Biology 103

This paper reflects the research and thoughts of a student at the time the paper was written for a course at Bryn Mawr College. Like other materials on Serendip, it is not intended to be "authoritative" but rather to help others further develop their own explorations. Web links were active as of the time the paper was posted but are not updated.

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Dr. Me

Jeanne Braha

Here on the east coast, spring is a gorgeous time of year. Birds sing, flowers bloom, the temperature is just right and the humidity hasn't yet set in. My hair even looks sort of normal. But lately, spring has brought out the ugly side of some. Lyme Disease is one of the newest hot topics of concern. And, as with any impediment to our freedom to roll in the grass, nobody can quite agree on how to view this condition. Is it fairly innocuous, wiped out with four weeks of antibiotics? Do I really have to tuck my socks into my pants and look like a goober? Or could Lyme disease sock me with years of achy joints, neurological decline and gall-bladder-harming medications? Patients, researchers and clinicians have drawn up the battle lines. Some try to strip doctor s of their licenses; others create web sites that aim to sully the reputation of well-respected research institutions. Some parents keep their children inside and out of any fun.

The medical profession is not a perfect science. In fact, most practicioners would contend it is an art in its own right. But what happens when the consumer's health hangs in the balance? What rights do I have as a patient to demand the treatment that I think is best? How can I be sure that the M.D. is making a reasonable decision in my best interest? Especially with the increasing amount of medical information (and disinformation) available to the public, this is becoming a contentious issue. Lyme disease is only one example of this trend. Matters are further complicated when insurance companies step in with financial considerations.

Some Background on Lyme Disease

Ticks have gotten a bad rap for a long time. Humans' initial impressions are bound to be negative, due to our tendency to clump all those little critters that scurry around with their exoskeletons and multiple legs into one big category of "get that thing off of me!" To compound the situation even further, Ixodes scapularis (the black-legged or deer tick) has been maligned as the cause of Lyme disease throughout the northeastern United States. (1). A veritable war has been declared on the little scamps: before taking off on a hike, people douse themselves with a variety of tick-killing chemicals; cover their extremities in light colored clothes to more easily spot the ticks and make mental notes to mow down the vegetation creeping up on their yards at home. As a person living in the high-incidence region, I feel the need to educate myself about the issue. So off to the information superhighway....

I. scapularis (also referred to as I. dammini) does not do much to enhance its reputation by feeding, in part, on human blood. But are these arthropods the sole cause of Lyme disease? No. They are simply the vector for Borrelia burgdorferi, the bacterium that is transmitted at these mealtimes and is the actual catalyst for the human reactions classified as the clinical illness Lyme disease. (6).

B. burgdorferi is a corkscrew-shaped, non pus-producing bacterium. It is commonly referred to as a spirochete because of its shape. The strain that infects humans in the United States is B. burgdorferi, sensu stricto. There are two other strains that have been identified, but they are dominant only in Europe. (6).

The bacterium takes a strange path through the tick's midgut via at least one vertebrate. I. scapularis has three stages (nymph, larva and adult) in its life cycle over a two-year period. In each of the stages, the tick crawls from the tip of a blade of grass or the leaf of a short bush onto the host. Ticks cannot jump or fly; they do not drop onto the heads of hosts from overhanging tree branches. Once on the animal, it spends a few days with its mouthparts under the host's skin and takes in a leisurely meal of blood. Once satiated, the tick then drops off and molts into the next stage. Adult females drop off deer in early spring or summer of their second year to lay eggs, and then die. The eggs hatch in the summer and ticks emerge in larval form. (1). These larvae tend to feed on smaller mammals, such as white-footed mice, through the summer and early fall. Over the winter they are relatively inactive, then molt into nymphs in the spring. The nymphs feed on small mammals or birds during the spring and summer. In the fall, they molt into adults and feed on larger mammals, especially the white-tailed deer, until the following spring, when the cycle is renewed.

As they feed, ticks can transmit B. burgdorferi to the animal serving as their meal, or acquire the spirochete from such an organism. The ticks need to be attached to their host for a minimum of 24 hours(1). (some sources say two full days) (6). to transmit the bacteria through salivation or regurgitation. A great amount of saliva is secreted during feeding, so this is generally considered to be the main means of transmission to the host. An additional method of giving the bacteria to the host is if the animal grooms itself and crushes the tick in the process, thereby exchanging fluids with the critter. This is a concern for folks removing ticks found attached to themselves - if improperly removed, they can inadvertently crush the tick's body. (4). Also, a very small number of ticks are born carrying the bacteria if their mother carried it as well.

