The Lyme Twilight Zone

8 05 2012

Beth Marie Mole

 

by Beth Marie Mole

When my mom said she was headed to the doctor for a sore knee last month, I didn’t think much of it. I figured she probably just twisted it doing yard work or something. But, when she called back to say her swollen knee was Lyme arthritis, she had my attention. And I braced myself for the dizzying world we were about to walk into.

Lyme is one of those diseases you almost can’t mention in mixed company – unless you want to pick a fight. It exists in a world where patient advocate groups distrust the medical community; where advocate-backed legislation rather than clinical evidence defines treatment options; where seemingly ordinary doctors practice “alternative” medicine; and where a long standing disease has no settled diagnostics, treatment, or even definition.

Since scientists identified it in Lyme, Connecticut in 1975, it has become the most common tick-born disease in North America. Lyme disease is endemic to the Northeast and the Pacific coast, and it’s spreading. Disease ecologists consider it a high priority emerging infectious diseases.

Yet, nearly everything else about it is hotly contested.

An adult black leg tick (deer tick)
Public domain image

Last fall, in the medical journal The Lancet, a group of doctors equated people who believe in “chronic Lyme disease” to people who deny the existence of AIDS (1). On the other side, patient advocate groups, such as the Lyme Disease Association, disagree with standard medical guidance set by the Infectious Disease Society of America (IDSA), and endorsed by the Centers for Disease Control and Prevention. Many have pushed (successfully) for laws that protect patients and doctors who believe in chronic illness and don’t follow standard treatments.

To say the least, the divide is unfortunate, says Dr. Robert Lane, a leading tick-born disease expert and epidemiologist at UC Berkeley. “I think that both sides want to get to the truth,” he says.

Part of the controversy stems from Lyme disease’s vague start. Nymph ticks the size of poppy seeds or slightly larger adults can deliver the spiral bacteria, Borrelia burgdorferi, to skin, where they mount their attack. The result might be the famous bulls-eye rash. But, advocate groups claim that as little as 30 percent of infected people will have/see this rash. While doctors who side with CDC guidelines say as much as 80 percent will have/see it. My mom didn’t even notice a tick.

After that, things get fuzzier. Early Lyme disease symptoms include fatigue, headache, fever, and depression. If you miss those super obvious signs, the bacteria invade the body, and launch late stage disease. This can fire up months to years later as fatigue, joint pain (Lyme arthritis), mental fogginess, and sometimes even heart and liver problems. For some patients, it can be a slow road to a proper diagnosis, where relationships with doctors erode along the way.

It doesn’t help that many advocate groups believe that standard tests for Lyme—ELISAs and Western blots—are wildly inaccurate. An ELISA measures the bacteria’s presence indirectly, by detecting antibodies—your immune system’s response to the infection. Advocate groups claim that immune responses fluctuate, and are unreliable. Western blots, which also detect antibodies, may miss dormant infections, they also claim. Ultimately, advocacy groups—one of the most vocal is the California based LymeDisease.org—feel that Lyme disease is under-diagnosed. Some patients with similarly vague symptoms believe they have the disease without positive diagnostics.

Members of the IDSA, which is comprised of over 9000 physicians, scientists and health care professionals, acknowledge that no test is perfect and that the ELISA test may not be accurate in the first few weeks of infection (before your immune system mounts a response). But they point to clinical data validating its use for diagnosis (2, 3). ELISAs are also a common diagnostic tool for many other infections, including West Nile virus and HIV.

However it happens, once someone is diagnosed with Lyme, the IDSA recommends (4) two weeks of an oral antibiotic, such as doxycycline or ceftriaxone, for early disease. It’s a four-week course for late stage. When my mom got her diagnosis, she immediately went on a 28-day course of doxycycline and started feeling better. But a week after she finished, she felt run down and her headaches returned.

