Coinfection With Tickborne Agents
In addition to infection with B. burgdorferi, tickborne coinfections are being recognized more frequently. If a patient is treated for Lyme disease and has symptoms that have persisted or worsened, the lack of improvement may be due to the presence of Babesia, Anaplasma, Ehrlichia, or Bartonella coinfection . Coinfection with Babesia and Ehrlichia has been shown to exacerbate Lyme disease in mouse models and also in humans . Traditionally, Babesia, Anaplasma, Ehrlichia and Bartonella are thought to produce acute fulminant infections, but in fact these pathogens may cause low-grade infections that can increase the severity and duration of Lyme disease .
A disturbing study from New Jersey examined the prevalence of coinfections in Ixodes ticks that transmit Lyme disease . In that study, the prevalence of B. burgdorferi infection was 33.6%, but the prevalence of Bartonella infection was 34.5%. Thus, Bartonella species were found more often than the Lyme spirochete in these ticks. This observation presages a greater problem with Bartonella infection associated with tick exposure in the near future.
Pathophysiology Of Lyme Disease
B. burgdorferi is a fascinating bacterium . It has < 1500 gene sequences with at least 132 functioning genes. In contrast, Treponema pallidum, the spirochetal agent of syphilis, has only 22 functioning genes. The genetic makeup of B. burgdorferi is quite unusual. It has a linear chromosome and 21 plasmids, which are extrachromosomal strands of DNA. This is 3 times more plasmids than any other known bacteria . Plasmids are thought to give bacteria a kind of rapid response system that allows them to adapt very rapidly to changes in the environment, and the complex genetic structure of B. burgdorferi suggests that this is a highly adaptable organism .
In addition to its complex genetic makeup, B. burgdorferi engages in so-called stealth pathology to evade the human immune response . Stealth pathology involves 4 basic strategies: immunosuppression genetic, phase, and antigenic variation physical seclusion and secreted factors . These strategies are outlined below.
Stealth pathology of Borrelia burgdorferi.
Azlocillin Comes Out On Top
The drug, which is not on the market, was tested in mouse models of Lyme disease at seven-day, 14-day and 21-day intervals and found to eliminate the infection. For the first time, azlocillin was also shown to be effective in killing drug-tolerant forms of B. burgdorferi in lab dishes, indicating that it may work as a therapy for lingering symptoms of Lyme disease.
Pothineni and Rajadas have patented the compound for the treatment of Lyme disease and are working with a company to develop an oral form of the drug. Researchers plan to conduct a clinical trial.
Rajadas is also a professor of bioengineering and therapeutic sciences at the University of California-San Francisco.
Other Stanford co-authors are Hari-Hara S. K. Potula, PhD, senior research scientist postdoctoral scholars Aditya Ambati, PhD, and Venkata Mallajosyula, PhD senior research scientist Mohammed Inayathullah, PhD and intern Mohamed Sohail Ahmed.
A researcher at Loyola College in India also contributed to the work.
The study was funded by the Bay Area Lyme Foundation and Laurel STEM Fund.
- Tracie White
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Antibiotics And Alternative Medicine
Of course, LLMDs would beg to differ. Many maintain that one of the best ways to treat chronic Lyme patients is with a long-term course of antibiotics, claiming the typical month-long course of treatment isnt enough to eradicate the disease in certain individuals.
Londons Lyme Disease Clinic founder and medical director Dr Joshua Berkowitz says: Long-term treatment with antibiotics is necessary to target and kill all the different pleomorphic forms of the bacteria and parasitic infections associated with chronic Lyme disease. Most of these bacteria have the ability to survive based on different mechanisms and they can easily change their shape and surface.
They can hide in other body cells and in intracellular spaces, plus they can invade specific tissues like connected tissue where there is no presence of immune cells which can kill them off. With the support of antibiotics we are able to take care of all these escape mechanisms, but it requires long-term treatment to do so.
Many chronic Lyme patients given a long-term course of antibiotics report feeling better afterwards. But, feeling better on an antibiotic is not a sure fire way to establish that it has actually killed a harmful bacteria, and some argue this approach can actually be dangerous.
