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July 11, 2000

Dirty Secrets of Bloodthirsty Ticks


CDC; James Occi

The usual suspects, from left to right: two nymph deer ticks; two adult deer ticks; and an American dog tick.

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Dr. Stephen K. Wikel, an entomologist at the University of Connecticut Health Center, is studying tick saliva to find a vaccine that could deter ticksThomas McDonald for The New York Times.

Dr. Stephen K. Wikel pulled a little gauze-topped glass jar from a warm, damp incubator in his laboratory, and, with the heat from his palm and a puff of exhaled breath, roused the tiny blood-sucking creatures inside.

"These are the beasts," he said.

Bristly brown dots, each the size of a poppy seed, began to mill across the gauze, excited by the heat and gust of carbon dioxide that signaled the presence of a possible meal ticket on the other side.

One dot was immobilized on some cellophane tape and placed under a microscope, revealing just a few of the myriad tools that enable Ixodes scapularis, the deer tick and the main carrier of Lyme disease, to detect, climb aboard and surreptitiously dine on a host.

It is this diminutive eight-legged arachnid, a cousin of spiders, that has taken the carefree pleasure out of a summertime walk in the woods for millions of people in the Northeast. Other Ixodes species are spreading Lyme disease on the West Coast and in parts of Europe.

The visible features of the tick are impressive enough, including forearm hooks that snag fur or fabric on a passing target, a pair of cutting mouth parts -- like scissor blades with the sharp edge outward -- and a serrated tube that serves both as an anchor and a drinking straw. Ticks are the "Inspector Gadget" of parasites.

But it is the tick's invisible armamentarium, dozens of elaborate chemical weapons in its saliva, that have become the prime focus of Dr. Wikel, an entomologist at the University of Connecticut Health Center, which sits on a hilltop near Hartford overlooking wooded suburban yards that are prime tick habitat.

He and other experts in tick biology have found that the seemingly primitive parasites use an array of sophisticated chemical strategies to subvert a host's immune defenses, to prevent blood from clotting, and to muffle any itch or pain that might elicit scratching that could dislodge a tick and ruin a vital blood meal.

Ticks, which spend their lives stealthily avoiding detection, are beginning to give up some of their secrets.

A central goal of the scientists is to develop a vaccine from some of the molecules pumped into a host when a tick bites, thereby turning its own weapons against it.

A vaccine that deters the Ixodes tick, Dr. Wikel and other tick experts say, could prove more useful than the existing vaccine for Lyme disease, which only attacks the bacteria transmitted by the tick, not the tick itself.

Recent research has shown that deer ticks carry at least two other diseases besides Lyme -- human granulocytic ehrlichiosis and babesiosis. So an "anti-tick" vaccine, Dr. Wikel said, could essentially be "a three-in-one" vaccine.

Some preliminary work has shown that the strategy can be effective, and one anti-tick vaccine is being used against a different species that infests cattle in Australia -- sometimes with up to 20,000 ticks on a single host.

But it will be years before scientists clearly identify the structure and purpose of the soup of molecules in tick spit, Dr. Wikel said, and years more before there is a marketable human vaccine.

In the meantime, other scientists are finding that tick saliva is fertile territory for seeking potential new drugs, especially for controlling clotting and inflammation.

"Ticks know everything we know and don't know about pharmacology," said Dr. Jose M. C. Ribeiro, a tick expert at the parasitology laboratory of the National Institutes of Health in Bethesda, Md.

Dr. Ribeiro, Dr. Wikel and others studying ticks have practical ends in mind, but almost all of these scientists say they were drawn to these persistent pests mainly by their complex, often astonishing, abilities. "Biologically, a tick is a box inside a box inside a box," Dr. Ribeiro said.

Another tick expert, Dr. James E. Keirans, recalled his wonderment 30 years ago when he was based in western Montana and hiked paths leading into the foothills of the Rockies in the spring, when adult dog ticks emerge.

There, when you crouch down with the light behind you, he said, "you can see the ticks up on the grass blades, just sitting there attached by their third pair of legs. You can take off your hat and pass a shadow over them and see 60 or 70 ticks at once moving their legs."

There are about 840 tick species, divided into two families, those with leathery bodies like the dog and deer tick -- which have three life stages and take only one big, momentous meal during each stage -- and others with soft bodies, which behave more like fleas, feeding repeatedly and often.

Ticks feed on just about every kind of back-boned animal except fish, said Dr. Keirans, the curator of the National Tick Collection, which is owned by the Smithsonian Institution but is located at Georgia Southern University in Statesboro, Ga.

He rattled off a few examples, including ticks that hopscotch continents on migrating seabirds, specialized ticks that may soon become extinct as the rhinoceroses on which they feed dwindle, even ticks that only feed on the Galapagos tortoise. The largest is a tick that feeds only on sloths in the American tropics. When fully engorged, he said, it is the size of a Ping-Pong ball.

There is some debate, but many biologists say that ticks probably evolved more than 300 million years ago, possibly feeding on dinosaurs and amphibians.

"For them, the mass extinction of dinosaurs just meant a menu change," said Dr. Ribeiro. A new target, the mammal, had a new feature in its blood, platelets, which aid clotting and would have thrown a roadblock at ticks. But, Dr. Ribeiro said, evolution carried on and ticks -- in the endless spy-versus-spy game of life -- developed ways to keep the blood flowing.

"They have a very ancient wisdom about how to take blood," he said.