The tick can be infected with the Lyme-causing bacteria at any stage in its life and can feed on humans at any stage. The animals suggested above are simply the most common. However, the bacteria are transmitted to humans most frequently during the nymphal stage. (1). Nymphs are most active in the spring and summer, making that the time to play it extra safe. The pattern of transmission is not exclusively because more nymphs than ticks in other stages feed on humans. A number of other factors come into play: the nymphs are harder to spot and remove than adults; and nymphs are more active in warmer months, when exposure to tick habitat is greater for humans. Even a fully-fed (and thus larger) adult can be small to spot on one's skin. They almost look like freckles or moles. A close inspection reveals that the "freckle" is in a strange position - pointing outwards instead of lying flat on the skin. It is theoretically possible to contract Lyme disease through blood transfusions or coming into contact with infected blood or urine. However, the United States Center for Disease Control (CDC) has found no solid evidence of such an event. I've now conquered the first stage of this exercise: I have an idea about how the disease is contracted. Now I can consider the most prudent preventative measures so I will not have to be a medical consumer. I know that I don't want my ankles to get too close to a blade of grass with a tick on it. I should not smoosh ticks on me, and should check carefully for them after being outside. I have a day-long window to remove them. Spring is the trickiest time of year - those little nymphs are hard to see.

This is great to know, but if I were to contract Lyme disease, I need to be prepared to consult with my doctor about the best course of treatment. This is where a large part of the battle is raging. A vocal group of folks who have had Lyme disease claim it is a chronic ailment, accompanied for years by arthritic pain, memory loss and sundry other irritating symptoms. Several doctors who agree with them have been prosecuted for their long-term prescription of antibiotics to these patients. (12)Dr. Allan Steere, the first M.D. to name the disease, was confronted by angry protestors during his celebration of the 25th anniversary of the naming. He says that Lyme is overdiagnosed and overtreated. His opponents, notably the Lyme Alliance, claim that his endorsement of the shorter course of antibiotics gave insurance companies the impetus to refuse coverage for any further treatment, even when patients exhibit chronic symptoms. These patients can get nasty, referring to Steere's colleagues as his "cronies" and other terms less suitable for a school paper. (12)

This antipathy is just one expression of the changing relationship between doctors and patients as the latter enter the exam room armed with greater quantities of information than ever before. The example of this dynamic is easiest to see with regards to "direct-to-consumer" ads for pharmaceutical products. Ever more popular periodicals have DTC ads that encourage people to ask their physicians about the next wonder drug. Dr. Richard Kravitz, co-author of a study on this topic, explains that "there are upsides and downsides of DTC advertising for consumers, patients and physicians, as well as the healthcare system as a whole. Costs -- at least pharmaceutical costs -- are bound to increase as a result. But such advertising does empower the patient, and perhaps fosters important communication behaviors for patients and physicians." (11) Instead of the more traditional rapport in which the doctor is viewed as omniscient and advice is usually followed, doctor-patient relations are now more even in some ways. However, the issue at hand is whether the information available to the layperson is accurate enough to be heeded and whether the common patient is capable of understanding its full implications. I'll return to the example of Lyme disease.

I Think I Have Lyme

Information about how to spot Lyme disease if more or less the same at all sources. Hallmark symptoms are the keys that I should consult my physician. Once infected with B. burgdorferi, most humans exhibit an erythema migrans (EM), more commonly known as the bull's eye rash. This occurs at the site of the bite, but secondary EMs might appear elsewhere after a brief incubation period. Ticks seem to prefer to crawl up humans to dark, moist areas such as the groin, armpits, and trunk. The incubation period, the time from the bacteria's entrance into the body until symptoms such as EM appear, can be anywhere from three to thirty days. One to two weeks is a more common timeframe for the bacteria to spread throughout the body via the bloodstream, the lymphatic system and via the skin. Initial symptoms other than the rash usually are quite similar to those of the flu. This can lead to many missed diagnoses.

Later symptoms of untreated Lyme disease include arthritis, neurological irregularities, especially facial nerve palsy, some cognitive disorders and, very rarely, cardiac abnormalities. Lyme disease does not usually result in death. The most common late-stage symptoms for infections caused by B. burgdorferi, sensu stricto are musculoskeletal manifestations, such as arthritis and inflamed joints. (1) This tells me that I definitely want to get a professional opinion if I think I might be infected. Better safe than sorry.

