. The vaccine induced broad changes in pre-challenge abomasal immune profiles and reduced parasite burden and egg output post-challenge, regardless of age. However, age affected how vaccinated lambs responded to infection across multiple immune pathways: adaptive immune pathways were typically age-dependent. Identification of age-dependent and age-independent protective immune pathways may help refine the formulation of vaccines, and indicate specificities of pathogen-specific immunity more generally.
RESUMEN
BACKGROUND: Sheep scab is considered an endemic disease of great welfare and economic significance in the UK. METHOD: This paper provides an up-to-date assessment of the impact of Sheep Scab (Scotland) Order 2010 on sheep scab notifications in Scotland between 1 January 2014 and 31 December 2019, using data collected by the APHA. RESULTS: In total, 564 sheep scab notifications were reported from 503 unique holdings, of which 44 holdings (8.7%) reported more than one incident. The number of notifications did not differ between years, with 81, 84, 93, 101, 109 and 97 notifications recorded in 2014, 2015, 2016, 2017, 2018 and 2019, respectively: representing an average annual notification prevalence of 0.63% (1/159 flocks/year). A total of 413/564 records documented how notifications were resolved, with macrocyclic lactone and organophosphate treatments accounting for 79.6% and 20.4% of resolutions, respectively. CONCLUSION: Our results suggest that the Order has facilitated the notification of sheep scab in Scotland (including trends and preferred methods of resolution), allowed industry and government to identify previously unidentified potentially free areas as well as recurrent incidents on sheep farms, and start to understand better the geographical and temporal nature of scab outbreaks. However, concerns remain about a potential lack of engagement, evidenced by the low notification prevalence and stagnant annual notification rates.
Asunto(s)
Infestaciones Ectoparasitarias , Infestaciones por Ácaros , Enfermedades de las Ovejas , Animales , Brotes de Enfermedades/veterinaria , Infestaciones Ectoparasitarias/epidemiología , Infestaciones Ectoparasitarias/veterinaria , Infestaciones por Ácaros/epidemiología , Infestaciones por Ácaros/veterinaria , Escocia/epidemiología , Ovinos , Enfermedades de las Ovejas/epidemiologíaRESUMEN
The increasing resistance to anthelmintics has necessitated the exploration of alternative control strategies of gastrointestinal nematode (GIN) infections. A sustainable option is genetic selection based on differences in susceptibility to GIN infection between and within breeds of sheep. Here, three-month-old Canaria Hair breed (GIN-resistant) and Canaria Sheep breed (GIN-susceptible) showed no significant between-breed differences after trickle infection with Teladorsagia circumcincta, whereas considerable individual variability was found in both breeds. Next, data from lambs of both breeds were used to explore the relationships between parasitological variables and T. circumcincta-specific IgA levels, local immune cell populations, and abomasal lymph node gene expression to understand the possible mechanisms underlying resistance. Mucosal IgA levels as well as numbers of globular leukocytes and MHC-II+ cells were associated with protection. Analysis of lymph node gene expression revealed the associations between lower parasite numbers and cumulative fecal egg counts and several immune pathways, such as leukocyte cell adhesion, activation and differentiation of T cells, in particular CD4+ and IL-4 production. The data obtained here may inform on the relationship between phenotypic resistance variability and protective responses at the humoral, cellular, and transcriptomic levels, thus contributing to identifying immune responses in young lambs that could be used as markers for selection.
