Editorial by Thomas M. Grier, M.S. ©
Lyme disease is a multi-system, multi-organ disease caused by a bacterial spirochete that can penetrate a multitude of tissues. Most people who are treated get better, but not all of them get well.
While antibiotic therapy often improves Lyme patient’s symptoms, in cases of late-stage Lyme disease most patients will have at least one or more lingering symptom. In post-treatment follow-up studies, the symptoms most often seen six months to a year after treatment were short-term memory problems, fatigue, joint and muscle pain, and depression.*
(Asch-Bujak, Haupl-Krause, Natole-Schindeling, MIBDEC patient survey, Vanderhoof patient survey)
The question is, what is causing these lingering symptoms. Is it tissue damage, a chemical imbalance, an induced autoimmune response, psychological, or lingering active infection? I think it would be a very dangerous assumption to make an all or nothing hypothesis here and say it is all psychological or all active infection, etc. However, there must be a primary reason why such a significant number of Lyme patients continue to experience lingering symptoms post-antibiotic treatment. An argument for all of these reasons contributing to post-disease sequela could be made.
Here are five case histories of Lyme patients that suggest even long-term treatments of high dose antibiotics may not be enough to completely eradicate the Lyme pathogen from human tissues.
Case Histories and patient follow-up studies:
1. Ann Med 1999;31:225-232 (Jarmo Oski, M. Marjamaki, et al)
Abstract: A total of 165 patients with disseminated Lyme borreliosis (diagnosed in 1990-94, all seropositive except one culture-positive patient) were followed after antibiotic treatment, and 32 of them were regarded as having a clinically defined treatment failure. Of the 165 patients, 136 were tested by polymerase chain reaction (PCR) during the follow-up. PCR was positive from the plasma of 14 patients 0-30 months after discontinuation of the treatment, and 12 of these patients had a clinical relapse. In addition, Borrelia burgdorferi was cultured from the blood of three patients during the follow-up. All three patients belonged to the group with relapse, and two of them were also PCR positive. This report focuses on the 13 patients with clinical relapse and culture or PCR positive. Eight of the patients had culture or PCR-proven initial diagnosis; the diagnosis of the remaining five patients was based on positive serology only. All 13 patients were primarily treated for more than 3 months with intravenous and/or oral antibiotics (11 of them received intravenous ceftriaxone, nine for 2 weeks, one for 3 weeks and one for 7 weeks, followed by oral antibiotics). The treatment caused only temporary relief in the symptoms of the patients. All but one of them had negative PCR results immediately after the first treatment. The patients were retreated usually with intravenous ceftriaxone for 4-6 weeks. None of them was PCR positive after the retreatment. The response to retreatment was considered good in nine patients. We conclude that the treatment of Lyme borreliosis with appropriate antibiotics for even more than 3 months may not always eradicate the spirochete. By using PCR, it is possible to avoid unnecessary retreatment of patients with ‘post-Lyme syndrome’ and those with ‘serological scars’ remaining detectable for months or years after infection.
This abstract makes the point that PCR blood tests should be able to detect relapses. The article, however, did not compare PCR to other methods of diagnosis to know how many patients relying on PCR alone may miss. Also, all but one of the patients was PCR negative immediately after antibiotic therapy. The others did not become PCR positive until the patient’s symptoms made it clear that they had experienced a relapse. Fevers, sweats, and general malaise are usually indicative of infections in the blood. In other words, PCR of blood seems most likely to be positive when the infection has reseeded back into the bloodstream, but may not be able to detect treatment failures before the infection has become blood-borne a second time. It seems likely that a longer follow-up period after treatment could result in an even higher number of relapses. We simply don’t know how long it takes a sequestered infection hidden in an immune privileged site to seed back into the blood stream. It is likely that this is highly variable and cannot be predicted from patient to patient.
If the binding affinity of Borrelia burgdorferi to the central nervous system tissues is higher than the organism’s affinity for the blood stream, then the seeding back into the blood could simply be an accidental consequence of growing infection elsewhere in the body. Traveling back to the blood stream, and therefore the immune system, serves no advantage to the organism
If, as animal models suggest, the target tissues of the organism are the brain, heart, tendons, joints, and bladder, then blood samples are a poor choice for determining relapse. It is probably more of a convenience than using costlier, more time-consuming sampling methods that carry greater risks to the patient. A brain biopsy is generally not an option, but the following case history will show that a brain tissue sample is sometimes more revealing than a blood test.
