This past Friday, Dr. Nevena Zubcevik, attending physician at Harvard Medical School and co-director of Dean Center for Tick Borne Illness at Spaulding Rehabilitation Hospital in Charlestown (SRH) traveled to one of the nation’s front lines in the public health battle against Lyme disease to speak to a group of Martha’s Vineyard Hospital physicians. “I wanted to do this presentation by Skype because of all the ticks you have here,” she joked.
Dr. Zubcevik was at Martha’s Vineyard Hospital (MVH) to speak at grand rounds, a weekly meeting of clinicians, which on this day was open to the public, resulting in an overflow crowd at the Community Room just off the hospital lobby.
Over the course of the hour, she shared the most recent findings that she and her colleagues have made on the diagnosis and treatment of Lyme disease, in particular on the 10 to 15 percent of patients who suffer long-term symptoms, defined by Centers for Disease Control (CDC) as post-treatment Lyme disease syndrome (PTLDS). She discussed the protean nature of tick-borne diseases, the importance of public awareness, and the urgent need for the medical community to step up its game.
“Graduating medical students and doctors really aren’t educated about the gravity of this epidemic,” she said. “There’s a gap there that needs to be filled. We’re all responsible to educate our young doctors about what this entails.”
Dr. Zubcevic said the recent revelation that actor, singer, and songwriter Kris Kristofferson was cured of dementia once he was properly diagnosed with Lyme disease should be a lesson for medical professionals on how pervasive the disease is, and how often it is overlooked.
“Sudden-onset dementia should really be a red flag for Lyme [disease], especially in people with compromised immune systems,” she said.
“Everyone over 50 has a compromised immune system.”
Dr. Zubcevik said that doctors and parents should know that Lyme presents differently in children than it does in adults. “71 percent of the time, headache is the most common symptom in children,” she said. “Mood disturbance, fatigue, and irritability are also frequent symptoms in children. If they are acting out in school all of a sudden, get them tested.”
Dr. Zubcevik cited a particularly compelling example of undiagnosed Lyme disease where a 29-year-old male had been institutionalized four times for schizophrenia. After a series of tests, and in concert with a psychiatrist, Dr. Zubcevik began a course of daily antibiotics on him. “The first month he could remember what he had for breakfast,” she said. “The second month he could read a chapter of a book, and after six months he was back to normal. He could tolerate light and sound again, which he couldn’t before.”
Tick truths challenged
Dr. Zubcevik said recent research debunks several commonly held beliefs about the transmission and treatment of tick-borne diseases.
“The conception that the tick has to be attached for 48 hours to inject the bacteria is completely outdated,” she said. “There are studies that show that an attachment of 15 minutes can give you anaplasmosis,10 minutes for the Powassan virus, and for the different strains of Borrelia burgdorferi, we have no idea.”
Dr. Zubcevic said the notion that children, infants, or pregnant women should not be given doxycycline is also outdated. “Dermatologists have prescribed doxycycline to kids for years to treat acne; why not for such a debilitating disease?”
She also said the two-day course of doxycycline, often prescribed for people who find a tick embedded on their body, has little or no prophylactic value. “It should be 100 to 200 milligrams of doxycycline twice a day for 20 days, regardless of the time of engorgement,” she said. “It is not a two-day thing.”
The blood tests currently used to detect the presence of the Borrelia burgdorferi bacterium are the enzyme-linked immunosorbent assay (ELISA) and the Western blot test.
Dr. Zubcevik said research has shown there are 10 different strains of Lyme disease in the United States, and many of them do not test positive on the traditional Western blot or ELISA tests. In a previous email to The Times, she wrote that with current testing, 69 out of 100 patients who have Lyme disease may go untreated.
“The bull’s-eye rash only happens 20 percent of the time,” she said. “It can often look like a spider bite or a bruise. If you get a bull’s-eye it’s like winning the lottery. Borrelia miyamotoi, which we have a lot in Massachusetts, will not test positive on either test. That’s a huge problem, so the CDC is moving toward a different kind of test.”
Borrelia miyamotoi also has the potential to spread rapidly, since it’s transmitted directly from mother to offspring. Nymphal deer ticks need to feed on a mammal, most likely the white-footed mouse, to contract the virulent Borrelia burgdorferi bacterium.
In addition to Lyme disease, Islanders are also vulnerable to coinfections such as babesiosis, anaplasmosis, ehrlichiosis, and tularemia, which can also go undetected. “Babesiosis is a malaria-like disease that can persist for months or even years,” she said. “Patients who can’t catch their breath are a red flag for babesiosis.”
Dr. Zubcevik described deer tick nymphs as “the perfect vector” because of their diminutive size — the size of the “D” on a dime — and because of the analgesic in their saliva that often makes their bite almost undetectable.
The bacteria they inject are equally crafty.
