For decades now, patients, parents, clinicians and researchers have come face to face with the shortcomings in our healthcare system in relation to Lyme disease and the co-infections of Lyme. CanLyme president Janet Sperling is no exception; Janet and her husband Felix, both entomologists and researchers, faced one roadblock after another when their son became ill with what was eventually found to be Lyme disease and co-infections of Lyme. Janet and Felix chronicled their experience and wrote a chapter for the book Ending Denial: The Lyme Disease Epidemic: A Canadian Public Health Disaster.
In this moving and revealing account (below), Janet and Felix convey some of the struggles, frustrations and successes they encountered as they worked tirelessly to overcome the obstacles that many people with these diseases encounter within our healthcare system. They are clear to acknowledge the role that their knowledge base and support system played, and point out that many others face these hurdles in addition to the obstacles they encounter within the healthcare system and with the disease itself.
Testing, diagnosis and treatment
Janet and Felix outline some of the limitations with current testing protocols, including failure of the tests to include many strains of the Lyme bacteria. They also point out that the accuracy of these tests is evaluated in a way that fails to capture all expressions of the disease. In addition to the limitations in testing, their experiences reveal the limitations of the standard IDSA treatment protocol and the limiting nature of an under investigated psychiatric diagnosis. They illustrate the importance of embracing a differential diagnosis of Lyme disease, making a clinical diagnosis and fully treating the disease, and gaining a broader understanding of where Lyme disease can be acquired, both in Canada and internationally.
Advocating for change; supporting research
As a result of the struggles Janet and Felix encountered while pursuing proper diagnosis and effective treatment for their son, Janet has become a fierce advocate for change. As President of the Canadian Lyme Disease Foundation, and through her own research, Janet continues to support research and education, creating positive change and fostering hope for a better future for people living with Lyme disease.
Ending Denial: The Lyme Disease Epidemic: A Canadian Public Health Disaster can also be found at various libraries and used book stores, both online and in person.
Ferrie, H. (2010). Ending Denial: The Lyme Disease Epidemic: A Canadian Public Health Disaster. Caledon, On, Canada: KOS Publishing Inc.
CHAPTER 3: LYME DISEASE CAN BE A DIAGNOSIS OF HOPE
By Felix Sperling PhD and
Janet Sperling MSc, Edmonton, Alberta
Identifiers have been removed from this digital version to protect the subject’s privacy.
Lyme disease, or Lyme borrelioses as we prefer to call it, is a devilishly complicated disease. It has challenged many of our most firmly held preconceptions and turned our personal world upside down. In the darkest stages of E’s story, the most honorable players have been psychiatrists, administrators, lawyers, and politicians— professions that we had previously viewed with suspicion. Our respect for the power of clinical diagnoses has multiplied in spite of their inherent subjectivity, while our regard for the kind of evidence-based medical diagnoses that focus on machine readouts has diminished in spite of their apparent objectivity. But our son’s story has had a happy ending that underscores the power of reason and persistence. The story has unfolded in four phases. First came our frantic search for answers, with dread clutching more tightly with every strange new development in our son’s condition. Then came the growing realization that both the answer and a relatively simple solution lay in plain view, but the struggle to get E’s primary physicians to see it that way would become a willful confrontation. This was followed by our son’s slow, unsteady recovery, which continued to test everyone’s resolve. Finally we entered a period in which E has moved on with his life but we as his parents have become increasingly more determined that no other Lyme sufferers should have to deal with a systemic failure that reflects as much about our medical system as it does about a bacterial assault on a Lyme patient. In the end this is not a narrative about one patient, one family, or one medical group, but about a deep, unresolved conflict at multiple biological and social levels.
July 2005: Desperately seeking answers
The following is a lightly edited version of a description of E’s symptoms that we wrote in late July 2005. We had hit a wall of intransigence and incomprehension among his doctors. As a desperate measure we sent this description to several colleagues and contacts that we hoped might be able to point us in a positive direction. Our audience was expected to be familiar with a variety of medical terms that might be obscure to more general readers.
E is a bright, personable youth with a delightful, gentle sense of humor. He retains that sense of humor in spite of his increasingly depressing circumstances. Currently 110 pounds and 5 feet 4 inches, he could be described as having a slight build. A year ago he would have seemed a bit chubby, with strong bones but short. He has always been exceptionally intelligent and energetic, and has read voraciously across a wide range of topics. He has ranked nationally in various math contests in recent years, and has easily maintained high grades in all his classes. He has an infectious enthusiasm for science and engineering, which is encouraged by numerous academics and engineers in his extended family and neighborhood in Edmonton, Alberta. His physical activities have included moderate levels of cross country skiing and sailing, and he has consistently been a strong walker. He is the oldest of four boys (the youngest being 3 years old) in a stable family. Born one month premature, he has remained relatively small for his age but he has been healthy except for moderate asthma and a transient allergy to milk.
E’s present alarming medical condition apparently started with a persistent but otherwise innocuous flu-like illness in late November 2004. His most noticeable symptoms were low energy levels and moderate congestion, periods of low fever and serious headache, a declining appetite, and eventually an apparent sinus infection. He had a period of dry, cracked lips in mid December. He seemed to be recovering later in December, and had no problem continuing with school until the winter holiday started on December 20th. In late November he weighed 135 lbs, a weight he had maintained through the previous year even though he grew almost 8 centimeters and become noticeably slimmer during this time.
E’s first neurological symptoms were exhibited on the evening of December 25th, when we noticed that he was pacing around the house restlessly but pausing frequently to check the time on different clocks around the house. His explanation was that he kept losing track of time. This phase stopped after a couple of hours, after which he went back to sitting quietly on a sofa, which he had been doing more frequently during the preceding weeks. He had stopped eating and drinking freely a few days before this, needing to be prompted to finish his meals, and had commented on his mouth filling up with mucous at the same time, which we attributed to draining sinuses. E had previously been eating and drinking with gusto. He had been learning to cook, had no aversion to any foods and had an omnivorous diet, including occasional wild game in his early years.
December 26th was less eventful, though E remained lethargic. We took him to our regular health clinic on the first day it was open, December 27th, and the GP prescribed Biaxin antibiotic for what he considered to be a “terrible sinus infection.”
A return visit on December 30th showed significant improvement, and we left that afternoon to visit E’s grandparents four hours drive away, near Calgary. On December 31st, after a modest amount of physical activity outside in snowy but dry conditions, he began to feel nauseous and went inside, but after an hour he began to vomit. This continued until he was taken to emergency at a Calgary hospital three hours later, where he was rapidly diagnosed with a small pneumothorax (presumably due to the vomiting). Most alarmingly, he had blood sodium levels of 166 mmol/L, though his potassium levels were in the normal range. He was transferred to Alberta Children’s Hospital in Calgary for a week, with his sodium levels being gradually brought down to normal levels by the end of the week. No underlying cause was found for his electrolyte imbalance. He was admitted at about 100 lbs, but climbed to nearer 110 within a few days. He received three days of IV antibiotics. Near the end of this week, he began to show a slight twisting motion of his head when he tried to read; he did not ever read books on his own even though reading had previously been his favorite pastime. His discharge summary was that he had idiopathic hypernatraemia (unexplained unusual blood salt concentrations). When E returned to Edmonton upon his release from hospital in Calgary on January 7th, his most noticeable symptom was fatigue, though he also had prominent, contracted neck muscles. He continued to have strong but intermittent headaches. He returned to school three days later, in response to medical advice that it was best to get him back into a stimulating environment. By the end of the week, however, it became clear that his ability to read and focus was continuing to decline. He was able to read very slowly, with continuous prompting, and invariably showed some twisting of his head at the same time. He described the problem as getting stuck on words, which was helped by using head motions to force his eyes to move forward on the line. He was admitted to the local children’s research hospital in Edmonton on January 14th. Neurological examination resulted in a diagnosis that he was suffering either from conversion syndrome (a controversial, purely psychological condition in which mental trauma is expressed physiologically) or from an autoimmune reaction, such as PANDAS, though no sign of a strep infection was later found. Consequently, he was given intravenous immunoglobulin, but almost immediately his blood pressure plummeted to 60/38. He hovered near that level for several hours even though the IVIG injection was stopped soon after his blood pressure initially declined. During this physiological crisis, we as E’s parents were each, separately and sternly reprimanded by a resident for apparently creating his condition by being overanxious. The next day E was put on IV steroids for three days. He remained profoundly lethargic for most of that period.
