Prevalence Of Insect Bite Hypersensitivity Research Articles

Establishment of a protocol for preventive vaccination against equine insect bite hypersensitivity

Insect bite hypersensitivity (IBH) is a seasonal dermatitis of horses caused by IgE-mediated reactions to bites of Culicoides midges characterized by an imbalance of T-cell subsets. Iceland is free of the causative species but the prevalence of IBH in exported Icelandic horses is especially high. We have shown that intralymphatic (i.l.) vaccination with r-Culicoides allergens in Aluminum hydroxide (alum) and monophosphoryl lipid A (MPLA) adjuvants induces a desired Th1/regulatory T-cell response. The aim of this study was to compare i.l. to subcutaneous (s.c.) injection. Twelve healthy Icelandic horses were injected, i.l. or s.c., three times with four-week interval, using purified r-Culicoides allergens in alum/MPLA. Serum antibody levels and cytokine profile following in vitro re-stimulation of PBMC were analysed. Comparable allergen-specific IgG antibodies were induced following both routes of vaccinations. The antibodies showed similar capacity to block binding of IgE from IBH-affected horse to the allergens. Upon re-stimulation of PBMC, IL-10 was induced. Horses vaccinated i.l. produced more IFN-γ and less IL-4 as compared to the horses injected s.c., but the difference did not reach significance. It can be concluded that applying the simpler s.c. injection instead of i.l. to obtain a suitable immune response could be option in IBH immunotherapy.

Comparison of recombinant Culicoides allergens produced in different expression systems for IgE serology of insect bite hypersensitivity in horses of different origins

Insect bite hypersensitivity (IBH) is an allergic dermatitis of horses, an IgE-mediated reaction to Culicoides midges. Causative Culicoides spp. are not indigenous in Iceland resulting in high prevalence of IBH in horses born in Iceland and exported as compared to Icelandic horses born in a Culicoides rich environment. The aims were (i) to compare IgE levels in sera of IBH-affected horses born in Iceland (n = 47) with horses of the Icelandic breed (n = 23) and of other breeds (n = 27) born in Culicoides infested area; (ii) to investigate if barley could be a useful production system of allergens for IBH immunoassays.IgE binding in sera was tested by ELISA on two recombinant Culicoides allergens, rCul n 3 and rCul n 4, each produced in E. coli, insect cells and barley. Significantly more IgE was detected against all allergens in sera from IBH-affected compared to healthy horses. Icelandic-born Icelandic horses stand out with higher IgE levels against the allergens and higher area under the curve (AUC) on rCul n 4 as compared to the European-born horses. The barley and E.coli produced allergens had very similar performance in distinguishing between IBH-affected and healthy horses.

Association of inbreeding and regional equine leucocyte antigen homozygosity with the prevalence of insect bite hypersensitivity in Old Kladruber horse.

SummaryInbreeding depression is the reduction of performance caused by mating of close relatives. In livestock populations, inbreeding depression has been traditionally estimated by regression of phenotypes on pedigree inbreeding coefficients. This estimation can be improved by utilising genomic inbreeding coefficients. Here we estimate inbreeding depression for insect bite hypersensitivity (IBH) prevalence, the most common allergic horse disease worldwide, in Old Kladruber horse. In a deep pedigree with 3214 horses (187 genotyped), we used a generalised linear mixed model with IBH phenotype from 558 horses examined between 1996 and 2009 (1368 records). In addition to the classical pedigree information, we used the single‐step approach that enabled joint use of pedigree and genomic information to estimate inbreeding depression overall genome and equine leucocyte antigen (ELA) class II region. Significant inbreeding depression was observed in all models fitting overall inbreeding coefficients (odds ratio between 1.018 and 1.074, P < 0.05) with the exception of Kalinowski’s new inbreeding (P = 0.0516). The increase of ELA class II inbreeding was significantly associated with increased prevalence of IBH (odds ratio 1.018; P = 0.027). However, when fitted jointly with the overall inbreeding coefficient, the effect of ELA class II inbreeding was not significant (odds ratio 1.016; P = 0.062). Overall, the higher ELA class II and/or overall inbreeding (pedigree or genomic) was associated with increased prevalence of IBH in Old Kladruber horses. The single‐step approach provides an efficient use of all the available pedigree, genomic, and phenotype information for estimation of overall and regional inbreeding effects.

