In severe sweet itch cases, scabs and sores extend down the mane, along the back, to the base of the tail and on the flanks, belly and legs. The inset shows a typical response to an injection of midge proteinsDr Doug Wilson, a lecturer in virology at the University of Bristol School of Veterinary Sciences, outlines his research on one of the horseworld’s most distressing conditions.
Why can’t you vets do something about sweet itch?” asked one mum when I arrived to pick up my children from Pony Club.
The story was a familiar one of a young pony purchased in winter that suddenly developed the characteristic rubbing and weeping sores of sweet itch the following summer. The vendor said the pony had shown no signs of the disease the previous year, which may well be true. The peak age of sweet itch onset is about four and it can also appear for the first time in older horses.
I agreed that it was time something was done about something affecting about 3% of equines in Britain. As a vet with an interest in immunology I was in an undeniably good position, but before one can fix anything it’s essential to understand the exact nature of the problem.
Midges are to blame
Sweet itch is most often an allergic reaction to the bites of midges, which occur in almost every country where horses are kept. Midges are a couple of millimetres long and only the females feed on blood — they need a high-protein diet to lay eggs.
Although sweet itch has been known for centuries, the first scientific link with midge bites was made in Australia in the 1950s. A vet noticed that the disease occurred only in areas where midges were abundant, then showed that when the skin of affected horses was injected with an extract of midges, a small swelling appeared within a few minutes. This “acute” reaction is typically seen in certain types of immune hypersensitivity or allergy, so he concluded that sweet itch was an allergy to midge bites.
The top panel shows a female midge looking for a meal. The bottom left below shows a midge salivary gland (stained pink), where the antibodies in horse blood have bound it in the area next to the arrow. A similar picture (below right) shows serum from a Icelandic horse, with no antibodiesWhy do midges spit?
Midges are most active around dawn and dusk or on overcast days, when there’s less risk of them drying out. After landing, they crawl down the hair shafts to the skin surface. Their mouthparts are too short to probe for a blood vessel like mosquitoes, so they chew their way through the skin’s tough outer layers. They secrete saliva containing a mixture of enzymes that digest and soften the skin tissue, as well as “vasodilators” to encourage extra blood flow and several factors that prevent the blood clotting. A small pool of blood forms just under the skin surface and is sucked up by the midges.
Once full, they make their way back to the ends of the hairs and, laden with blood and weighing twice as much as when they arrived, fly off. The whole process takes about 15-20min and over one evening a horse may receive hundreds or even thousands of midge bites.
The immune system’s response
When an animal is injected with something “foreign”, its immune system responds by making antibodies that bind on to the foreign proteins. The action of antibodies is often compared to that of a key: one end is like the handle, while the other has a unique shape that fits the lock or in the case of antibodies allows them to bind to their target.
Antibodies are made by specialised B-cells. Each cell is programmed to make a unique antibody and a horse (or human) has millions of B-cells. But one B-cell on its own will not make much antibody, so when it encounters a foreign substance that binds its own unique antibody, it is stimulated to grow and divide. In a few days, there are thousands of cells.
That’s how a flu vaccine works. Your horse is injected with a small amount of the influenza virus and the B-cells increase in number. When a real flu virus turns up, there are lots of B-cells primed with antibodies to neutralise the virus and prevent the infection spreading.
If the immune system of horses with sweet itch is reacting to the saliva of midges, the horses should carry antibodies that will bind specifically to the proteins in midge saliva. The first stage in our research, funded by the Horse Trust, was to identify which midge proteins are important.
We found that all British horses had antibodies. We were also able to get serum from horses in Iceland, one of the few places in the world where there are no midges. This contained no antibodies.
The top panel shows a female midge looking for a meal. The bottom left below shows a midge salivary gland (stained pink), where the antibodies in horse blood have bound it in the area next to the arrow. A similar picture (below right) shows serum from a Icelandic horse, with no antibodiesA special kind of antibody
If they all carry antibodies, why doesn’t every British horse develop sweet itch? The answer lies in the immune system. The B-cell can produce antibodies for different purposes. For example, one type is best for an influenza virus, while a different type is needed to deal with the strangles bacteria. In this case, the antibodies bind to the bacteria’s surface, enabling white blood cells to ingest and destroy it.
The antibody important in allergies like sweet itch is Immunoglobulin E (IgE). Its real role is in immune responses to parasites such as worms or worm larvae living under the skin. To protect against worms, the immune system uses one of its most powerful weapons, the “mast cell”. These coat themselves in IgE antibodies and lie in wait. When the IgE binds its target, the mast cell releases a cocktail of chemicals that cause a severe inflammatory reaction and attract other immune cells to injure or kill the parasite.
Allergies occur when the immune system makes a mistake. In people, this response could be to peanuts. In horses, the most common allergy is to midge saliva.
We only found IgE antibodies in the serum from horses with sweet itch, confirming that this disease is an allergic response to midge bites.
What does the horse react to?
The next task was to identify the proteins in midge saliva. We did this first by isolating the genes containing the instructions for making the proteins in the saliva. By reading the genes’ coded messages, we can work out which are most common in midge saliva and are most likely to be the genes of the proteins that cause sweet itch.
The second approach is to look at the proteins themselves by breaking them into fragments. A computer programme compares the pattern of the fragment sizes with those we’d expect to find and we can work out the most common proteins in midge saliva.
Once the genes or relevant proteins have been isolated, we can produce a pure protein equivalent to the contents of several million midges’ saliva glands and use this to re-programme the immune system of allergic horses.
Over one evening a horse may receive thousands of midge bites
When midge saliva proteins are separated, they form spots (top picture). The long chains of amino acids can be measured by a mass spectrometer, which uniquely identifies each protein. The bottom picture shows separated midge saliva proteins stained with IgE antibody from a horse with sweet itch. The darker grey smudges indicate the midge proteins to which this horse is allergicA case of mistaken identity
The B-cell is warned of a potential enemy through chemical messages sent by another group of immune cells called T-cells. These are told what to do by yet another type of cell called a dendritic cell, which detects foreign substances and can tell if they are from bacteria, viruses or are of parasitic origin.
A migrating parasite has to break down tissue and to do this secretes enzymes similar to those the midge uses to weaken skin. Like midges, migrating parasites also release factors that can interfere with blood clotting. The horse’s immune system interprets these as an invading parasite, when in fact it’s only a midge bite. It looks like sweet itch is a case of mistaken identity, leading to the wrong messages being sent down the chain of command.
Can we re-programme the immune system?
Immunotherapy is used to re-programme the immune system of people or animals with allergies through repeatedly exposing it to small amounts of the allergen. It will take time to work out how this can be done safely in horses.
For example, would mixing midge proteins with some parts of bacteria fool the immune system? Could feeding horses midge protein convince the immune system that it is harmless? Should all foals be inoculated with midge proteins at an early age?
It’s taken almost 10 years to get this far but we are making progress. One thing is certain in science — it always takes longer that you think. Yet one day we will indeed be able to “do something about sweet itch”.