This is where things get crazy. The IDSA would say she may just have residual symptoms, and, at most, should try another four weeks of antibiotics. Patient advocate groups say she may need antibiotics for *six months to multiple years* and that her disease could be chronic.

In multiple double blind, randomized clinical trials, long-term antibiotic therapies did not improve symptoms or the rate of recovery (5,6,7).

A deer tick on a fingernail
Copyright Stuart Meek, Creative Commons License

When I contacted the California Department of Public Health for their opinion on chronic Lyme disease, they said they had no comment.

Some doctors who believe in chronic infection support unsafe “alternative” treatments such as injections of toxic dinitrophenol, which is banned in the U.S. Such doctors call themselves Lyme Literate MDs. LLMDs are difficult to separate from infectious disease specialists who treat Lyme disease within standard protocols. In fact, to identify a LLMD, you usually have to go through patient advocate group that will give you a referral after you sign up on their website. Moreover, many LLMDs have conflicts of interest with laboratories that produce alternative tests, or have sanctions by medical licensing boards, or been in trouble with federal agencies (8,9,10). In 2008, a Kansas state court found an LLMD guilty of killing a Lyme patient with bismuth injections (11).

“[The LLMDs] are very clandestine— for good reason,” says Dr. Paul Auwaerter, a Lyme disease specialist at Johns Hopkins and the lead author on The Lancet opinion piece. At his clinic, most of the patients that come in with a chronic Lyme disease diagnoses never even had Lyme disease. Rather, they were suffering from something else, he says.

In the Northeast, where over 90 percent of Lyme disease cases are diagnosed, less than 3 percent of doctors used chronic Lyme disease as a diagnosis.

Right now, my mom is waiting for her next appointment with an infectious disease doctor (not a LLMD, I checked). She may be in the 5 percent pool of patients that need another round of antibiotics, or may just get something to treat her symptoms. Either way, she’ll get some bug spray—from me—for the next time she does yard work.

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What zombie snails and teenage mutant frogs tell us about ecosystems

26 04 2012

Beth Marie Mole

by Beth Marie Mole

The first mutant frog the kids found probably seemed like a sad fluke. The poor Northern Leopard Frog had one normal hind leg and one frail, fleshless one. But, then the class, which was out on a nature walk in 1995, found another misshapen frog—this one with only one leg—then limped another, and another. Half of the frogs in the southern Minnesota pond were mutants.

The frogs got national news coverage after that and scientists added the pond to the list of mutant hotspots. It was a growing list amid dwindling amphibian populations. Reports of creepy croakers came in from all across the West and Midwest during the mid-90s, and speculation of the cause ranged from pesticides to UV radiation.

Spidey, the Pacific chorus frog (Pseudacris regilla) that has extra hind limbs due to infection with a trematode parasite (Ribeiroia ondatrae, left).
Photo courtesy of D. Herasimtschuk & P. Johnson

Despite the high profile, ecological mystery, it wasn’t until 2010 that I learned about the disfigured frogs. It was during my first visit to Mendocino county where I met Dan Preston, a disease ecology graduate student from the University of Colorado, Boulder, who was there studying the freaky frogs.

Back in Boulder—where he has an eight-legged Pacific Chorus frog named “Spidey”—he works with ecologist Pieter Johnson, who was one of the scientific detectives that solved the mystery.

A year after the Minnesota pond hit news stands, Johnson hopped to another hotspot for misshapen frogs, Santa Clara County, to study 30 ponds. He and his colleagues discovered that afflicted amphibians were always in ponds that also had snails, which happen to be the first host of a vicious parasite – a tiny, flatworm trematode in the genus Ribeiroia.

Flatworm eggs hatch in water and make their way inside certain freshwater snails, such as the Ramshorn snail. Then, they take over. They feed on the snail’s reproductive tract – castrating their victims – and turning them into parasite factories. A month or so later, the more mature worms abandon their zombie snail-homes and set their sites on fish or amphibians. When they invade frogs, the Ribeiroia trematodes settle in the hind limbs—a telltale location.

