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.
Two Standards Of Care For Lyme Disease Treatment
There is significant controversy in science, medicine, and public policy regarding Lyme disease. Two medical societies hold widely divergent views on the best approach to diagnosing and treating Lyme disease. The conflict makes it difficult for patients to be properly diagnosed and receive treatment.
One medical society, the Infectious Diseases Society of America , regards Lyme disease as hard to catch and easy to cure with a short course of antibiotics. IDSA claims that spirochetal infection cannot persist in the body after a short course of antibiotics. The group also denies the existence of chronic Lyme disease.
In contrast, the International Lyme and Associated Diseases Society , regards Lyme disease as often difficult to diagnose and treat, resulting in persistent infection in many patients. ILADS recommends individualized treatment based on the severity of symptoms, the presence of tick-borne coinfections and patient response to treatment.
LDo believes that patients and their doctors should make Lyme disease treatment decisions together. This requires that patients be given sufficient information about the risks and benefits of different treatment options. Then, patient and health care provider can collaborate to reach an informed decision, based on the patients circumstances, beliefs and preferences.
Risk Factors For Post
Youre at a greater risk for post-treatment Lyme disease syndrome if youre infected by the bite of a diseased tick. If the infection progresses to the chronic stage, your symptoms might continue for weeks, months, or even years after the initial tick bite.
You may also be at a higher risk for these long-term symptoms if youre not treated with the recommended antibiotics. However, even people who receive antibiotic therapy are at risk. Because the cause of post-treatment Lyme disease syndrome is unknown, theres no way to determine whether it will progress to the chronic stage.
Typically, the symptoms of post-treatment Lyme disease syndrome resemble those that occur in earlier stages. People with persistent symptoms often experience lingering episodes of:
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What Is The Treatment For Lyme Disease
The first-line standard of care treatment for adults with Lyme disease is doxycycline, a tetracycline antibiotic. Other antibiotics that have activity against borrelia include the penicillin-like antibiotic, amoxicillin, and the second generation cephalosporin, Ceftin. The mainstay of treatment is with oral antibiotics, but intravenous antibiotics are sometimes indicated for more difficult to treat cases of neurologic-Lyme disease, such as meningitis, and cases of late Lyme arthritis.
Considerations While On Lyme Treatment
Antibiotics can wipe out beneficial intestinal flora, leading to a wide variety of additional health problems. It is important to take probiotics while on antibiotics to maintain a healthy balance of gut bacteria. Furthermore, antibiotics may interact with other drugs, supplements or food. The National Institutes of Healths MedLinePlus website gives information about drug interactions.
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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.
Treatment Approach To Chronic Lyme Disease
What is the approach for a patient who presents with persistent symptoms of Lyme disease ? First, the Lyme Western blot should be repeated, and coinfection testing should be performed by a laboratory that is proficient in tickborne disease analysis. At the same time, other medical problems that could cause persistent symptoms should be ruled out. Measurement of the CD57 natural killer cell level, which is an immunologic marker that can be used to monitor treatment in chronic Lyme disease, should be performed . If neurologic symptoms are severe, a single-photon emission CT SPECT brain scan should be obtained, to see how much inflammation is present in the brain. Neuropsychiatric evaluation may also be helpful .
On the basis of these results, coinfections should be treated first, if any are present, and then oral or parenteral antibiotics should be used to treat symptoms of persistent Lyme disease. Antibiotic therapy should be administered in a rotating and open-ended manner, in conjunction with probiotics, to minimize adverse effects . Monitoring of clinical symptoms, CD57 natural killer cell levels, and markers of inflammation should be performed in conjunction with treatment .
Precedents for prolonged antibiotic therapy.
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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.
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.
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Why This Is Important
The use and duration of antibiotics for chronic Lyme disease treatment is controversial because there is no biomarker that can determine whether the Lyme bacteria has been eradicated in CLD patients. Patients are often told that either chronic Lyme disease does not exist or that it is incurable. If this were true, we would not expect more well and substantially improved patients to be taking antibiotics. Instead, we might have expected the percentage of people using antibiotics to be roughly the same among the patient subgroups.
How To Prevent Post
While you may not be able to prevent post-treatment Lyme disease syndrome, you can take precautions to prevent coming into direct contact with infected ticks. The following practices can reduce your likelihood of getting Lyme disease and developing persistent symptoms.
If a tick bites you, contact your doctor. You should be observed for 30 days for signs of Lyme disease. You should also learn the signs of early Lyme disease and seek prompt treatment if you think youre infected. Early antibiotic intervention may reduce your risk of developing chronic symptoms.
The signs of early Lyme disease can occur from 3 to 30 days after a bite from an infected tick. Look for:
- a red, expanding bulls-eye rash at the site of the tick bite
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Supporting Patients With Long
There has been controversy about Lyme disease , first about whether people really can have persistent problems after Lyme disease, and then about whether more antibiotic treatment is beneficial if they do still have symptoms. This overview compiles into one summary information about what the studies have found about the cause of the symptoms and the possible treatments, so that GPs are better able to advise patients who have the long-term problems.
Some patients have persistent symptoms after LD, despite having had the recommended antibiotic treatment. A small proportion of LD patients have a relevant delay in treatment, which may increase their risk for the development of problems that can last a long time, perhaps a few years. These delays can sometimes result from the difficulty of diagnosis, particularly as many LD cases do not have the erythema migrans rash. Catching LD while holidaying abroad may make a delay more likely because it may be some time before the patient returns home and sees a doctor. The Royal College of General Practitioners has prepared an LD toolkit and mentions post-treatment Lyme disease syndrome as one term used to describe these long-term problems. PTLDS can significantly impact quality of life and recovery may be extremely slow, with no apparent improvement from one month to the next, although very subtle improvement may be seen from one year to the next.
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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Genetic Phase And Antigenic Variation
B. burgdorferi engages in genetic, phase, and antigenic variation that shares various features with other organisms . For example, gene switching is similar to what is seen with trypanosomes, mutation and recombination are typical of HIV, variable antigen expression is seen with Neisseria species, autoinduction of dormant organisms occurs in mycobacterial infection, and fibronectin binding occurs with staphylococcal and streptococcal infection.
B. burgdorferi may assume a dormant state with cyst formation . Although spirochetal persistence in the cyst form is a controversial issue, it has recently been shown that neutrophil calprotectin can induce a dormant state in the spirochete, allowing it to persist in tissue without replicating and providing the means to avoid antibiotics .
Although antibiotic resistance associated with gene mutation was previously thought to be rare in B. burgdorferi infection , recent studies have demonstrated gene mutations in the Lyme spirochete that confer in vitro resistance to various antibiotics . The clinical implication of these gene mutations is uncertain at present.
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.
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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.
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.
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What Are The Side Effects Of Lyme Disease Treatments
Antibiotics, like all medications, have the potential for side effects. Any antibiotic can cause skin rashes, and if an itchy red rash develops while on antibiotics, a patient should see their physician. Sometimes symptoms worsen for the first few days on an antibiotic. This is called a Herxheimer reaction and occurs when the antibiotics start to kill the bacteria. In the first 24 to 48 hours, dead bacterial products stimulate the immune system to release inflammatory cytokines and chemokines that can cause increased fever and achiness. This should be transient and last no more than a day or two after the initiation of antibiotics.
The most common side effect of the penicillin antibiotics is diarrhea, and occasionally even serious cases caused by the bacteria Clostridium difficile. This bacterial overgrowth condition occurs because antibiotics kill the good bacteria in our gut. It can be helpful to use probiotics to restore the good bacteria and microbiome balance.
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.
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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.