Lyme Disease – Underreported, Underdiagnosed and Undertreated
It is a disease which affects almost any part of the body and produces a bafflingly wide range of symptoms, including skin lesions, meningitis, progressive muscular and joint pain, mood changes and behavioural problems.
Doctors don’t know how best to diagnose or treat it, and can’t easily tell when it has been cured. Yet, left untreated, it can become incurable a lifelong debilitating illness characterised by neurological disorders, emotional and mental disorders, serious pain syndromes in the bones and muscles, and even fatal heart disease and respiratory failure.
Lyme disease, or Lyme borreliosis, is a blood borne disease first recognised in the US in 1975 after a mysterious outbreak of arthritis in 51 residents of the Atlantic seaside town of Lyme, Connecticut. Since then, reports of Lyme disease have increased dramatically in the US and western Europe, and it is now recognised as an important public health problem.
Suggestions that Lyme disease is overdiagnosed have caused an outcry from physicians who specialise in the disease. While this may have been so in the early days, genuine cases are growing year by year. In the US, the number of cases has doubled during 1992-1998 (MMWR, 2000; 49: 1-11) while the UK has shown an alarming fivefold increase from 0.06/100,000 during 1986-1992 to 0.32/100,000 since 1996.
The infection is due to Borrelia burgdorferi, a spiral shaped bacterium known as a spirochaete, spread by the bite of ticks of the genus Ixodes, which normally live off the blood of the white footed mouse, white tailed deer, birds and other mammals, including dogs and cats. Blood transfusions may also be a means of infection though debate rages as to how high the risk is (see box).
Ixodes ticks are no bigger than a pinhead in the larval and nymphal stages, and adults are about the size of a poppyseed. The ticks transmit Lyme disease to humans mostly during the nymph stage, probably because they have not yet developed their stronger preference for mice and deer. Because of their small size, the nymphs are rarely noticed, and so have ample time to feed and transmit infection (usually after two or more days of feeding).
Larvae rarely carry the infection and, although adult ticks can transmit the disease, they are more likely to be discovered and removed. The adults are also more active during the cooler months of the year, when human outdoor activity is limited.
Lyme disease is largely a product of environmental mismanagement, deforestation and reforestation, and squeezing of wildlife and humans into smaller and smaller designated spaces, such as deer parks and nature reserves (see Garrett L, The Coming Plague, Penguin, 1994). Most humans with Lyme disease live in wooded areas inhabited by common wild animals such as deer, squirrels, chipmunks with an absence of natural predators such as wolves, cougars and coyotes that keep these animals in check. Scrubby areas near the seaside are also common sites for Lyme carrying ticks.
Difficulty in diagnosis
Immunologists view the disease as a simple infection, leading to diagnostic tests that look for immunological factors, such as antibodies in the blood and cerebrospinal fluid (CSF).
However, reviews of such antibody detecting tests have revealed their generally dismal performance and considerable interlaboratory variability (J Infect Dis, 1987; 155: 1325-7; J Am Med Assoc, 1992; 268: 891- 5). Indeed, it is believed that the standard two test approach to diagnosis using either an enzyme linked immunosorbent assay (ELISA) or immunofluorescent assay (IFA), followed by Western immunoblot testing in positive or equivocal specimens, can miss up to 87 per cent of infected patients.
One reason for such a poor performance is the sheer number of factors that can interfere with the accuracy of serological tests (see box). Also, a patient can be infected and have a variety of symptoms, yet show no antibodies to the bacteria in the blood, as antibody response can wax and wane over time. The spirochaetes can also be released into the blood and, for reasons as yet not understood, retreat into host body tissues until conditions are optimal for their spread and reproduction. These phenomena are known as seronegative disease.
In such patients, it is often possible to culture live spirochaetes from the blood (Infection, 1989; 17: 355-9). In one study of transplacental transmission, over half the mothers with adverse pregnancy outcomes and fetuses or infants with B. burgdorferi were sero negative (Rheum Dis Clin N Am, 1989; 15: 657-77).