“I’ve seen some frogs with 20 or so “limb-like appendages” coming off the back end,” Preston says.

Back in the lab, Johnson and his colleagues found that tadpoles swimming in trematode-infested waters developed the same deformities seen in the ponds. But even now, nobody is sure exactly how the trematodes botch leg development.

“There are two lines of thought: that it causes a mechanical disturbance of cells around the limb bud leading to development problems, or that it secretes some type of chemical compound that triggers haywire cell development,” Preston says. “Personally, I think it’s more of a mechanical thing than a biochemical process.”

Regardless of the means, the resulting gimpy frogs probably help the trematodes complete their nefarious plot; the limping croakers are easy targets for predators like birds and mammals – the trematode’s final host. Inside, say a bird, the trematode happily spews eggs into the bird’s feces, which could land back near a pond for the cycle to start again.

A California red-legged frog with an extra hind foot. This species is listed on the
endangered species act. Photo courtesy of D. Preston

Although the mystery might be at rest, the plight of mutant amphibians has only raised more questions, such as “Is this new?” and, “Is it getting worse?” Though Johnson and his colleagues have pieced together historical records of unusual amphibians—some dating back 200 years— it’s tricky to say if amphibian malformations caused by tretmatodes are new. But from what they can tell, they do seem to be increasing.

The boom in buggered pond-life has led Johnson and Preston to start dissecting how the trematode is triumphant and what it might mean for the rest the pond and beyond. At Hopland, Preston was trying to understand how changes in snails matter. After all, they are the first host and their populations might increase with nutrient pollution from urban and agricultural runoff. When I met him in 2009, he had set up rows and rows of black, plastic mini-pools, the size of small bathtubs, in a field at University of California’s Hopland Research station. In each mock pond, he had different types of snail communities, some with just the snails that could become zombie, parasite-factories, and others that had a mix of snails, some resistant to the wicked worms.

He and Johnson just published the results in the journal Ecology, which show that if snail populations were whittled down to just the susceptible species—low biodiversity—the trematode was in welcoming waters. When they compared their results to 320 ponds around California with snail and trematode populations, they found that the snail communities in natural ponds mirrored those in the experiment, suggesting that snail diversity might be able to reduce amphibian deformities.

But snail populations aren’t the only link to leggy hoppers. Johnson and Preston are also looking into how sitting-duck frogs change the pond’s food web and colleagues are examining the impacts of global warming on trematode populations.

In the meantime, amphibian populations are still sinking and malformed frogs have bleak outlooks. Spidey, however, is doing just fine.





Buzzline: Community Scientist at Work

2 12 2011

Daniela Hernandez

 

 

 

By Daniela Hernandez (Twitter: @danielaphd)

Neuroscience, physics, biology and birds are recurring topics of my conversations with Dennis Taylor, the community conversations editor at The Salinas Californian, where I interned during fall quarter.

Western bluebird perched on bare branch. Photo Credit: Wikimedia Commons

Every time I speak with Dennis about anything remotely scientific, a look of genuine excitement and interest comes over him. During one of our chats, he told me about the work he does with the National Audubon Society as a citizen scientist in Gilroy, California.

Here is a brief Q&A about his work. It has been edited for clarity:

 

What inspired you to volunteer at the Audubon Society?

I have always stayed abreast of developments in threatened species – what are the pressures reducing their numbers? And overwhelmingly the greatest pressure is habitat loss. I stumbled into the Audubon Society because I wrote a story about an older gent who I would walk with as he would check “bird houses” constructed by the Audubon Society that were hung in trees or perched atop poles in open grasslands. Norm was his name, and what we were doing was providing habitat that was lost to sprawling home construction.  He had several miles of trails with over 100 houses he would need to check weekly. He died about a year after we began working together and Audubon came to me because no one knew the species and the trails like I did.

What kind of work have you done for them?