During E’s second hospital visit, we discovered that he had serious problems in doing any visual puzzles, and he appeared to have virtually no ability to read silently to himself. However when he was asked to read out loud he was able to do so fluently for multiple pages, though he eventually had to stop because of fatigue. He was released on January 19th. His discharge summary from hospital in Edmonton stated he had obsessive compulsive disorder and possible Tourette’s. However, two visits to a psychiatrist shortly after his release produced a strong statement that his condition was not due to OCD or any other psychiatric illness.
E remained at home in the care of his mother and did not return to school during the ensuing 4 weeks. His ability to read seemed to decline through February to the point where he found it painfully difficult and exhausting to read out loud to the end of a paragraph. He read out several words at one time, and these were interspersed by a minute or so of circular motions with his hand (a motion that replaced his earlier head twisting). In early February, he took a battery of cognitive tests from a clinical psychologist, which showed that he had high intelligence but seriously diminished processing speed and ability to perform sequential operations. Throughout January and February, he experienced numerous periods of low blood pressure and low peripheral body temperature. However he was able to go on short walks (less than 1 km) and showed no balance problems even when walking in icy conditions. He needed to be spoon fed some of the time, but could dress himself slowly and go to the bathroom independently. He was kept stimulated by listening to the radio or books on tape, by regular visits with his grandparents at the end of the street, and by the normal household disruptions caused by his siblings. Throughout this period, E kept optimistically estimating that he would be largely recovered in about two weeks, which was in keeping with his generally positive and persistent nature.
Beginning in early March, his condition seemed to improve slightly. On the advice of doctors, he returned to school for one class per day, though he still had serious problems reading even a paragraph. On even days he attended a help session for a distance learning class in Social Studies. His lessons were read to him by a sympathetic teacher’s aide and he was encouraged to read small sections for himself. On odd days he sat in on a lecture or discussion in the same Social Studies class that he would have taken with his original class cohort. Other students seemed to be uniformly sympathetic and supportive. During this period we discovered that he was able to write things out by hand fairly well, as long as he did not read what he was writing. We started to go on longer walks of 2–4 km every 2 or 3 days, during which E seemed to be sure footed, showed stamina (albeit with an oddly rapid pace at the start of each walk), and took pride in keeping ahead of his father. However, he remained completely indecisive whenever asked what direction he wanted to walk, and got lost easily.
In order to provide support as well as to respond to apparent pigeon-holing as OCD by hospital staff, E began visits with a private psychologist in early April. Visits continued on a monthly basis, after an initial 2 week interval. The psychologist was supportive, and unambiguously stated from the beginning that the underlying problem was neurological, not psychiatric.
In early April, E was able to compose short but lucid and grammatically correct essays of up to a page in length for his school work. At this time, all his symptoms started to improve more rapidly and in parallel. On about April 11th, he started to eat entire meals with only minor prompting at the start of the meal, instead of needing to be prompted for every mouthful. He also would usually go to the bathroom, or put on his clothes, and return without getting stalled. He no longer seemed to accumulate as much saliva in his mouth. By Friday April 22nd he seemed to have made a 70% recovery (estimate of parents) of his previously high energy levels, academic performance, and good humor.
On April 23rd, E was woken up complaining of fatigue and mental fogginess. Overnight, he had apparently reverted to the condition he had in February. There was no evident change in diet or stress levels. He seemed to have caught a cold virus, which some of his other siblings also came down with at that time, though his cold symptoms did not seem particularly pronounced. On the next Monday, his ability to read and to interact with his teacher’s aide was also obviously greatly diminished. In the following weeks, his abilities continued to decline, which he found to be profoundly disheartening. He continued to be able to walk strongly during this period but, ominously, he started to occasionally exhibit sudden, transient halts in mid stride. When questioned about it, he had no explanation.
He was buoyed up briefly during May 16–19, during a previously scheduled period of day admission to the university hospital in order to facilitate his examination by a series of specialists in multiple medical disciplines. For one day in this time, he was able to partially feed himself without assistance. Nonetheless, in spite of an MRI, EEG, and examination by endocrinologists, neurologists, and specialists in infectious diseases and metabolic diseases, all tests returned results fully within the normal scale. One endocrinologist insisted that psychiatric problems were the most likely explanation, and the final discharge, by a neurologist, provided no summary statement or recommendations. E was particularly exhausted and demoralized when he returned home after the last day.
In late May, E lost the ability to open his school locker before going to class, even though he had had few difficulties with this task for the previous two months. Earlier in May, he started to consistently get disoriented as to what day it was and where to go in his school. This culminated with him getting caught up outside his locker on May 27th, unable to go forward or backward or even aware of the problem, while his teacher’s aide waited upstairs for him for 80 minutes and eventually hundreds of students streamed by him in the hall during the break.
Now at the end of July, E still has periods of substantial declines in blood pressure and peripheral body temperature. These seem to have no clear correlation with any triggering conditions, although onset commonly occurs after he eats a meal. These symptoms appear to have declined over time, though it is hard to tell whether the improvement, compared to February, is due to substantially warmer summer weather conditions. Early in his illness, he had a strong mottled red flush on his cheeks, particularly back toward his ears but not below the eyes. This has declined gradually but remains noticeable.
Throughout his illness, E has remained verbally articulate, with no slurring of words, or syntax problems. He has some difficulty in finding words and his speech has slowed. Moreover he speaks only when spoken to, and most responses are monosyllabic, though he has no problem with complex answers or logically well formulated responses when there is strong stimulation. From the beginning, he has expressed a strong aversion to eating or drinking, and says that he has no hunger at all. Apparently food has no appeal even when he has not eaten for extended periods, even though he claims that he has no problem in tasting differences.
He has been enrolled since early June in Pilates exercises and piano once per week. He seems to be learning chords well in the piano lessons though he tires rapidly. He continues to be competent in ping pong, with an instinctively fast reaction time, but cannot keep track of the score. Since late March, he has also visited once per week with an older friend who is a demonstrator in physics, while teaching labs are being set up. E’s enthusiasm for this meeting has always been high, which is not surprising because this is the kind of thing in which he has taken the greatest pleasure ever since he was very young. However, he became much more passive in May and may be showing a slowly declining ability to keep up conceptually. His walks with family members became impractical in early June, when the frequency of his halt-walking increased to the point where it was happening every few steps. He has recently started to twist his head or upper body from side to side when he is standing for extended periods of time. He sometimes fidgets and taps his feet repetitively when he is left alone, although this is of less concern because he commonly did that before his illness.
In the year prior to E’s health problems, he spent the first 8 months of 2004 in Canberra, Australia, with several weeks camping in numerous locations ranging from South Australia to Queensland. The only health issues noticed during this period were recurring sinus inflammation. Throughout his life, E spent a moderate amount of recreational time outdoors with his family, including Alberta (western Canada) during 1999-2004, California during 1994–1999, and Ontario or upstate New York during 1989-1994.