Culicoides spp. found near Lusitano stud farms in mainland Portugal which may contribute for IBH studies.

Insect Bite Hypersensitivity (IBH) is a common cutaneous disease, affecting a large number of horses worldwide. Several studies have identified Culicoides spp. saliva as a clinically relevant allergen source. The prevalence of IBH in Portugal, particularly in Lusitano horses, is still not known. However, the environmental characteristics of the national territory are favorable to the activity of Culicoides, and several species of this genus can be found, namely C. imicola and C. obsoletus/C. scoticus. In this study we characterized the Culicoides population present in Lusitano stud farms with a history of IBH. Thirteen stud farms with Lusitano horses were selected in several regions of mainland Portugal for having a previous history of IBH-affected horses, with a minimum of 5 affected horses. Culicoides were collected in May and June 2016 using OVI traps, placed in these stud farms, and we were able to identify several Culicoides species. We could also verify that C. obsoletus/C. scoticus, and C. imicola were the ones most frequently found, but other species like C. pulicaris were also found.

Genetic parameters of insect bite hypersensitivity in the Old Grey Kladruber horse.

The objective of this study was to assess the genetic parameters of insect bite hypersensitivity (IBH) in the Old Grey Kladruber horse, an original Czech warmblood horse breed. Insect bite hypersensitivity is a recurrent allergic skin disease affecting horses worldwide. Its etiology is multifactorial. The defect is genetically controlled, and the starting impulse is a bite by midges of the spp. and less frequently spp. Knowledge about the associated genes is limited. Horses were kept by the National Stud in Kladruby (1,146 measurements) and by 10 private breeders (63 measurements). The horses were visually scored by the same inspector over a period of 13 yr from 1996 to 2009. A linear logistic model with a binary variable was used for subsequent statistical analysis. The fixed effects of the farm, year of evaluation, age of evaluation, and sex were significant, and the nonsignificant effect was the intensity of greying. The animals from the National Stud were more strongly affected by IBH than animals from private studs. The National Stud is located near the Labe River, at an altitude of 206 m; there are bottomland pastures in the vicinity, blind river arms, and numerous pools and marshes, and the climate is mild. These conditions are convenient for horse keeping but also for the propagation of . The stallions were less affected than the mares. The occurrence in years of age was influenced by selection; scoring began in the first year of age, and when the young animal was repeatedly positive, it was eliminated from breeding. The estimated h differed significantly from 0, and the direct h were 0.626 in the animal model with a maternal effect, 0.359 in the animal model without a maternal effect, and 0.363 in the animal model without correlation between direct and maternal effect. The maternal h was 0.305. The estimated repeatabilities were 0.636 with a maternal effect, 0.615 without a maternal effect, and 0.623 without correlation. The h of IBH was found to be medium to high, so there is a possibility to reduce the prevalence of IBH by selection.

Oral administration of transgenic barley expressing a Culicoides allergen induces specific antibody response.

Insect bite hypersensitivity is an immunoglobulin (Ig)E-mediated dermatitis of horses initiated by bites of midges of the genus Culicoides. Culicoides spp. are not indigenous to Iceland and the prevalence of insect bite hypersensitivity is much higher in horses born in Iceland and exported as compared to Icelandic horses born in a Culicoides rich environment. Immunotherapy is therefore needed. The aim of the study was to express an allergen from Culicoides in barley grain and investigate whether an immune response could be obtained in healthy Icelandic horses by oral treatment with transgenic barley expressing the allergen. In vivo experiment. The allergen was expressed in barley grain with the Orfeus technique. A device was developed to treat horses orally with barley flour. Four Icelandic horses were treated with transgenic barley and 3 with control barley, in total 500 g in 7 feedings. Serum and saliva samples were collected for measuring specific antibodies. The allergen Cul n 2, a hyaluronidase originating from the salivary gland of Culicoides nubeculosus, was expressed in barley. Horses treated with the transgenic barley mounted a Cul n 2 specific IgG1 and IgG4/7 response in serum and saliva. The serum response was significantly different between the transgenic and control barley treated horses for both subclasses and the saliva response for IgG1. The induced serum antibodies bound to the corresponding allergen from Culicoides obsoletus, rCul o 2 and were able to partially block binding of Cul n 2 as well as Cul o 2 specific IgE from insect bite hypersensitivity affected horses. Small number of horses. This study shows that specific antibody response can be induced in horses not exposed to Culicoides, using oral treatment with transgenic barley expressing an allergen. Further studies will determine whether this approach is a useful alternative for prevention and treatment of equine insect bite hypersensitivity.