Asunto(s)
Enfermedades Gastrointestinales , Enfermedades de las Ovejas , Tricostrongiloidiasis , Animales , Heces , Inmunoglobulina A/genética , Ovinos/genética , Enfermedades de las Ovejas/genética , Transcriptoma , Trichostrongyloidea , Tricostrongiloidiasis/inmunología , Tricostrongiloidiasis/veterinariaRESUMEN
Many obligate blood-sucking arthropods rely on symbiotic bacteria to provision essential B vitamins that are either missing or at sub-optimal levels in their nutritionally challenging blood diet. The poultry red mite Dermanyssus gallinae, an obligate blood-feeding ectoparasite, is a serious threat to the hen egg industry. Poultry red mite infestation has a major impact on hen health and welfare and causes a significant reduction in both egg quality and production. Thus far, the identity and biological role of nutrient provisioning bacterial mutualists from D. gallinae are little understood. Here, we demonstrate that an obligate intracellular bacterium of the Rickettsiella genus is detected in D. gallinae mites collected from 63 sites (from 15 countries) across Europe. In addition, we report the genome sequence of Rickettsiella from D. gallinae (Rickettsiella - D. gallinae endosymbiont; Rickettsiella DGE). Rickettsiella DGE has a circular 1.89Mbp genome that encodes 1,973 proteins. Phylogenetic analysis confirms the placement of Rickettsiella DGE within the Rickettsiella genus, related to a facultative endosymbiont from the pea aphid and Coxiella-like endosymbionts (CLEs) from blood feeding ticks. Analysis of the Rickettsiella DGE genome reveals that many protein-coding sequences are either pseudogenized or lost, but Rickettsiella DGE has retained several B vitamin biosynthesis pathways, suggesting the importance of these pathways in evolution of a nutritional symbiosis with D. gallinae. In silico metabolic pathway reconstruction revealed that Rickettsiella DGE is unable to synthesize protein amino acids and, therefore, amino acids are potentially provisioned by the host. In contrast, Rickettsiella DGE retains biosynthetic pathways for B vitamins: thiamine (vitamin B1) via the salvage pathway; riboflavin (vitamin B2) and pyridoxine (vitamin B6) and the cofactors: flavin adenine dinucleotide (FAD) and coenzyme A (CoA) that likely provision these nutrients to the host.
RESUMEN
Gastrointestinal (GI) infections in sheep have significant implications for animal health, welfare and productivity, as well as being a source of zoonotic pathogens. Interactions between pathogens and epithelial cells at the mucosal surface play a key role in determining the outcome of GI infections; however, the inaccessibility of the GI tract in vivo significantly limits the ability to study such interactions in detail. We therefore developed ovine epithelial organoids representing physiologically important gastric and intestinal sites of infection, specifically the abomasum (analogous to the stomach in monogastrics) and ileum. We show that both abomasal and ileal organoids form self-organising three-dimensional structures with a single epithelial layer and a central lumen that are stable in culture over serial passage. We performed RNA-seq analysis on abomasal and ileal tissue from multiple animals and on organoids across multiple passages and show the transcript profile of both abomasal and ileal organoids cultured under identical conditions are reflective of the tissue from which they were derived and that the transcript profile in organoids is stable over at least five serial passages. In addition, we demonstrate that the organoids can be successfully cryopreserved and resuscitated, allowing long-term storage of organoid lines, thereby reducing the number of animals required as a source of tissue. We also report the first published observations of a helminth infecting gastric and intestinal organoids by challenge with the sheep parasitic nematode Teladorsagia circumcincta, demonstrating the utility of these organoids for pathogen co-culture experiments. Finally, the polarity in the abomasal and ileal organoids can be inverted to make the apical surface directly accessible to pathogens or their products, here shown by infection of apical-out organoids with the zoonotic enteric bacterial pathogen Salmonella enterica serovar Typhimurium. In summary, we report a simple and reliable in vitro culture system for generation and maintenance of small ruminant intestinal and gastric organoids. In line with 3Rs principals, use of such organoids will reduce and replace animals in host-pathogen research.
Asunto(s)
Intestinos , Organoides , Animales , Interacciones Huésped-Patógeno , Rumiantes , Ovinos , EstómagoRESUMEN
Scanning surveillance facilitates the monitoring of many endemic diseases of livestock in Great Britain, including sheep scab, an ectoparasitic disease of major welfare and economic burden. There is, however, a drive to improve the cost-effectiveness of animal health surveillance, for example by thoroughly exploiting existing data sources. By analysing the Veterinary Investigation Diagnosis Analysis (VIDA) database, this study aimed to enhance the use of existing scanning surveillance data for sheep scab to identify current trends, highlighting geographical "hotspots" for targeted disease control measures, and identifying a denominator to aid the interpretation of the diagnostic count data. Furthermore, this study collated and assessed the impact of past targeted disease control initiatives using a temporal aberration detection algorithm, the Farrington algorithm, to provide an evidence base towards developing cost-effective disease control strategies. A total of 2,401 positive skin scrapes were recorded from 2003 to 2018. A statistically significant decline in the number of positive skin scrapes diagnosed (p < 0.001) occurred across the study period, and significant clustering was observed in Wales, with a maximum of 47 positive scrapes in Ceredigion in 2007. Scheduled ectoparasite tests was also identified as a potential denominator for the interpretation of positive scrapes by stakeholders. Across the study period, 11 national disease control initiatives occurred: four in Wales, three in England, and four in Scotland. The majority (n = 8) offered free diagnostic testing while the remainder involved knowledge transfer either combined with free testing or skills training and the introduction of the Sheep Scab (Scotland) Order 2010. The Farrington algorithm raised 20 alarms of which 11 occurred within a period of free testing in Wales and one following the introduction of the Sheep Scab (Scotland) Order 2010. In summary, our analysis of the VIDA database has greatly enhanced our knowledge of sheep scab in Great Britain, firstly by identifying areas for targeted action and secondly by offering a framework to measure the impact of future disease control initiatives. Importantly this framework could be applied to inform future strategies for the control of other endemic diseases.