During the past 7 months, E had been examined by more than 30 medical specialists, mainly at the local university children’s hospital. He has not been on any medication since his hospital stays in January, other than antibiotics for another sinus infection in February. Apparently his endocrine levels are normal, and he shows no signs of an elevated immune response. He had MRIs in January and May, and an EEG in May, which were deemed normal. He tested negative for Huntington’s Disease, and did not have elevated copper levels (Wilson’s disease). We are unclear what tests for pathogens have been performed; and the response to our repeated questions about the possibility of Lyme Disease or Western Equine Encephalitis was that the timing and nature of E’s symptoms made these exceedingly unlikely. Prions (nvCJD) were considered a possibility, but no tests were performed and permission was never granted by the hospital for a tonsilar biopsy because of unspecified ethics concerns. One complicating factor in E’s condition is that he is at his most alert when he is meeting people for the first time, such as at a medical examination, whereas he soon thereafter seems more exhausted and unresponsive than ever. However, by this time his condition is not visible to medical personnel.
No consensus has emerged, either for a diagnosis or a treatment plan. Medical opinions have varied from E’s condition being primarily psychiatric (conversion syndrome, or obsessive compulsive disorder), an autoimmune reaction (PANDAS, ADEM, or Sydenham’s Chorea), an unspecified mitochondrial metabolic disorder, or post-infection damage to the basal ganglia. Each opinion has had at least one other conflicting opinion, and it is notable that a psychiatrist and psychologist each expressed strong opinions that E’s condition was primarily neurological and not psychiatric, whereas most neurologists have favored psychiatric diagnoses while others have reserved their opinions.
We are desperate to find something that might reverse our son’s decline. Our wonderfully bright, considerate, and courageous boy is slipping away as his medical care goes around in circles. Is there a chance that his condition can be reversed, such as by treating a previously undetected pathogen with antibiotics? If we put him on a round of L-dopamine, as suggested by one doctor as an “exploratory” measure, would we be putting him on a one-way conveyor belt with a Russian roulette ending (as implied by Oliver Sacks’ book Awakenings)?
Does anyone have ideas on how we can possibly help our son—please!?
December 2005: Increasing conflict while time runs out. In response to our plea for diagnostic advice at the end of July 2005, friends and colleagues kept presenting Lyme disease as a possibility. When we started to pay more attention to this idea during the fall we were perplexed by the depth of resistance to it. We had been trained as researchers, albeit as entomologists who were more interested in the physiological and genetic diversity of insects than with humans. The following is how we perceived the situation when we provided a description of our son’s case to a prominent law professor who was a leading scholar in the area of health law. By December 2005, E’s condition had reached its lowest point, and our frustrations had peaked. We were desperately worried that we would lose our son, and we could not accept the consistently dismissive responses by medical specialists with whom we were trying to discuss E’s condition.
Over the year prior to December, E’s health had deteriorated to the point where he was in a zombie-like state and needed continuous assistance to perform even the most simple actions. Throughout this time, we had been dealing with doctors at the local children’s hospital who seemed to have decided in the first week that his illness was either psychiatric or completely out of their realm and not worth treating. Meanwhile, we gathered supporting evidence that he had Lyme disease, and we tried desperately to get doctors to take this diagnosis seriously. We remained open to alternate diagnoses; however continued inaction was not an option while our son’s condition continued to deteriorate. We were now seeking to either ensure appropriate treatment locally or to get access to sympathetic and knowledgeable medical treatment outside of Alberta.
E was now 16 years old and prior to this illness he had rarely had any kind of health problem. He had always been very bright and mentally stable. When he first got sick with a serious sinus infection late in 2004, it seemed quite unremarkable for him to be treated with antibiotics by our family doctor. After his physiological crisis with low sodium, we had returned to Edmonton with instructions to see a particular pediatrician at the local children’s hospital within a week if we had any further concerns. We phoned this doctor repeatedly because we feared potential brain damage since E couldn’t read without moving his head. He had strange writhing and jerking movements and was drooling. But we were told by the pediatrician to go to the nearest shopping mall to see an optometrist. As surprising as this response was, it became clear over the following months that it indicated a widespread attitude by the doctors at this hospital.
Eventually (January 14, 2005) we were able to see a different doctor, who admitted E for investigation. When he suffered a drastic drop in his blood pressure after being given intravenous immunoglobulin, he was given steroids to depress his immune system. At discharge, E was diagnosed as having an unspecified tic disorder (a reference to nervous tics, not arthropod ticks) by a specialist trained in infectious diseases and another trained in neurology. A week later, a psychiatrist disagreed strongly with this diagnosis and sent us back for further investigation. Another neurologist then diagnosed conversion syndrome and sent E back to the psychiatrist who again disagreed. For the next 6 months E was batted back and forth between the physiological and mental health doctors. During this time we asked a private psychologist to examine E, and he was emphatic that E was suffering from a neurological rather than a psychiatric condition.
During February, E was given oral antibiotics for three weeks to treat an apparent resumption of his serious sinus problems. This was the only medical treatment that any doctors would give him between mid January and November 2005. During late March and throughout the month of April, E’s condition slowly improved to the point where he was able to read laboriously and to feed himself. However in the last few days of April his condition declined precipitously again over a period of just a few days and then gradually worsened so that in a few weeks he was as bad as he had been in late January. E was examined again by a series of doctors at the local children’s hospital in mid May, but was discharged without a treatment plan and with only a vague diagnosis of neurological degeneration. No doctors seemed willing or able to help, though there was no shortage of opinions that implied that the situation was either psychological (E or his parents) or too mysterious to fathom. To our horror, more than one doctor suggested that the mystery would be cleared up upon autopsy.
After seven months of getting passed from one doctor to another, with numerous contradicting opinions, the original psychiatrist admitted E to another hospital for three weeks in August in order to more definitively evaluate potential psychiatric diagnoses. At the end of this period, he stated that he did not believe that E’s medical problems were psychiatric in origin.
Throughout E’s illness, we repeatedly asked his doctors whether it might be possible that he had an infectious disease like West Nile Virus, Western Equine Encephalitis, and especially Lyme disease. We were repeatedly told that it was not worth following up on those potential diagnoses, even though we had just returned from eight months in Australia, and had also lived in areas like California where we had removed potentially infected ticks from E when we were camping. Eventually, we became more insistent that Lyme disease should be taken more seriously. It became clear that all the doctors at the local children’s hospital were part of a camp that believes that Lyme disease does not exist in Alberta or perhaps even Canada. We were also told that he must have contracted his illness in Alberta since there had been too long a period between a possible exposure to Lyme or any other diseases outside of Alberta and the time that E fell ill.
Nonetheless, we insisted that the possibility should be considered, and E saw a specialist in infectious diseases at the local children’s hospital on August 30th. She stated that she was willing to request an ELISA and Western Blot for Lyme disease although she was certain that this was not Lyme disease. We did not receive any further communication from her until November 3.
