Parasitology
Sheep scab: towards vaccination
Dr John Huntley
The problem
Figure 1: Psoroptes ovis, the mite responsible for causing sheep scab . |
Sheep scab has been identified as an allergic dermatitis caused by the mite Psoroptes ovis (Figure 1), which lives on the skin of sheep. Since lesions can rapidly become extensive and the disease is highly contagious, sheep scab has significant economic and welfare importance in the UK. The dramatic increase in the disease, concerns for human health and the environment, the safety issues that have been associated with plunge dipping and the emergence of strains of P. ovis resistant to organophosphates and synthetic pyrethroid compounds have created an urgent need for alternative methods of control. While injectable macrolide endectocides or macrocyclic lactones are effective at present, it is thought by many that it is only a matter of time before the mites become resistant to these chemicals as well. Moreover, their frequent use for the control of scab will only intensify the development of resistance of gastrointestinal nematode worms.
Scottish Sheep Scab Initiative (SSSI)
This initiative, which was launched in 2003, is led by the National Farmers Union of Scotland (NFUS) and a number of representatives from the sheep industry, including Moredun, in order to provide an action framework to control sheep scab. The initiative emphasises the concern which farmers now face with the increasing prevalence of infection and the aims of the initiative are to reduce the number of sheep scab outbreaks in Scotland through the promotion and support of best practice (flock biosecurity), minimising the impact of outbreaks by effective and coordinated treatment and by maximising the effects of preventative action by targeting risk and coordinating treatment.
The disease
Figure 2: Scab lesions can cover almost the entire skin surface . |
The scab lesion starts as a small inflamed area of skin surrounded by yellow scabs, under which the mites feed. As the mite numbers increase, the lesion area slowly grows and can cover almost the entire skin surface after 8 -10 weeks of infection (Figure 2). The itching which this lesion causes is intense; animals can become so preoccupied with trying to alleviate the itch that they cease drinking and eating which results in a dramatic loss in condition. In some cases (1-3%) this itching can trigger fits and a few of these animals do not recover. Studies have been investigating the underlying cause of the disease and the antigens and allergens which provoke the characteristic skin reaction. The extensive work and knowledge gained from studies on the allergens of the house dust mite, which are a major cause of human allergy, have been invaluable during this work. Studies at Moredun have shown that the scab mite also excretes or secretes potent allergens similar to those produced by the house dust mite. Several of these have now been identified including an enzyme almost identical to Der p 1 which is found in the gut and faeces of the house dust mite and is a major cause of human allergic asthma. In addition, a number of other allergens have recently been identified including a tropomyosin (similar to a protein responsible for shell fish allergies), a paramyosin (a similar protein is being trialed as a vaccine to schistosomiasis in water buffalos), and a vitellogenin/ apolipophorin which is thought to be important in embryonic protein reserves and lipid transport. Because these allergens appear to be vital for the mites’ normal function and survival they are good vaccine candidates. These are now in the process of being synthesized in bacteria or yeast as recombinant proteins in order to be tested in a vaccine.
Figure 3: Section of scab lesion, showing the dramatic influx of B cells (stained brown) into the skin. |
Histopathological studies on the early stages of the lesion have shown rapid changes in the epidermis, including a massive influx of eosinophils and immune cells (Figure 3), an up-regulation in the major inflammatory cytokine, Tumour Necrosis Factor-alpha (TNF ) and death (apoptosis) of keratinocytes. These changes are also observed when mite antigens are applied to the skin surface. To aid this work a technique has been developed where small plastic chambers are affixed to the skin surface within which mites or their products can be placed. This minimises the effects of infection and discomfort to the animal and allows the testing of a number of proteins which aids in identifying the active mite agents which induce this remarkable pathology.
Towards a vaccine
Studies at Moredun have investigated the feasibility of vaccination and have shown that previous exposure to mites results in the development of a substantial protective immunity in sheep following challenge infestation. This protection is accompanied by the development of both IgG and IgE antibodies and these latter antibodies are the cause of the allergic reaction. Parallel vaccine-challenge trials in sheep have shown that partial protection can be achieved with saline extracts of P.ovis, but not with detergent or urea extracts of mite membranes. This protective extract was subsequently fractionated by ion exchange and gel filtration chromatography and the most effective fraction reduced lesion areas and mite numbers by more than 4 and 15 fold, respectively. However, due to the difficulties of fractionating large numbers of proteins in sufficient quantities together with the high cost of these vaccine-challenge studies, the current focus is on determining the complex host-parasite interactions through microarray. It is envisaged that these studies, funded by DEFRA and SEERAD, will provide a detailed analysis on the factors involved in lesion development and lead to new candidates for vaccine or alternative control strategies. In addition to this work, a diagnostic blood test is being developed, which is being based on the immune response to the allergens. A highly sensitive, specific and robust assay will be of value in determining the prevalence and monitoring of disease, and be of particular relevance in any control or eradication program.
This research is funded by SEERAD.