2. A Case History of Dementia and Death in a Lyme Patient:
Journal of Neuropsychiatry Vol. 7, No.3 Summer 1995 (Cristina Waniek M.D., Isak Prohovnik Ph.D, Mavis A. Kaufman M.D., Andrew J. Dwork M.D.) Rapidly Progressive Frontal-Type Dementia Associated With Lyme Disease
This article describes a 47-year-old man who was a teacher and football coach for 25 years. He started having abrupt personality changes that affected his family and work. Although he had no other prior symptoms of Lyme disease, he lived and worked in an endemic area and was tested. He had a positive ELISA test. He was treated with four weeks of IV Rocephin, followed by six more weeks of high dose oral antibiotics. He experienced a significant improvement and returned to work. Five months later, he began to deteriorate again and had a rapid deterioration of cognitive abilities. His second ELISA test was negative. He was eventually admitted to a psychiatric hospital and placed on Haldol and other tranquilizers. At age 52, he died of aspiration pneumonia (Due to repeatedly choking because of his difficulty in swallowing). Silver staining (Dieterle Satin) of the cortical regions of his brain revealed spirochetes consistent with the Lyme bacteria, Borrelia burgdorferi.
The key here is to understand that the chances of his positive ELISA test cross-reacting to syphilis is about 1 in 10,000. It is most likely the spirochetes were, at the very least, borrelia – if not Borrelia burgdorferi, which are endemic to his neighborhood.
The result of an infection cleared from the bloodstream by antibiotics is that the immune system will slow down or stop the production of antibodies. This is not the same thing as suppression of the immune system. It is simply removing the stimulus for an antibody response, namely the bacteria. Since the brain is not immuno-competent (no cells in the brain can produce antibodies), an infection trapped in the brain but absent from the bloodstream could result in negative serologies for antibodies. In other words, the incomplete treatment of this infection not only resulted in the infection surviving in the brain, it also contributed to the body shutting down its natural immunity to continue fighting the infection. The loss of stimulation of the immune cells by active infection in the blood may contribute to worsening the patient’s condition if the infection is trapped in immune-sequestered areas of the body, such as the brain. If you take away the body’s immune defenses and then take away the antibiotics prematurely, what is left to stop a growing infection trapped in the brain? *
* (This is a theory that has yet to be tested in the primate model of Lyme disease.)
3. A Case History of Culture Positive Lyme disease Post-Prolonged Antibiotic Therapy:
Infectious Disease In Clinical Practice, Vol.3, No.3 (Ed Masters M.D.) Spirochetemia After Continuous High-Dose Oral Amoxicillin Therapy
A 40-year-old white male from Southern Illinois received a bite from a Lonestar tick and developed a bull’s-eye rash consistent with Lyme disease. He then started to develop multi-system symptoms consistent with Lyme disease, including short-term memory loss, heart palpitations, paratheisias, and joint and muscle pain. He was placed on 1500 mg of amoxicillin three times a day for six months. His symptoms improved. After discontinuing the medication, he had a prompt relapse of symptoms and within two weeks of discontinuation of the amoxicillin, he started worsening again. One month later, his serum was placed in BSK culture media and sent to the Texas department of health, where spirochetes consistent with Borrelia burgdorferi were successfully cultured and transferred to a new culture. The cultures stained for Borrelia burgdorferi membrane and were also PCR positive for Borrelia OSP-A and OSP-B DNA primers.
Both the dosage and the length of antibiotic treatment were considered adequate, if not excessive, by the standard of care at the time. Despite a lengthy treatment and an improvement of symptoms, a relapse in symptoms occurred almost immediately after discontinuation of therapy, and the infection was cultured. This indicates that the Lyme spirochete has mechanisms by which it can survive in the human body despite massive amounts of antibiotics given for extended lengths of time.
4. Case History: Recurrence of Lyme Disease as a Chest Wall Mass
Craig P. Cleveland M.D., Patricia S. Dennler R.N. (Abstract presented at the 1993 LDF International Conference on Lyme Disease)
A 59-year-old white male was vacationing with his wife in Buffalo, New York. He developed multiple symptoms consistent with Lyme disease, including fevers, sweats, chills, fatigue, irritation of the bladder, chest pain, palpitations, joint and muscle pain, parathisias (numbness and tingling in hands and feet), confusion, memory loss, and sleep disturbances. Although he tested negative by ELISA test for Lyme disease, his wife, who was experiencing similar symptoms, was highly positive. Both were treated and the wife responded well. The husband was treated with 400 mg of Suprax twice a day for three months. Due to lack of a strong recovery, he was placed on 2 grams of IV Rocephin for an additional five months. He responded and was doing well off the antibiotics until he developed a discomfort in his chest. A growing fibrous mass approximately 3 inches by 4 inches was found extending into the ribs and eroding the sternum. The mass was surgically removed and sent to pathology. Spirochetes identified as Borrelia burgdorferi were discovered in several biopsies of the mass.