Eventually, a pediatrician at a third hospital checked the Western Blots on the computer system and discovered that they were negative. Knowing that the Lyme ELISA is notoriously inaccurate, we flew to Victoria, B.C., on October 22 to meet with Dr. Murakami, who had treated many cases of Lyme disease. He believed that E had Lyme disease based on his clinical experience. He ordered tests for co-infections with Lyme disease and was surprised to receive a phone call a few days later from the Alberta provincial lab saying that the Babesia test (a co-infection) was suspicious. We then received a phone call from the infectious diseases doctor to discuss E’s case, since she had heard from a colleague who was also one of our neighbors that we had taken E to Dr. Murakami. She said her receptionist had been asked to book a follow up appointment but had not gotten around to it. Her opinion was that Babesia only caused a mild and self limiting disease and there was no evidence of anything else, after which our discussion over the phone deteriorated. On November 8th, one day after our frustrating conversation with this infectious diseases doctor, we got a requisition from a sympathetic family doctor for blood to be drawn from E. We had it sent at our own expense to a highly rated lab, IGeneX, which tests for Lyme and associated diseases in California.
After it became clear that the specialist in infectious diseases who had seen him on August 30th would not grant E another appointment, a different infectious diseases doctor agreed to see E on November 14th, The second ID specialist reluctantly allowed a trial of doxycycline with the comment that it was equivalent to giving a teenager antibiotics for acne. She stated that she was sure that E’s condition was not Lyme disease, even though we cited research studies that had found low doxycycline doses to be ineffective for treating chronic Lyme disease (which E’s condition would have become due to the lack of treatment for at least a year). We agreed to this treatment because we hoped that it would at least halt his continued deterioration.
Four days after starting doxycycline in mid November, E became very ill and suffered extremely low blood pressure much like he experienced in late December and early January. Although it was quite worrisome, this condition was nonetheless consistent with a reaction known to be typical in antibiotic treatment of Lyme borrelioses, called a Jarisch-Herxheimer reaction, which is considered by many Lyme-literate doctors to be strong evidence for the existence of Lyme disease. When we told the doctor about E’s reaction to the doxycycline, she did not consider it to be medically significant, implying that she was dubious that Herxheimer reactions even occur in Lyme disease.
On November 29th we found that IGeneX had returned to our family physician a positive Lyme disease result for IgM on a Western Blot and a borderline positive on the IgG component. However, a second Babesia test that was ordered in Alberta by the ID specialist was delayed many weeks and came back as negative.
Consequently, by December we believed that E suffered from a Borrelia (= Lyme disease) infection which he acquired either in North America or Australia. This was supported by 1) E’s symptoms, 2) Dr. Murakami’s clinical diagnosis, 3) the Herxheimer reaction, and 4) IGeneX test results. He may also have had Babesia (a common co-infection with Borrelia) which he could have acquired in Australia, with the Babesia testing weakly positive because only North American strains were tested.
We anticipated continued recalcitrance on the part of the local children’s hospital doctors in spite of the positive test result from IGeneX, and so we contacted an Edmonton MLA, to help us be taken more seriously. His people contacted a senior administrator at the children’s hospital who interceded on our behalf. Very reluctantly, the second ID doctor agreed to put E on a two week round of IV antibiotics, which he started on December 12th. But we were aware of published research that showed that two weeks of IV antibiotics often was not nearly enough to cure chronic Lyme disease. The crux of the problem was that if E really had Lyme disease, then he probably needed several months of antibiotics, not just two weeks. In retrospect, it was likely that his brief period of partial recovery in March and April was due to the antibiotics he got in February, and that the Borrelia that cause Lyme resurged at the end of April. However the infectious diseases doctor treating E in early December 2008 was at most willing to extend the IV treatment from two weeks to 28 days, but was very clear in saying that she would not extend it beyond that.
We tried for a full year to work with the doctors at the local children’s hospital but by the end of 2005 our frustrations overwhelmed us. We had come full circle back to one of the doctors who made the original psychiatric diagnoses that colored the opinions of subsequent doctors. This infectious diseases doctor was resistant to our interpretation of E’s behaviour as well as to considering any objective data such as blood pressure readings. For example she neglected to order blood tests before, during, or after E started taking doxycycline. The antibiotics that E did get were viewed as a palliative measure in response to strong parental and administrative pressure, not a serious medical intervention.
We didn’t understand why the doctors at the local children’s hospital were so resistant to a diagnosis of Lyme disease. No one offered any positive treatment plans, and we had been the only ones to come up with a plausible explanation for E’s completely disabling condition. In numerous interactions with doctors, we were told to “relax,” “let nature take its course,” or “be glad you have other children,” leaving us with the overwhelming implication that these doctors expected him to die. They didn’t really know what the medical problem was, but they seemed to want to keep some connection with his case in the eventuality that an interesting autopsy result came out of it and they could write up a research paper. They were clearly not considering the circumstances from the stance of trying to maximize E’s chances of recovery. The risk of adverse effects from antibiotic treatment were minor compared to the disabling condition that E now suffered, but all the doctors we dealt with were reluctant to give him the kind of treatment that would maximize the chances of his recovery as recommended by Lyme experts. Instead it appeared that the doctors at the local children’s hospital were more interested in upholding each other’s psychiatric diagnoses than reading up on Lyme disease. When we asked for clarification, the only response was that they were following minimal CDC guidelines for a disease that they didn’t believe E had.
This left us with a plea to a prominent health lawyer for any way that he could help us through this complicated mess so that we could continue to get appropriate medical treatment for our son. Was our main alternative to go deeply in debt and split up our family by moving E to a place where there were Lyme-literate doctors?
2006 and 2007: A slow return to health
Upon meeting with us, the law professor’s immediate and generous response was to write a formal letter informing the pertinent hospital that he was taking on our case. Privately, he told us that he appreciated being able to make a constructive contribution to a legal case before a tragedy had run its course, while there still was some opportunity to truly help the patient.
The response by the local children’s hospital was to assign us to a senior administrator. With her mediation, E’s care was transferred to another pediatrician. A temporary IV line was installed in E’s arm, and for three agonizing months, with us making a new case for continued treatment every couple of weeks, E’s condition slowly started to improve.
We took hope from knowing about a case in British Columbia where a Lyme patient received IV antibiotics for three months before her condition made a more dramatic improvement. More fundamentally, we took refuge in the simple logic that, of all the dire diagnoses that E had been offered, including MS, Parkinson’s, and a variety of immunological and genetic meltdowns like ALS and Huntington’s, only Lyme borreliosis truly offered hope of a sustained recovery. Between the certainty of death and a very small chance of success, it was only reasonable to treat for the disease where the treatment would make a difference rather than to assume that the condition was due to alternatives that provide no hope.
Instead we were offered a variety of counter arguments. The first and most persistently proffered was that “excessive” use of antibiotics would breed antibiotic resistance. It is a fine argument if the main consideration is to reduce costs due to long term antibiotics. But it requires that we as a society accept that some proportion of patients will die for the sake of the extending the useful life of a particular antibiotic, even though that antibiotic might have saved the patient. In practice even animal breeders have not followed this advice, instead releasing tonnes of antibiotics into the environment in animal feed, meat products, or farm effluent. The real test is whether the doctors concerned would deny their own children antibiotics under the same conditions, and we never got a straight answer when we posed the question that way.
The second objection was that Lyme borreliosis is very rare in Alberta and really not worth investing energy into pursuing. It is a valid approach when a disease first presents—a reasonable doctor will start by investigating the most prevalent diagnoses that will explain the symptoms. But it is not reasonable after the most likely prior explanations have been eliminated, since under these conditions a rare illness becomes increasingly more likely as the more common illnesses are removed as explanations. As Sir Arthur Conan Doyle had Sherlock Holmes say, once you have eliminated the impossible, whatever remains, however improbable, must be true. But we were amazed that more than one medical specialist clung to a repetition of the statement that Lyme borreliosis was vanishingly rare in Alberta and the diagnosis therefore could not apply.