A 2015 report in Clinical Infectious Diseases found that the efficacy for these unconventional treatments could not be supported by scientific evidence, and many could potentially be harmful.
Treatment Of Lyme Disease
With this background concerning the clinical diagnostic problems, complex pathophysiology, and testing difficulties related to B. burgdorferi, we arrive at the topic of this debate, which is treatment failure in Lyme disease. Documented treatment failure with culture-confirmed B. burgdorferi infection was first reported < 17 years ago by Preac-Mursic et al. , so it was surprising to see a quotation in the New York Times by 2 members of the Infectious Diseases Society of America Lyme disease guidelines committee stating that is no credible scientific evidence for the persistence of symptomatic B. burgdorferi infection after antibiotic treatment . Let’s review the credible scientific evidence for persistence of this infection taken from articles published over the past 17 years.
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Potential Treatment For Lyme Disease Kills Bacteria That May Cause Lingering Symptoms Study Finds
Screening thousands of drugs, Stanford scientists determined that in mice, azlocillin, an antibiotic approved by the Food and Drug Administration, eliminated the bacteria that causes Lyme disease.
Deer ticks are vectors of Borrelia burgdorferi, the bacteria that causes Lyme disease.Scott Bauer/USDA Agricultural Research Service
For decades, the routine treatment for Lyme disease has been standard antibiotics, which usually kill off the infection. But for up to 20% of people with the tick-borne illness, the antibiotics dont work, and lingering symptoms of muscle pain, fatigue and cognitive impairment can continue for years sometimes indefinitely.
A new Stanford Medicine study in lab dishes and mice provides evidence that the drug azlocillin completely kills off the disease-causing bacteria Borrelia burgdorferi at the onset of the illness. The study suggests it could also be effective for treating patients infected with drug-tolerant bacteria that may cause lingering symptoms.
This compound is just amazing, said Jayakumar Rajadas, PhD, assistant professor of medicine and director of the Biomaterials and Advanced Drug Delivery Laboratory at the Stanford School of Medicine. It clears the infection without a lot of side effects. We are hoping to repurpose it as an oral treatment for Lyme disease. Rajadas is the senior author of the study, which was published online March 2 in Scientific Reports. The lead author is research associate Venkata Raveendra Pothineni, PhD.
Success With Botanicals And Essential Oils
Botanical medicines are the cornerstones of any Functional Medicine approach, and there are plenty of protocols that have proved effective for treating Lyme Disease. In fact, one of the things Dr. Kahn and our team do here at our Spring, Texas location is figure out which botanicals and oils will prove most effective in individual cases.
The Buhner Protocol this is centered around Cats Claw, Andrographis, and Japanese Knotweed, with the potential for additions like Smilax and Astragalus depending on the patients unique situation.
These companies all provide natural formulas for treating
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What Are The Risk Factors For Post Treatment Lyme Disease
Risk factors for Post Treatment Lyme Disease include:
- Delay in diagnosis
- Increased severity of initial illness
- Presence of neurologic symptoms
Increased severity of initial illness, the presence of neurologic symptoms, and initial misdiagnosis increase the risk of Post Treatment Lyme Disease. PTLD is especially common in people that have had neurologic involvement. The rates of Post Treatment Lyme Disease after neurologic involvement may be as high as 20% or even higher. Other risk factors being investigated are genetic predispositions and immunologic variables.
In addition to Borrelia burgdorferi, the bacteria that causes Lyme disease, there are several other tick-borne co-infections that may also contribute to more prolonged and complicated illness.
Prolonged Lyme Disease Treatment: Enough Is Enough
- Lorraine Johnson, JD, MBA
Dr. Halperin’s editorial accompanies publication of the long-awaited NIH- sponsored randomized controlled trial by Fallon et al. from Columbia University. The Columbia study concludes that patients with chronic neurologic symptoms of Lyme disease benefit from longer therapy with intravenous antibiotics, despite the fact that these patients had been sick for an average of nine years and had failed prior treatment. Halperin disagrees with the study conclusion.