“Borrelia burgdorferi is an amazing organism; I have a lot of respect for it,” she said. “It is a spirochete, meaning it can corkscrew into tissue as well as travel in the bloodstream. It can do whatever it wants. It’s twice the speed of a [white blood cell], which is our fastest cell. It’s so strong it can swim against the flow of the bloodstream.”
Dr. Zubcevik said there are videos that show a white blood cell pursuing a spirochete, which evades capture by drilling into tissue.
“It’s really easy to see why this adaptive bug can avoid the immune system,” she said.
Dr. Zubcevik said doxycycline stops the bacteria from replicating, but it doesn’t kill them. The rest is up to the body’s immune system, which is the reason some people suffer for so long.
“There’s a lot of neurotoxicity, which is why people feel so bad all over. It’s like a toxic warfare going on inside the patient’s body.”
Last week, Governor Charlie Baker rejected the legislature’s controversial budget amendment that would have required insurance companies to cover the cost of long-term antibiotic treatment which chronic Lyme Disease (CLD) advocates maintain is the most effective treatment for their symptoms. The Massachusetts Infectious Disease Society, representing more than 500 infectious disease specialists, does not recognize CLD, and urged the governor to reject the amendment, asserting that long-term intravenous antibiotic therapy can be dangerous and possibly lead to “superbugs” that are immune to current treatments.
The CDC also does not recognize CLD or the use of long-term antibiotics for PTLDS. “Regardless of the cause of PTLDS, studies have not shown that patients who received prolonged courses of antibiotics do better in the long run than patients treated with placebo,” the CDC website states. “Furthermore, long-term antibiotic treatment for Lyme disease has been associated with serious complications.”
However, the website also says, “Recent animal studies have given rise to questions that require further research.”
Dr. Zubcevik diagnoses the condition with a different name — “persistent symptoms related to Lyme disease.”
“I’m new to this field,” she said. “For me there’s no controversy. We have to innovate, we have to find solutions. [SRH] has connected with top scientists from all around the country. Studies show that after treatment in mice, dogs, and monkeys, Borrelia burgdorferi bacteria are still there. This has also been shown in human tests.”
Citing the work of Dr. Ying Zhang at Johns Hopkins Lyme Center, she said the most likely effective remedy will be a combination of several antibiotics. In a previous interview with The Times, Dr. Zhang said he has worked on an effective PTLDS treatment for six years, and that current Lyme disease treatments may not clear bacterial debris, or “persisters,” which may be one of the possible causes of PTLDS. Dr. Zhang said that his work on tuberculosis (TB) is his primary focus; however, advances in fighting TB, e.g. using new combinations of drugs already approved by the Food and Drug Administration (FDA), have yielded promising results in the fight against “persisters.”
“There’s also a need to develop a more sensitive test,” he said.
Although she started out at Spaulding Rehabilitation Hospital focusing on the neuropathy of concussions, Dr. Zubcevik branched out into treating people with Lyme disease in part because both maladies can cause similar cognitive impairment. “I heard Lyme disease patients say they can’t remember what they had for breakfast, or they get lost driving home,” she said. “It sounded the same as concussion symptoms, so we started doing PET scans.”
Positron emission tomography, or PET scan, is an imaging test that uses a radioactive substance that shows brain functioning. Dr. Zubcevik said PET scan of a patient with persistent Lyme disease symptoms showed a brain colored in blue and purple hues, where a healthy brain presented with shades of yellow and green. She showed an image of the patient’s brain after six months of intravenous antibiotics, which was dominated by shades of yellow and green.
Dr. Zubcevik told the hospital gathering that many patients she sees have been suffering the physical, mental, and emotional effects of the disease for so long, they have lost the will to live. “I literally have patients who were just done,” she said. “They couldn’t go on. The first thing I do is validate their experience, and tell them, ‘I believe you.’ Sometimes they start crying because somebody finally listened. Some patients show symptoms of post-traumatic stress disorder because they’ve been ignored for so long. Marriages dissolve all the time because one spouse thinks the other is being lazy. Many chronically ill patients end up alone.”
Treatment at SRH borrows from many different disciplines. In addition to medication, it can include nutrition counseling, physical therapy, occupational therapy, speech language therapy, mental health counseling, and referrals to infectious disease and other specialists as necessary.
Dr. Zubcevik said that the program was initially funded by a donation from a patient who was treated shortly after the clinic opened. “We’re always looking for more funding,” she said.
The current wait list at Spaulding is about four months.
Prevention, prevention, prevention
“Once patients are doing better, I will call harass them on the weekend to check if they are taking the proper precautions,” Dr. Zubcevik said. “Are they using repellant? Are they doing daily checks? Are they treating their dogs? I don’t want to do another PICC line [intravenous drug access] or PET scan.”
Dr. Zubcevik also said many people need to know proper tick removal — using tweezers to grab the head of the tick, not at the body.
“Don’t don’t squeeze the belly of the tick, it will inject the bacteria into your bloodstream. Do not use oils; it can make the tick vomit the bacteria into the bloodstream. If the tick is deeply embedded, go to the doctor.”