The hard-bodied ticks have been the focus of most research in North America because they are the predominant carrier here of diseases that affect people and their livestock and pets. (Wildlife, of course, is not immune. Biologists have documented the presence in northern forests of "ghost moose" -- moose that have as many as 400,000 ticks feeding on them and that lose all their hair as they rub hopelessly against trees.)

In its life cycle and habits, the deer tick is typical of many species, said Dr. Daniel E. Sonenshine, a biology professor at Old Dominion University in Norfolk, Va., and author of the two-volume "Biology of Ticks" (Oxford University Press, 1991 and 1993). A tick's prime goal is to find an appropriate host, climb aboard, find the ideal spot to latch on, and to dine on red blood cells, the source of the globin molecules needed to molt and mature and, in the end, for females to make and lay eggs.

In each stage of life -- larva, nymph and adult -- the process of finding and feeding on a host is almost exactly the same. Only the targets change. The larvae almost always feed on mice, while the adult deer tick, which is big enough that it tends to be detected by a person and brushed or plucked off, targets mainly deer.

For deer ticks, the nymph stage -- the stage milling around in Dr. Wikel's jar -- is the main transmitter of disease to people, with its peak of activity coming from late spring to late summer.

A nymph's day generally starts in a moist, protected place, typically buried in leaf litter and only rarely out in the middle of a mowed lawn. Without adequate moisture it can quickly dry out and die.

As the hours pass, it begins to "quest," in the parlance of tick biology, climbing instinctively in the opposite direction of gravity, usually up a blade of grass or a twig, and generally no more than a foot or two off the ground.

It sits poised, waiting. In this posture, resumed daily, the tick is like a land mine, primed and ready and patient as can be, with weeks or even months passing before a potential target comes along. Most, Dr. Keirans said, never find a meal.

But enough do. They detect a rustling vibration and a whiff of carbon dioxide and maybe a slight sensation of warmth. A shadow passes, triggering nerves attuned to changes in light. Holding onto the perch with that third pair of legs, they wave the rest of their appendages. Especially active are the forearms, which contain a sensory organ that is exquisitely tuned to sense chemical changes.

The legs are tipped with sharp hooks. The lucky ones snag a ride.

But, Dr. Sonenshine said, for the tick, the job has only just begun.

It begins to explore the host, he said, generally moving up against gravity until it either reaches an obstruction -- the elastic of underpants or a tight shirt collar -- or until it finds an ideal feeding spot, a place exuding sweat and warmth, indicating an ample blood supply.

The sensory tools that led it to this place are now disregarded and it relies on its palps, paired arms next to its cutting mouth parts, to select an ideal dining spot.

Once there, ticks do not bite like a horsefly or use a syringe like a mosquito. Unlike these insects, which eat and run, ticks have taken an evolutionary path requiring them to settle in for the long haul.

Ticks dig a well.

Using their serrated mouth parts, they excavate a pool beneath the host's skin from which they draw sustenance using the hypostome, a straw-like tube that resembles a drywall anchor and holds the animal almost as effectively.

A tough, rubbery cement is released, helping hold the tick in place.

The meal unfolds over up to five or even seven days, which is why people are generally not apt to acquire Lyme disease from a tick bite if the offender is removed within a couple of days of attachment, researchers say.

The tick only sips tentatively at first, while steadily pumping into the wound saliva that carries a variety of ingredients that help it stay attached, avoid detection, suppress the immune system and keep blood flowing.

The result is a pool brimming with just what the tick wants, red blood cells. The white blood cells that would normally flood a wound have been tricked to stay away.

"Ticks are very finicky, like one of those brats who will only eat cookies," said Dr. Sonenshine. "The tick has this choice of all these wonderful things -- a big cafeteria of cells, muscle, other tissue. But it says no thanks. Just give me red blood cells."

Finally, there comes what tick biologists call "the big sip," a binge of feeding reserved until the end so there is the least risk that the now rapidly growing parasite will be detected.

As it ingests blood, it has to expel water, and it does so through its saliva, accelerating the passage of any hitchhiking Lyme bacteria into the host.

Researchers stress that old methods for removing ticks -- like touching it with a burned match or daubing with alcohol -- probably cause it to expel even more spit into the wound. The best approach, they say, is to use steady pressure with small tweezers to draw the tick away from the skin until it pulls free.

As the meal comes to a close, the tick grows sometimes a hundredfold in weight before finally dropping from the host and crawling into leaf litter and -- in the case of adult females -- laying thousands of eggs and starting the cycle all over again.

Dr. Ribeiro has spent more than a decade hunting in tick saliva for all the hidden molecules used during feeding. A few have been identified by him or other researchers:

•Apyrase, an enzyme that destroys substances released by injured cells that would normally cause platelets and white blood cells to accumulate.

•Prostaglandin E2 , which suppresses some immune defenses and dilates capillaries, increasing blood flow.

•Kininase, an enzyme that blocks several molecules that create the itch sensation and swelling when skin is injured.

And there are probably dozens more, Dr. Ribeiro, Dr. Wikel and other researchers said.

Increasingly, it appears that the infections transmitted by ticks take advantage of the conditions created by this chemical cocktail, Dr. Wikel said.

All the more reason to find a way to vaccinate potential hosts so that the body -- instead of being tricked by the influx of weapons -- recognizes one of them and mounts a counterattack, he said.

Dr. Wikel, who once enlisted a small army of students to dissect salivary glands out of 10,000 ticks, said that genetic sequencing techniques were accelerating the research.

Even so, he said, "We probably have a lifetime of work ahead of us to look at all these products, develop the proteins and use them in vaccination trials."


Copyright 2000 The New York Times Company




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