A third objection was that none of the accepted tick vectors were known to be established in Alberta, or that an onset of illness in late November implied too long an incubation period for it to have been tick-borne. Here we were on firm ground, as entomologists, but that didn’t seem to give us much credibility. We knew that Ixodes ticks belonging to undoubtedly competent vector species had occasionally been found in Alberta, both on birds and on humans. It is also quite normal for ticks to bite in late September or October, and that initial symptoms like the characteristic bulls-eye rash may be missed or simply not manifested. All of this assumed that E contracted his illness in Alberta, but we had been in tropical Australia in late August. There is also ample evidence that Lyme and many other bacterial infections can have a relatively latent period of months or even years, and so our residency in Lyme endemic areas of the US was relevant. But all this was deemed too far-fetched to be worth considering, with vague psychiatric diagnoses made by non-psychia trists being the main alternatives that were offered.
A fourth objection to the possibility of Lyme, held up as irrefutable by various specialists, was that the Canadian tests had definitively shown that E did not have Lyme. The problem there was that we were able to find a great deal of peer-reviewed research literature that demonstrated a dismal rate of false negatives for those tests even when they were performed at fully accredited institutions. Other studies documented a substantial amount of genetic diversity in Borrelia genotypes across North America. These studies carried the logical corollary that genetic diversity in disease causing organisms can be expected to lead to variation in diagnostic effectiveness if, as is the case for Lyme, the accredited diagnostic tests were standardized on the basis of a single strain from the eastern USA. An additional wild card was the suite of other kinds of bacteria or even viruses that routinely are co-transmitted with Borrelia when a tick bites. Pathogens such as Babesia, Bartonella and Ehrlichia can have synergistic effects with Borrelia but may need to be treated with completely different antibiotics. However when we made these counterarguments, fully supported by research literature, we were usually summarily written off. Most doctors simply don’t have the time or the training to think about diseases that don’t fit predefined boxes. Holistic diagnoses that require an integrated understanding of statistical probability and biological diversity are more conveniently referred to a “soft” specialty like psychiatry.
Meanwhile, as spring 2006 spread its warmth in Edmonton, a miracle started to unfold. E’s IV antibiotics were stopped, with our agreement, in mid March, but he continued on oral antibiotics both for Borrelia and Babesia, under the care of a supportive psychiatrist. In early May, E’s rate of improvement accelerated, but his involuntary halting continued into June, with a brief but alarming reversal in early July. Problems with jerky coordination continued through to the end of 2006, though he was able to start school again full time in September.
A strange set of stretch marks appeared in July 2006, spreading over large parts of E’s back and shoulders in the ensuing months. Only when we stumbled across images of Bartonella-infected patients with red stripes almost identical to those on E, did we have any clue what the cause might be. Within two weeks of starting antibiotics for Bartonella in mid December, E’s brothers were remarking how much “less flippy” his motions seemed, and he continued to improve incrementally during the next year, 2007, although his stretch marks took much longer to fade. It seems too incredible to be true, and yet it is well established that a single tick can contain two or three or even more kinds of pathogens. Nor did E necessarily get everything that made him sick from one tick or even during one narrow period of time. The fact is that, when he was eventually treated as if he had Lyme borreliosis, he got better in a manner that was consistent with him having been infected by Borrelia. When he was subsequently treated as if he had also acquired other tick borne bacterial infections, his health improved even more. Eventually, it took until the end of 2007 before the cloud seemed to fully lift from E’s brow.
In addition to a few beleaguered health professionals who stood by E within the medical system (most of whom prefer not to have attention drawn to their coura geous, peer-disapproved actions), he received excellent support from a devoted teacher’s aide (Rita Fraser) within a supportive Edmonton public school system, an innovative exercise facility for disabled patients (the Steadward Center at the University of Alberta), a patient music teacher, a substantial extended family, a full time mother, and a father’s medical benefits plan that absorbed most of the financial costs. But it took all of these, along with his own natural resilience, to pull through. Not many other Lyme sufferers have had the same advantages, and have ended up losing their homes, their families, and eventually most remnants of a normal life.
Wouldn’t it be so much more humane—and cost effective—if our medical establishment were to take Lyme borreliosis seriously in the first place?
2008 and onward: Can we fix the machine?
In June 2008, E finished high school, having lost only a year because he had support during his illness and was able to catch up once his health returned. During the summer, he went off to French language school in Quebec for five weeks with his next younger brother. He returned happy, healthy, and ready to plunge into the rigors of first year engineering, which he passed a year later with a solid array of A’s and B’s. Understandably, he became increasingly more reluctant to be identified as “that kid who had Lyme,” preferring to immerse himself in designing and building racing cars as part of an engineering club.
For us as E’s parents, however, there was a sense of unfinished business. During the period of E’s recovery, Dr. Murakami was forced into retirement through the stress of continued investigations by the B.C. College of Physicians and Surgeons. One of the most public medical advocates of Lyme patients in Canada had been removed. We had been fortunate to be able to get support from Dr. Murakami and a few other sympathetic medical people, most of whom were limited in what they could do because infectious diseases were not their specialty. We were also able to use our own research training, our contacts, and our knowledge of the system to help our son recover in spite of a medical system that was divided against itself. But adherents to the dominant medical opinion were willing, for various ideological reasons, to let patients like E perish. What could rural patients or First Nations people do to help themselves if they were suffering from Lyme? After all they are far more likely to be exposed to ticks than city dwellers would be. How could we even know if dozens of people have not already died of Lyme borreliosis in Alberta? Between flawed tests and a severe reluctance to even consider the diagnosis, we may never know how many ALS, MS, or Parkinson’s deaths might really have had a preventable bacterial origin. It simply didn’t seem fair.
The need to help shift the balance of this profoundly wrong situation has offered a kind of therapy for us that has helped us to cope with some horrific memories. Janet began to get increasingly more involved with the Canadian Lyme Disease Foundation, a group that advocates for greater investment in Lyme disease research in Canada. She has participated in rallies in Ottawa, met several times with the
Deputy Minister of Health and Wellness in Manitoba, organized a Lyme Wall of Hope in Edmonton, successfully elicited a private member’s statement on Lyme Disease in the Alberta Legislature (K. Taft, November 20, 2008), and written briefs to the health authorities across Canada (e.g. Appendix 1 and 2). The two of us have coauthored a peer-reviewed overview of Lyme borreliosis in Canada from the viewpoint of entomologists. Felix has shifted the focus of his lab to include the population genetics and evolution of ticks in Alberta. Much work is left before our understanding of Lyme borreliosis is on a solid footing in Canada.
Much of that unfinished work lies in translating research results into policy that allows effective diagnoses and treatment of a complex disease like Lyme in spite of a variety of constraining factors like institutional inertia and incomplete medical certainty. To illustrate this point, Appendix 1 and 2 below are emails sent by Janet to British Columbia public health authorities to support more flexible consideration of clinical diagnoses of Lyme disease. In spite of a polite acknowledgement of receipt, accompanied by the statement that a reply would be forthcoming shortly, no response or refutation has ever been received. The same brief has also been submitted by Lyme patient advocates to the Federal Public Health Agency, again without anything more than an acknowledgement of receipt.
So we end on an optimistic note, even though the saga remains unfinished. Considering the alternatives, Lyme really is a diagnosis of hope when it is the most treatable disease among grim alternatives. After a period of panic and confusion, we were able to concentrate on doing whatever it took to provide our son E with treatment that ultimately had few differences from the long term antibiotic regimes widely accepted for bacterial diseases like tuberculosis. When he was properly treated for Lyme borreliosis, he got better as if he had had the disease. After that, it didn’t really matter whether he actually had the particular strains or even species that current Lyme immunological diagnostics are narrowly focused on.