Genetic parameters and estimated breeding values of insect bite hypersensitivity in Belgian Warmblood horses

Genetic factors involved in susceptibility to insect bite hypersensitivity (IBH) in Belgian Warmblood horses (BWP) were investigated. Data relating to 3409 horses were collected using a questionnaire, administered to owners during sport competitions, BWP breeding days, breeder visits and after phone calls. Horses were classified as IBH-affected or unaffected, based on two ‘disease classifiers’: a lifetime record, based on owner information (life_status) and another based on whether or not the horse was showing clinical signs at the time of questioning (clin_status). IBH prevalence was 10% based on life_status, and 6.2% based on clin_status. The heritabilities estimated using threshold animal models varied from 0.65 to 0.78 on the underlying scale (0.18–0.26 on the observed scale). These research findings indicate that susceptibility to IBH is a heritable trait in BWP.

Expression of Interleukin-4 Receptor and CCL5 Chemokine is not Related to Insect Bite Hypersensitivity in Horses

Insect bite hypersensitivity (IBH) in horses represents a type I or sometimes a type IV hypersensitivity to salivary antigens from numerous Culicoides spp and some other insects. Until now, there has been no curative treatment available, but there are clear indications that the susceptibility to IBH is partly heritable. Identification of equine genes that are associated with susceptibility to IBH could lead to the development of a marker-assisted selection method. The aim of this study was to investigate the expression of functional candidate genes in relation to IBH. Based on literature, the interleukin-4 receptor (IL4R) and chemokine CCL5 (CCL5) genes were selected for examination by quantitative reverse transcription-PCR (qRT-PCR). Expression levels were determined in 16 horses: 8 IBH-positive horses, all showing clinical IBH symptoms at sampling; and 8 IBH-negative horses, stabled at the same location (case-control set up). Peripheral blood mononuclear cells (PBMC) were isolated from whole- blood samples, and expression levels of IL4R and CCL5 were measured. No differential expression was found for IL4R and CCL5 in PBMC between IBH-positive and IBH-negative horses (P = .58 and P = .63). Expression of CCL5 and IL4R in PBMC is not related to insect bite hypersensitivity in warmblood horses. Research toward a marker-assisted selection procedures could reduce IBH prevalence in horse populations by means of selection.

Risk factors for insect bite hypersensitivity in Friesian horses and Shetland ponies in The Netherlands

Insect bite hypersensitivity (IBH) is an equine skin allergy caused by bites of Culicoides spp. and impacts on the welfare of affected horses. The aim of this study was to identify and quantify risk factors for IBH. Data from 3453 Friesian horse mares and 7074 Shetland pony mares scored for IBH by inspectors during obligatory foal inspections were analysed using breed-specific multivariable logistic regression models. The combined effect of month and year of scoring, Province and inspector were significantly associated with IBH in both breeds. In Shetland pony mares, withers height and coat colour were also significantly associated with IBH, while body condition had a nearly significant effect. The outcomes from this study on risk factors might contribute to the development of more efficient measures to reduce the prevalence of IBH.