Furthermore, while other tests such as urinalysis are not given routinely, examination of a patient’s urine may reveal B. burgdorferi specific antigen in symptomatic patients given the all clear on the basis of seronegative test results (J Clin Microbiol, 1993; 31: 1961-3).
What all of this means, say Lyme disease specialists, is that a diagnosis of the infection simply cannot be made on the basis of blood tests alone. In fact, the US National Institutes of Health (NIH) guidelines are clear that Lyme disease is a clinical diagnosis one made on the basis of patient history and symptoms (Clin Courier, 1991; 9 [Aug]: 5-8).
However, there may be problems even with a clinical diagnosis unless the process is thorough. For instance, it has been widely assumed that all patients bitten by the tick will get a rash resembling a bull’s eye, or erythema migrans. In fact, only 40-60 per cent of light skinned patients develop such a rash. On dark skinned subjects, it may look more like a bruise. Because the tick itself is so small and the rash is not a given, many people never know they have been bitten.
Even more frustrating is that an individual may be infected and yet remain asymptomatic, often for a long time. When scientists analysed blood samples obtained through the Blood Transfusion Service in Ireland, they found that the overall prevalence of positive samples in donors with no symptoms was 9.75 per cent (Zentralbl Bakteriol, 1991; 275: 382-9). In blood samples from those living in high risk areas, the prevalence of positive samples was 15 per cent.
In a survey of Swiss orienteers (people who pursue a sport involving map reading and running through the countryside), 26.1 per cent were positive for antibodies, but only 2-3 per cent had a history of probable or definite Lyme borreliosis (J Infect Dis, 1991; 163: 305-10). On a second blood sample taken six months later, 8 per cent of those who originally tested negative had become positive, though only 2.2 per cent developed clinical signs of the disease.
The refusal to acknowledge the possibility of seronegative disease has other implications. When Lyme is studied, generally only those with a positive blood test diagnosis of Lyme are included. But this denies Lyme patients who lack confirmatory blood tests treatment and encourages the underreporting of the true incidence of the disease. Only when a study population is defined by more than just blood test measures can the true incidence of Lyme disease become clear.
These diagnostic difficulties have also meant that many patients are misdiagnosed with other diseases. The literature is wellsupplied with case studies of the similarities and misdiagnoses of Lyme as Parkinson’s disease, trigeminal neuralgia, Guillain-Barr syndrome, demy elination and multiple sclerosis (Rev Neurol, 1997; 25: 1919-21; J Orthop Sports Phys Ther, 1996; 24: 268-78; Eur J Pediatr, 1993; 152: 810-2; Neurology, 1982; 32: 1302-5; Wien Med Wochenschr, 1995; 145: 188-90; Acta Neurol [Napoli], 1993; 15: 253-7) while lupus, juvenile chronic arthritis, ADHD and Alzheimer’s disease have been mistaken for Lyme disease (Lupus, 1995; 4: 131-7; J Pediatr, 1986; 109: 753-8; Psychiatr Clin North Am, 1998; 21: 693-703; Neuro report, 1993; 4: 841-8).
The antibiotic debate
The conservative line is that Lyme disease is easily treated with three or four weeks of antibiotics. After this time, the patient is pronounced ‘cured’. Many physicians, however, withhold antibiotic treatment until a blood or urine test confirms the presence of antibodies to B. burgdorferi.
However, for short term antibiotic treatment to be successful, it must be initiated immediately certainly no more than six weeks after the tick bite. And tested early after a bite, the body is unlikely to show antibodies to the spirochaetes thus, the patient is unlikely to receive the necessary urgent treatment.