We strongly believe that patient and doctor education can make a positive difference. But effective support and protection are needed for medical practitioners who are willing to try to treat Lyme patients on the basis of flexible clinical judgment. Continued research into the diversity of Lyme, Lyme-like and associated bacteria is sure to pay dividends. In a fundamentally important sense, Lyme disease is also a metaphor for our trying times, as we struggle to simultaneously manage diversity, complexity and change.
Appendix 1: Lyme diagnosis
E-mail letter to British Columbia Deputy Provincial Health Officer, August 2008. I am a member of CanLyme with an interest in peer-reviewed literature on Lyme disease. I am also an entomologist by training and the mother of a now-recovered Lyme victim. My understanding is that you are particularly interested in Lyme research concerning diagnosis and treatment. Here I will deal with the diagnosis of Lyme disease. In my second email, I will cover its treatment.
British Columbia uses a two tier testing protocol that starts with an ELISA. If that is positive then the sample is further tested with a Western Blot before the patient is considered to have tested positive for Lyme disease. If the ELISA is negative, a Western Blot is rarely attempted. The rigid interpretation of these tests is what we are challenging.
The ELISA is a first step that is generally considered more sensitive than the Western Blot; however numerous reports contradict this (Cordoliani et al 1997, Evans et al 2005, Harrer et al 2007, Mantovani et al 2007). An ELISA is a more economical test to run and is more easily automated than a Western Blot, which presumably explains the use of an ELISA as an initial screening test.
The CDC criteria (MMWR 1995 44: 590–591) for interpreting Lyme disease Western Blots are used in British Columbia as well as by the CDC in Washington. The problem is that the criteria are both too specific and not specific enough.
The criteria for interpretation of the Western Blot are based on two serotypes of Borrelia, strain G39/40 (Dressler et al 1993) and strain 297 (Engstrom et al 1995), which do not reflect the extensive and well documented diversity of strains found in North America (Bunikis et al 2004). The choice of strains G39/40 and 297 is especially perplexing since they are considered to be non-infectious strains (Coburn et al 1994) and G39/40 is rarely referenced in later work. These criteria, established at a conference in 1994, were designed to produce a statistically relevant pattern of banding. Yet they specifically exclude both Osp A and Osp B (Dressler et al 1993) even though these bands are highly informative, so much so that Osp A was chosen as a target for vaccine development (Bergstrom et al 2002). Since the criteria include cross reacting proteins such as flagellin, but exclude more strain specific proteins such as Osp A and Osp B, it is possible in British Columbia to have a banding pattern that includes Osp A, Osp B, and flagellin proteins and still be considered negative for Lyme disease. Flagellin proteins may cross-react with other spirochetes but I am not aware of cross reacting proteins for either Osp A or Osp B.
Current commercial test kits generally rely on strain B31, a strain that is highly associated with the arthritis form of Lyme and not neuroborreliosis (Assous et al 1993). In Table 4 of Aguero-Rosenfeld et al (2005) they indisputably demonstrate that circular logic is involved in Lyme Disease diagnosis using the two-tier approach. Their Table 4 shows only 38% sensitivity (early EM) to 87% (early neuroborreliosis) to 97% with Lyme arthritis. Thus the two-tier approach is skewed to favor a restricted view of Lyme disease. It is circular logic to state that Lyme arthritis can be detected in 97% of cases and that therefore Lyme arthritis is the main manifestation of Lyme disease, since the test was designed using the arthritic form of Lyme in the first place. This doesn’t help people with early Lyme or those with neuroborreliosis, and these are the people who come to CanLyme desperate for help because their ELISA did not pick up 13% or more of these real Lyme cases.
In Europe, where multiple strains of Lyme disease are acknowledged, Western Blots are interpreted differently. A positive result can be based on the presence of 2 or 3 bands for a specific series of proteins for Borrelia burgdorferi. At no point are 5 bands required for a positive result (Robertson et al 2000).
In Brazil a positive Western Blot is defined as 4 bands for IgG, 2 for IgM or 2 IgG associated with one IgM. Significant positive clinical response to antibiotics has been documented for patients who exhibit the reduced number of bands (Mantovani et al 2007). Their condition is termed a ‘Lyme Disease-like syndrome’ because of the fewer number of Western Blot bands than the strict CDC definition for Lyme. Consequently, in Brazil, the diagnosis of Lyme Disease is made based on the clinical picture and serology is only used as supporting evidence.
Another recent article that shows that the best diagnosis of Lyme disease is clinical is Pavan (2002) who concludes that the diagnosis of LB is mainly clinical, while laboratory testing is a valid help but insufficient to make a diagnosis (and listing 9 references to support his statement).
On the other hand, some authors of the Infectious Diseases Society of America’s guidelines for the treatment of Lyme disease represent an extremely restrictive view of Lyme Disease and state that neuroborreliosis is self-limited in most patients even without antibiotic treatment (Wormser and Halperin 2008). This stance trivializes the suffering of our members, and is only weakly supported by two older references from 1983 and 1990. This view is not supported by any peer reviewed treatment guidelines. Antibiotic treatment to differing degrees is recommended in all peer reviewed guidelines as I will demonstrate in my next email. The attitude of these vocal and influential IDSA practitioners has resulted in considerable suffering from undiagnosed and untreated Lyme disease in British Columbia.
We at CanLyme believe that many desperately ill British Columbians are suffering from a treatable illness. The peer reviewed literature, when examined from the perspective of empirical success when a clinical diagnosis is given, clearly shows that the use of serology to diagnose Lyme disease is an inexact art. The use of negative serology to deny a Lyme disease diagnosis, the current standard in British Columbia, is highly inappropriate. We are dealing with many serologically and genetically distinct strains of a putatively single disease that has correspondingly diverse manifestations ranging from mild to severe.
In short, the current tests for Lyme disease are inadequate. We strongly advocate diagnosis on the basis of clinical symptoms, supported but not limited by testing that takes into account the serological diversity of Borrelia, as well as any associated diseases.
Aguero-Rosenfeld ME, Wang G, Schwartz I, Wormser GP. 2005. Diagnosis of Lyme Borreliosis. Clinical Microbiology Reviews 18: 484-509.
Assous MV, Postic D, Paul G, Nevot P, Baranton G. 1993. Western Blot Analysis of Sera from Lyme Borreliosis Patients According to the Genomic Species of the Borrelia Strains Used as Antigens. European Journal of Clinical Microbiology and Infectious Disease. 12: 261-268.
Bergstrom S, Noppa L, Gylfe A, Ostberg,Y. 2002. Molecular and Cellular Biology of Borrelia burgdorferi sensu lato. Chapter 3 pages 47–90 in Lyme Borreliosis: Biology, Epidemiology and Control (eds J Gray, O Kahl,R Lane and G. Stanek)
Bunikis J, Garpmo U, Tsao J, Berglund J, Fish D, Barbour AG. 2004. Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe. Microbiology 150: 1741–1755.
Coburn J, Barthold SW, Leong JM. 1994. Diverse Lyme disease spirochetes bind integrin alpha IIb beta 3 on human platelets. Infection and Immunity 62: 5559–5567.
Cordoliani F, Vignon-Pennamen MD, Assous, MV, Vabres P, Dronne P, Rybojad M, Morel P. 1997. Atypical Lyme borreliosis in an HIV-infected man. British Journal of Dermatology 37: 437-439.