I begin in early spring by checking all the houses to get rid of roosting waste from the winter and make sure there are no wasp or yellow jacket nests built inside the houses. Then I walk and watch. Within a couple of weeks I begin to see mating flights, flirtatious mid-air dances. Within another week or two, I begin to see the birds carrying debris for their nests. (Different species use different materials for their nests; some use straw, others use twigs.)

When I don’t see the mother out flying, I carefully lift open a special door to the box and feel for eggs gently with one finger. I record the number of eggs in each of the 100 houses. After another week or two, there’s usually a furry head: the chicks. I compare the number of chicks hatched to the number of eggs and note the mortality rate. Then I walk and watch some more, and when I see little heads sticking out I know they are about to fledge, so I count the fledglings and compare that number with the number of chicks to see if there were additional deaths.

I collect that data onto a spreadsheet and transfer it to a database at Cornell University, which tracks bird populations all over the country. So when you read a story about “Western Bluebirds in Decline,” that’s how they know. The program used to be called the Bluebird Recovery Project, but about three years ago it was changed to the Cavity Nesting Project, to more accurately reflect what we do.

Western Bluebird Sialia. Photo Credit: Wikimedia Commons

We track all species of birds that must nest in hollows of trees. In my region this includes western bluebirds, tree swallows, chestnut-backed chickadees and white-breasted nuthatches. When you cut a tree to build a house in an oak forest, you eliminate habitat for these particular birds.

You mentioned you worked with kids. What do you teach them during the field trips?

My teaching is geared to the age of the children that come with me on a particular field trip. “Certain birds will only have babies in holes of trees,” for the youngest. Or, “The way certain species protect themselves is by entering a cavity in a tree that is only millimeters wider than they are, protecting them from larger predators like other birds, raccoons and even snakes,” for the older kids.

I take the kids on one of my shorter walks during which I usually pull down a house [so they can see the birds]. I usually wait until the chicks are about to fledge but can’t quite fly yet. This reduces the chance of injury to the fledglings [and the kids!]. I point out characteristics such as yellow bands that often appear on the inside of the beaks of the fledglings that help the moma bird zero in on the little mouths when they are dropping food such as insects.

Sometimes I will gently reach in the nest and pull out a fledgling and let the kids gently stroke its head. One time I was doing that, and as I was feeling down in the nest I found a dead chick. I need to remove dead chicks straight away because as they decompose it creates opportunistic bacterial infections for the other chicks whose immune system isn’t fully developed. So I hid dead chick back in my palm, covering it with a couple of fingers, while pulling the live one out with my thumb and index finger. [The kids] were never the wiser.

Western Bluebird using Nest Box. Brood unknown. Photo Credit: Wikimedia Commons

And then there was The Day of the Blue Jay. One nest had fledglings that could actually fly a little ways, to my surprise. Three bolted out of the nest and a cacophony of screams followed three skirting chestnut-backed chickadee fledglings down the path we were on. I caught one, and my assistant caught another. As I turned to go after the third, a blue blur whizzed by a few feet to my right, down the slope on the side of the trail. Of course I had 20 pairs of little eyes following the jay as he swooped down on the fledgling and … poof! …. Little brown feathers exploded into the air. Little heads slowly turned to me, mouths agape. “Well,” I said, “Blue jay chicks need to eat too.”

As the kids were walking back down the trail, my partner turns to me and says, “Blue jay chicks need to eat too? That’s the best line you could come up with?”  And we begin laughing. So I’m sure in the kids’ minds Mr. Birdman was not only a chickadee chick killer, he’s a sinister one that laughs about it.

Then of course I tell the kids that if we keep cutting down trees the babies you are looking at will have no place to live.

Why do you volunteer?

It’s cathartic for me. We tend to view biology in compartmentalized frames – birds in this sector, canines over there, and humans in this square. We don’t live in a vacuum, and the sooner we realize that the better off we and other living things will be. Author John Muir (and my grandmother, less eloquently) said “that when we try to pick anything out by itself, we find it hitched to everything else in the universe.”