Because of this, the very patients who are unable to generate detectable levels of free antibodies, whose immune systems are least able to deal with the infection and who may present with more serious illness among those infected are least likely to be offered treatment (J Clin Microbiol, 1993; 31: 1961-3). After six weeks, up to 95 per cent of patients may have antibodies to B. burgdorferi but, by then, antibiotic treatment is unlikely to be effective.
Some specialists among them, Dr Joseph J. Burrascano, Jr believe that the only way to treat chronic or severe Lyme disease is with long term antibiotics. Dr Burrascano is an international expert on Lyme disease, whose Diagnostic Hints and Treatment Guidelines for Lyme and Other Tick Borne Illnesses (available at www.lymenet.com), in its 13th edition, is now a standard text on the subject.He has treated more than 7000 Lyme patients over the last 15 years.
Dr Burrascano advocates long term antibiotic treatment especially for intractable cases which can, in rare circumstances, last for years. For this reason, he is currently being prosecuted by the New York Office of Professional Medical Conduct (OPMC) as such a practice flies in the face of the medical partyline, which states that Lyme disease is easily cured with short term antibiotic treatment. Another 50 physicians in several different states are also currently under investigation for sharing views similar to Dr Burrascano’s.
The charges against Dr Burrascano were not brought about by patients, but by the OPMC which, after raiding his offices, selected the files of nine patients as evidence of failing to treat patients properly. The patients deny the charges and claim Dr Burrascano has brought them back to health in some cases, after long periods of suffering.
Rheumatologist Dr Allen Steere, credited with discovering and naming the disease, is an advisor to the American Lyme Disease Foundation (ALDF). His conservative practice guidelines for the treatment of Lyme disease are widely accepted by the majority of doctors and by official agencies such as the Centers for Disease Control (CDC) and the NIH.
Dr Steere often provides testimony against physicians who do not follow his guidelines. In 1993, he and his colleagues went so far as to suggest that Lyme disease was “overdiagnosed and overtreated” which has since become his mantra (J Am Med Assoc, 1993; 269: 1812-6). They claimed, among other things, that the reason so many patients failed to respond to antibiotic treatment was that they were either not ill in the first place or had been misdiagnosed.
Dr Steere and company came to this conclusion using a new serological test of their own design, which showed that 98 per cent of patients with active Lyme disease tested as seropositive whereas, of those who had never had the disease but were evaluated because of suspected Lyme disease, none was seropositive. The most remarkable thing about this claim was that it indicated that they had come up with a testing protocol that was vastly superior to any other in existence. That no seronegative patients were found in their study, however, is contrary to all that is known about seronegative culture positive cases.
In spite of the controversy caused by this claim, medical insurance companies unhappy at the prospect of paying upwards of £20,000 for long term antibiotic treatment seized upon it as ‘proof’ from a reliable source that patients who claimed to have the disease, but who could produce no measurable antibodies, were frauds.
Just before the Steere et al. paper appeared at the Fifth International Conference on Lyme Borreliosis, it was revealed that organisers had tried to remove certain study abstracts from the conference pack because they allegedly lacked ‘scientific merit’. These abstracts were, not surprisingly, those which challenged the prevailing view that Lyme disease is easily diagnosed and treated. Pressure from patient groups reinstated the abstracts (Science, 1992; 257: 1384, 1845).
The offending abstracts showed, for example, that researchers had recovered spirochaetes from patients who had undergone long term antibiotic therapy (Liegner K et al. Abstract 63; Masters E et al. Abstract 65; Fifth International Conference on Lyme Borreliosis, 1992). They also showed that B. burgdorferi can persist in human endothelial cells of the heart, lungs, blood and lymph vessels (Infect Immun, 1991; 59: 671) and fibro blasts (connective tissue cells) where they are not affected by immune responses thus explaining why infected patients don’t always produce antibodies to the spirochaetes.
Despite the impression given by the medical board that Dr Burrascano is practising some kind of hocus pocus, Burrascano’s own guidelines for the diagnosis and treatment of Lyme are rigourous, and viewed by many as both innovative and practical. His guidelines also emphasise aspects of medical care that have often fallen by the wayside, such as thorough history taking, physical and mental examination, individualised treatment and compassion.