Dressler F, Whalen JA, Reinhardt BN, Steere AC. 1993. Western blotting in the serodiagnosis of Lyme disease. The Journal of Infectious Diseases 167: 392–400. Engstrom SM, Shoop E, Johnson RC. 1995. Immunoblot interpretation criteria for serodiagnosis of early Lyme disease. Journal of Clinical Microbiology 33: 419-27.
Evans R, Mavin S, Ho-Yin D. 2005. Audit of the laboratory diagnosis of Lyme disease in Scotland. Journal of Medical Microbiology 54: 1139-41.
Harrer T, Geißdörfer W, Schoerner C, Lang E, Helm G. 2007. Seronegative Lyme neuroborreliosis in a patient on treatment for chronic lymphatic leukemia, Infection 35: 110–113.
Heikkilä T, Seppälä I, Saxén H, Panelius J, Peltomaa M, Julin T, Carlsson SA, Lahdenne P. 2002. Recombinant BBK32 protein in serodiagnosis of early and late Lyme borreliosis. Journal of Clinical Microbiology 40: 1174–1180.
Mantovani E, Costa IP, Gauditano G, Bonoldi VL, Higuchi, ML, Yoshinari NH. 2007. Description of Lyme disease-like syndrome in Brazil. Is it a new tick borne disease or Lyme disease variation? Brazilian Journal of Medical and Biological Research 40: 443-56.
Oksi J, Nikoskelainen J, Hiekkanen H, Lauhio A, Peltomaa M, Pitkäranta A, Nyman D, Granlund H, Carlsson S-H, Seppälä I, Valtonen V, Viljanen M. 2007. Duration of antibiotic treatment in disseminated Lyme borreliosis: a double-blind, randomized, placebo-controlled, multicenter clinical study. European Journal of Clinical Microbiology and Infectious Diseases 26: 571–581
Pavan, WO. 2002. Need of interdisciplinary competence and the role of the Department of Health in the struggle against Lyme borreliosis ACTA Dermatovenerologica 11 (1) http://ibmi.mf.uni-lj.si/acta-apa/acta-apa-02- 1/pavan.html
Robertson J, Guy E, Andrews N, Wilske B, Anda P, Granstrom M, Hauser U, Moosmann Y, Sambri V, Schellekens J, Stanek G, Gray J. 2000. A European multicenter study of immunoblotting in serodiagnosis of Lyme borreliosis. Journal of Clinical Microbiology 38: 2097–2102.
Wormser GP and Halperin JJ. 2008. Oral doxycycline for neuroborreliosis. The Lancet Neurology 7: 665-666.
Appendix 2: Lyme disease treatment
Email letter to a BC Deputy Provincial Health Officer, August 2008. This is the second of two emails describing Lyme disease from the perspective of an entomologist whose son has now made a complete recovery from Lyme disease. My purpose is to demonstrate, based on peer reviewed research publications, that the current treatment of Lyme disease based on IDSA guidelines is inadequate and that a sincere investment in further research is crucial, owing to many unresolved issues relating to long term persistence and co-infections.
Lyme is most successfully treated early in the course of the disease (Cameron et al 2004, Diterich et al 2001, Evison et al 2006, Exner 2004, Vanousova and Hercogova 2008). Conversely, any delay in diagnosis causes increasing challenges in achieving successful treatment. While doctors are understandably reluctant to make a clinical diagnosis for a disease that they have rarely confronted, diagnosis remains problematic throughout the course of the disease (as described in my email on Lyme diagnosis). The fundamental fact remains that early diagnosis and treatment of Lyme can save lives. Our daily newspapers are chronicling the consequences of neglect of the same principle for Listeria.
Dissemination to distant tissues and long term persistence are pathogenic processes found for all major human spirochetal infections (Wormser 2006). Yet in the IDSA Guidelines authored by Wormser et al (2006), only 14- 30 days of antibiotic are recommended. Other treatment recommendations for later stages of Lyme range from no antibiotics (Steere et al 1983) to 12 weeks of Ceftriaxone and open ended antibiotics (Harvey and Martz 2007). The most contentious issue in peer reviewed literature is not the early treatment but the endpoint. Acceptance of long term disability is the basis of the current IDSA Guidelines which include a category of ‘Post-Lyme Disease Syndromes’, an ill defined and progressively disabling constellation of symptoms.
The practice parameter review for neurologists produced by Halperin et al (2007) is instructive. They have chosen to interpret as ‘excellent’ a response to treatment in which 63% of patients improved, 22% improved but relapsed, and 15% remained unchanged. This left 37% of patients unsatisfied with the outcome of their treatment. A further study used by Halperin et al (2007) to support their point of view states that at post-treatment follow-up, half the patients reported headache and concentration problems. A third study states that 25% of patients assessed 5 years after treatment reported persistent “neurologic” difficulties. Thus a large body of research shows that many patients are not returning to their previous good health, a remarkable result considering that Halperin (2008) claims that the medical establishment has reached consensus over short term treatment of Lyme disease. The clear message for a substantial proportion of Lyme patients is that it is the accepted medical norm to give up on them.
In our experience, many Canadian doctors (Johnston and Conly 2005, Bowie 2007), cite Klempner et al (2001) as the basis to deny treatment of Lyme disease. Yet Cameron’s 2006 analysis has unambiguously demonstrated numerous flaws in that study. The Klempner study enrolled the subset of patients who were the most difficult to treat—those who had been ill for several years and had previously failed treatment. Then the trial was halted when no significant difference in health-related quality of life was experienced by patients who received 30 days IV plus 60 days oral antibiotic compared to those receiving a placebo, even though those patients represented a group preselected for their lack of prior response to treatment. No consideration was given to the tautology in the study or the possibility that incomplete prior treatment may have selected for bacterial strains that exhibited resistance to subsequent antibiotic treatments.
Study designs, like Klempner et al (2001), that presuppose a particular narrow definition of Lyme disease and then draw conclusions based on a preselected subset of patients are the norm. In contrast, a study by Oksi et al (2007) enrolled patients with both definite and possible Lyme borreliosis. As with other studies, they reported good or excellent response to extended antibiotic in only 79% of cases, with three weeks of IV followed by 100 days oral penicillin being insufficient to improve the health of 21% of the patients. However, this study not only confirmed the refractory nature of a substantial proportion of Lyme cases, but it demonstrated the existence of seronegative Lyme, a finding that was made possible by enrolling a less restricted subset of patients. Thus it is clear that the results of any study are contingent on the prior definition of Lyme that is used to admit patients into a study, a practice that may increase the chances of confirming a prior hypothesis but one that is not conducive to allowing better treatment or understanding of Lyme disease.
In an even more recent study, Fallon et al (2008) showed that 10 weeks of IV antibiotics resulted in short term cognitive improvement, reduced pain and increased physical functioning. However, the cognitive improvements observed upon cessation of antibiotics were not maintained 24 weeks after commencement of the antibiotic, although improvement in pain and physical functioning was sustained. The fact that 10 weeks of IV did not result in long term cognitive improvement in patients who had previously received IV therapy was taken to suggest that IV therapy did not eradicate the motile form of Lyme in sequestered or immune privileged sites (Fallon et al 2008), and may also be explained by persistence of a cystic form of Lyme disease (Alban et al 2000, Brorson and Brorson 2004, Murgia and Cinco 2006, Brorson and Brorson 2007).
Hodzic et al (2008) used xenodiagnosis in mice to unambiguously demonstrate that Borrelia burgdorferi (specifically the N40 strain also known for its virulence in humans) is able to survive and retain its infectivity after three months of antibiotic, especially when treatment was started after the infection was advanced. Hodzic et al (2008) thus convincingly showed that infectious spirochetes are able to survive treatment that was previously assumed to eradicate the motile form of Borrelia. Infective spirochetes persisted in various tissues as well as collagen, with collagen being a major niche for both spirochete survival and possibly immune evasion.