[The work is] also immensely interesting. The longer I do it, the more science I learn – migratory patterns, food variables, acute avian viruses (because of West Nile I’ve taken to wearing masks and latex gloves when opening the houses, but I draw a smiley face on the mask – hey, it works for human babies), seasonal nesting variations, anomalies in any of these, and on and on.

Is there anything else you want to tell me?

Programs like this are critical to supplementing children’s science educations. With standardized testing, the lion’s share of effort is being spent on math and language arts. Sacrificed are the sciences and humanities. The broader science community needs to step up and help get children excited about science – no better place than in the field.

Follow Dennis Taylor (@scribedenny) on Twitter.

You can read more about his work in an article by the Gilroy Dispatch.

 





Thanksgiving Lemur Lessons

23 11 2011

Beth Marie Mole

 

By Beth Marie Mole

 

Did you remember to invite your relatives to Thanksgiving?

How about your extremely distant relatives?

Lemur Feast. Courtesy of the San Francisco Zoo

 

The folks at the San Francisco Zoo remembered. In fact, they laid out their fine china, cooked a colorful feast, and pulled up chairs for 15 distant relatives—the zoo’s lemurs.

In an event called ‘Feast for the Beasts,’ the zoo’s adorable primitive primates enjoyed a banner Thanksgiving banquet. The menu included green beans, fruit salad, sweet potatoes, and a faux turkey made from monkey chow. Guests drank from champagne glasses filled with apple juice and adorned with grapes. No word on whether they made a toast, though.

The party started in proper seats, according to zoo official Lora LaMarca. But the lively lemurs quickly threw the ‘elbow rule’ aside—along with general etiquette—as they hopped onto the table to enjoy their good eats.

Keep your tail off the table! A lemur enjoys some fruit while committing a feast faux pas. Photo courtesy of Susan Schafer

The Thanksgiving feast isn’t just a special treat for them, though; it’s also an exercise. Zookeepers wrapped some of the food in little boxes, providing a playful search that employs the foraging skills they would rely on in the wild.

The fifteen lemurs—6 ring-tailed, 4 red-ruffed, 3 black and white, and 2 black—live and monkey-around in the zoo’s lemur forest, which was founded in collaboration with the Madagascar Fauna Group. The group works on conservation efforts in the lemur’s homeland of Madagascar where they face deforestation, hunting, and illegal pet traders.

A red-ruffed lemur enjoying some juice. Photo courtesy of Susan Schafer

Madagascar, which is roughly the size of Texas, hosts 5% of the world’s plant and animal species.  There are approximately 100 species of lemurs there—depending on how you define species—and they’re all considered either endangered or threatened.

Madagascar is located off the eastern coast of Africa and is the world's fourth largest island. Photo by Beth Mole

But in San Francisco, the only thing they’re in danger of is having bad table manners.

Happy Thanksgiving!





Undead Science

28 10 2011

Beth Marie Mole

by Beth Marie Mole

Zooommbieeees…

Hordes of people—numbed by the Great Recession, perhaps—have once again staggered toward fresh zombie fare. But unlike other zombie fever outbreaks, splatters from the pop-culture feast are landing in the far corners of science—and they’re leaving quite the mark.

Zombie Science Invasion

From left to right, zombified Dustin Adams, Julia Kelly, and Stephanie Lukin invade UCSC's science hill.

Since George Romero’s 1968, genre-defining film, Night of the Living Dead, zombie zeal has lurched in and out of popularity.  Some link their recurring resurrections to the economy—zombie apocalypse as blue-collar strife?—others to their flexibility.

I side more with the latter.

A few years ago, a friend and I hosted a seven-week long zombie movie series, presenting a doubleheader each week. We started with Romero’s Living Dead series then ventured to the work of successors, including Sam Raimi and Dan O’Bannon, and humorous homage, such as Slither and Shaun of the Dead.