Nevertheless, treating severe or chronic Lyme disease with long term antibiotics remains controversial and may have devastating consequences for patients. On the other hand, those given long term treatment have often run out of options so, for them, the risk is worth the possibility of cure. Many patients swear they get better with treatment according to Dr Burrascano’s guidelines, but there are failures as well.
Also relevant is the fact that, while some blood tests may reveal the presence of antibodies to spirochaetes, there is no test to demonstrate ‘cure’ of the disease. Thus, it is impossible to know for certain if the patient is rid of the bacteria or simply in remission (J Am Med Assoc, 1993; 270: 2682-3).
It is well known that B. burgdorferi can be cultured from the skin or CSF of patients who have had conventional antibiotic treatment and ‘cured’ (Infection, 1989; 17: 355). Even after long term treatment, cure is not guaranteed. One study demonstrated that B. burgdorferi was grown from CSF after 21 days of parenteral cefotaxime and four months of minocyline (J Clin Microbiol, 1993; 31: 1961-3).
To reconcile these discrepancies, conventional medicine has invented a new disease post Lyme syndrome. Post Lyme syndrome explains away persistent symptoms by suggesting that the causal spirochaete has somehow permanently damaged the body. Some scientists say the disease is probably a form of fibromyalgia for which nothing can be done.
Post Lyme syndrome, however, is not an acknowledged medical condition. It is simply a convenient tag used by some to explain away treatment failures.
Sidebar: In the blood
Can Lyme disease be transmitted by blood? While many physicians would say no, the fact is that Lyme disease is a blood borne disease. As detection of the disease remains so haphazard, officials really can’t be sure that the disease is not being passed on to blood transfusion recipients.
Infection by blood rather than tix has benefited from a good degree of scientific investigation. Unfortunately, there is no consistency in the findings of these enquiries. The best that can be said is that, while the risk may be low, it is nevertheless a risk.
For instance, studies have shown that B. Burgdorferi can survive in processed blood for up to 48 days at 4°C (J Infect Did, 1990; 162:557-9).
It is also known that babesiosis, A tick borne disease caused by protozoa of the genus Babesia, can be transmitted through blood transfusion.
The type of blood product is also influential. Recipients of blood plasma and blood products such as immune globulin or not thought to be affected by Lyme disease, all the recipients of whole blood may be a greater risk
Sidebar: Putting tests to the test
The Western immunoblot test is the most widely used test for diagnosing Lyme disease. Recently, the US Centers for Disease Control (CDC) revised their criteria for the test. These new criteria fail to include the most significant antigens and so may fail to make the diagnosis even when disease is present.
In addition, other factors can interfere with the diagnosis when testing blood, including:
Recent infection before an immune response
- The causal spirochaete bacteria may be encapsulated by host tissue
- There may be no spirochaetes in the body fluid on the day of the test
- The test only looks for one strain of B. burg dorferi, yet there are over 300 strains
- Recent antibiotic or anti inflammatory treatment
- Babesiosis co-infection (another tick borne disease) may cause immunosuppression
- There may be other causes of immunosup pression (e.g. immunosuppressive drugs)
- The lab test is not standardised to detect late stage disease
- The lab may have a poor technical capability for detecting Lyme disease.