RESUMEN
BACKGROUND: The blood feeding poultry red mite (PRM), Dermanyssus gallinae, causes substantial economic damage to the egg laying industry worldwide, and is a serious welfare concern for laying hens and poultry house workers. In this study we have investigated the temporal gene expression across the 6 stages/sexes (egg, larvae, protonymph and deutonymph, adult male and adult female) of this neglected parasite in order to understand the temporal expression associated with development, parasitic lifestyle, reproduction and allergen expression. RESULTS: RNA-seq transcript data for the 6 stages were mapped to the PRM genome creating a publicly available gene expression atlas (on the OrcAE platform in conjunction with the PRM genome). Network analysis and clustering of stage-enriched gene expression in PRM resulted in 17 superclusters with stage-specific or multi-stage expression profiles. The 6 stage specific superclusters were clearly demarked from each other and the adult female supercluster contained the most stage specific transcripts (2725), whilst the protonymph supercluster the fewest (165). Fifteen pairwise comparisons performed between the different stages resulted in a total of 6025 Differentially Expressed Genes (DEGs) (P > 0.99). These data were evaluated alongside a Venn/Euler analysis of the top 100 most abundant genes in each stage. An expanded set of cuticle proteins and enzymes (chitinase and metallocarboxypeptidases) were identified in larvae and underpin cuticle formation and ecdysis to the protonymph stage. Two mucin/peritrophic-A salivary proteins (DEGAL6771g00070, DEGAL6824g00220) were highly expressed in the blood-feeding stages, indicating peritrophic membrane formation during feeding. Reproduction-associated vitellogenins were the most abundant transcripts in adult females whilst, in adult males, an expanded set of serine and cysteine proteinases and an epididymal protein (DEGAL6668g00010) were highly abundant. Assessment of the expression patterns of putative homologues of 32 allergen groups from house dust mites indicated a bias in their expression towards the non-feeding larval stage of PRM. CONCLUSIONS: This study is the first evaluation of temporal gene expression across all stages of PRM and has provided insight into developmental, feeding, reproduction and survival strategies employed by this mite. The publicly available PRM resource on OrcAE offers a valuable tool for researchers investigating the biology and novel interventions of this parasite.
Asunto(s)
Infestaciones por Ácaros , Ácaros , Enfermedades de las Aves de Corral , Animales , Pollos , Femenino , Humanos , Masculino , Ácaros/genética , Aves de Corral , TranscriptomaRESUMEN
BACKGROUND: The avian haematophagous ectoparasite Dermanyssus gallinae, commonly known as the poultry red mite, causes significant economic losses to the egg-laying industry worldwide and also represents a significant welfare threat. Current acaricide-based controls are unsustainable due to the mite's ability to rapidly develop resistance, thus developing a novel sustainable means of control for D. gallinae is a priority. RNA interference (RNAi)-mediated gene silencing is a valuable tool for studying gene function in non-model organisms, but is also emerging as a novel tool for parasite control. METHODS: Here we use an in silico approach to identify core RNAi pathway genes in the recently sequenced D. gallinae genome. In addition we utilise an in vitro feeding device to deliver double-stranded (ds) RNA to D. gallinae targeting the D. gallinae vATPase subunit A (Dg vATPase A) gene and monitor gene knockdown using quantitative PCR (qPCR). RESULTS: Core components of the small interfering RNA (siRNA) and microRNA (miRNA) pathways were identified in D. gallinae, which indicates that these gene silencing pathways are likely functional. Strikingly, the P-element-induced wimpy testis (PIWI)-interacting RNA (piRNA) pathway was absent in D. gallinae. In addition, feeding Dg vATPase A dsRNA to adult female D. gallinae resulted in silencing of the targeted gene compared to control mites fed non-specific lacZ dsRNA. In D. gallinae, dsRNA-mediated gene knockdown was rapid, being detectable 24 h after oral delivery of the dsRNA, and persisted for at least 120 h. CONCLUSIONS: This study shows the presence of core RNAi machinery components in the D. gallinae genome. In addition, we have developed a robust RNAi methodology for targeting genes in D. gallinae that will be of value for studying genes of unknown function and validating potential control targets in D. gallinae.