Genome‐wide association study of insect bite hypersensitivity in Dutch Shetland pony mares

Insect bite hypersensitivity (IBH) is the most common allergic disease present in horses worldwide. It has been shown that IBH is under genetic control, but the knowledge of associated genes is limited. We conducted a genome-wide association study to identify and quantify genomic regions contributing to IBH in the Dutch Shetland pony population. A total of 97 cases and 91 controls were selected and matched on withers height, coat colour and pedigree to minimise the population stratification. A blood sample was collected from participating Shetland pony mares, their IBH phenotype was scored and the owner filled in a questionnaire. A total of 40 021 single-nucleotide polymorphisms (SNPs) were fitted in a univariable logistic model fitting an additive effect. Analysis revealed no effects of population stratification. Significant associations with IBH were detected for 24 SNPs on 12 chromosomes [-log(10) (P-value) > 2.5]. Odds ratios of allele substitution effects of the unfavourable allele were between 1.94 and 5.95. The most significant SNP was found on chromosome 27, with an odds ratio of 2.31 and with an allele frequency of the unfavourable allele of 0.72 in cases and 0.53 in controls. Genome-wide association studies on additional horse populations are desired to validate the identified associations, to identify the genes involved in IBH and to develop genomic tools to decrease IBH prevalence.

Various Circumstances Regarding Initial Allergen Exposure and Their Influence on Development of Insect Bite Hypersensitivity in Horses

Insect bite hypersensitivity (IBH), an allergic reaction to the saliva of Culicoides, occurs in all horse breeds and is a severe problem. In this study, we aimed at exploring whether exterior conditions, such as duration of allergenic exposure during the first summer and age of the horses at the time of import, influence the development of IBH. Additionally, data were analyzed regarding the period IBH started after birth and after import. Datasets for 582 horses were collected. The horses were locally born Icelandic horses and horses of other breeds with IBH, as well as imported Icelandic horses, both affected and nonaffected. For locally born horses, time of birth and duration of allergen exposure during the first summer had no influence on the prevalence of IBH. The disease started mostly in their third year of life. The majority of the imported horses affected caught IBH during their first year in Central Europe. Older imported horses seemed to develop IBH quicker than younger animals. Animals imported in their first winter are exposed to the allergen when they are at least 7 months old. They experienced approximately the same low risk of developing IBH as locally bred horses. The risk of IBH increased with the horses’ age at import. From our data, we conclude that the period to develop successful immune tolerance goes beyond the perinatal phase and is longer than formerly supposed.

Genetic parameters of insect bite hypersensitivity in Dutch Friesian broodmares1

Insect bite hypersensitivity (IBH) is a seasonal allergic skin disease in horses caused by bites of certain Culicoides spp. The aim of our study was to investigate the maternal effect on IBH and to estimate the heritability and repeatability of IBH in the Dutch Friesian horse population. Data consisted of 3,453 Dutch Friesian broodmares with 3,763 visual observations on IBH clinical symptoms scored by 12 inspectors during organized foal inspections in 2004 and 2008. Nine percent of the mares (n = 310) were scored in both years. Mares descended from 144 sires and 2,554 dams and 26.2% of the dams (n = 669) had more than 1 offspring in the data set (range: 2 to 6). Insect bite hypersensitivity was analyzed as a binary trait with a threshold animal model with and without a maternal effect, using a Bayesian approach. Observed IBH prevalence in Dutch Friesian broodmare population was 18.2%. Heritability on the liability scale was 0.16 (SD = 0.06); heritability on the observed scale was 0.07; and repeatability was 0.89 (SD = 0.03). Maternal effect was 0.17 (SD = 0.06) and significantly differed from zero, although the animal model without a maternal effect fitted the data better. These results show that genetic and permanent environmental factors affect IBH in Dutch Friesian horses. The dam affected the IBH development of her offspring through an additive genetic influence but also by being part of their rearing environment.