In a contrasting interpretation of similar results, Ljøstad et al (2008) compared results of oral doxycycline and IV ceftriaxone in patients who were serologically positive for B. afzelii, one of the European variants of Lyme disease. They followed patients for 4 months and reported that 59% of patients had residual symptoms. These results coincided with two other studies that showed that two to five years after treatment 25–59% of patients reported residual symptoms (Berglund et al 2002, Vrethem et al 2002). However, Ljøstad et al (2008) discounted the possibility of bacterial survival and did not back up their interpretation with evidence or references, despite older studies that contradict this stance (Alban et al 2000, Brorson and Brorson 2004, Murgia and Cinco 2006, Brorson and Brorson 2007). This interpretation is further undermined by a recent Hodzic et al (2008) study which shows that Borrelia can survive antibiotic levels in excess of those used in any of these studies.
Borrelia are not alone in their ability to survive long term antibiotics. For example, lifelong prophylaxis is recommended for severe rheumatic fever (World Health Organization 2001). Rheumatic fever is similar to Lyme disease in that erythema marginatum, infective arthritis and Sydenham’s chorea are major manifestations. The World Health Organization report states: “It is evident from the preceding discussion that the pathogenesis of RF and RHD is a complex maze of events that are immunologically intricate, pathologically significant, and clinically devastating for the patients. It is ironic that a rather innocuous “sore throat” should extract such a high price from the host. As scientific research evolves, it is hoped that the gaps in our understanding will be filled, and better strategies for prophylaxis and treatment will become available.” The same can certainly be said for Lyme disease. Other diseases for which long term antibiotic treatment is the accepted norm include, but are certainly not limited to, latent TB (9 months antibiotic—Inge and Wilson 2008), leprosy (12 months of multidrug therapy—World Health Organization 1997) and actinomycosis (IV for 2–6 weeks and 6–12 months of oral antibiotic—Russo 2008). This raises an obvious question: if long term antibiotic treatment is freely accepted for numerous other bacterial diseases, why is it so vigorously opposed by the IDSA for Lyme disease?
In addition to the simple persistence of Borrelia, whatever the life form, another complication that can cause Lyme disease to remain refractory to treatment is the presence of co-infections by other bacteria. The fact that late Lyme disease is some times associated with treatment failure (Bratton et al 2008, Ogden et al 2008) has resulted in differing approaches to treatment. For example, a Czech treatment protocol for Lyme disease emphasizes the importance of considering co-infections, especially when treatment results in a worsening of symptoms (Vanousova and Hercogova 2008). This principle is also emphasized in the ILADS treatment protocol described in Cameron et al (2004).
A suite of several diseases is commonly associated with borreliosis, and these are often reported simultaneously in the tick vectors (Alekseev and Dubinina 2003, Belongia 2002, Hamer et al 2007, Pichon et al 2006). For example, Eskow et al (2001) have recommended that patients with incomplete resolution of their symptoms should be routinely assessed for evidence of Bartonella as a co-infection. Co-infec tion of Borrelia and Babesia results in increased severity of arthritis in dogs (Moro 2006). In fact, Harvey and Martz (2007) have postulated that co-infection of Borrelia and Babesia may cause antibiotic responsive ALS, a disease that is normally considered a death sentence and for which the disadvantages of antibiotics cannot reasonably be considered sufficiently important to deny treatment for the individual. As a further complication, multiple co-infections may result in confusing laboratory results (Walid et al 2007). Consequently, the complexity of Lyme disease and its treatment has led Owen (2006) to suggest that Lyme disease is actually a polymicrobial disease.
Interestingly, the existence of co-infections is much less contentious than is the view that such simultaneous infections may have any influence on each other. For example, although Wormser et al (2006) acknowledge that concurrent infection by Babesia, Anaplasma and Borrelia is possible, they see each disease as a single independent entity. As with Lyme disease, they discount the possibility that testing for co-infections may result in a false negative result or that the infections may be synergistic, especially at the level of the individual patient. In contrast, Diterich et al (2001 and 2003) maintain that the host immune response is modulated by Borrelia infection. Babesia infections, especially Babesia microti are also capable of transient immune suppression (Allred 2003). Telfer et al (2008) have written an excellent review of the impact of co-infecting bacterial or even viral species and elegantly describe an interaction network for a field vole, a potential reservoir host for Borrelia burgdorferi and its co-infections (Brisson et al 2008). In light of the strong evidence for the importance of co-infections in animal models, the neglect of these same processes by the IDSA guidelines (Wormser et al 2006) seems perversely retrograde for humans.
Co-infections are not the only factors that necessitate variable and flexible treatment for Lyme disease. The recent spread of a high-virulence strain of Borrelia burgdorferi in North America has now been established (Qiu et al 2008), and these authors suggest that this pathogenic strain may also be successful in infecting a broad range of host as well as vector species. Furthermore, the ranges of the accepted tick vectors of Lyme disease, Ixodes scapularis and I. pacificus, may be expanding due to global climate change (Ogden et al 2008). Thus the current practice of treating Lyme disease only in geographical areas where I. scapularis or I. pacificus is known to be endemic, as has been recommended in Canada by Barker and Lindsay (2000), is likely to unnecessarily limit the effective treatment of individuals.
As further demonstration of the lack of consensus on the treatment of Lyme disease (in contrast to the non-independent claims made by the joint authors of both the IDSA and neurology guidelines), some other respected medical bodies have refrained from issuing similar statements. For example, the Cochrane Collaboration is a highly respected global network of volunteers who review medical interventions, publish their results in a library of evidence based medicine, and are considered free from conflicted funding. They have not yet published an accepted protocol for Lyme treatment. A proposal for a Cochrane study (Cadavid et al 2008) specifically excludes ‘post Lyme syndrome’ an action that implies that there remains considerable difference of opinion on treatment of late Lyme disease and they consider its treatment to not yet be at the stage of consensus.
Based on the peer reviewed literature summarized above, it should be abundantly clear that the treatment of Lyme disease requires an open-minded, flexible approach tailored to each individual patient. The medical adage ‘treat the patient, not the disease’ is especially appropriate in light of co-infections and other complications that mean that Lyme borreliosis is not a simple, single entity. Unfortunately, the experience of CanLyme members demonstrates that, in our technologically driven medical system that often emphasizes machine readouts over clinical diagnoses, few patients are fortunate enough to receive meaningful treatment at any stage of infection.
In recognition of the lack of real consensus on the treatment of Lyme disease, I consider it important to emphasize that CanLyme members are supportive of any treatment protocol that results in improved quality of life for its members, from those with a recent tick bite and spreading rash to those with late Lyme disease. If you are aware of any double-blind study that shows that the ILADS treatment protocol, with its emphasis on treating co-infections and extended antibiotics, does not result in improved quality of life, I would appreciate the reference. In every study that I have read, the limitations of viewing Lyme as ‘easy to diagnose and easy to treat’ are tragically clear and the shortcomings of the IDSA treatment guidelines can only ultimately be explained by a lack of appreciation of the suffering of our members.
I sincerely hope to be able to continue our discussion and to thereby contribute to resolving the current impasse in the treatment of Lyme disease. Numerous patients continue to suffer from both Lyme disease as well as a serious misinterpretation of their symptoms. If you, in your position as deputy medical officer of health, could foster a climate that encourages real flexibility and research on Lyme disease as it exists in British Columbia, this would surely make a huge difference in alleviating the suffering of Lyme patients and their families.
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