Sidebar: Spirochaetes: know your enemy
Tom Grier, a microbiologist and Lyme disease suffer, and author of The Lyme Disease Survival Manual, has spent years delving into the complex microbiology of the Lyme spirochaete. His work makes disturbing reading as it highlights just how robust, intelligent and well programmed for survival the organism is. For instance:
- It is the largest of the spirochaetes
- It has a superefficient internal propulsion system, which allows it to swim quickly through blood and tissue
- It is covered with a clear gel like coat of glycoproteins, sometimes called the slime layer, or S-layer. This coating acts like a deflector shield, protecting the bacteria from attack by the immune system and antibiotics
- It replicates slowly. Bacteria replicate by a process of division and most only take 20 minutes to divide. The division time of B. burgdorferi is 12-24 hours. This is important since most antibiotics can only kill bacteria while they are dividing. A slow doubling time means that B. burgdorferi is less exposed to antibiotics. While most bacteria are killed in 10-14 days by antibiotic treatment, for a Lyme spirochaete to get the same amount of lethal exposure, the antibiotic would have to be present 24 hours a day for one and a half years!
- The Lyme spirochaete can remain in the body for years in a state of suspended animation. Since it does not divide during this time, antibiotics will not kill it. A Lyme spirochaete in this state will wait for conditions to be right before releasing itself into the blood stream to cause new symptoms or a relapse of old ones
- The Lyme spirochaete appears to be selective and able to enter ‘safe’ human cells, and hide in the body, evading the immune system and medication. For instance, the spirochaete can enter human fibroblasts (the cells that make scar tissue). In this situation, the bacteria remain protected from the immune system and can thrive without assault. Laboratory tests have shown that, even when these fibroblast cultures were flooded with massive doses of antibiotics, they still yielded live spirochaetes after two weeks.
For details of how to obtain a copy of Grier’s book, write to: The Lyme Disease Survival Manual, 902 Grandview Avenue, Duluth, MN 55812-1146, USA.
Sidebar: Treatment alternatives
If you believe you are suffering from Lyme disease, but are having trouble convincing your physician to take action, you may wish to read more about Dr Burrascano’s guidelines. You can either obtain a copy of his book or download an extract from it from the online library at www.lymenet.com.
Alternative medicine has not been proven particularly successful at treating chronic and severe Lyme disease. However, there are several things you can do to support your system as it fights the infection while taking conventional treatment.
Watch out for Candida. Patients being treated with antibiotics can develop a yeast overgrowth. To combat this, take two high quality probiotics after each meal and follow a strict anti Candida diet, which contains no sugars. If you can tolerate dairy, you may include live yoghurt daily in your diet
Avoid caffeine, alcohol and smoking, all of which put your immune system under greater stress
Sleep as and when you need to
Supplements are a must, although improvement may not be noticeable for a few weeks. A good quality multivitamin and mineral supplement should be augmented by extra magnesium, 400-800 mg daily (helpful for tremors, headaches, twitches and cramps), and vitamin B-complex, at least 50-100 mg daily (to help combat neurological symptoms)
Increase essential fatty acid intake. To get a good balance, Dr Burrascano recommends 1000 mg of cod liver or other fish oil, or flaxseed (linseed) oil (rich in omega-3) four times daily, and 1000 mg of borage, evening primrose or blackcurrant seed oil (rich in omega-6) four times daily
Try coenzyme Q10 (ubiquinone) to deal with symptoms related to poor heart function, stamina and immune response. Lyme patients need around 200-300 mg daily of standard brands, or 90 mg daily of pharmaceutical quality brands, divided into two daily doses
Treatment with homoeopathic nosodes made from Borrelia burgdorferi may be of benefit, says WDDTY panellist Patrick Kingsley. He cautions, however, that as with antibiotics improvement may be slow and, often, treatment is needed for as long as 40-60 days. Similarly, deer antler, cultivated and used throughout China and Russia, has been suggested as a possible therapy for Lyme disease (Townsend Lett Docs, 1991; 91/2: 154-5)
Whatever treatment you take, give it time to work. The Jarish-Herxheimer, or Herx, reaction is not uncommon in the treatment of Lyme disease. As the spirochaetes die during antibiotic therapy, they give off toxins, causing you to feel worse before you feel better. The Herx reaction is a normal and good result, and a sign that the treatment is working.
- This article first appeared in the June 2001 (volume 12 number 3) edition of What Doctors don’t Tell You