Treatment Options

Treatment of Lyme disease with antibiotics has been largely successful, according to some reports. Recovery is fairly quick and most late-stage symptoms are avoided. (3). The overwhelming consensus at this point seems to be to take the antibiotics as prescribed by a physician. Those in support of this theory contend that Lyme is not a chronic condition. Dr. Eugene Shapiro of Yale University goes so far as to suggest that any long-term symptoms are actually psychological in nature. Opponents say that Lyme tests have been returned positive years after the initial infection occurred, lending substance to their claims of the chronic nature of the disease.(7) A Lyme specialist in New York is currently on trial before the state health department for treating patients in a manner consistent with this viewpoint. For medicating Lyme sufferers for several years, he is in danger of losing his license. (8) This is where I, as a patient, must carefully weigh all facets of the argument. Ultimately, treatment decisions lie with the patient, who is advised by the doctor. But contradicting a physician can be difficult: these are the people trained to care for you.

A large gap in the web documentation of this battle is empirical evidence supporting one side or the other. The CDC offers plenty of information about the disease transmission and recommends the short-term treatment course. However, I was unable to locate any explanation of how the doses of antibiotics were determined. (1) How do they know that a month of the drugs will remove the bacteria from the human body? Is it an issue of quantity? Bacterial lifespan? A healthy level of skepticism would raise these questions.

Vaccination?

A recent addition to the conversation is the Lymerix(r) vaccine, which is administered to humans to prevent contraction of Lyme disease. According to the CDC, the vaccine is made of "lipidated rOspA", from the bacterium that transmits Lyme. Each dose contains "30 ug of purified [rOspA] adsorbed onto an aluminum hydroxide adjuvant." (1)If the tick is a larva or nymph, it is now incapable of transmitting the spirochetes to another animal in any further feedings, because the spirochetes undergo changes while hanging on to my inner thigh with those gross mouthparts. Its antigens switch from rOspA to rOspC. The main difference in the two antigens is a protein (A in the former, C in the latter) that is expressed on the outer membrane of the macromolecule. While being bitten, a person gets mostly rOspC. The vaccine is designed to prevent the bacteria from reaching this stage, by attacking it before that point. Clinical trials have been conducted in subjects aged 15 to 70 years. Results have been up to 83% positive for preventing Lyme during the year after all three doses have been administered.

Okay. I can hear the two sides screaming at this point: it's safe, take the vaccine. Someone got the vaccine and had worse side effects than people with Lyme. Lyme is chronic, you need to take all measures to prevent it. Four weeks of antibiotics and you're good as new. Why take a big risk on the vaccine until it's undergone more trials, if treatment is that easy?.......

As a savvy medical consumer, I checked out the info on the CDC site, and even read their recommendations (too expensive to administer given the low incidence of the disease. It's only cost effective if the rate is above 2% - even in hot zones it's still under 1%) (9) Then I sashayed into the kitchen for a grain of salt and to grab my bio text from under the short leg of the table. What did all that stuff about rOspA mean? Am I really qualified to make a clinical decision for myself?

I'll start with some basics on vaccines. Vaccines are like training wheels for the immune system. They give it a preview of a small amount of an antigen that it might have to defend against one day so it can practice producing the antibodies that will go to battle if need be. Antigens are just the stuff that provokes the lymph system. It does that with proteins. Antibodies are the genetically unique cells that are randomly produced to identify intruders (antigens) and eliminate them from the body. When an antibody is found to be of use, the lymph system replicates it so we have a nice set to take on all that (of the type of antigen identified) dare. (10)

Now I'm ready to think about "lipidated rOspA". I know that the second half of that phrase is a protein that is hanging out of the antigen. So it must be the part that communicates with the antibodies. Lipidated sounds like the whole thing is embedded or encased in lipids. Why would that be? I know that most cell membranes have a lipophosphate bilayer. Does lipidation give the vaccine a structure that allows stuff (maybe the antibodies or at least part of them) to get inside? Lipidated is not in my textbook. It's not in the dictionary (lip gloss was where it should be). So call Molly, best bud and chem. major. Her books and her brain offer no more than my best guess. She did offer to do a hydrogenated reaction with lipids in general and launched into a diatribe about how tasty hydrogenated oils are, despite the fact that they are now more saturated with hydrogen molecules and have fewer double bonds and will surely lead to a heart attack or will endlessly please my lipophilic (that was in her glossary) hips.....