Heritability and repeatability of insect bite hypersensitivity in Dutch Shetland breeding mares1

Insect bite hypersensitivity (IBH) is a seasonal recurrent allergic reaction of horses to the bites of certain Culicoides spp. and is found throughout the world. The aim of our study was to estimate the heritability and repeatability of IBH in the Dutch Shetland pony population. A total of 7,924 IBH scores on 6,073 mares were collected during foal inspections in 2003, 2005, and 2006. Mares were scored for clinical symptoms of IBH from June until February by 16 inspectors. Of all mares, 74.4% (n = 4,520) had a single observation, 20.7% (n = 1,255) had 2 observations, and 4.9% (n = 298) had 3 observations in different years. The overall mean IBH prevalence was 8.8%. Heritability was 0.08 (SE = 0.02) on the observed binary scale and 0.24 (SE = 0.06) on the underlying continuous scale. Repeatability was 0.30 (SE = 0.02) and indicates that including repeated observations of the clinical symptoms of IBH will improve the accuracy of breeding values for IBH. We conclude that IBH, based on clinical symptoms, is a heritable trait in the Dutch Shetland pony population. Therefore, the IBH prevalence in this population can be decreased by selection.

Identification of environmental factors affecting the prevalence of insect bite hypersensitivity in Shetland ponies and Friesian horses in the Netherlands

It is expected that climate and habitat factors influence the prevalence of culicoides and, therefore, the prevalence of insect bite hypersensitivity (IBH), but very little is described in the literature to prove the association of these factors. Prevalence varies widely from 3% in certain areas of Great Britain to 60% in certain parts of Australia. To describe the influence of environmental factors on the prevalence of IBH in Shetland ponies and Friesian horses in The Netherlands. Data on 3284 Shetland and 2824 Friesian mares (n = 6108) were collected in The Netherlands, based on 90 regions, according to postal codes. The climate components, amount of rainfall, number of warm days, number of cold days, and habitat components of soil type and type of vegetation were collected for each region. Prevalence of IBH varied widely from 0-71.4% per region. The results showed that the environment with low IBH-prevalence had high rainfall, many cold days and few warm days per year. Habitats with a low IBH-prevalence were based along the coast line. Habitats with increasing prevalence of IBH had soils of clay with heather and woody vegetation. Friesian mares had a higher IBH prevalence than Shetland mares, which could indicate an effect of genetic background or an effect of year. There is an environmental effect on IBH prevalence within The Netherlands, which is caused by climate and habitat factors. The results provide a more accurate description of environmental factors and their impact on development of IBH; and should help better to understand habitat and climate effects, and to distinguish these from other effects, such as animal factors (genetics, age or sex).

Evaluation of an in vitro sulphidoleukotriene release test for diagnosis of insect bite hypersensitivity in horses

Insect bite hypersensitivity (IBH) is an IgE-mediated allergic dermatitis caused by bites of Culicoides and Simulium species, and improved means of diagnosis are required. The cellular antigen simulation test (CAST) with C. nubeculosus and S. vittatum extracts was assessed in a population of IBH-affected and healthy horses. Variations in test results over a one year period and possible cross-reactivity between different insect extracts was studied. A total of 314 mature horses were studied using the CAST. Influence of severity of clinical signs, gender and age were evaluated, and 32 horses were tested repeatedly over one year. The kappa reliability test was used to assess agreement of the test results with different insect extracts. Horses with IBH had significantly higher sLT release than controls with C. nubeculosus and S. vittatum. The highest diagnostic sensitivity and specificity levels were attained when using adult C. nubeculosus extracts with the CAST (78% and 97%, respectively), suggesting that most horses with IBH are sensitised against Culicoides allergens. A proportion of IBH-affected horses was found to be sensitised to allergens of Simulium spp. in addition to those of C. nubeculosus. The CAST with C. nubeculosus had positive and negative predictive values > or = 80% for a true prevalence of IBH of 12-52%. In the follow-up study, the proportion of IBH-affected horses with a positive test result ranged from 90% in November to 68% in March. Severity of clinical signs or age did not influence test results significantly. However, IBH-affected males achieved significantly more positive test results than IBH-affected females. The CAST with adult C. nubeculosus has high specificity and good sensitivity for diagnosis of IBH. Horses with IBH are mainly sensitised to Culicoides allergens, and some horses are additionally also sensitised to allergens in Simulium spp. The CAST is likely to be a useful test for diagnosis of IBH, even allowing the identification of IBH-affected but asymptomatic horses. This test may also help in further characterisation of allergens involved in this condition.