Our audience was mostly our science comrades from biology, ecology, spatial epidemiology, and sociology, and there was something for everyone.

The zombie skeleton supports a wide variety of meaty topics—as the plumpness of the genre demonstrates—allowing writers and directors to dissect complex social issues and our fear of unknowns.  But in the latest zombie outbreak, scientists are the ones biting. In fact, they’ve clamped on and welcomed shuffling zombies into narrow allies of science, including zombie parasitology, apocalypse preparation, disease ecology and zombie infection modeling, and zombified anesthesiology.

Then there’s Dr. Bradley Voytek, a cognitive neuroscientist at the University of California at San Francisco, and the leading zombie brain expert with the Zombie Research Society.

Using current understandings of the brain, advances in imaging, and a careful “examination” of zombie behavior, Voytek and his colleague, Dr. Timothy Verstynen at the University of Pittsburgh, diagnosed the undead with ‘Consciousness Deficit Hypoactivity Disorder’ and modeled how a zombie brain looks.

Crunching the numbers on zombie apocalypse modeling (Munz et al., 2009)

He defines CDHD by “ the loss of rational, voluntary, and conscious behavior replaced by delusional/impulsive aggression, stimulus-driven attention, and the inability to coordinate linguistic behavior.”

After Voytek presented their findings at this year’s Comic-Con and ZomBcon, I tracked him down to see if the undead are bringing life to scientific discussion (all the while denying my nerdy impulse to ask him what it’s like to sit next to Romero and his take on the heated question of fast zombies). It turns out zombies are spreading science.

At Comic-Con, Voytek sat on a panel with Max Brooks, author of The Zombie Survival Guide and World War Z, which is being made into a movie starring Brad Pitt.

“After our panel and during the Q&A session things got a little awkward; the majority of the questions weren’t directed at him, but rather were questions for me about the zombie brain. It was amazing,” Voytek says. “I had questions from students studying psychology and neuroscience, from a man who had suffered a stroke, a deaf gentleman, and so on. A group of us hung out and chatted about zombie movies and neuroscience for about 30 minutes after the panel.”

In his presentations, Voytek went through the seven classic symptoms of being undead and presented the neural explanation of each one.  For example, the most obvious symptom, reactive-impulsive aggression—that unrelenting desire to devour the living—is likely caused by abnormalities in the orbital frontal cortex, the lower part of the frontal lobe.  The orbital frontal cortex usually shuts down rage signals pumped out of by amygdala, a little almond shaped region in front of the orbital cortex.

In a case study of a man who had a steel rod go through his orbital frontal cortex, scientists found that without it you might switch from relaxing on the couch with some tea to savagely attacking someone in the garden.

“At its heart, the zombie genre is horrific. There are a lot of scary things in the world, and entertainment lets us encounter and confront our fears in a very safe way.”

Voytek and Verstynen developed explanations for the other six symptoms (loss of impulse control, motor deficits, language difficulties, attention problems, and memory loss), which Voytek chronicled this week in blogs. The final product is a comprehensive view of the zombie brain.

A normal brain compared to the brain of someone suffering with CDHD

While the zombie brain has the public salivating, Voytek has gotten cheers from other scientists for his zombie breakthroughs.  At zomBcon, members of the audience asked Voytek about the ‘herding’ behaviors of zombies in this season’s premier of The Walking Dead.  A professor of wildlife ecology approached him afterward to say he enjoyed seeing the public engaged in a scientific discussion.

“It’s funny to me that the best method I’ve found to engage the public in science is with something so fantastical and made up! I think it’s similar to how pulp sci-fi novels from the 1950s and 60s got so many people interested in the space sciences in the 60s and 70s,” he says.

Whether it’s the horror, exploring the unknown, or the economy, the zombification of science is drawing people in.

“The wonder and imagination is what draws people to science,” Voytek says. “The joy of discovery is what keeps them there.

Join us…