Asunto(s)
Proteínas de Artrópodos/genética , Técnicas de Silenciamiento del Gen/métodos , Genómica/métodos , Infestaciones por Ácaros/veterinaria , Ácaros/genética , Aves de Corral/parasitología , Interferencia de ARN , Adenosina Trifosfatasas/genética , Animales , Pollos/parasitología , Simulación por Computador , Femenino , MicroARNs/genética , MicroARNs/metabolismo , Infestaciones por Ácaros/parasitología , Infestaciones por Ácaros/prevención & control , Enfermedades de las Aves de Corral/parasitologíaRESUMEN
PURPOSE: The most common techniques used to repair umbilical hernias are open and laparoscopic. As the obesity epidemic in the United States is growing, it is essential to understand how this morbidity affects umbilical hernia repairs. This study compares laparoscopic versus open umbilical hernia repairs in obese patients. METHODS: All patients with body mass index (BMI) ≥ 30 kg/m2 who underwent elective, open or laparoscopic repair of a primary umbilical hernia with mesh were identified from the Americas Hernia Society Quality Collaborative (AHSQC). A retrospective review of the prospectively collected data was conducted. Outcomes of interest included surgical site infections (SSI), surgical site occurrences requiring procedural intervention (SSOPI), hernia-related quality-of-life survey (HerQles), and long-term recurrence. A logistic regression model was used to generate propensity scores. RESULTS: Of 1507 patients who met the inclusion criteria, 322 were laparoscopic, and 1185 were open cases. The laparoscopic group had higher mean BMI (37 ± 6 vs. 35 ± 5 kg/m2 , P < 0.001 ) and mean hernia width (3 cm ± 1 vs. 2 cm ± 2, P < 0.001). Using a propensity score model, we controlled for several clinically relevant covariates. Propensity score adjustment showed no differences in the 30-day HerQles score (OR 0.93, 95% CI 0.58-1.49), SSI (OR 1.57, 95% CI 0.52-4.77), SSOPI (OR 2.85, 95% CI 0.84-9.62) or hernia recurrence (hazard ratio 0.86, 95% CI 0.50-1.49). CONCLUSION: In obese patients with primary umbilical hernias, there is likely no benefit to laparoscopy over open umbilical hernia repair with mesh with regard to wound morbidity. Although, the long-term recurrence also showed no difference between these two approaches, overall follow up was lacking.