The Columbia study found improvement after 10 weeks of retreatment, but relapse when treatment was withdrawn. This clinical pattern has been reported for years in Lyme disease patients, consistent with persistent infection with the Lyme spirochete. . The Columbia study confirms that the quality of life in chronic Lyme disease is worse than in congestive heart failure. For these patients the math is simple: without treatment, there can be no improvement in quality of life. In treatment terms, not enough is not enough.
References
3. Johnson L, Stricker RB. Treatment of Lyme disease: A medicolegal assessment. Expert Rev Anti-Infect Ther 2004 2:533-557.
4. Phillips SE, Harris NS, Horowitz R, Johnson L, Stricker RB. Lyme disease: scratching the surface. Lancet 2005 366:1771.
5. Stricker RB. Counterpoint: Long-term antibiotic therapy improves persistent symptoms associated with Lyme disease. Clin Infect Dis 2007 45:149-157.
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Hosp: Patient: With: Ivjpg
The Centers for Disease Control and Prevention published five case studies today in Morbidity and Mortality Weekly Report of patients who experienced serious complications and bacterial infections after receiving treatments for “chronic Lyme” disease.
There is no medical definition of “chronic Lyme” and no treatment guidelines instead, the term is used by patients and some providers to describe several symptoms, including fatigue and muscular pain, attributed to prior infection with Lyme disease. Many patients with a chronic Lyme diagnosis, however, test negative for Borrelia burgdorferi, the bacteria associated with the ticks that carry Lyme.
Some practitioners, including alternative medicine professionals who advertise themselves as being “Lyme literate” prescribe long-term courses of antibiotics and immunoglobulin therapy. But the CDC warns that treating an undiagnosed condition with an unregulated treatment plan can be dangerous for patients.
“At least five randomized, placebo-controlled studies have shown that prolonged courses of IV antibiotics in particular do not substantially improve long-term outcome for patients with a diagnosis of chronic Lyme disease and can result in serious harm, including death,” the authors write.
Symptoms Of Post Treatment Lyme Disease
- Include severe fatigue, musculoskeletal pain, & cognitive problems
- Can significantly impact patients health and quality of life
- Can be debilitating and prolonged
Our research indicates the chronic symptom burden related to PTLD is significant. Although often invisible to others, the negative impact on quality of life and daily functioning is substantial for PTLD sufferers.
The chronic symptom burden related to Lyme disease is considerable, as shown on the left side of the graph above, and statistically significantly greater than the aches and pains of daily living experienced by the control group, on the right.
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Has Niaid Looked At Whether Infection Persists After Antibiotic Therapy
Several recent studies suggest that B. burgdorferi may persist in animals after antibiotic therapy. In one study, NIAID-supported scientists found that remnants of B. burgdorferi remained in mice after antibiotic treatment. Another team of NIAID-supported investigators found that intact B. burgdorferi persist in nonhuman primates after antibiotic treatment. It was not possible to culture these bacteria and it is not clear whether they are infectious. More recent work by Hodzic et al. replicated the earlier finding of persisting DNA but non-cultivatable B. burgdorferi after antibiotic treatment using a mouse model. In 2017, scientists at the Tulane National Primate Research Centers, funded in part by an NIH research resources grant, reported evidence of persistent and metabolically active B. burgdorferi after antibiotic treatment in rhesus macaques.
In a first-of-its-kind study for Lyme disease, NIAID-supported researchers have used live, disease-free ticks to see if Lyme disease bacteria can be detected in people who continue to experience symptoms such as fatigue or arthritis after completing antibiotic therapy). This study remains underway.
Type Of Clinician Overseeing Care
We asked patients to tell us the type of clinician overseeing their care. Choices included: family physicians, internists, rheumatologists, infectious disease specialists, and clinicians whose practice focused on tick-borne diseases . Very few patients selected an infectious disease specialist. Seventy-five percent of high responders and well patients report having their care overseen by an LLMD.
Physicians who treat Lyme disease as their primary focus might be expected to have better results than physicians who dont simply because volume of cases handled means a greater experience level. It is commonly recognized in medicine that volume of cases is associated with better treatment outcomes . Just as patients with cancer commonly seek out physicians who specialize in that area, perhaps patients with chronic Lyme disease should also.