Minor detour to the kitchen to read a few labels, then back to my quest. I'm starting to think that I'm reaching the limits of what I (a) can figure out for myself and (b) the amount of time I care to put in to this research. The internist I see regularly spent four years in medical school learning the basics, then at least three years in a residency refining her skills and reads stuff like the Journal of the American Medical Association so she can give me just such advice. She might even take a few minutes to explain lipidation to me.

So was this entire exercise a waste of time? No, I am now in a much more educated position to make a decision based on the doctor's advice. This becomes increasingly more important as the severity of my ailments increase. If I had Lyme disease, I might take up one side of the battle based on my research and the advice of at least one trusted physician. I might even draw a sign and jump into a protest if Dr. Shapiro dared celebrate another anniversary.

What if I didn't know this stuff. Last year, I was thumbing through an issue of People magazine (only because I'm in a doctor's waiting room and I really do have a serious opinion on the case of Celine Dion's new haircut) and saw an ad for Lymerix. They have such beautiful photos of hikers frolicking in the woods with shorts on. No pants in socks. No faces frozen in various stages of fright or paranoia. Just good, clean fun. Who am I to doubt its necessity and efficacy? Well, I did my homework. But others might simply jump on the bandwagon and demand the shots.

When I am finally taken back, poked, prodded and palpated a bit, and then left to sit in the exam room for a while, I have the chance to ponder the initial debate about Lyme disease. I have pretty much resolved the vaccine issue in my mind, and am back on the first topic. Do I have the information and knowledge necessary to decide that one? Probably not. Does my physician? Probably not. So what do we do?

I actually had Lyme disease when I was 16. I had a gorgeous EM on the inside of my left leg and about a week's worth of fever, achiness and fatigue. My doctor prescribed four weeks of antibiotics, which I dutifully took and I haven't really thought about it since. At that point, I think my mother was making the big decisions with my doctor, because my fever was raging and I was less than totally coherent. But her agreement with the doctor was based on the lack of evidence to the contrary. She didn't have a whole lot of supporting evidence, but the treatment course sounded better than nothing, and I was sick. She knew that Lyme was a bacterial infection and that antibiotics have been terribly successful in other such situations. Why not? If I had exhibited long-term symptoms, I guess we'd have returned to the doctor for another consultation.

The point of this paper is not to come to a specific conclusion about Lyme. I know in my mind what I plan to do if I get sick. However, the point I am trying to make is that, despite the wide range of information accessible to the public, we are still not qualified to make most complex medical decisions independently. The final decision for anyone of legal majority is, of course, in their own hands. But it would be wise to pay attention to professional advice and to have an understanding of the issues. Doctors go through rigorous training so that we don't each need to have all the information about every disease and course of treatment we might encounter in our lifetime. As well, the human body is an incredibly complex organism and every issue is multi-faceted, rather than easily answerable. Get second and third opinions. Look stuff up. But don't base important decisions about your health on an ad in People magazine and the knowledge acquired in Bio 103.

One final thought: imagine you're buying a car. This is a big purchase that is going to be with you for quite a while. How much thought do you put into that question? Health care decisions merit just as much deliberation. And, just as you don't want all your background on your new car to be from the guy on the showroom floor in the plaid jacket, be sure you maintain a healthy skepticism about your doctor's advice. Because science - and medicine - is not about being right all the time. It's about getting it less wrong. Disconcerting, no?

WWW Sources

1)CDC Division of Vector-Borne Infectious Disease - Lyme Disease, This was the most comprehensive site I found, with plenty of great photos and factual information. If the direct link doesn't work, go to www.cdc.gov, then access the Lyme information through the index of health topics (a-z) on the home page.

2)Lymetruth , Website and newsletter for and by survivors of Lyme disease. Fairly supportive of the chronic theory.

3)Tick - Brittanica.com - basic background information

4)Tick Biology

5)Tick Removal Tools

6)Tick Research Laboratory, Fantastic visuals (even movies!) of ticks, mouthparts, etc. close up, based on work done by the "Tick Pickers of Rhode Island". Probably the biggest tick research institute I found.

7)Dissenting Docs - Medical Community at Odds Over Lyme Disease

8)Newsweek article about the Lyme debate

9)CDC vaccine recommendations

10)Immune system background, courtesy of Dr. Grobstein's outline

11)How doctor-patient relationships have been affected by drug ads

12)Site belonging to a chronic Lyme sufferer




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