Asunto(s)
Hernia Umbilical , Hernia Ventral , Laparoscopía , Hernia Umbilical/complicaciones , Hernia Umbilical/cirugía , Hernia Ventral/epidemiología , Hernia Ventral/cirugía , Herniorrafia/efectos adversos , Humanos , Obesidad/complicaciones , Obesidad/epidemiología , Estudios Retrospectivos , Mallas Quirúrgicas , Estados Unidos/epidemiologíaRESUMEN
Scabies is a neglected tropical disease of global significance. Our understanding of host-parasite interactions has been limited, particularly in crusted scabies (CS), a severe clinical manifestation involving hyper-infestation of Sarcoptes scabiei mites. Susceptibility to CS may be associated with immunosuppressive conditions but CS has also been seen in cases with no identifiable risk factor or immune deficit. Due to ethical and logistical difficulties with undertaking research on clinical patients with CS, we adopted a porcine model which parallels human clinical manifestations. Transcriptomic analysis using microarrays was used to explore scabies pathogenesis, and to identify early events differentiating pigs with ordinary (OS) and crusted scabies. Pigs with OS (n = 4), CS (n = 4) and non-infested controls (n = 4) were compared at pre-infestation, weeks 1, 2, 4 and 8 post-infestation. In CS relative to OS, there were numerous differentially expressed genes including pro-inflammatory cytokines (IL17A, IL8, IL19, IL20 and OSM) and chemokines involved in immune cell activation and recruitment (CCL20, CCL27 and CXCL6). The influence of genes associated with immune regulation (CD274/PD-L1 and IL27), immune signalling (TLR2, TLR8) and antigen presentation (RFX5, HLA-5 and HLA-DOB) were highlighted in the early host response to CS. We observed similarities with gene expression profiles associated with psoriasis and atopic dermatitis and confirmed previous observations of Th2/17 pronounced responses in CS. This is the first comprehensive study describing transcriptional changes associated with the development of CS and significantly, the distinction between OS and CS. This provides a basis for clinical follow-up studies, potentially identifying new control strategies for this severely debilitating disease.
Asunto(s)
Interacciones Huésped-Parásitos/inmunología , Sarcoptes scabiei/inmunología , Escabiosis/veterinaria , Sus scrofa/inmunología , Sus scrofa/parasitología , Animales , Citocinas/genética , Citocinas/inmunología , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/genética , Inmunomodulación/inmunología , Escabiosis/inmunología , Escabiosis/patología , Piel/inmunología , Piel/parasitología , Piel/patología , Porcinos , Enfermedades de los Porcinos/inmunología , Enfermedades de los Porcinos/parasitología , Células Th17/inmunología , Células Th2/inmunología , Transcriptoma/genéticaRESUMEN
AIMS: Serodiagnosis of sheep scab is an established diagnostic method and has become popular in recent years. However, the current diagnostic antigen, Pso o 2, has shown promise as a component of a recombinant vaccine for scab, making it incompatible with discriminating between infected and vaccinated animals (DIVA). Here, we describe the discovery and characterization of a novel Psoroptes ovis immunodiagnostic antigen, P. ovis-Early Immunoreactive Protein-1 (Pso-EIP-1). METHODS AND RESULTS: Pso-EIP-1 is a highly abundant member of a six-gene family with no known homologs, indicating its potential uniqueness to P. ovis. Expression of recombinant Pso-EIP-1 (rPso-EIP-1) required a C-terminal fusion protein for stability and specific IgG immunoreactivity against rPso-EIP-1 was observed in sheep serum from 1 to 2 weeks post-infestation, indicating its highly immunogenic nature. Two of the three in silico-predicted B-cell epitopes of Pso-EIP-1 were confirmed by in vitro epitope mapping and, in a direct comparison by ELISA, Pso-EIP-1 performed to the same levels as Pso o 2 in terms of sensitivity, specificity and ability to diagnose P. ovis on sheep within 2 weeks of infestation. CONCLUSION: Pso-EIP-1 represents a novel diagnostic antigen for sheep scab with comparable levels of sensitivity and specificity to the existing Pso o 2 antigen.
Asunto(s)
Proteínas de Artrópodos/inmunología , Infestaciones por Ácaros/veterinaria , Psoroptidae/inmunología , Pruebas Serológicas/veterinaria , Enfermedades de las Ovejas/diagnóstico , Animales , Inmunoglobulina G/sangre , Infestaciones por Ácaros/diagnóstico , Proteínas Recombinantes de Fusión/inmunología , Sensibilidad y Especificidad , Pruebas Serológicas/métodos , OvinosRESUMEN
BACKGROUND: Incisional hernia repair with mesh improves long-term outcomes, but the ideal mesh position remains unclear. This study compared intraperitoneal versus retromuscular or preperitoneal sublay (RPS) mesh positions for open incisional hernia repairs. METHODS: All patients who had elective open incisional hernia repairs were identified retrospectively in the Americas Hernia Society Quality Collaborative database. The primary outcome was the rate of 30-day surgical-site infection (SSI). Other outcomes of interest included 30-day surgical-site occurrences requiring procedural intervention (SSOPI), hernia-related quality-of-life survey (HerQLes) scores and long-term recurrence. A logistic model was used to generate propensity scores for mesh position using several clinically relevant co-variables. Regression models adjusting for propensity score and baseline characteristics were developed to assess the effect of mesh placement. RESULTS: A total of 4211 patients were included in the study population: 587 had intraperitoneal mesh and 3624 had RPS mesh. Analysis with propensity score adjustment provided no evidence for differences in SSOPI (odds ratio (OR) 0·79, 95 per cent c.i. 0·49 to 1·26) and SSI (OR 0·91, 0·50 to 1·67) rates or HerQLes scores at 30 days (OR 1·20, 0·79 to 1·82), or recurrence rates (hazard ratio 1·28, 0·90 to 1·82). CONCLUSION: Mesh position had no effect on short- or long-term outcomes, including SSOPI and SSI rates, HerQLes scores and long-term recurrence rates.