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Why Are Antibiotics The First Line Of Treatment For Lyme Disease
The use of antibiotics is critical for treating Lyme disease. Without antibiotic treatment, the Lyme disease causing bacteria can evade the host immune system, disseminate through the blood stream, and persist in the body. Antibiotics go into the bacteria preferentially and either stop the multiplication of the bacteria or disrupt the cell wall of the bacteria and kill the bacteria . By stopping the growth or killing the bacteria the human host immune response is given a leg up to eradicate the residual infection. Without antibiotics, the infection in Lyme disease can evade the host immune system and more readily persist.
What Is Post Treatment Lyme Disease
Post Treatment Lyme Disease represents a research subset of patients who remain significantly ill 6 months or more following standard antibiotic therapy for Lyme disease. PTLD is characterized by a constellation of symptoms that includes severe fatigue, musculoskeletal pain, sleep disturbance, depression, and cognitive problems such as difficulty with short-term memory, speed of thinking, or multi-tasking. In the absence of a direct diagnostic biomarker blood test, PTLD has been difficult to define by physicians, and its existence has been controversial. However, our clinical research shows that meticulous patient evaluation when used alongside appropriate diagnostic testing can reliably identify patients with a history of previously treated Lyme disease who display the typical symptom patterns of PTLD.
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Early Lyme Disease Treatment
ILADS doctors are likely to recommend more aggressive and longer antibiotic treatment for patients. They may, for instance, treat high risk tick bites where the tick came from an endemic area, was attached a long time, and was removed improperly. They may treat a Lyme rash for a longer period of time than the IDSA recommends, to ensure that the disease does not progress. They are unlikely to withhold treatment pending laboratory test results.
For Memory Concentration And Focus
Improving memory is a challenge. In Lyme disease, short-term memory problems and word-retrieval problems are common. These often improve substantially with appropriate antibiotic therapy. Over time, most patients regain their cognitive function.
When memory is a problem, consider that this could due to a primary problem with attention or with mood. An individual who can’t focus won’t be able to remember because he/she didn’t “attend” to the item in the first place. This happens to all of us when we hear someone’s name at a party if we don’t focus on the name and perhaps make a mental association to the name to enhance memory storage, we will forget that name within minutes. Patients with depression often experience problems with memory and verbal fluency when the depression is resolved, the memory and verbal fluency typically resolve as well.
- Medications: Attention can be improved with certain medications, such as bupropion , atomoxetine , modafinil , or stimulants . Medications that temporarily slow cognitive decline in Alzheimer’s disease or memantine ) have not been studied in Lyme disease.
- There is some evidence that online brain training programs can enhance concentration or processing speed.
- Neurofeedback may be helpful in improving attention, as well as in improving sleep and reducing pain. This has been studied for migraines, fibromyalgia, and ADHD.
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What If Lyme Disease Treatment Goes On For Years
While the media and the Internet tend to report the very worst cases of Lyme disease, about 80 percent of people who get the disease get over it in a few weeks. In 10 to 20 percent of people who have Lyme disease, however, the symptoms go on for months or years.
Other studies have looked at long-term antibiotic therapy for Lyme disease. The Persistent Lyme Empiric Antibiotic Study Europe study involved 280 people who had symptoms, on average, for 2-1/2 years. These were people who had had the bulls eye rash or persistently achy joints or other symptoms of Lyme disease for years, but who had not been diagnosed at the likely time of the tick bite. Everyone was given Rocephin by IV for 14 days to “knock out” the infection, and then they were given the same treatment options as the groups mentioned above. When symptoms were longstanding, doxocycline was superior in controlling Lyme disease to placebo, but not by much, and about half the people who received antibiotics had problems with diarrhea, nausea, or allergic rashes. These problems did not occur in the placebo group.
Concern Over Resistance Other Complications
According to the CDC, it is not known how many people seek treatment for chronic Lyme, or how many complications occur during the course of treatment.
“In addition to the dangers associated with inappropriate antibiotic use, such as selection of antibiotic-resistant bacteria, these treatments can lead to injuries related to unnecessary procedures, bacteremia and resulting metastatic infection, venous thromboses, and missed opportunities to diagnose and treat the actual underlying cause of the patients symptoms,” the authors conclude.
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