Despite eight months of high dose, continuous therapy, this patient had an active Lyme infection that was either causing or contributing to the fibrous mass growing in the patient’s chest. We now know that N-Acetyl Glucosamine (NAG) is a food source for the bacteria, and pathologically the Lyme bacteria is often found associated with fibrous tissues, including connective tissue, joints, tendons, and in between the purkinge of the heart fibers (a network of nerves that induce the heart to contract), where NAG is abundant.
A key point to notice in this case history is that the wife had fewer symptoms and responded better to therapy. She also had a high antibody titer. In other words, she had a higher level of natural immunity than her husband. His Lyme antibodies were too low to measure with a standard ELISA test. This might suggest that patients with low or negative antibody responses are more prone to extended infections with more complications. Why do some patients have a better antibody response?
5. Borrelia burgdorferi revealed in the cortical areas of the brain of a patient diagnosed with early, but rapidly progressive senile dementia.
A 65-year-old man living in northern Wisconsin started developing chest pains, palpitations, memory loss, confusion, and loss of motor skills. After a period of several years of worsening symptoms, he was placed in full-time nursing care. Around the same time, his youngest son was diagnosed with advancing rheumatoid arthritis and depression, and his other son was diagnosed with multiple sclerosis and depression. All three were avid hunters and fishermen who traveled throughout Lyme-endemic areas of Wisconsin. The two sons were eventually diagnosed with Lyme disease and responded slowly to high-dose antibiotics. They questioned whether their father’s similar symptoms were also being caused or worsened by Lyme disease. The physicians tending their father were adamant that neither the father nor the sons could have Lyme disease, and they refused to administer any test for the disease. When the father died, the family had his brain sectioned and stained for spirochetes by Dr. Alan MacDonald, a pathologist familiar with the procedure. Documented in over twelve cross- sections of the cortical region of the brain was the presence of clearly defined spirochetes consistent with Borrelia burgdorferi. A serial cross-section of a cluster of neurons revealed a spirochete that was halfway penetrated into a brain cell. Intracellular invasion of brain neurons had not been seen before in either human nor primate models of Lyme disease.
This case represents a failure of the medical community to address the possibility that the patient had Lyme disease prior to death. Their decision was based on the fact that no bull’s-eye rash had been observed as well as their belief that prior antibiotic use for pneumonia and skin infections would have been curative if he had had Lyme disease. However, I believe that we have a case of three close family members with a severe form of Lyme disease who responded poorly and slowly to antibiotics and had low levels of naturally occurring antibodies.
In light of a recent book, ‘Plague Time’, by Dr. Paul Ewald, rather than abandoning these three individuals as being unrelated cases of Lyme disease, we should be looking for genetic markers suggesting a propensity, or affinity, of the Lyme organism to take hold in these individuals. A genetic weakness that allows the infection to thrive and the immune system to not respond would explain why Lyme disease devastates some families and others are only briefly inconvenienced.
In his book, Dr. Paul Ewald explains that much illness not normally associated with bacteria and viruses, such as multiple sclerosis, may in fact be initiated, or exacerbated, by infections. Those individuals who succumb to the infection may have genetic reasons why they are more at risk than others. With each new decade, we are in fact finding more association of infection with diseases, such as cancer and leukemia. If this theory turns out to have merit, then before having a blood test for Lyme disease, we may have a genetic marker test that will tell us which diseases we are at greatest risk for, and which patients may require more sustained therapy than others.
It is evident from case histories of Lyme patients that not all respond the same way to infection, nor do they respond equally to treatment. The question we must answer is why? Genetic tropisms may account for some of the differences. Rather than investigate this area of science, the majority of the medical community lump Lyme patients into an all-or-nothing category of diagnosis and treatment; diagnosis through a blood test and treatment for two weeks using the least expensive antibiotic available. (MIBDEC Lyme Patient Survey)
Until we understand why some Lyme patients respond to short-term antibiotic treatment while others don’t, any treatment guidelines setting limitations on therapy are going to condemn some individuals to severe, unabated infections. How many Lyme patients are disabled – or die – from complications of incompletely treated Lyme disease? This can only be determined by doing extensive autopsies on Lyme patients who die from undetermined causes.