ANTECEDENTES: La reparación de una eventración con malla mejora los resultados a largo plazo, pero sigue sin estar definida cuál es la posición ideal de colocación de la malla. Este estudio comparó los resultados de la reparación abierta de una eventración con malla en posición intraperitoneal versus retromuscular o preperitoneal (retromuscular or preperitoneal sublay, RPS). MÉTODOS: Se identificaron de forma retrospectiva todos los pacientes a los que se reparó una eventración por via abierta en el Americas Hernia Society Quality Collaborative. La variable principal fue la tasa de infección de la herida quirúrgica (surgical site infections, SSI) a los 30 días. Se analizaron también las incidencias acaecidas en la herida que hubieran precisado algún tratamiento (surgical site occurrences requiring procedural intervention, SSOPI) dentro de los 30 días postintervención, los resultados de una encuesta de calidad de vida relacionada con la hernia (HerQles) y la recidiva a largo plazo. Se utilizó un modelo logístico con diferentes covariables clínicas relevantes para generar puntajes de propensión con respecto a la posición de malla. Para analizar el efecto de la posición de la malla, se desarrollaron diferentes modelos de regresión ajustados por las características basales y el puntaje de propensión. RESULTADOS: Se incluyeron en el estudio 4.211 pacientes, 587 con malla intraperitoneal y 3.624 con malla RPS. El análisis con ajuste por puntaje de propensión no mostró diferencias en SSOPI (razón de oportunidades, odds ratio, OR 0,624, i.c. del 95% 0,364-1,07), SSI (OR 0,927, i.c. del 95% 0,475-1,81), puntuación HerQles a 30 días (OR 1,19, i.c. del 95% 0,79-1,8) o en el índice de recidivas (OR 1,28, i.c. del 95% 0,897-1,82). CONCLUSIÓN: La posición de la colocación de la malla no tuvo efecto en los resultados a corto o largo plazo, incluidas las tasas de SSOPI y SSI, las puntuaciones de HerQles y la tasa de recidiva a largo plazo.
Asunto(s)
Hernia Incisional/cirugía , Mallas Quirúrgicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Infección de la Herida Quirúrgica/epidemiología , Resultado del TratamientoRESUMEN
Game theory examines strategic decision-making in situations of conflict, cooperation, and coordination. It has become an established tool in economics, psychology and political science, and more recently has been applied to disease control. Used to examine vaccination uptake in human medicine, game theory shows that when vaccination is voluntary some individuals will choose to "free-ride" on the protection provided by others, resulting in insufficient coverage for control of a vaccine-preventable disease. Here, we use game theory to examine farmer uptake of a new diagnostic ELISA test for sheep scab-a highly infectious disease with an estimated cost exceeding £8M per year to the UK industry. The stochastic game models decisions made by neighboring farmers when deciding whether to adopt the newly available test, which can detect subclinical infestation. A key element of the stochastic game framework is that it allows multiple states. Depending on infestation status and test adoption decisions in the previous year, a farm may be at high, medium or low risk of infestation this year-a status which influences the decision the farmer makes and the farmer payoffs. Ultimately, each farmer's decision depends on the costs of using the diagnostic test vs. the benefits of enhanced disease control, which may only accrue in the longer term. The extent to which a farmer values short-term over long-term benefits reflects external factors such as inflation or individual characteristics such as patience. Our results show that when using realistic parameters and with a test cost around 50% more than the current clinical diagnosis, the test will be adopted in the high-risk state, but not in the low-risk state. For the medium risk state, test adoption will depend on whether the farmer takes a long-term or short-term view. We show that these outcomes are relatively robust to change in test costs and, moreover, that whilst the farmers adopting the test would not expect to see large gains in profitability, substantial reduction in sheep scab (and associated welfare implications) could be achieved in a cost-neutral way to the industry.
RESUMEN
Cyathostomins are ubiquitous parasitic nematodes of horses. These worms spend substantial periods as intestinal wall stage encysted larvae, which can comprise up to 90% of the total burden. Several million larvae have been reported in individuals. Emergence of these larvae from the gut wall can lead to life-threatening colitis. Faecal egg count tests, increasingly used by horse owners to inform anthelmintic treatments, do not correlate with the intra-host burden of cyathostomins; this represents a key gap in the diagnostic toolbox. Previously, a cyathostomin Gut Associated Larval Antigen was identified as a promising marker for the intra-host stages of infection. Here, cyathostomin Gut Associated Larval Antigen and an additional protein, Cyathostomin Immuno-diagnostic antigen, were investigated to examine their value in providing information on cyathostomin burden. ELISA analyses examined serum IgG(T) responses to recombinant proteins derived from individual cyathostomin species. Receiver Operator Characteristic curve analysis was performed on the ELISA data; proteins with the highest Area Under the Curve values were selected to test protein combinations to investigate which were the most informative in identifying the infection status of individuals. Three cocktail combinations were tested, comprising: (a) Cy-GALA proteins from two species and a Cy-CID protein from a third species (CT3), (b) Cy-GALA proteins from five species (CT5), and (c) all CT5 components, plus a Cy-CID protein from an additional species (CT6). The best predictive values for infection were obtained using CT3 and CT6, with similar values achieved for both. Proteins in CT3 are derived from the most commonly reported species, Cyathostomum catinatum, Cylicocyclus nassatus and Cylicostephanus longibursatus. This combination was selected for future development since it represents a more commercially viable format for a diagnostic test.
Asunto(s)
Antígenos Helmínticos/inmunología , Caballos , Infecciones Equinas por Strongyloidea , Strongyloidea/inmunología , Animales , Antihelmínticos/uso terapéutico , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/veterinaria , Enfermedades de los Caballos/diagnóstico , Enfermedades de los Caballos/tratamiento farmacológico , Enfermedades de los Caballos/inmunología , Enfermedades de los Caballos/parasitología , Caballos/inmunología , Caballos/parasitología , Inmunoglobulina G , Infecciones Equinas por Strongyloidea/diagnóstico , Infecciones Equinas por Strongyloidea/tratamiento farmacológico , Infecciones Equinas por Strongyloidea/inmunologíaRESUMEN
PURPOSE: Relying solely on in-person encounters to assess long-term outcomes of hernia repair leads to substantial loss of information and patients lost-to-follow-up, hindering research and quality improvement initiatives. We aimed to determine if inguinal hernia recurrences could be assessed using the Ventral Hernia Recurrence Inventory (VHRI), a previously existing patient-reported outcome (PRO) tool that can be administered through the telephone and has already been validated for diagnosing ventral hernia recurrence. METHODS: A prospective, multicentric comparative study was conducted. Adult patients from two centers (United States and Brazil) at least 1 year after open or minimally invasive inguinal hernia repair were asked to answer the questions of the VHRI in relation to their prior repair. A physical exam was then performed by a blinded surgeon. Testing characteristics and diagnostic performance of the PRO were calculated. Patients with suspected recurrences were preferentially recruited. RESULTS: 128 patients were enrolled after 175 repairs. All patients answered the VHRI and were further examined, where a recurrence was present in 32% of the repairs. Self-reported bulge and patient perception of a recurrence were highly sensitive (84-94%) and specific (93-94%) for the diagnosis of an inguinal hernia recurrence. Test performance was similar in the American and Brazilian populations despite several baseline differences in demographic and clinical characteristics. CONCLUSION: The VHRI can be used to assess long-term inguinal hernia recurrence and should be reestablished as the Hernia Recurrence Inventory (HRI). Its implementation in registries, quality improvement efforts, and research could contribute to improving long-term follow-up rates in hernia patients.